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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)

    Highlights: ► Burkholderia xenovorans LB400 biphenyl dioxygenase (BphAELB400) metabolizes PCBs. ► Asn338Gln/Leu409Phe double mutation speeds up electron transfer of enzyme reaction. ► We tested how the mutations affect the PCB-degrading abilities of BphAELB400 variants. ► The same mutations also broaden the PCB substrate range of BphAELB400 variants. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAELB400) catalyzes the dihydroxylation of biphenyl and of several polychlorinated biphenyls (PCBs) but it poorly oxidizes dibenzofuran. In this work we showed that BphAERR41, a variant which was previously found to metabolize dibenzofuran more efficiently than its parent BphAELB400, metabolized a broader range of PCBs than BphAELB400. Hence, BphAERR41 was able to metabolize 2,6,2′,6′-, 3,4,3′,5′- and 2,4,3′,4′-tetrachlorobiphenyl that BphAELB400 is unable to metabolize. BphAERR41 was obtained by changing Thr335Phe336Asn338Ile341Leu409 of BphAELB400 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

    International Nuclear Information System (INIS)

    Highlights: ► Regiospecificity of BphAERR41 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 (BphAELB400) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAELB400 and obtained BphAERR41. This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAELB400. However, the regiospecificity of BphAERR41 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 BphAERR41 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 BphAERR41:dibenzofuran. In BphAERR41:2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAERR41:dibenzofuran, and strong enough in the BphAERR41:2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

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

    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.

  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

    International Nuclear Information System (INIS)

    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

  9. Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD)

    Energy Technology Data Exchange (ETDEWEB)

    Awata, H.; Endo, F.; Matsuda, I. [Kumamoto Univ. (Japan)

    1994-10-01

    4-Hydroxyphenylpyruvic acid dioxygenase (HPD) is an important enzyme in tyrosine catabolism in most organisms. The activity of this enzyme is expressed mainly in the liver and developmentally regulated in mammals, and a genetic deficiency in this enzyme in humans and mice leads to hereditary tyrosinemia type 3. Using human HPD cDNA as a probe, a chromosomal gene related to HPD was isolated from human gene libraries. The human HPD gene is over 30 kb long and is split into 14 exons. The extract sizes and boundaries of exon blocks were determined, and all of the splice donor and acceptor sites conformed to the GT/AG rule. Analysis of the 5{prime} flanking sequence of the gene suggests that expression of the gene is regulated by hepatocyte-specific and liver-enriched transcription factors, as well as by hormones. These features of the 5{prime} flanking region of the gene are similar to those of other genes that are specifically expressed in hepatocytes and that are developmentally regulated. 41 refs., 2 figs., 1 tab.

  10. Structural investigations of the ferredoxin and terminal oxygenase components of the biphenyl 2,3-dioxygenase from Sphingobium yanoikuyae B1

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    Gibson David T

    2007-03-01

    Full Text Available Abstract Background The initial step involved in oxidative hydroxylation of monoaromatic and polyaromatic compounds by the microorganism Sphingobium yanoikuyae strain B1 (B1, previously known as Sphingomonas yanoikuyae strain B1 and Beijerinckia sp. strain B1, is performed by a set of multiple terminal Rieske non-heme iron oxygenases. These enzymes share a single electron donor system consisting of a reductase and a ferredoxin (BPDO-FB1. One of the terminal Rieske oxygenases, biphenyl 2,3-dioxygenase (BPDO-OB1, is responsible for B1's ability to dihydroxylate large aromatic compounds, such as chrysene and benzo[a]pyrene. Results In this study, crystal structures of BPDO-OB1 in both native and biphenyl bound forms are described. Sequence and structural comparisons to other Rieske oxygenases show this enzyme to be most similar, with 43.5 % sequence identity, to naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. While structurally similar to naphthalene 1,2-dioxygenase, the active site entrance is significantly larger than the entrance for naphthalene 1,2-dioxygenase. Differences in active site residues also allow the binding of large aromatic substrates. There are no major structural changes observed upon binding of the substrate. BPDO-FB1 has large sequence identity to other bacterial Rieske ferredoxins whose structures are known and demonstrates a high structural homology; however, differences in side chain composition and conformation around the Rieske cluster binding site are noted. Conclusion This is the first structure of a Rieske oxygenase that oxidizes substrates with five aromatic rings to be reported. This ability to catalyze the oxidation of larger substrates is a result of both a larger entrance to the active site as well as the ability of the active site to accommodate larger substrates. While the biphenyl ferredoxin is structurally similar to other Rieske ferredoxins, there are distinct changes in the amino acids near

  11. Molecular Cloning and Characterization of a New Cold-active Extradiol Dioxygenase from a Metagenomic Library Derived from Polychlorinated Biphenyl-contaminated Soil

    Institute of Scientific and Technical Information of China (English)

    REN He-jun; LU Yang; ZHOU Rui; DAI Chun-yan; WANG Yan; ZHANG Lan-ying

    2012-01-01

    To find new extradiol dioxygenases(EDOs,EC 1.13.11.2),a metagenomics library was constructed from polychlorinated biphenyl-contaminated soil and was screened for some dioxygenase with aromatic ring cleavage activity.A novel EDO,designated as BphC_A,was identified and heterologously expressed in Escherichia coli.The deduced amino acid sequence of BphC_A exhibited a homology of less than 60% with other known EDOs.Phylogenetic analysis of BphC_A suggests that the protein is a novel member of the EDO family.The enzyme exhibits higher substrate affinity and catalytic efficiency toward 3-methylcatechol than toward 2,3-dihydroxybiphenyl or catechol,the preferred substrate of other known EDOs.The optimum activity of purified BphC_A occurred at pH=8.5 and 35 ℃,and BphC_A showed more than 40% of its initial activity at 5 ℃.The activity of purified BphC_A was significantly induced by Mn2+ and slightly reduced bv Al3+,Cu2+ and Zn2+.

  12. Anaerobic crystallization and initial X-ray diffraction data of biphenyl 2,3-dioxygenase from Burkholderia xenovorans LB400: addition of agarose improved the quality of the crystals

    International Nuclear Information System (INIS)

    Biphenyl 2,3-dioxygenase from B. xenovorans LB400 and its variants BPDOP4 and BPDORR41 were crystallized using agarose gel and the crystals were characterized using X-ray diffraction. Biphenyl 2,3-dioxygenase (BPDO; EC 1.14.12.18) catalyzes the initial step in the degradation of biphenyl and some polychlorinated biphenyls (PCBs). BPDOLB400, the terminal dioxygenase component from Burkholderia xenovorans LB400, a proteobacterial species that degrades a broad range of PCBs, has been crystallized under anaerobic conditions by sitting-drop vapour diffusion. Initial crystals obtained using various polyethylene glycols as precipitating agents diffracted to very low resolution (∼8 Å) and the recorded reflections were diffuse and poorly shaped. The quality of the crystals was significantly improved by the addition of 0.2% agarose to the crystallization cocktail. In the presence of agarose, wild-type BPDOLB400 crystals that diffracted to 2.4 Å resolution grew in space group P1. Crystals of the BPDOP4 and BPDORR41 variants of BPDOLB400 grew in space group P21

  13. Isolation and characteristics of a novel biphenyl-degrading bacterial strain, Dyella ginsengisoli LA-4

    Institute of Scientific and Technical Information of China (English)

    LI Ang; QU Yuanyuan; ZHOU Jiti; GOU Min

    2009-01-01

    A novel biphenyl-degrading bacterial strain LA-4 was isolated from activated sludge. It was identified as Dyella ginsengisoli according to phylogenetic similarity of 16S rRNA gene sequence. This isolate could utilize biphenyl as sole source of carbon and energy, which degraded over 95 mg/L biphenyl within 36 h. The major metabolites formed from biphenyl, such as 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and benzoic acid, were identified by LC-MS. The crude cell extract of strain LA-4 exhibited the activity of 2,3-dihydroxybiphenyl 1,2-dioxygenase (2,3-DHBD) and the kinetic parameters were Km= 26.48 μmol/L and Vmax= 8.12 μmol/mg protein. A conserved region of the biphenyl dioxygenase gene bphA1 of strain LA-4 was amplified by PCR and confirmed by DNA sequencing.

  14. Pivotal role of anthranilate dioxygenase genes in the adaptation of Burkholderia multivorans ATCC 17616 in soil.

    Science.gov (United States)

    Nishiyama, Eri; Ohtsubo, Yoshiyuki; Yamamoto, Yasuhiro; Nagata, Yuji; Tsuda, Masataka

    2012-05-01

    In our recent screen for soil-induced genes, the expression of andA operon (andAcAdAbAa) for anthranilate catabolism in Burkholderia multivorans ATCC 17616 was found to increase dramatically in a soil sample (Nishiyama et al., Environ Microbiol 12: 2539, 2010). The operon was preceded by andR encoding a putative transcriptional regulator for the andA operon. In this study, the andA promoter was induced by tryptophan and anthranilate in an andR-dependent manner. The andA promoter in a deletion mutant lacking tryptophan dioxygenase (one of enzymes for the catabolism of tryptophan to anthranilate) did not respond to tryptophan, indicating that not tryptophan but anthranilate is the effector of AndR. Although both anthranilate and tryptophan were under the detection levels in the soil sample, andA promoter showed higher activity in the soil sample than in a laboratory medium. Such induction required andR and was moderately dependent on the ferric uptake regulator (Fur). The proliferation ability of andAc mutant in the sterile soil was low compared with the co-incubated wild-type cells. These findings suggested that in the soil environment, anthranilate dioxygenase genes are induced by AndR and Fur, and play a pivotal role in the proliferation in the soil environment. PMID:22360670

  15. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.

    Science.gov (United States)

    Rüetschi, U; Cerone, R; Pérez-Cerda, C; Schiaffino, M C; Standing, S; Ugarte, M; Holme, E

    2000-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.

  16. 2,3-Dihydroxybiphenyl dioxygenase gene was first discovered in Arthrobacter sp. strain P J3

    Institute of Scientific and Technical Information of China (English)

    YANG MeiYing; MA PengDa; LI WenMing; LIU JinYing; LI Liang; ZHU XiaoJuan; WANG XingZhi

    2007-01-01

    Bacterium strain PJ3, isolated from wastewater and identified as Arthrobacter sp. bacterium based on its 16S rDNA gene, could use carbazole as the sole carbon, nitrogen and energy source. The genomic libraryof strain PJ3 was constructed and a positive clone JM109 (pUCW402) was screened out for the expression of dioxygenase by the ability to form yellow ring-fission product. A 2,3-dihydroxybiphenyl dioxygenase (23DHBD) gene of 933 bp was found in the 3360 bp exogenous fragment of pUCW402 by GenSCAN software and BLAST analysis. The phylogenetic analysis showed that 23DHBD from strain PJ3 formed a deep branch separate from a cluster containing most known 23DHBD in GenBank.Southern hybridization confirmed for the first time that the 23DHBD gene was from the genomic DNA of Arthrobacter sp. PJ3. In order to test the gene function, recombinant bacterium BL21 (pETW-8) was constructed to express 23DHBD. The expression level in BL21 (pETW-8) was highest compared with the recombinant bacteria JM109 (pUCW402) and strain PJ3. We observed that 23DHBD was not absolute specific. The enzyme activity was higher with 2,3-dihydroxybiphenyl as a substrate than with catechol.The substrate specificity assay suggested that 23DHBD was essential for cleavage of bi-cyclic aromatic compounds during the course of aromatic compound biodegradation in Arthrobacter sp. strain PJ3.

  17. Structure of 4-hydrophenylpyruvic acid dioxygenase (HPD) gene and its mutation in tyrosinemic mouse strain III

    Energy Technology Data Exchange (ETDEWEB)

    Awata, H.; Endo, F.; Matsuda, I. [Kumamoto Univ. Medical School (Japan)] [and others

    1994-09-01

    4-Hydroxphenylpyruvic acid dioxygenase (HPD) is an important enzyme in tyrosine catabolism in most organisms. The activity of this enzyme is expressed mainly in the liver and is developmentally regulated in mammals. A genetic deficiency of the enzyme in man and mouse leads to hereditary tyrosinemia type 3. Using human HPD cDNA as a probe, a chromosomal gene related to HPD was isolated from human and mouse gene libraries. The human HPD gene is over 30 kilo-bases long and is split into 14 exons. Analysis of the 5{prime} flanking sequence of the gene suggests that expression of the gene is regulated by hepatocyte-specific and liver-enriched transcription factors, as well as by hormones. These features of the 5{prime} flanking region of the gene are similar to those of other genes which are specifically expressed in hepatocytes and which are developmentally regulated. The gene for mouse HPD has a similar structure and we obtained evidence for a nucleotide substitution which generates a termination codon in exon 7 of the HPD gene in III mice. This mutation associates a partial exon skipping and most of the mRNA lacks sequences corresponding to exon 7. The partial exon skipping apparently is the result of a nonsense mutation in the exon. Thus, mouse strain III can serve as a genetic model for human tyrosinemia type 3. Ongoing studies are expected to elucidate the disease process involved in hereditary tyrosinemia type 1 and to shed light on mechanisms that mediate developmental regulation of HPD gene expression. In addition, mouse strain III together with recently established models for tyrosinemia type 1 will facilitate studies on hereditary tyrosinemias.

  18. Novel aromatic ring-hydroxylating dioxygenase genes from coastal marine sediments of Patagonia

    Directory of Open Access Journals (Sweden)

    Ferrero Marcela A

    2008-03-01

    Full Text Available Abstract Background Polycyclic aromatic hydrocarbons (PAHs, widespread pollutants in the marine environment, can produce adverse effects in marine organisms and can be transferred to humans through seafood. Our knowledge of PAH-degrading bacterial populations in the marine environment is still very limited, and mainly originates from studies of cultured bacteria. In this work, genes coding catabolic enzymes from PAH-biodegradation pathways were characterized in coastal sediments of Patagonia with different levels of PAH contamination. Results Genes encoding for the catalytic alpha subunit of aromatic ring-hydroxylating dioxygenases (ARHDs were amplified from intertidal sediment samples using two different primer sets. Products were cloned and screened by restriction fragment length polymorphism analysis. Clones representing each restriction pattern were selected in each library for sequencing. A total of 500 clones were screened in 9 gene libraries, and 193 clones were sequenced. Libraries contained one to five different ARHD gene types, and this number was correlated with the number of PAHs found in the samples above the quantification limit (r = 0.834, p nahAc-like genes, phnAc-like genes as identified in Alcaligenes faecalis AFK2, and phnA1-like genes from marine PAH-degraders from the genus Cycloclasticus. Conclusion These results show the presence of hitherto unidentified ARHD genes in this sub-Antarctic marine environment exposed to anthropogenic contamination. This information can be used to study the geographical distribution and ecological significance of bacterial populations carrying these genes, and to design molecular assays to monitor the progress and effectiveness of remediation technologies.

  19. 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.

  20. Identification and expression pattern of a new carotenoid cleavage dioxygenase gene member from Bixa orellana.

    Science.gov (United States)

    Rodríguez-Ávila, N L; Narváez-Zapata, J A; Ramírez-Benítez, J E; Aguilar-Espinosa, M L; Rivera-Madrid, R

    2011-11-01

    Carotenoid cleavage dioxygenases (CCDs) are a class of enzymes involved in the biosynthesis of a broad diversity of secondary metabolites known as apocarotenoids. In plants, CCDs are part of a genetic family with members which cleave specific double bonds of carotenoid molecules. CCDs are involved in the production of diverse and important metabolites such as vitamin A and abscisic acid (ABA). Bixa orellana L. is the main source of the natural pigment annatto or bixin, an apocarotenoid accumulated in large quantities in its seeds. Bixin biosynthesis has been studied and the involvement of a CCD has been confirmed in vitro. However, the CCD genes involved in the biosynthesis of the wide variety of apocarotenoids found in this plant have not been well documented. In this study, a new CCD1 gene member (BoCCD1) was identified and its expression was charaterized in different plant tissues of B. orellana plantlets and adult plants. The BoCCD1 sequence showed high homology with plant CCD1s involved mainly in the cleavage of carotenoids in several sites to generate multiple apocarotenoid products. Here, the expression profiles of the BoCCD1 gene were analysed and discussed in relation to total carotenoids and other important apocarotenoids such as bixin. PMID:21813796

  1. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.

    Science.gov (United States)

    Tomoeda, K; Awata, H; Matsuura, T; Matsuda, I; Ploechl, E; Milovac, T; Boneh, A; Scott, C R; Danks, D M; Endo, F

    2000-11-01

    The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD may lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been postulated that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency. Hawkinsin is a sulfur amino acid identified as (2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid. Patients with hawkinsinuria excrete this metabolite in their urine throughout their life, although symptoms of metabolic acidosis and tyrosinemia improve in the first year of life. We performed analyses of the HPD gene in a patient with tyrosinemia type III and two unrelated patients with hawkinsinuria. A homozygous missense mutation predicting an Ala to Val change at codon 268 (A268V) in the HPD gene was found in the patient with tyrosinemia type III. A heterozygous missense mutation predicting an Ala to Thr change at codon 33 (A33T) was found in the same HPD gene in the two patients with hawkinsinuria. These findings support the hypothesis that alterations in the structure and activity of HPD are causally related to two different metabolic disorders, tyrosinemia type III and hawkinsinuria.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III

    Energy Technology Data Exchange (ETDEWEB)

    Endo, Fumio; Awata, Hisataka; Matsuda, Ichiro [Kumamoto Univ. (Japan)

    1995-01-01

    4-Hydroxyphenylpyruvic acid dioxygenase (HPD; EC 1.13.11.27) is an important enzyme in tyrosine catabolism in most organisms. Decreased activity of 4-hydroxyphenylpyruvic acid dioxygenase in the liver of mouse strain III is associated with tyrosinemia. We report a nucleotide substitution that generates a termination codon in exon 7 of the 4-hydroxyphenylpyruvic acid dioxygenase gene in III mice. This mutation is associated with partial exon skipping, and most of the mRNA lacks sequences corresponding to exon 7. The partial exon skipping apparently is the result of a nonsense mutation in the exon. Mouse strain III is a model for human tyrosinemia type 3 (McKusick 276710), and this train together with recently established models for tyrosinemia type 1 will facilitate studies of hereditary tyrosinemias.

  4. A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III.

    Science.gov (United States)

    Endo, F; Awata, H; Katoh, H; Matsuda, I

    1995-01-01

    4-Hydroxyphenylpyruvic acid dioxygenase (HPD; EC 1.13.11.27) is an important enzyme in tyrosine catabolism in most organisms. Decreased activity of 4-hydroxyphenylpyruvic acid dioxygenase in the liver of mouse strain III is associated with tyrosinemia. We report a nucleotide substitution that generates a termination codon in exon 7 of the 4-hydroxyphenylpyruvic acid dioxygenase gene in III mice. This mutation is associated with partial exon skipping, and most of the mRNA lacks sequences corresponding to exon 7. The partial exon skipping apparently is the result of a nonsense mutation in the exon. Mouse strain III is a model for human tyrosinemia type 3 (McKusick 276710), and this strain together with recently established models for tyrosinemia type 1 will facilitate studies of hereditary tyrosinemias.

  5. 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.)

  6. Localization of the human indoleamine 2,3-dioxygenase (IDO) gene to the pericentromeric region of human chromosome 8

    Energy Technology Data Exchange (ETDEWEB)

    Burkin, D.J.; Jones, C. (Eleanor Roosevelt Institute for Cancer Research, Denver, CO (United States)); Kimbro, K.S.; Taylor, M.W. (Indiana Univ., Bloomington, IN (United States)); Barr, B.L.; Gupta, S.L. (Hipple Cancer Research Center, Dayton, OH (United States))

    1993-07-01

    Indoleamine 2,3-dioxygenase (IDO) is the first enzyme in the catabolic pathway for tryptophan. This extrahepatic enzyme differs from the hepatic enzyme, tryptophan 2,3-dioxygenase (TDO), in molecular as well as enzymatic characteristics, although both enzymes catalyze the same reaction: cleavage of tryptophan into N-formylkynurenine. The induction of IDO by IFN-[gamma] plays a role in the antigrowth effect of IFN-[gamma] in cell cultures and in the inhibition of intracellular pathogens, e.g., Toxoplasma gondii and Chlamydia psittaci. Tryptophan is also the precursor for the synthesis of serotonin, and reduced levels of tryptophan and serotonin found in AIDS patients have been correlated with the presence of IFN-[gamma] and consequent elevation of IDO activity. The IDO enzyme has been purified and characterized, and its cDNA and genomic DNA clones have been isolated and analyzed. DNA from hybrid cells containing fragments of human chromosome 8 was used to determine the regional localization of the IDO gene on chromosome 8. The hybrids R30-5B and R30-2A contain 8p11 [yields] qter and 8q13 [yields] qter, respectively. Hybrid 229-3A contains the 8pter [yields] q11. The hybrid R30-2A was negative for the IDO gene, whereas R30-5B and 229-3A were positive as analyzed by PCR and verified by Southern blotting. Only the region close to the centromere is shared by R30-5B and 229-3A hybrids. The results indicate that the IDO gene is located on chromosome 8p11 [yields] q11.

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

    International Nuclear Information System (INIS)

    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

  8. The Reaumuria trigyna leucoanthocyanidin dioxygenase (RtLDOX) gene complements anthocyanidin synthesis and increases the salt tolerance potential of a transgenic Arabidopsis LDOX mutant.

    Science.gov (United States)

    Zhang, Huirong; Du, Chao; Wang, Yan; Wang, Jia; Zheng, Linlin; Wang, Yingchun

    2016-09-01

    Reaumuria trigyna is a typical, native desert halophyte that grows under extreme conditions in Inner Mongolia. In a previous transcriptomic profiling analysis, flavonoid pathway-related genes in R. trigyna showed significant differences in transcript abundance under salt stress. Leucoanthocyanidin dioxygenase (LDOX, EC 1.14.11.19) is one of three dioxygenases in the flavonoid pathway that catalyzes the formation of anthocyanidins from leucoanthocyanidins. In this study, we cloned the full-length cDNA of R. trigyna LDOX (RtLDOX), and found RtLDOX recombinant protein was able to replace flavanone-3-hydroxylase (F3H, EC 1.14.11.9), another dioxygenase in the flavonoid pathway, to convert naringenin to dihydrokaempferol in vitro. R. trigyna LDOX can complement the Arabidopsis LDOX mutant transparent testa11 (tt11-11), which has reduced proanthocyanin (PA) and anthocyanin levels in seeds, to accumulate these two compounds. Thus, RtLDOX acts as a multifunctional dioxygenase to effect the synthesis of PA and anthocyanins and can perform F3H dioxygenase activities in the flavonoid biosynthesis pathway. The RtLDOX promoter harbored many cis-acting elements that might be recognized and bound by transcription factors related to stress response. RtLDOX expression was strongly increased under salt stress, and RtLDOX transgenic Arabidopsis mutant under NaCl stress accumulated the content of flavonoids leading to an increased antioxidant activities and plant biomass. These results suggest that RtLDOX as a multifunctional dioxygenase in flavonoid biosynthesis involves in enhancing plant response to NaCl stress. PMID:27219053

  9. Redox proteins of hydroxylating bacterial dioxygenases establish a regulatory cascade that prevents gratuitous induction of tetralin biodegradation genes.

    Science.gov (United States)

    Ledesma-García, Laura; Sánchez-Azqueta, Ana; Medina, Milagros; Reyes-Ramírez, Francisca; Santero, Eduardo

    2016-01-01

    Bacterial dioxygenase systems are multicomponent enzymes that catalyze the initial degradation of many environmentally hazardous compounds. In Sphingopyxis granuli strain TFA tetralin dioxygenase hydroxylates tetralin, an organic contaminant. It consists of a ferredoxin reductase (ThnA4), a ferredoxin (ThnA3) and a oxygenase (ThnA1/ThnA2), forming a NAD(P)H-ThnA4-ThnA3-ThnA1/ThnA2 electron transport chain. ThnA3 has also a regulatory function since it prevents expression of tetralin degradation genes (thn) in the presence of non-metabolizable substrates of the catabolic pathway. This role is of physiological relevance since avoids gratuitous and wasteful production of catabolic enzymes. Our hypothesis for thn regulation implies that ThnA3 exerts its action by diverting electrons towards the regulator ThnY, an iron-sulfur flavoprotein that together with the transcriptional activator ThnR is necessary for thn gene expression. Here we analyze electron transfer among ThnA4, ThnA3 and ThnY by using stopped-flow spectrophotometry and determination of midpoint reduction potentials. Our results indicate that when accumulated in its reduced form ThnA3 is able to fully reduce ThnY. In addition, we have reproduced in vitro the regulatory circuit in the proposed physiological direction, NAD(P)H-ThnA4-ThnA3-ThnY. ThnA3 represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent gratuitous induction. PMID:27030382

  10. Redox proteins of hydroxylating bacterial dioxygenases establish a regulatory cascade that prevents gratuitous induction of tetralin biodegradation genes

    Science.gov (United States)

    Ledesma-García, Laura; Sánchez-Azqueta, Ana; Medina, Milagros; Reyes-Ramírez, Francisca; Santero, Eduardo

    2016-01-01

    Bacterial dioxygenase systems are multicomponent enzymes that catalyze the initial degradation of many environmentally hazardous compounds. In Sphingopyxis granuli strain TFA tetralin dioxygenase hydroxylates tetralin, an organic contaminant. It consists of a ferredoxin reductase (ThnA4), a ferredoxin (ThnA3) and a oxygenase (ThnA1/ThnA2), forming a NAD(P)H–ThnA4–ThnA3–ThnA1/ThnA2 electron transport chain. ThnA3 has also a regulatory function since it prevents expression of tetralin degradation genes (thn) in the presence of non-metabolizable substrates of the catabolic pathway. This role is of physiological relevance since avoids gratuitous and wasteful production of catabolic enzymes. Our hypothesis for thn regulation implies that ThnA3 exerts its action by diverting electrons towards the regulator ThnY, an iron-sulfur flavoprotein that together with the transcriptional activator ThnR is necessary for thn gene expression. Here we analyze electron transfer among ThnA4, ThnA3 and ThnY by using stopped-flow spectrophotometry and determination of midpoint reduction potentials. Our results indicate that when accumulated in its reduced form ThnA3 is able to fully reduce ThnY. In addition, we have reproduced in vitro the regulatory circuit in the proposed physiological direction, NAD(P)H–ThnA4–ThnA3–ThnY. ThnA3 represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent gratuitous induction. PMID:27030382

  11. Oxidation of polychlorinated biphenyls by Pseudomonas sp. strain LB400 and Pseudomonas pseudoalcaligenes KF707.

    OpenAIRE

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

    1993-01-01

    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 the substrate specificity of the biphenyl 2,3-dioxygenases from both organisms.

  12. 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.

  13. Abundance of Novel and Diverse tfdA-Like Genes, Encoding Putative Phenoxyalkanoic Acid Herbicide-Degrading Dioxygenases, in Soil▿ †

    OpenAIRE

    Zaprasis, Adrienne; Liu, Ya-Jun; Liu, Shuang-Jiang; Drake, Harold L.; Horn, Marcus A.

    2009-01-01

    Phenoxyalkanoic acid (PAA) herbicides are widely used in agriculture. Biotic degradation of such herbicides occurs in soils and is initiated by α-ketoglutarate- and Fe2+-dependent dioxygenases encoded by tfdA-like genes (i.e., tfdA and tfdAα). Novel primers and quantitative kinetic PCR (qPCR) assays were developed to analyze the diversity and abundance of tfdA-like genes in soil. Five primer sets targeting tfdA-like genes were designed and evaluated. Primer sets 3 to 5 specifically amplified ...

  14. Patchwork assembly of nag-like nitroarene dioxygenase genes and the 3-chlorocatechol degradation cluster for evolution of the 2-chloronitrobenzene catabolism pathway in Pseudomonas stutzeri ZWLR2-1.

    Science.gov (United States)

    Liu, Hong; Wang, Shu-Jun; Zhang, Jun-Jie; Dai, Hui; Tang, Huiru; Zhou, Ning-Yi

    2011-07-01

    Pseudomonas stutzeri ZWLR2-1 utilizes 2-chloronitrobenzene (2CNB) as a sole source of carbon, nitrogen, and energy. To identify genes involved in this pathway, a 16.2-kb DNA fragment containing putative 2CNB dioxygenase genes was cloned and sequenced. Of the products from the 19 open reading frames that resulted from this fragment, CnbAc and CnbAd exhibited striking identities to the respective α and β subunits of the Nag-like ring-hydroxylating dioxygenases involved in the metabolism of nitrotoluene, nitrobenzene, and naphthalene. The encoding genes were also flanked by two copies of insertion sequence IS6100. CnbAa and CnbAb are similar to the ferredoxin reductase and ferredoxin for anthranilate 1,2-dioxygenase from Burkholderia cepacia DBO1. Escherichia coli cells expressing cnbAaAbAcAd converted 2CNB to 3-chlorocatechol with concomitant nitrite release. Cell extracts of E. coli/pCNBC exhibited chlorocatechol 1,2-dioxygenase activity. The cnbCDEF gene cluster, homologous to a 3-chlorocatechol degradation cluster in Sphingomonas sp. strain TFD44, probably contains all of the genes necessary for the conversion of 3-chlorocatechol to 3-oxoadipate. The patchwork-like structure of this catabolic cluster suggests that the cnb cluster for 2CNB degradation evolved by recruiting two catabolic clusters encoding a nitroarene dioxygenase and a chlorocatechol degradation pathway. This provides another example to help elucidate the bacterial evolution of catabolic pathways in response to xenobiotic chemicals.

  15. Cysteine dioxygenase and cysteine sulfinate decarboxylase genes of the deep-sea mussel Bathymodiolus septemdierum: possible involvement in hypotaurine synthesis and adaptation to hydrogen sulfide.

    Science.gov (United States)

    Nagasaki, Toshihiro; Hongo, Yuki; Koito, Tomoko; Nakamura-Kusakabe, Ikumi; Shimamura, Shigeru; Takaki, Yoshihiro; Yoshida, Takao; Maruyama, Tadashi; Inoue, Koji

    2015-03-01

    It has been suggested that invertebrates inhabiting deep-sea hydrothermal vent areas use the sulfinic acid hypotaurine, a precursor of taurine, to protect against the toxicity of hydrogen sulfide contained in the seawater from the vent. In this protective system, hypotaurine is accumulated in the gill, the primary site of sulfide exposure. However, the pathway for hypotaurine synthesis in mollusks has not been identified. In this study, we screened for the mRNAs of enzymes involved in hypotaurine synthesis in the deep-sea mussel Bathymodiolus septemdierum and cloned cDNAs encoding cysteine dioxygenase and cysteine sulfinate decarboxylase. As mRNAs encoding cysteamine dioxygenase and cysteine lyase were not detected, the cysteine sulfinate pathway is suggested to be the major pathway of hypotaurine and taurine synthesis. The two genes were found to be expressed in all the tissues examined, but the gill exhibited the highest expression. The mRNA level in the gill was not significantly changed by exposure to sulfides or thiosulfate. These results suggests that the gill of B. septemdierum maintains high levels of expression of the two genes regardless of ambient sulfide level and accumulates hypotaurine continuously to protect against sudden exposure to high level of sulfide.

  16. 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...

  17. Overexpression of the rice carotenoid cleavage dioxygenase 1 gene in Golden Rice endosperm suggests apocarotenoids as substrates in planta.

    Science.gov (United States)

    Ilg, Andrea; Yu, Qiuju; Schaub, Patrick; Beyer, Peter; Al-Babili, Salim

    2010-08-01

    Carotenoids are converted by carotenoid cleavage dioxygenases that catalyze oxidative cleavage reactions leading to apocarotenoids. However, apocarotenoids can also be further truncated by some members of this enzyme family. The plant carotenoid cleavage dioxygenase 1 (CCD1) subfamily is known to degrade both carotenoids and apocarotenoids in vitro, leading to different volatile compounds. In this study, we investigated the impact of the rice CCD1 (OsCCD1) on the pigmentation of Golden Rice 2 (GR2), a genetically modified rice variety accumulating carotenoids in the endosperm. For this purpose, the corresponding cDNA was introduced into the rice genome under the control of an endosperm-specific promoter in sense and anti-sense orientations. Despite high expression levels of OsCCD1 in sense plants, pigment analysis revealed carotenoid levels and patterns comparable to those of GR2, pleading against carotenoids as substrates in rice endosperm. In support, similar carotenoid contents were determined in anti-sense plants. To check whether OsCCD1 overexpressed in GR2 endosperm is active, in vitro assays were performed with apocarotenoid substrates. HPLC analysis confirmed the cleavage activity of introduced OsCCD1. Our data indicate that apocarotenoids rather than carotenoids are the substrates of OsCCD1 in planta. PMID:20549230

  18. Expression of Biphenyl Synthase Genes and Formation of Phytoalexin Compounds in Three Fire Blight-Infected Pyrus communis Cultivars.

    Directory of Open Access Journals (Sweden)

    Cornelia Chizzali

    Full Text Available Pear (Pyrus communis is an economically important fruit crop. Drops in yield and even losses of whole plantations are caused by diseases, most importantly fire blight which is triggered by the bacterial pathogen Erwinia amylovora. In response to the infection, biphenyls and dibenzofurans are formed as phytoalexins, biosynthesis of which is initiated by biphenyl synthase (BIS. Two PcBIS transcripts were cloned from fire blight-infected leaves and the encoded enzymes were characterized regarding substrate specificities and kinetic parameters. Expression of PcBIS1 and PcBIS2 was studied in three pear cultivars after inoculation with E. amylovora. Both PcBIS1 and PcBIS2 were expressed in 'Harrow Sweet', while only PcBIS2 transcripts were detected in 'Alexander Lucas' and 'Conference'. Expression of the PcBIS genes was observed in both leaves and the transition zone of the stem; however, biphenyls and dibenzofurans were only detected in stems. The maximum phytoalexin level (~110 μg/g dry weight was observed in the transition zone of 'Harrow Sweet', whereas the concentrations were ten times lower in 'Conference' and not even detectable in 'Alexander Lucas'. In 'Harrow Sweet', the accumulation of the maximum phytoalexin level correlated with the halt of migration of the transition zone, whereby the residual part of the shoot survived. In contrast, the transition zones of 'Alexander Lucas' and 'Conference' advanced down to the rootstock, resulting in necrosis of the entire shoots.

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

    Directory of Open Access Journals (Sweden)

    Zohar Ben-Simhon

    Full Text Available 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

  20. Expression of Biphenyl Synthase Genes and Formation of Phytoalexin Compounds in Three Fire Blight-Infected Pyrus communis Cultivars

    Science.gov (United States)

    Chizzali, Cornelia; Swiddan, Asya K.; Abdelaziz, Sahar; Gaid, Mariam; Richter, Klaus; Fischer, Thilo C.; Liu, Benye; Beerhues, Ludger

    2016-01-01

    Pear (Pyrus communis) is an economically important fruit crop. Drops in yield and even losses of whole plantations are caused by diseases, most importantly fire blight which is triggered by the bacterial pathogen Erwinia amylovora. In response to the infection, biphenyls and dibenzofurans are formed as phytoalexins, biosynthesis of which is initiated by biphenyl synthase (BIS). Two PcBIS transcripts were cloned from fire blight-infected leaves and the encoded enzymes were characterized regarding substrate specificities and kinetic parameters. Expression of PcBIS1 and PcBIS2 was studied in three pear cultivars after inoculation with E. amylovora. Both PcBIS1 and PcBIS2 were expressed in ‘Harrow Sweet’, while only PcBIS2 transcripts were detected in ‘Alexander Lucas’ and ‘Conference’. Expression of the PcBIS genes was observed in both leaves and the transition zone of the stem; however, biphenyls and dibenzofurans were only detected in stems. The maximum phytoalexin level (~110 μg/g dry weight) was observed in the transition zone of ‘Harrow Sweet’, whereas the concentrations were ten times lower in ‘Conference’ and not even detectable in ‘Alexander Lucas’. In ‘Harrow Sweet’, the accumulation of the maximum phytoalexin level correlated with the halt of migration of the transition zone, whereby the residual part of the shoot survived. In contrast, the transition zones of ‘Alexander Lucas’ and ‘Conference’ advanced down to the rootstock, resulting in necrosis of the entire shoots. PMID:27410389

  1. 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

  2. Cloning and expression of the transposable chlorobenzoate-3,4-dioxygenase genes of Alcaligenes sp. strain BR60.

    OpenAIRE

    Nakatsu, C. H.; Wyndham, R. C.

    1993-01-01

    Growth on 3-chlorobenzoate was found to induce the enzymes of the protocatechuate meta ring fission pathway in Alcaligenes sp. strain BR60. The chlorobenzoate catabolic genes, designated cba, were localized to a 3.7-kb NotI-EcoRI fragment within the nonrepeated region of the composite transposon Tn5271. The cba genes were cloned onto two broad-host-range vectors and expressed in Escherichia coli and Alcaligenes sp. strain BR6024. In E. coli, expression of the cba genes with the IPTG (isopropy...

  3. New target carotenoids for CCD4 enzymes are revealed with the characterization of a novel stress-induced carotenoid cleavage dioxygenase gene from Crocus sativus.

    Science.gov (United States)

    Rubio-Moraga, Angela; Rambla, José Luis; Fernández-de-Carmen, Asun; Trapero-Mozos, Almudena; Ahrazem, Oussama; Orzáez, Diego; Granell, Antonio; Gómez-Gómez, Lourdes

    2014-11-01

    Apocarotenoid compounds play diverse communication functions in plants, some of them being as hormones, pigments and volatiles. Apocarotenoids are the result of enzymatic cleavage of carotenoids catalyzed by carotenoid cleavage dioxygenase (CCD). The CCD4 family is the largest family of plant CCDs, only present in flowering plants, suggesting a functional diversification associated to the adaptation for specific physiological capacities unique to them. In saffron, two CCD4 genes have been previously isolated from the stigma tissue and related with the generation of specific volatiles involved in the attraction of pollinators. The aim of this study was to identify additional CCD4 members associated with the generation of other carotenoid-derived volatiles during the development of the stigma. The expression of CsCCD4c appears to be restricted to the stigma tissue in saffron and other Crocus species and was correlated with the generation of megastigma-4,6,8-triene. Further, CsCCD4c was up-regulated by wounding, heat, and osmotic stress, suggesting an involvement of its apocarotenoid products in the adaptation of saffron to environmental stresses. The enzymatic activity of CsCCD4c was determined in vivo in Escherichia coli and subsequently in Nicotiana benthamiana by analyzing carotenoids by HPLC-DAD and the volatile products by GC/MS. β-Carotene was shown to be the preferred substrate, being cleaved at the 9,10 (9',10') bonds and generating β-ionone, although β-cyclocitral resulting from a 7,8 (7',8') cleavage activity was also detected at lower levels. Lutein, neoxanthin and violaxanthin levels in Nicotiana leaves were markedly reduced when CsCCD4c is over expressed, suggesting that CsCCD4c recognizes these carotenoids as substrates.

  4. Identifying a Carotenoid Cleavage Dioxygenase 4a Gene and Its Efficient Agrobacterium-Mediated Genetic Transformation in Bixa orellana L.

    Science.gov (United States)

    Sankari, Mohan; Hemachandran, Hridya; Anantharaman, Amirtha; Babu, Subramanian; Madrid, Renata Rivera; C, George Priya Doss; Fulzele, Devanand P; Siva, Ramamoorthy

    2016-07-01

    Carotenoids are metabolized to apocarotenoids through the pathway catalysed by carotenoid cleavage oxygenases (CCOs). The apocarotenoids are economically important as it is known to have therapeutic as well as industrial applications. For instance, bixin from Bixa orellana and crocin from Crocus sativus are commercially used as a food colourant and cosmetics since prehistoric time. In our present study, CCD4a gene has been identified and isolated from leaves of B. orellana for the first time and named as BoCCD4a; phylogenetic analysis was carried out using CLUSTAL W. From sequence analysis, BoCCD4a contains two exons and one intron, which was compared with the selected AtCCD4, RdCCD4, GmCCD4 and CmCCD4a gene. Further, the BoCCD4a gene was cloned into pCAMBIA 1301, transformed into Agrobacterium tumefaciens EHA105 strain and subsequently transferred into hypocotyledons and callus of B. orellana by agro-infection. Selection of stable transformation was screened on the basis of PCR detection by using GUS and hptII specific primer, which was followed by histochemical characterization. The percent transient GUS expression in hypocotyledons and callus was 84.4 and 80 %, respectively. The expression of BoCCD4a gene in B. orellana was confirmed through RT-PCR analysis. From our results, the sequence analysis of BoCCD4a gene of B. orellana was closely related to the CsCCD4 gene of C. sativus, which suggests this gene may have a role in various processes such as fragrance, insect attractant and pollination. PMID:26922728

  5. Gene therapy with adenovirus-delivered indoleamine 2,3-dioxygenase improves renal function and morphology following allogeneic kidney transplantation in rat

    NARCIS (Netherlands)

    Vavrincova-Yaghi, Diana; Deelman, Leo E.; van Goor, Harry; Seelen, Marc; Kema, Ido P.; Smit-van Oosten, Annemieke; de Zeeuw, Dick; Henning, Robert H.; Sandovici, Maria

    2011-01-01

    BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the tryptophan catabolism, has recently emerged as an important immunosuppressive enzyme involved in the regulation of both physiologic (maternal tolerance), as well as pathologic (neoplasia, autoimmune diseases, asthma) proc

  6. Characterization of estrogen receptor α activities in polychlorinated biphenyls by in vitro dual-luciferase reporter gene assay

    International Nuclear Information System (INIS)

    Polychlorinated biphenyls (PCBs) are thought to cause adverse health effects, particularly endocrine disruption. However, results on the estrogenic activities of a large set of PCB congeners through hormone receptors have not been fully studied. In this study, we evaluated the anti/estrogenic effects of 20 PCBs using an in vitro dual-luciferase reporter gene assay. PCB 18, 28, 49, 52, 99, 101, 103, 110, and 128 exhibited estrogenic effects, whereas PCB 118, 138, 163, 170, 180, 187, 194, 199 and 203 behaved as anti-estrogens. In particular, PCB 30 and 44 exhibited both agonistic and antagonistic activities in the dual-luciferase reporter gene assay. The results obtained from the dual-luciferase reporter gene assay, yeast two-hybrid assay and E-SCREEN were compared, suggesting that the dual-luciferase reporter gene assay is a useful approach for high-throughput screening. We also predicted the possible relationship between the chemical structures and the estrogenic effects of PCBs. - Highlights: • Of 20 PCBs tested, 11 PCBs exhibited estrogenic effects. • Of 20 PCBs tested, 11 PCBs exhibited anti-estrogenic effects. • PCB 30 and 44 showed both agonistic and antagonistic activities. - The agonist and antagonist activities of 20 PCBs were investigated and compared in in vitro models

  7. Construction of a Bioluminescent Reporter Strain To Detect Polychlorinated Biphenyls

    OpenAIRE

    Layton, A C; Muccini, M.; Ghosh, M. M.; Sayler, G. S.

    1998-01-01

    A bioluminescent reporter strain, Ralstonia eutropha ENV307(pUTK60), was constructed for the detection of polychlorinated biphenyls by inserting the biphenyl promoter upstream of the bioluminescence genes. In the presence of a nonionic surfactant, which enhances the solubility of chlorinated biphenyls, bioluminescence was induced three- to fourfold over background by biphenyl, monochlorinated biphenyls, and Aroclor 1242. The minimum detection limits for these compounds ranged from 0.15 mg/lit...

  8. Effects of Homologous Expression of 1,4-Benzoquinone Reductase and Homogentisate 1,2-Dioxygenase Genes on Wood Decay in Hyper-Lignin-Degrading Fungus Phanerochaete sordida YK-624.

    Science.gov (United States)

    Mori, Toshio; Koyama, Genki; Kawagishi, Hirokazu; Hirai, Hirofumi

    2016-10-01

    We investigated the function of 1,4-benzoquinone reductase (BQR)- and homogentisate 1,2-dioxygenase (HGD)-like genes in wood degradation by Phanerochaete sordida YK-624, which exhibits high ligninolytic activity and selectivity. We determined homologous expression in the genomic and cDNA sequences of BQR- and HGD-like genes in P. sordida YK-624 (PsBQR and PsHGD). Both genes shared high homology (≥90 % amino acid sequence similarity) with the corresponding genes in Phanerochaete chrysosporium. These genes were co-transformed with a reporter gene into an uracil auxotrophic mutant of P. sordida YK-624. The PsBQR and PsHGD co-transformants exhibited lower holocellulolytic activity and higher ligninolytic selectivity than the control transformants. In liquid culture with vanillin, both co-transformants significantly accelerated vanillin degradation. Thus, we suggest that the rapid metabolism of low-molecular weight lignin fragments, due to the homologous expression of BQR- and HGD-like genes, affects quinone redox cycling to produce hydroxyl radicals, thereby decreasing holocellulose degradation and increasing ligninolytic selectivity. PMID:27363425

  9. Insights into the genetic diversity of initial dioxygenases from PAH-degrading bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Moser, R.; Stahl, U. [Technische Univ. Berlin, Inst. fuer Biotechnologie, Mikrobiologie und Genetik, Berlin (Germany)

    2001-07-01

    Alpha subunit genes of initial polyaromatic hydrocarbon (PAH) dioxygenases were used as targets for the PCR detection of PAH-degrading strains of the genera Pseudomonas, Comamonas and Rhodococcus which were obtained from activated sludge or soil samples. Sequence analysis of PCR products from several Pseudomonas strains showed that alpha subunits (nahAc allele) of this genus are highly conserved. PCR primers for the specific detection of alpha subunit genes of initial PAH dioxygenases from Pseudomonas strains were not suitable for detecting the corresponding genes from the genera Comamonas and Rhodococcus. Southern analysis using a heterologous gene probe derived from the P. putida OUS82 PAH dioxygenase alpha subunit identified segments of the PAH-degradation gene cluster from C. testosteroni strain H. Parts of this gene cluster containing three subunits of the initial PAH dioxygenase were isolated. These three subunits [ferredoxin (pahAb), alpha (pahAc) and beta (pahAd) subunit] were amplified by PCR as one fragment and expressed in Escherichia coli DH5{alpha}, resulting in an active initial dioxygenase with the ability to transform indole and phenanthrene. The DNA sequence alignment of alpha subunits from C. testosteroni H and various PAH-degrading bacteria permitted the design of new primers and oligonucleotide probes which are useful for the detection of the initial PAH dioxygenases from strains of Pseudomonas, Comamonas and Rhodococcus. (orig.)

  10. 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.

  11. Construction of a bioluminescent reporter strain to detect polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Layton, A.C.; Muccini, M.; Ghosh, M.M.; Sayler, G.S. [Univ. of Tennessee, Knoxville, TN (United States)

    1998-12-01

    A bioluminescent reporter strain, Ralstonia eutropha ENV307 (pUTK60), was constructed for the detection of polychlorinated biphenyls by inserting the biphenyl promoter upstream of the bioluminescence genes. In the presence of a nonionic surfactant, which enhances the solubility of chlorinated biphenyls, bioluminescence was induced three- to fourfold over background by biphenyl, monochlorinated biphenyls, and Aroclor 1242. The minimum detection limits for these compounds ranged from 0.15 mg/liter for 4-chlorobiphenyl to 1.5 mg/liter for Aroclor 1242.

  12. An aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic.

    Science.gov (United States)

    Overwin, Heike; González, Myriam; Méndez, Valentina; Seeger, Michael; Wray, Victor; Hofer, Bernd

    2016-09-01

    The bacterial dioxygenation of mono- or polycyclic aromatic compounds is an intensely studied field. However, only in a few cases has the repeated dioxygenation of a substrate possessing more than a single aromatic ring been described. We previously characterized the aryl-hydroxylating dioxygenase BphA-B4h, an artificial hybrid of the dioxygenases of the biphenyl degraders Burkholderia xenovorans LB400 and Pseudomonas sp. strain B4-Magdeburg, which contains the active site of the latter enzyme, as an exceptionally powerful biocatalyst. We now show that this dioxygenase possesses a remarkable capacity for the double dioxygenation of various bicyclic aromatic compounds, provided that they are carbocyclic. Two groups of biphenyl analogues were examined: series A compounds containing one heterocyclic aromatic ring and series B compounds containing two homocyclic aromatic rings. Whereas all of the seven partially heterocyclic biphenyl analogues were solely dioxygenated in the homocyclic ring, four of the six carbocyclic bis-aryls were converted into ortho,meta-hydroxylated bis-dihydrodiols. Potential reasons for failure of heterocyclic dioxygenations are discussed. The obtained bis-dihydrodiols may, as we also show here, be enzymatically re-aromatized to yield the corresponding tetraphenols. This opens a way to a range of new polyphenolic products, a class of compounds known to exert multiple biological activities. Several of the obtained compounds are novel molecules. PMID:27147529

  13. Conversion of 3-chlorocatechol by various catechol 2,3-dioxygenases and sequence analysis of the chlorocatechol dioxygenase region of Pseudomonas putida GJ31

    NARCIS (Netherlands)

    Mars, Astrid E.; Kingma, Jaap; Kaschabek, Stefan R.; Reineke, Walter; Janssen, Dick B.

    1999-01-01

    Pseudomonas putida GJ31 contains an unusual catechol 2,3-dioxygenase that converts 3-chlorocatechol and 3-methylcatechol, which enables the organism to use both chloroaromatics and methylaromatics for growth, A 3.1-kb region of genomic DNA of strain GJ31 containing the gene for this chlorocatechol 2

  14. Evidence for Acquisition in Nature of a Chromosomal 2,4-Dichlorophenoxyacetic Acid/(alpha)-Ketoglutarate Dioxygenase Gene by Different Burkholderia spp

    OpenAIRE

    Matheson, V. G.; Forney, L J; Suwa, Y.; Nakatsu, C. H.; A. J. Sexstone; Holben, W E

    1996-01-01

    We characterized the gene required to initiate the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) by the soil bacterium Burkholderia sp. strain TFD6, which hybridized to the tfdA gene of the canonical 2,4-D catabolic plasmid pJP4 under low-stringency conditions. Cleavage of the ether bond of 2,4-D by cell extracts of TFD6 proceeded by an (alpha)-ketoglutarate-dependent reaction, characteristic of TfdA (F. Fukumori and R. P. Hausinger, J. Bacteriol. 175:2083-2086, 1993). The TFD6 tfdA g...

  15. 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

  16. Expression, purification and kinetic characterization of recombinant benzoate dioxygenase from Rhodococcus ruber UKMP-5M

    Directory of Open Access Journals (Sweden)

    Arezoo Tavakoli

    2016-09-01

    Full Text Available In this study, benzoate dioxygenase from Rhodococcus ruber UKMP-5M was catalyzed by oxidating the benzene ring to catechol and other derivatives. The benzoate dioxygenase (benA gene from Rhodococcus ruber UKMP-5M was then expressed, purified, characterized, The benA gene was amplified (642 bp, and the product was cloned into a pGEM-T vector.The recombinant plasmid pGEMT-benA was digested by double restriction enzymes BamHI and HindIII to construct plasmid pET28b-benA and was then ligated into Escherichia coli BL21 (DE3. The recombinant E. coli was induced with 0.5 mM isopropyl β-D-thiogalactoside (IPTG at 22˚C to produce benzoate dioxygenase. The enzyme was then purified by ion exchange chromatography after 8 purification folds. The resulting product was 25 kDa, determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE and western blotting. Benzoate dioxygenase activity was found to be 6.54 U/mL and the optimal pH and temperature were 8.5 and 25°C, respectively. Maximum velocity (Vmax and Michaelis constant (Km were 7.36 U/mL and 5.58 µM, respectively. The end metabolite from the benzoate dioxygenase reaction was cyclohexane dione, which was determined by gas chromatography mass spectrometry (GC-MS.

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

    OpenAIRE

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

    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" po...

  18. Sphingobium fuliginis HC3: a novel and robust isolated biphenyl- and polychlorinated biphenyls-degrading bacterium without dead-end intermediates accumulation.

    Directory of Open Access Journals (Sweden)

    Jinxing Hu

    Full Text Available Biphenyl and polychlorinated biphenyls (PCBs are typical environmental pollutants. However, these pollutants are hard to be totally mineralized by environmental microorganisms. One reason for this is the accumulation of dead-end intermediates during biphenyl and PCBs biodegradation, especially benzoate and chlorobenzoates (CBAs. Until now, only a few microorganisms have been reported to have the ability to completely mineralize biphenyl and PCBs. In this research, a novel bacterium HC3, which could degrade biphenyl and PCBs without dead-end intermediates accumulation, was isolated from PCBs-contaminated soil and identified as Sphingobium fuliginis. Benzoate and 3-chlorobenzoate (3-CBA transformed from biphenyl and 3-chlorobiphenyl (3-CB could be rapidly degraded by HC3. This strain has strong degradation ability of biphenyl, lower chlorinated (mono-, di- and tri- PCBs as well as mono-CBAs, and the biphenyl/PCBs catabolic genes of HC3 are cloned on its plasmid. It could degrade 80.7% of 100 mg L -1 biphenyl within 24 h and its biphenyl degradation ability could be enhanced by adding readily available carbon sources such as tryptone and yeast extract. As far as we know, HC3 is the first reported that can degrade biphenyl and 3-CB without accumulation of benzoate and 3-CBA in the genus Sphingobium, which indicates the bacterium has the potential to totally mineralize biphenyl/PCBs and might be a good candidate for restoring biphenyl/PCBs-polluted environments.

  19. Cloning and Characterization of a Sulfonate/α-Ketoglutarate Dioxygenase from Saccharomyces cerevisiae

    OpenAIRE

    Hogan, Deborah A.; Auchtung, Thomas A.; Hausinger, Robert P.

    1999-01-01

    The Saccharomyces cerevisiae open reading frame YLL057c is predicted to encode a gene product with 31.5% amino acid sequence identity to Escherichia coli taurine/α-ketoglutarate dioxygenase and 27% identity to Ralstonia eutropha TfdA, a herbicide-degrading enzyme. Purified recombinant yeast protein is shown to be an Fe(II)-dependent sulfonate/α-ketoglutarate dioxygenase. Although taurine is a poor substrate, a variety of other sulfonates are utilized, with the best natural substrates being is...

  20. 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)

    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 (R2 ≥ 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

  1. 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

  2. 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

  3. Molecular Dynamics Simulation of Nitrobenzene Dioxygenase Using AMBER Force Field

    OpenAIRE

    Pabis, Anna; Geronimo, Inacrist; York, Darrin M.; Paneth, Piotr

    2014-01-01

    Molecular dynamics simulation of the oxygenase component of nitrobenzene dioxygenase (NBDO) system, a member of the naphthalene family of Rieske nonheme iron dioxygenases, has been carried out using the AMBER force field combined with a new set of parameters for the description of the mononuclear nonheme iron center and iron–sulfur Rieske cluster. Simulation results provide information on the structure and dynamics of nitrobenzene dioxygenase in an aqueous environment and shed light on specif...

  4. 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....

  5. Discovery of Key Dioxygenases that Diverged the Paraherquonin and Acetoxydehydroaustin Pathways in Penicillium brasilianum.

    Science.gov (United States)

    Matsuda, Yudai; Iwabuchi, Taiki; Fujimoto, Takayuki; Awakawa, Takayoshi; Nakashima, Yu; Mori, Takahiro; Zhang, Huiping; Hayashi, Fumiaki; Abe, Ikuro

    2016-09-28

    Paraherquonin (1), a fungal meroterpenoid produced by Penicillium brasilianum NBRC 6234, possesses a unique, highly congested hexacyclic molecular architecture. Here we identified the biosynthetic gene cluster of 1 (the prh cluster) and elucidated the pathway up to berkeleydione (2), which serves as the key intermediate for the biosynthesis of 1 as well as many other meroterpenoids. Interestingly, the nonheme iron and α-ketoglutarate-dependent dioxygenase PrhA constructs the cycloheptadiene moiety to afford 2 from preaustinoid A1 (6), probably via the homoallyl-homoallyl radical rearrangement. Additionally, another fungal strain, P. brasilianum MG11, which produces acetoxydehydroaustin instead of 1, was found to have a gene cluster nearly identical to the prh cluster. The dioxygenase encoded by the cluster shares 92% sequence identity with PrhA, and also accepts 6 but produces preaustinoid A3 (17) with a spiro-lactone system, generating a diverging point for the two different meroterpenoid pathways in the same species.

  6. Molecular evolution of bacterial indoleamine 2,3-dioxygenase.

    Science.gov (United States)

    Yuasa, Hajime J; Ushigoe, Akiko; Ball, Helen J

    2011-10-01

    Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that catalyze the first step in L-Trp catabolism via the kynurenine pathway. In mammals, TDO is mainly expressed in the liver and primarily supplies nicotinamide adenine dinucleotide (NAD(+)). TDO is widely distributed from mammals to bacteria. Active IDO enzymes have been reported only in vertebrates and fungi. In mammals, IDO activity plays a significant role in the immune system while in fungal species, IDO is constitutively expressed and supplies NAD(+), like mammalian TDO. A search of genomic databases reveals that some bacterial species also have a putative IDO gene. A phylogenetic analysis clustered bacterial IDOs into two groups, group I or group II bacterial IDOs. The catalytic efficiencies of group I bacterial IDOs were very low and they are suspected not to contribute significantly to L-Trp metabolism. The bacterial species bearing the group I bacterial IDO are scattered across a few phyla and no phylogenetically close relationship is observed between them. This suggests that the group I bacterial IDOs might be acquired by horizontal gene transmission that occurred in each lineage independently. In contrast, group II bacterial IDOs showed rather high catalytic efficiency. Particularly, the enzymatic characteristics (K(m), V(max) and inhibitor selectivity) of the Gemmatimonas aurantiaca IDO are comparable to those of mammalian IDO1, although comparison of the IDO sequences does not suggest a close evolutionary relationship. In several bacteria, TDO and the kynureninase gene (kynU) are clustered on their chromosome suggesting that these genes could be transcribed in an operon. Interestingly, G. aurantiaca has no TDO, and the IDO is clustered with kynU on its chromosome. Although the G. aurantiaca also has NadA and NadB to synthesize a quinolinic acid (a precursor of NAD(+)) via the aspartate pathway, the high activity of the G. aurantiaca IDO flanking

  7. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice.

    Science.gov (United States)

    Ball, Helen J; Sanchez-Perez, Angeles; Weiser, Silvia; Austin, Christopher J D; Astelbauer, Florian; Miu, Jenny; McQuillan, James A; Stocker, Roland; Jermiin, Lars S; Hunt, Nicholas H

    2007-07-01

    Indoleamine 2,3-dioxygenase (INDO) and tryptophan 2,3-dioxygenase (TDO) each catalyze the first step in the kynurenine pathway of tryptophan metabolism. We describe the discovery of another enzyme with this activity, indoleamine 2,3-dioxygenase-like protein (INDOL1), which is closely related to INDO and is expressed in mice and humans. The corresponding genes have a similar genomic structure and are situated adjacent to each other on human and mouse chromosome 8. They are likely to have arisen by gene duplication before the origin of the tetrapods. The expression of INDOL1 is highest in the mouse kidney, followed by epididymis, and liver. Expression of mouse INDOL1 was further localized to the tubular cells in the kidney and the spermatozoa. INDOL1 was assigned its name because of its structural similarity to INDO. We demonstrate that INDOL1 catalyses the conversion of tryptophan to kynurenine therefore a more appropriate nomenclature for the enzymes might be INDO-1 and INDO-2, or the more commonly-used abbreviations, IDO-1 and IDO-2. Although the two proteins have similar enzymatic activities, their different expression patterns within tissues and during malaria infection, suggests a distinct role for each protein. This identification of INDOL1 may help to explain the regulation of the diversity of physiological and patho-physiological processes in which the kynurenine pathway is involved.

  8. Isolation, degradation characteristics and catechol 1,2 dioxygenase gene expression level of 1,2,4-TCB degrading bacterium under low temperature%低温1,2,4-TCB降解菌的选育、降解特性及邻苯二酚1,2-双加氧酶基因表达水平

    Institute of Scientific and Technical Information of China (English)

    胡日查; 孙立波

    2013-01-01

    从长期受l,2,4-三氯苯(1,2,4-TCB)污染的地下水中筛选出一株低温寡营养降解菌A2,对A2菌进行革兰氏染色鉴定和16S rDNA鉴定,研究了不同pH、温度、盐度等因素对A2菌降解l,2,4-TCB效果以及对邻苯二酚l,2-双加氧酶基因表达的影响,并进行了正交实验.结果表明,A2菌为革兰氏阴性短杆细菌,初步鉴定为假单胞菌;在pH值为7、培养温度30℃、盐度0.8%、培养时间6d时,A2菌对1,2,4-TCB降解效果最好,降解率达到88.14%,同时该条件下邻苯二酚1,2-双加氧酶基因相对表达水平最高;培养温度为10℃时,A2菌对1,2,4-TCB降解率可达到85.3%,同时邻苯二酚l,2-双加氧酶基因也有较高的相对表达水平 以上结果说明,将A2菌应用于低温寡营养地下水的生物修复是可能的.%An oligotrophic degrading bacterium named strain A2 was screened from groundwater long-term contaminated by 1 , 2 , 4-TCB under low temperature condition, strain A2 was identified by gram stain and 16S rDNA sequence, the impacts of different pH, temperature, salinity on degradation effect and catechol 1 ,2 dioxyge-nase gene expression level were studied, and orthogonality experiment was carried out. The results showed that strain A2 was gram negative short rods, and was identified as pseudomonas preliminarily. The degrading effect of strain A2 on 1 ,2,4-TCB and catechol 1 ,2 dioxygenase gene expression level showed best under the conditions; pH of 7, cultivation temperature of 30℃ , salinity of 0.8% , cultivation time of 6 days, and the degrading rate could reach 88. 14% . The degrading rate of 1 ,2,4-TCB by strain A2 could reach 85.3% at 10℃ , and catechol 1 ,2 dioxygenase gene expression level also showed a relative high expression level. This research demonstrated that it is possible to apply strain A2 in the bioremediation of oligotrophic groundwater under low temperature condition.

  9. Thermic decomposition of biphenyl

    International Nuclear Information System (INIS)

    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)

  10. Heme-containing dioxygenases involved in tryptophan oxidation.

    Science.gov (United States)

    Millett, Elizabeth S; Efimov, Igor; Basran, Jaswir; Handa, Sandeep; Mowat, Christopher G; Raven, Emma Lloyd

    2012-04-01

    Heme iron is often used in biology for activation of oxygen. The mechanisms of oxygen activation by heme-containing monooxygenases (the cytochrome P450s) are well known, and involve formation of a Compound I species, but information on the heme-containing dioxygenase enzymes involved in tryptophan oxidation lags far behind. In this review, we gather together information emerging recently from structural, mechanistic, spectroscopic, and computational approaches on the heme dioxygenase enzymes involved in tryptophan oxidation. We explore the subtleties that differentiate various heme enzymes from each other, and use this to piece together a developing picture for oxygen activation in this particular class of heme-containing dioxygenases.

  11. The "Gln-Type" Thiol Dioxygenase from Azotobacter vinelandii is a 3-Mercaptopropionic Acid Dioxygenase.

    Science.gov (United States)

    Pierce, Brad S; Subedi, Bishnu P; Sardar, Sinjinee; Crowell, Joshua K

    2015-12-29

    Cysteine dioxygenase (CDO) is a non-heme iron enzyme that catalyzes the O2-dependent oxidation of l-cysteine to produce cysteinesulfinic acid. Bacterial CDOs have been subdivided as either "Arg-type" or "Gln-type" on the basis of the identity of conserved active site residues. To date, "Gln-type" enzymes remain largely uncharacterized. It was recently noted that the "Gln-type" enzymes are more homologous with another thiol dioxygenase [3-mercaptopropionate dioxygenase (MDO)] identified in Variovorax paradoxus, suggesting that enzymes of the "Gln-type" subclass are in fact MDOs. In this work, a putative "Gln-type" thiol dioxygenase from Azotobacter vinelandii (Av) was purified to homogeneity and characterized. Steady-state assays were performed using three substrates [3-mercaptopropionic acid (3mpa), l-cysteine (cys), and cysteamine (ca)]. Despite comparable maximal velocities, the "Gln-type" Av enzyme exhibited a specificity for 3mpa (kcat/KM = 72000 M(-1) s(-1)) nearly 2 orders of magnitude greater than those for cys (110 M(-1) s(-1)) and ca (11 M(-1) s(-1)). Supporting X-band electron paramagnetic resonance (EPR) studies were performed using nitric oxide (NO) as a surrogate for O2 binding to confirm obligate-ordered addition of substrate prior to NO. Stoichimetric addition of NO to solutions of 3mpa-bound enzyme quantitatively yields an iron-nitrosyl species (Av ES-NO) with EPR features consistent with a mononuclear (S = (3)/2) {FeNO}(7) site. Conversely, two distinct substrate-bound conformations were observed in Av ES-NO samples prepared with cys and ca, suggesting heterogeneous binding within the enzymatic active site. Analytical EPR simulations are provided to establish the relative binding affinity for each substrate (3map > cys > ca). Both kinetic and spectroscopic results presented here are consistent with 3mpa being the preferred substrate for this enzyme. PMID:26624219

  12. 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.

  13. Degradation of polychlorinated biphenyls

    International Nuclear Information System (INIS)

    Polychlorinated biphenyls (PCB) are generally disposed of by incineration, an expensive and hazardous method. Moreover, in cases where the PCBs are a minor component of a nontoxic fluid, such as a dielectric fluid, incineration causes loss of the nontoxic fluid as well as the PCB. An alternative method for destroying PCBs is disclosed which is not only capable of detoxification of PCB-contaminated soils, sludges, and sediments, but can also remove PCBs from solution in a wide range of concentrations, permitting full recovery of the bulk of the solution free of PCBs. The process of the invention may be operated in a batch, continuous, or semicontinuous mode, and is advantageously used to detoxify organic liquids such as transformer oils. According to the invention, PCBs are chemically degraded by contact with a Lewis acid catalyst in a nonaqueous liquid medium, in the presence of a cation which combines with the chlorine on the PCB to form a solid chloride of the cation which will precipitate out from the liquid medium. Preferred Lewis acids are metal halides, particularly a combination of aluminum chloride and ferric chloride, and the preferred cation is potassium in the form of KOH. The Lewis acids may be supplied to the process by the adventitious corrosion of a vessel containing the PCB-contaminated matter. Experiments are described to illustrate the process of the invention. 3 figs

  14. Hemoglobin: A Nitric-Oxide Dioxygenase

    Directory of Open Access Journals (Sweden)

    Paul R. Gardner

    2012-01-01

    Full Text Available Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs. Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry.

  15. Structure and mechanism of mouse cysteine dioxygenase

    Science.gov (United States)

    McCoy, Jason G.; Bailey, Lucas J.; Bitto, Eduard; Bingman, Craig A.; Aceti, David J.; Fox, Brian G.; Phillips, George N.

    2006-01-01

    Cysteine dioxygenase (CDO) catalyzes the oxidation of l-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 Å. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical β-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme. PMID:16492780

  16. Expression Pattern and Clinicopathological Relevance of the Indoleamine 2,3-Dioxygenase 1/Tryptophan 2,3-Dioxygenase Protein in Colorectal Cancer.

    Science.gov (United States)

    Chen, I-Chien; Lee, Kuen-Haur; Hsu, Ying-Hua; Wang, Wei-Ran; Chen, Chuan-Mu; Cheng, Ya-Wen

    2016-01-01

    Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host's immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of the APC gene remains unknown. Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci. Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate of APC. Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate of APC, making IDO1 an interesting target for immunotherapy in CRC. PMID:27578919

  17. 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)

    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.

  18. 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

    Energy Technology Data Exchange (ETDEWEB)

    Al-Salman, Fadheela; Plant, Nick, E-mail: N.Plant@Surrey.ac.uk

    2012-08-15

    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.

  19. Cloning of 9-cis-epoxycarotenoid dioxygenase (NCED) gene encoding a key enzyme during abscisic acid (ABA) biosynthesis and ABA-regulated ethylene production in detached young persimmon calyx

    Institute of Scientific and Technical Information of China (English)

    LENG Ping; ZHANG GuangLian; LI XiangXin; WANG LiangHe; ZHENG ZhongMing

    2009-01-01

    Unlike the typical climacteric fruits,persimmons (Diospyros kaki Thunb.) produce higher levels of ethylene when they are detached from trees at a younger stage.In order to obtain detailed information on the role of abscisic acid (ABA) in ripening,we cloned the DKNCED1,DKACS2,and DKAC01 genes from the calyx.Water loss was first noted in the calyx lobe,and DKNCED1 was highly expressed 1 d after the fruits were detached,coinciding with an increase in the ABA content.Then,the DKACS2 and DKAC01 genes were expressed after some delay.In the calyx,the ABA peak was observed 2 d after the fruits were harvested,and this peak preceded the ethylene peak observed on day 3.The fruit firmness rapidly decreased on day 4,and the fruits softened completely 6 d after they were harvested.The increases in the expressions of ABA,ethylene,and the genes in the calyxes occurred earlier than the corresponding increases in the pulp,although the 3 increases occurred on different days.Exogenous ABA treatment increased ABA concentration,induced expression of both ACS and ACO,and promoted ethylene synthesis and young-fruit softening;by contrast,treatment with NDGA inhibited the gene expressions and ethylene synthesis and delayed young-fruit softening.These results indicate that ethylene biosynthesis in the detached young persimmon fruits is initially triggered by ABA,which is induced by water loss in the calyx,through the induction of DKACS2 and DKAC01 expressions.The ethylene produced in the calyx subsequently diffuses into the pulp tissue,where it induces autocatalytic ethylene biosynthesis,resulting in an abrupt increase in ethylene production.

  20. 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

  1. Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

    NARCIS (Netherlands)

    Padberg, Jan-Sören; Van Meurs, Matijs; Kielstein, Jan T; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Zijlstra, Jan G; Kovesdy, Csaba P; Kümpers, Philipp

    2012-01-01

    UNLABELLED: BACKGROUND: Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO) controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so

  2. Assays of polychlorinated biphenyl congeners and co-contaminated heavy metals in the transgenic Arabidopsis plants carrying the recombinant guinea pig aryl hydrocarbon receptor-mediated β-glucuronidase reporter gene expression system.

    Science.gov (United States)

    Shimazu, Sayuri; Ohta, Masaya; Ohkawa, Hideo; Ashida, Hitoshi

    2012-01-01

    The transgenic Arabidopsis plant XgD2V11-6 carrying the recombinant guinea pig (g) aryl hydrocarbon receptor (AhR)-mediated β-glucuronidase (GUS) reporter gene expression system was examined for assay of polychlorinated biphenyl (PCB) congeners and co-contaminated heavy metals. When the transgenic Arabidopsis plants were treated with PCB126 (toxic equivalency factor; TEF: 0.1) and PCB169 (TEF: 0.03), the GUS activity of the whole plants was increased significantly. After treatment with PCB80 (TEF: 0), the GUS activity was nearly the same level as that treated with 0.1% dimethylsulfoxide (DMSO) as a vehicle control. After exposure to a 1:1 mixture of PCB126 and PCB169, the GUS activity was increased additively. However, after exposure to a mixture of PCB126 and PCB80, the GUS activity was lower than that of the treatment with PCB126 alone. Thus, PCB80 seemed to be an antagonist towards AhR. When the transgenic plants were treated with each of the heavy metals Fe, Cu, Zn, Cd and Pb together with PCB126, Cd and Pb increased the PCB126-induced GUS activity. On the other hand, Fe, Cu and Zn did not affect the PCB126-induced GUS activity. In the presence of the biosurfactant mannosylerythritol lipid-B (MEL-B) and the carrier protein bovine serum albumin (BSA), the PCB126-induced GUS activity was increased, but the Cd-assisted PCB126-induced GUS activity was not affected. Thus, MEL-B and BSA seemed to increase uptake and transport of PCB126, respectively. PMID:22938576

  3. 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.

  4. Identification of a novel dioxygenase involved in metabolism of o-xylene, toluene, and ethylbenzene by Rhodococcus sp. strain DK17.

    Science.gov (United States)

    Kim, Dockyu; Chae, Jong-Chan; Zylstra, Gerben J; Kim, Young-Soo; Kim, Seong-Ki; Nam, Myung Hee; Kim, Young Min; Kim, Eungbin

    2004-12-01

    Rhodococcus sp. strain DK17 is able to grow on o-xylene, benzene, toluene, and ethylbenzene. DK17 harbors at least two megaplasmids, and the genes encoding the initial steps in alkylbenzene metabolism are present on the 330-kb pDK2. The genes encoding alkylbenzene degradation were cloned in a cosmid clone and sequenced completely to reveal 35 open reading frames (ORFs). Among the ORFs, we identified two nearly exact copies (one base difference) of genes encoding large and small subunits of an iron sulfur protein terminal oxygenase that are 6 kb apart from each other. Immediately downstream of one copy of the dioxygenase genes (akbA1a and akbA2a) is a gene encoding a dioxygenase ferredoxin component (akbA3), and downstream of the other copy (akbA1b and akbA2b) are genes putatively encoding a meta-cleavage pathway. RT-PCR experiments show that the two copies of the dioxygenase genes are operonic with the downstream putative catabolic genes and that both operons are induced by o-xylene. When expressed in Escherichia coli, AkbA1a-AkbA2a-AkbA3 transformed o-xylene into 2,3- and 3,4-dimethylphenol. These were apparently derived from an unstable o-xylene cis-3,4-dihydrodiol, which readily dehydrates. This indicates a single point of attack of the dioxygenase on the aromatic ring. In contrast, attack of AkbA1a-AkbA2a-AkbA3 on ethylbenzene resulted in the formation of two different cis-dihydrodiols resulting from an oxidation at the 2,3 and the 3,4 positions on the aromatic ring, respectively. PMID:15574904

  5. 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

    2012-01-01

    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. J. Cell. Physiol. 227: 3254–3257, 2012. © 2011 Wiley Periodicals, Inc. PMID:22105303

  6. 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.

  7. 枸杞脱落酸生物合成关键酶基因NCED的克隆及表达分析%Cloning and Characterization of 9-cis-epoxycarotenoid Dioxygenase Gene(NCED) Encoding a Key Enzyme during Abscisic Acid Biosynthesis in Lycium barbarum L.

    Institute of Scientific and Technical Information of China (English)

    陆平; 田跃胜; 王名雪; 李杉; 赵静雅

    2013-01-01

    Abscisic acid(ABA) regulates the essential physiological and developmental processes of plants and plays imporant roles in plant responses to various environmental stresses. 9-cis-epoxycarotenoid dioxygenase ( NCED)is the key regulatory enzyme in the biosynthesis pathway of ABA in higher plants. In the study,a full-lengh cDNA of NCED gene( LbNCED) was fristly isolated and characterized from the leaves of L. barbarum. LbNCED was 2316 bp, containing a 1824 bp ORF and encoding 607 amino acids. Comparative and bioinformatics analysis revealed that the homology amino acid sequence of Lycopersicon esculentum and Solarium tuberosum LbNCED was 90%. At the N-terminus of the LbNCED located a 15 amino acids putative chloroplast transit peptide. Southern blot analysis revealed that it was a low-copy gene in the genome of L. barbarum. Real-time Quantitative PCR ( RT-QPCR) analysis showed that LbNCED mRNA most abundantly accumulated in leaves. The RT-QPCR analysis revealed that dehydration and salt stress signficantly enhanced LbNCED transcript expression and ABA content accumulation.%脱落酸(abscisic acid,ABA)对植物的生长发育具有独特的调控功能,并在植物适应逆境环境中发挥重要作用.9-顺式环氧类胡萝卜素双加氧酶(NCED)是高等植物中ABA生物合成途径的一个关键酶.根据GenBank中的植物NCED基因的同源序列设计简并引物,通过RT-PCR及RACE技术从枸杞叶片中克隆到1个编码NCED的基因,命名为LbNCED.其cDNA全长为2316 bp,含有1个1824 bp的开放阅读框,编码1个含607氨基酸残基,分子量为67.38 kDa、等电点(pI)为6.43的假定蛋白,其氨基酸序列与番茄(Lycopersicon esculentum)和马铃薯(Solanum tuberosum)的同源性达90%,在N-末端具有1个含15个氨基酸的叶绿体转运肽.Southern杂交结果表明,该基因在枸杞基因组中以低拷贝形式存在.盐处理和脱水处理的枸杞叶片中LbNCED基因的表达与内源ABA的积累同步变化.

  8. Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes catalyzed by 2-nitropropane dioxygenase.

    Science.gov (United States)

    Francis, Kevin; Russell, Bethany; Gadda, Giovanni

    2005-02-18

    2-Nitropropane dioxygenase (EC 1.13.11.32) catalyzes the oxidation of nitroalkanes into their corresponding carbonyl compounds and nitrite. In this study, the ncd-2 gene encoding for the enzyme in Neurospora crassa was cloned, expressed in Escherichia coli, and the resulting enzyme was purified. Size exclusion chromatography, heat denaturation, and mass spectroscopic analyses showed that 2-nitropropane dioxygenase is a homodimer of 80 kDa, containing a mole of non-covalently bound FMN per mole of subunit, and is devoid of iron. With neutral nitroalkanes and anionic nitronates other than propyl-1- and propyl-2-nitronate, for which a non-enzymatic free radical reaction involving superoxide was established using superoxide dismutase, substrate oxidation occurs within the enzyme active site. The enzyme was more specific for nitronates than nitroalkanes, as suggested by the second order rate constant k(cat)/K(m) determined with 2-nitropropane and primary nitroalkanes with alkyl chain lengths between 2 and 6 carbons. The steady state kinetic mechanism with 2-nitropropane, nitroethane, nitrobutane, and nitrohexane, in either the neutral or anionic form, was determined to be sequential, consistent with oxygen reacting with a reduced form of enzyme before release of the carbonyl product. Enzyme-monitored turnover with ethyl nitronate as substrate indicated that the catalytically relevant reduced form of enzyme is an anionic flavin semiquinone, whose formation requires the substrate, but not molecular oxygen, as suggested by anaerobic substrate reduction with nitroethane or ethyl nitronate. Substrate deuterium kinetic isotope effects with 1,2-[(2)H(4)]nitroethane and 1,1,2-[(2)H(3) ethyl nitronate at pH 8 yielded normal and inverse effects on the k(cat)/K(m) value, respectively, and were negligible on the k(cat) value. The k(cat)/K(m) and k(cat) pH profiles with anionic nitronates showed the requirement of an acid, whereas those for neutral nitroalkanes were consistent with

  9. 吲哚胺2,3-双加氧酶基因转染对肝癌细胞凋亡的影响及相关机制研究%Effects of Hepatocellular Carcinoma Cells'Apoptosis and the Related Mechanisms after Indoleamine 2,3-Dioxygenase Gene Transfection

    Institute of Scientific and Technical Information of China (English)

    卜晓倩; 张瑞; 申慧琴; 罗静; 刘燕; 张路英; 刘春亮; 王琦

    2011-01-01

    目的:通过细胞培养和在体实验探讨吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因转染后对肝癌细胞凋亡的影响及相关细胞免疫机制的研究.方法:提取健康人外周血中的T细胞利用细胞培养和基因转染技术将T细胞和肝癌细胞混合培养.实验分为6组:根据是否加入D-1-MT分为未干预组和干预组,每组根据培养细胞的不同又分为T细胞与HepG2细胞组、T细胞与pcDNA3.1-HepG2细胞组、T细胞与pcDNA3.1-IDO-HepG2细胞组.于混合培养2天后应用流式细胞术、MTT法检测各组中HepG2细胞的凋亡情况和T细胞抗HepG2细胞的细胞毒活性.在混合培养5天后应用流式细胞术检测调节性T细胞(Regulatory T cell,Treg)的比例.并建立人肝癌细胞小鼠模型,用流式细胞仪检测荷瘤小鼠外周血中Treg细胞的比例.结果:1.混合培养2天后,转染IDO基因的肝癌细胞其凋亡率和T细胞抗HepG2细胞的细胞毒活性均明显降低,分别为(1.65±0.14)%和(35.00±2.20)%(p<0.05);加入1-MT干预后,以上指标均明显高于干预前,且干预前后比较有明显的统计学意义(P<0.05).2.混合培养5天后,IDO-HepG2细胞组Treg细胞的比例明显升高(10.53±1.05)%,与其余两个未干预组比较有统计学意义(p<0.05);加1-MT干预后,Treg细胞比例均明显降低(p<0.05).3.转染IDO的荷瘤小鼠模型中外周血Treg细胞比例明显升高(15.33±1.18)%,与其余两组比较有统计学意义(p<0.05).结论:1.IDO可能通过增加调节性T细胞的比例来抑制肝癌细胞(HepG2细胞)的凋亡和T细胞的免疫毒性功能.1-MT可抑制IDO的这种作用.2.在体实验证实IDO的过量表达可提高外周血Treg细胞的比例.%Objective : To explore after indoleamine-2 ,3-dioxygenase ( IDO) gene transfection the influence of the hepatocellular carcinoma cells' apoptosis and the related cellular immune mechanisms by cell culture and in vivo. Methods: By cell culture and gene transfection

  10. Indoleamine 2,3 Dioxygenase (IDO Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Roberta Mancuso

    Full Text Available Interferon gamma (IFN-γ production induces the transcription of indoleamine 2,3 dioxygenase (IDO resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS patients.IDO and interferon-γ (IFN-γ gene expression, serum IDO activity (Kynurenine/Tryptophan ratio and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS and 15 healthy controls (HC. PBMCs samples in AMS patients were collected before (BT-AMS and during glucocorticoids-based therapy (DT-AMS.IDO expression was increased and IFN-γ was decreased (p<0.001 in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001. Serum neopterin concentration followed the same trend as IDO expression and activity.Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS.

  11. 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.

  12. Analysis of multi-domain hypothetical proteins containing iron-sulphur clusters and fad ligands reveal rieske dioxygenase activity suggesting their plausible roles in bioremediation.

    Science.gov (United States)

    Sathyanarayanan, Nitish; Nagendra, Holenarasipur Gundurao

    2012-01-01

    'Conserved hypothetical' proteins pose a challenge not just for functional genomics, but also to biology in general. As long as there are hundreds of conserved proteins with unknown function in model organisms such as Escherichia coli, Bacillus subtilis or Saccharomyces cerevisiae, any discussion towards a 'complete' understanding of these biological systems will remain a wishful thinking. Insilico approaches exhibit great promise towards attempts that enable appreciating the plausible roles of these hypothetical proteins. Among the majority of genomic proteins, two-thirds in unicellular organisms and more than 80% in metazoa, are multi-domain proteins, created as a result of gene duplication events. Aromatic ring-hydroxylating dioxygenases, also called Rieske dioxygenases (RDOs), are class of multi-domain proteins that catalyze the initial step in microbial aerobic degradation of many aromatic compounds. Investigations here address the computational characterization of hypothetical proteins containing Ferredoxin and Flavodoxin signatures. Consensus sequence of each class of oxidoreductase was obtained by a phylogenetic analysis, involving clustering methods based on evolutionary relationship. A synthetic sequence was developed by combining the consensus, which was used as the basis to search for their homologs via BLAST. The exercise yielded 129 multidomain hypothetical proteins containing both 2Fe-2S (Ferredoxin) and FNR (Flavodoxin) domains. In the current study, 40 proteins with N-terminus 2Fe-2S domain and C-terminus FNR domain are characterized, through homology modelling and docking exercises which suggest dioxygenase activity indicating their plausible roles in degradation of aromatic moieties.

  13. Bioelectrochemical Immunoassay of Polychlorinated Biphenyl

    International Nuclear Information System (INIS)

    A simple, rapid, and highly sensitive bioelectrochemical immunoassay method based on magnetic beads (MBs) and disposable screen-printed electrodes (SPE) has been developed to detect polychlorinated biphenyls (PCBs). The principle of this bioassay is based on a direct competitive enzyme-linked immunosorbent assay using PCB-antibody-coated MBs and horseradish peroxidase (HRP)-labeled PCB (HRP-PCB). A magnetic process platform was used to mix and shake the samples during the immunoreactions and to separate free and unbound reagents after the liquid-phase competitive immunoreactions among PCB-antibody-coated MBs, PCB analyte, and HRP-PCB. After a complete immunoassay, the HRP tracers attached to MBs were transferred to a substrate solution containing o-aminophenol and hydrogen peroxide for electrochemical detection. The different parameters, including the amount of HRP-PCB conjugates, immunoreaction time, and the concentration of substrate that governs the analytical performance of the immunoassay have been studied in detail and optimized. The detection limit of 5 pg mL-1 was obtained under optimum experimental conditions. The performance of this bioelectrochemical immunoassay was successfully evaluated with untreated river water spiked with PCBs, and the results were validated by commercial PCB enzyme-linked immunosorbent assay kit, indicating that this convenient and sensitive technique offers great promise for decentralized environmental application and trace PCBs monitoring

  14. 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.

  15. Expression and post-translational modification of human 4-hydroxy-phenylpyruvate dioxygenase.

    Science.gov (United States)

    Aarenstrup, Lene; Falch, Anne Marie; Jakobsen, Kirsten K; Neve, Søren; Henriksen L, Linda Ø; Tommerup, Niels; Leffers, Henrik; Kristiansen, Karsten

    2002-01-01

    4-hydroxyphenylpyruvate dioxygenase (HPD) (EC 1.13.11.27) is a key enzyme involved in tyrosine catabolism. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. The severe type I tyrosinemia, caused by a deficiency of fumarylacetoacetate hydrolase which functions downstream of HPD in the tyrosine degradation pathway, is often associated with decreased expression of HPD, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. The HPD gene was previously mapped to the chromosomal region 12q24-->qter. In the present study high-resolution chromosome mapping localized the HPD gene to 12q24.31. DNase I footprinting, revealed that four regions of the HPD promoter were protected by rat liver nuclear proteins. Computer-assisted analyses suggested that these elements might bind Sp1/AP2, HNF4, HNF3/CREB, and C/EBP, respectively. In transient transfection experiments, the proximal 271bp of the promoter conferred basal transcriptional activation in human Chang cells. Sequences in intron 1 were able to enhance the activity of this basal promoter. Finally, vaccinia virus-based expression provided evidence that HPD is subject to phosphorylation, and furthermore, allowed mapping of the HPD protein in the human keratinocyte 2D database.

  16. Microbial transformation and degradation of polychlorinated biphenyls

    International Nuclear Information System (INIS)

    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 H2 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

  17. Cometabolic oxidation of polychlorinated biphenyls in soil with a surfactant-based field application vector.

    OpenAIRE

    Lajoie, C. A.; Layton, A C; Sayler, G. S.

    1994-01-01

    Polychlorinated biphenyl (PCB)-degradative genes, under the control of a constitutive promoter, were cloned into a broad-host-range plasmid and a transposon. These constructs were inserted into a surfactant-utilizing strain, Pseudomonas putida IPL5, to create a field application vector (FAV) in which a surfactant-degrading organism cometabolizes PCB. By utilizing a surfactant not readily available to indigenous populations and a constitutive promoter, selective growth and PCB-degradative gene...

  18. 40 CFR 129.105 - Polychlorinated biphenyls (PCBs).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Polychlorinated biphenyls (PCBs). 129... Polychlorinated biphenyls (PCBs). (a) Specialized definitions. (1) PCB Manufacturer means a manufacturer who produces polychlorinated biphenyls. (2) Electrical capacitor manufacturer means a manufacturer who...

  19. 40 CFR 721.5713 - Phenol - biphenyl polymer condensate (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phenol - biphenyl polymer condensate... Specific Chemical Substances § 721.5713 Phenol - biphenyl polymer condensate (generic). (a) Chemical... as a phenol - biphenyl polymer condensate (PMN P-00-1220) is subject to reporting under this...

  20. Ring-hydroxylating dioxygenase (RHD) expression in a microbial community during the early response to oil pollution.

    Science.gov (United States)

    Paissé, Sandrine; Goñi-Urriza, Marisol; Stalder, Thibault; Stadler, Thibault; Budzinski, Hélène; Duran, Robert

    2012-04-01

    The early functional response of a bacterial community from the sediments of a chronically oil-polluted retention basin located at the Etang de Berre (France) was investigated just after petroleum addition. After removing hydrocarbon compounds by natural abiotic and biotic processes, the sediments were maintained in microcosms and Vic Bilh petroleum was added. The diversity and the expression of genes encoding ring-hydroxylating dioxygenases (RHD) were examined just after the petroleum addition until 14 days focussing on the first hours following the contamination. RHD gene copy numbers and diversity were maintained throughout all the incubation period; however, transcripts were detected only during the first 2 days. One dominant RHD gene, immediately and specifically expressed in response to petroleum contamination, was related to RHD gene carried by a plasmid found in Pseudomonas spp. The expression of the RHD genes was correlated with high biodegradation levels observed for low molecular weight PAHs at 7 days of incubation. The study shows that the bacterial metabolism induced just after the oil input is a key stage that could determine the bacterial community structure changes. Monitoring the expression of RHD genes, key genes involved in hydrocarbon degradation, may provide useful information for managing bioremediation processes.

  1. Biodegradation of biphenyl and removal of 2-chlorobiphenyl by Pseudomonas sp. KM-04 isolated from PCBs-contaminated mine impacted soil

    Science.gov (United States)

    Nam, I.; Chon, C.; Kim, J.; Kim, Y.

    2013-12-01

    The aim of the present study is to remediate the PCBs contaminated mine soil using microcosm study. For that, the naturally occurring microorganisms are stimulated and enriched in soil itself by supplementing biphenyl as well as benzoic acid. As a result the biphenyl degrading organisms are induced to degrade the PCBs contamination. From the stimulated soil, the biphenyl degrading organisms are isolated and degraded metabolites are elucidated. Pseudomonas sp. strain KM-04 was isolated from PCBs-contaminated soil in a coal mine-impacted area, and identification of bacteria was done by sequencing the 16S rRNA gene analysis. The growth of Pseudomonas sp. strain KM-04 using biphenyl as the sole carbon source was investigated by culturing in 100-mL Erlenmeyer flasks containing 10 ml sterilized MSM and 10 μg/ml biphenyl, and the ability of KM-04 to remove biphenyl and 2-chlorobiphenyl from mine soil was investigated. Metabolite formation was confirmed by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometric analysis. Pseudomonas sp. strain KM-04 uses biphenyl as a sole carbon and energy source, and resting cells convert biphenyl to its metabolic intermediates, including dihydroxybiphenyl, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, and benzoic acid. Incubation of real soil collected from abandoned mine areas with resting cells of Pseudomonas sp. strain KM-04 for 10 days resulted in the 98.5 % of biphenyl and 82.3 % of 2-chlorobiphenyl in a slurry system. The ability of the Pseudomonas sp. strain KM-04 to bioremediate biphenyl and 2-chlorobiphenyl from abandoned mine soil was examined using soil microcosm studies under laboratory conditions. Treatment of mine soil with the Pseudomonas sp. strain KM-04 for 15 days resulted in 87.1 % reduction in biphenyl and 68.7 % in 2-chlorobiphenyl contents. The results suggest that Pseudomonas sp. strain KM-04 is a potential candidate for the biological removal of biphenyl and chlorinated derivatives

  2. 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 d

  3. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

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

    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 d

  4. Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

    Directory of Open Access Journals (Sweden)

    Padberg Jan-Sören

    2012-12-01

    Full Text Available Abstract Background Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so far. We thus aimed to study changes in blood pressure in parallel with tryptophan and kynurenine levels during experimental endotoxemia in humans. Findings Six healthy male volunteers were given E. coli lipopolysaccharide (LPS; 4 ng/kg as a 1-min intravenous infusion. They had levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 as well as IDO activity assessed as the kynurenine-to-tryptophan plasma ratio by liquid chromatography-tandem mass spectrometry at various time points during a 24 h time course. During endotoxemia, IDO activity significantly increased, reaching peak levels at 8 h after LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P Conclusions LPS is a triggering factor for the induction of IDO in men. Our findings strongly support the concept that the induction of IDO in the vascular endothelium contributes to hypotension in human sepsis.

  5. In vivo correction with recombinant adenovirus of 4-hydroxyphenylpyruvic acid dioxygenase deficiencies in strain III mice.

    Science.gov (United States)

    Kubo, S; Kiwaki, K; Awata, H; Katoh, H; Kanegae, Y; Saito, I; Yamamoto, T; Miyazaki, J; Matsuda, I; Endo, F

    1997-01-01

    Tyrosinemia type 3, caused by a genetic deficiency of 4-hydroxyphenylpyruvic acid dioxygenase (HPD) in tyrosine catabolism, is characterized by convulsion, ataxia, and mental retardation. The III mouse is a model of tyrosinemia type 3. HPD activity and protein are defective in the liver and its blood tyrosine levels are elevated, the range being between 1,100 and 1,656 microM. We constructed a recombinant adenoviral vector bearing the human HPD cDNA (AdexCAGhHPD), which is expressed under the control of a potent CAG promoter. III mice were injected with 1.0 x 10(8) to 1.0 x 10(9) pfu of AdexCAGhHPD through the tail vein. When 3.0 x 10(8) - 1.0 x 10(9) pfu were injected, blood tyrosine levels decreased within 3 hr, reached a normal range (under 300 microM), and remained at a low level for 2-6 weeks. Hepatic HPD activities also increased as early as 3 hr after the injection of 5.0 x 10(8) pfu, reached the levels comparable to the control mice in 3-7 days, and then decreased, and correlated well to blood tyrosine. Hepatic HPD expression was confirmed by Northern blot and immunoblot analyses. Histology revealed no difference (gross or microscopic) between the liver injected with AdexCAGhHPD and the control. No significant changes in blood tyrosine levels were noted after the second injection of 5.0 x 10(8) pfu of AdexCAGhHPD. Thus, the intravenous administration of the adenoviral vector bearing a foreign gene seems suitable for transient, early gene transfer into the liver.

  6. 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.

  7. Substrate Oxidation by Indoleamine 2,3-Dioxygenase: EVIDENCE FOR A COMMON REACTION MECHANISM.

    Science.gov (United States)

    Booth, Elizabeth S; Basran, Jaswir; Lee, Michael; Handa, Sandeep; Raven, Emma L

    2015-12-25

    The kynurenine pathway is the major route of L-tryptophan (L-Trp) catabolism in biology, leading ultimately to the formation of NAD(+). The initial and rate-limiting step of the kynurenine pathway involves oxidation of L-Trp to N-formylkynurenine. This is an O2-dependent process and catalyzed by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase. More than 60 years after these dioxygenase enzymes were first isolated (Kotake, Y., and Masayama, I. (1936) Z. Physiol. Chem. 243, 237-244), the mechanism of the reaction is not established. We examined the mechanism of substrate oxidation for a series of substituted tryptophan analogues by indoleamine 2,3-dioxygenase. We observed formation of a transient intermediate, assigned as a Compound II (ferryl) species, during oxidation of L-Trp, 1-methyl-L-Trp, and a number of other substrate analogues. The data are consistent with a common reaction mechanism for indoleamine 2,3-dioxygenase-catalyzed oxidation of tryptophan and other tryptophan analogues.

  8. Enhanced tolerance and remediation to mixed contaminates of PCBs and 2,4-DCP by transgenic alfalfa plants expressing the 2,3-dihydroxybiphenyl-1,2-dioxygenase.

    Science.gov (United States)

    Wang, Yan; Ren, Hejun; Pan, Hongyu; Liu, Jinliang; Zhang, Lanying

    2015-04-01

    Polychlorinated biphenyls (PCBs) and 2,4-dichlorophenol (2,4-DCP) generally led to mixed contamination of soils as a result of commercial and agricultural activities. Their accumulation in the environment poses great risks to human and animal health. Therefore, the effective strategies for disposal of these pollutants are urgently needed. In this study, genetic engineering to enhance PCBs/2,4-DCP phytoremediation is a focus. We cloned the 2,3-dihydroxybiphenyl-1,2-dioxygenase (BphC.B) from a soil metagenomic library, which is the key enzyme of aerobic catabolism of a variety of aromatic compounds, and then it was expressed in alfalfa driven by CaMV 35S promoter using Agrobacterium-mediated transformation. Transgenic line BB11 was selected out through PCR, Western blot analysis and enzyme activity assays. Its disposal and tolerance to both PCBs and 2,4-DCP were examined. The tolerance capability of transgenic line BB11 towards complex contaminants of PCBs/2,4-DCP significantly increased compared with non-transgenic plants. Strong dissipation of PCBs and high removal efficiency of 2,4-DCP were exhibited in a short time. It was confirmed expressing BphC.B would be a feasible strategy to help achieving phytoremediation in mixed contaminated soils with PCBs and 2,4-DCP.

  9. Crystal structure of thermostable catechol 2,3-dioxygenase determined by multiwavelength anomalous dispersion method

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The selenomethionyl derivative of the thermostable catechol 2,3-dioxygenase (SeMet-TC23O) is expressed,purified and crystallized. By using multiwave length anomalous dispersion (MAD) phasing techniques, the crystal structure of TC23O at 0.3 nm resolutions is determined.TC23O is a homotetramer. Each monomer is composed of N-terminal and C-terminal domains (residues 1~153 and 153~319, respectively). The two domains are proximately symmetric by a non-crystallographic axis. Each domain contains two characteristic motifs which are found in almost all of extradial dioxygenases.Kevwords: multiwavelength anomalous dispersion (MAD), X-ray diffraction, thermostable catechol 2,3-dioxygenase, crystal structure,synchrotron light source.

  10. Occupational exposure to polychlorinated biphenyls (PCBs).

    OpenAIRE

    Wolff, M S

    1985-01-01

    Human occupational exposure to polychlorinated biphenyls (PCBs) with varying chlorine content has been reported by several investigators, using analyses of blood or adipose samples or skin wipes to evaluate levels in the body. The intensity of occupational exposure is related to both duration and intensity of exposure. The qualitative nature of occupational exposure, as well as casual environmental exposure, has been shown to consist of less readily metabolized PCB congeners. The pattern of P...

  11. ADSORPTION OF POLYCHLORINATED BIPHENYLS BY SOILS

    OpenAIRE

    Mihaela Preda; Radu Lăcătuşu; Dumitru Marian Motelică; Nicoleta Vrînceanu; Veronica Tănase

    2010-01-01

    The behavior of polychlorinated biphenyls (PCBs) in soil is determined by several factors including adsorption, mobility and degradation. Adsorption, directly or indirectly, influences the other factors. Adsorption process is generally evaluated by using adsorption isotherms representing the relationship between the quantity of substance adsorbed per unit weight and concentration of the substance in solution at equilibrium. They allow determination of the adsorption constant, which is directl...

  12. Metabolism and metabolites of polychlorinated biphenyls (PCBs)

    OpenAIRE

    Grimm, FA; Hu, D.; Kania-Korwel, I.; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

    2015-01-01

    The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and ...

  13. Metal-Dependent Function of a Mammalian Acireductone Dioxygenase.

    Science.gov (United States)

    Deshpande, Aditi R; Wagenpfeil, Karina; Pochapsky, Thomas C; Petsko, Gregory A; Ringe, Dagmar

    2016-03-01

    The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate the metal ion identity and three-dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, which is the penultimate step in methionine salvage. The nickel-bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO), and 3-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe(2+)-bound protein, which shows about 10-fold higher activity than that of others, catalyzes on-pathway chemistry, whereas the Ni(2+), Co(2+), or Mn(2+) forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by the metal ion identity, with Ni(2+)-bound MmARD being the most stable, followed by Co(2+) and Fe(2+), and Mn(2+)-bound ARD being the least stable. Ni(2+)- and Co(2+)-bound MmARD were crystallized, and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination, and the catalytic mechanism. PMID:26858196

  14. Crystal Structures of Fe2+ Dioxygenase Superoxo, Alkylperoxo, and Bound Product Intermediates

    OpenAIRE

    Kovaleva, Elena G.; Lipscomb, John D.

    2007-01-01

    We report the structures of three intermediates in the O2 activation and insertion reactions of an extradiol ring-cleaving dioxygenase. A crystal of Fe2+-containing homoprotocatechuate 2,3-dioxygenase was soaked in the slow substrate 4-nitrocatechol in a low O2 atmosphere. The X-ray crystal structure shows that three different intermediates reside in different subunits of a single homotetrameric enzyme molecule. One of these is the key substrate-alkylperoxo-Fe2+ intermediate, which has been p...

  15. Metabolic and health consequences of occupational exposure to polychlorinated biphenyls.

    OpenAIRE

    Smith, A B; Schloemer, J; Lowry, L K; Smallwood, A W; Ligo, R N; Tanaka, S.; Stringer, W; Jones, M; Hervin, R; Glueck, C J

    1982-01-01

    In surveys of three groups of workers occupationally exposed to polychlorinated biphenyls (PCBs) serum PCB concentrations were quantitated as lower chlorinated biphenyls (L-PCBs) and higher chlorinated biphenyls (H-PCBs). Serum L-PCB and H-PCB concentrations were many times greater among workers employed in power capacitor manufacturing than exposed areas. Statistically significant positive correlations of symptoms suggestive of mucous membrane and skin irritation, of systemic malaise, and al...

  16. 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

  17. Robust crop resistance to broadleaf and grass herbicides provided by aryloxyalkanoate dioxygenase transgenes.

    Science.gov (United States)

    Wright, Terry R; Shan, Guomin; Walsh, Terence A; Lira, Justin M; Cui, Cory; Song, Ping; Zhuang, Meibao; Arnold, Nicole L; Lin, Gaofeng; Yau, Kerrm; Russell, Sean M; Cicchillo, Robert M; Peterson, Mark A; Simpson, David M; Zhou, Ning; Ponsamuel, Jayakumar; Zhang, Zhanyuan

    2010-11-23

    Engineered glyphosate resistance is the most widely adopted genetically modified trait in agriculture, gaining widespread acceptance by providing a simple robust weed control system. However, extensive and sustained use of glyphosate as a sole weed control mechanism has led to field selection for glyphosate-resistant weeds and has induced significant population shifts to weeds with inherent tolerance to glyphosate. Additional weed control mechanisms that can complement glyphosate-resistant crops are, therefore, urgently needed. 2,4-dichlorophenoxyacetic acid (2,4-D) is an effective low-cost, broad-spectrum herbicide that controls many of the weeds developing resistance to glyphosate. We investigated the substrate preferences of bacterial aryloxyalkanoate dioxygenase enzymes (AADs) that can effectively degrade 2,4-D and have found that some members of this class can act on other widely used herbicides in addition to their activity on 2,4-D. AAD-1 cleaves the aryloxyphenoxypropionate family of grass-active herbicides, and AAD-12 acts on pyridyloxyacetate auxin herbicides such as triclopyr and fluroxypyr. Maize plants transformed with an AAD-1 gene showed robust crop resistance to aryloxyphenoxypropionate herbicides over four generations and were also not injured by 2,4-D applications at any growth stage. Arabidopsis plants expressing AAD-12 were resistant to 2,4-D as well as triclopyr and fluroxypyr, and transgenic soybean plants expressing AAD-12 maintained field resistance to 2,4-D over five generations. These results show that single AAD transgenes can provide simultaneous resistance to a broad repertoire of agronomically important classes of herbicides, including 2,4-D, with utility in both monocot and dicot crops. These transgenes can help preserve the productivity and environmental benefits of herbicide-resistant crops.

  18. Robust crop resistance to broadleaf and grass herbicides provided by aryloxyalkanoate dioxygenase transgenes.

    Science.gov (United States)

    Wright, Terry R; Shan, Guomin; Walsh, Terence A; Lira, Justin M; Cui, Cory; Song, Ping; Zhuang, Meibao; Arnold, Nicole L; Lin, Gaofeng; Yau, Kerrm; Russell, Sean M; Cicchillo, Robert M; Peterson, Mark A; Simpson, David M; Zhou, Ning; Ponsamuel, Jayakumar; Zhang, Zhanyuan

    2010-11-23

    Engineered glyphosate resistance is the most widely adopted genetically modified trait in agriculture, gaining widespread acceptance by providing a simple robust weed control system. However, extensive and sustained use of glyphosate as a sole weed control mechanism has led to field selection for glyphosate-resistant weeds and has induced significant population shifts to weeds with inherent tolerance to glyphosate. Additional weed control mechanisms that can complement glyphosate-resistant crops are, therefore, urgently needed. 2,4-dichlorophenoxyacetic acid (2,4-D) is an effective low-cost, broad-spectrum herbicide that controls many of the weeds developing resistance to glyphosate. We investigated the substrate preferences of bacterial aryloxyalkanoate dioxygenase enzymes (AADs) that can effectively degrade 2,4-D and have found that some members of this class can act on other widely used herbicides in addition to their activity on 2,4-D. AAD-1 cleaves the aryloxyphenoxypropionate family of grass-active herbicides, and AAD-12 acts on pyridyloxyacetate auxin herbicides such as triclopyr and fluroxypyr. Maize plants transformed with an AAD-1 gene showed robust crop resistance to aryloxyphenoxypropionate herbicides over four generations and were also not injured by 2,4-D applications at any growth stage. Arabidopsis plants expressing AAD-12 were resistant to 2,4-D as well as triclopyr and fluroxypyr, and transgenic soybean plants expressing AAD-12 maintained field resistance to 2,4-D over five generations. These results show that single AAD transgenes can provide simultaneous resistance to a broad repertoire of agronomically important classes of herbicides, including 2,4-D, with utility in both monocot and dicot crops. These transgenes can help preserve the productivity and environmental benefits of herbicide-resistant crops. PMID:21059954

  19. 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

  20. 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

  1. Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.

    Science.gov (United States)

    Li, De Feng; Zhang, Jia Yue; Hou, Yan Jie; Liu, Lei; Hu, Yonglin; Liu, Shuang Jiang; Wang, Da Cheng; Liu, Wei

    2013-01-01

    Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.

  2. Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma

    NARCIS (Netherlands)

    de Jong, Renske A; Kema, Ido P; Boerma, Annemarie; Boezen, Hendrika; van der Want, Johannes J L; Gooden, Marloes J M; Hollema, Harmen; Nijman, Hans W

    2012-01-01

    Objective. Indoleamine-2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a l

  3. 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 toleran......, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general....

  4. 4-Nitrocatechol as a colorimetric probe for non-heme iron dioxygenases.

    Science.gov (United States)

    Tyson, C A

    1975-03-10

    4-Nitrocatechol is examined as an active site probe for non-heme iron dioxygenases and found to be of value, particularly with those containing iron in the Fe(II) oxidation state. 4-Nitrocatechol is astrong competitive inhibitor of substrate oxygenation by protocatechuate 3,4-dioxygenase, forming a reversible complex with this enzyme, and by pyrocatechase. The number of binding sites per enzyme molecule titrated spectrophotometrically with 4-nitrocatechol agrees with results from previous studies with either the principal substrate or other analogues, as expected of an effective probe. Despite these facts and the observation that both enzymes cleave the same substrates at the same carbon-carbon bond, the optical and electron paramagnetic resonance (EPR) spectra of their 4-nitrocatechol complexes are remarkably different. The 4-nitocatechol-protocatechuate 3,4-dioxygenase optical spectra resemble that of the 4-nitrocatecholate ion shifted 20 to 30 nm to longer wavelength. Concomitant with this change the EPR signal centered at g equal 4.28 shows increased rhombicity (g values at 4.74, 4.28, and 3.74). In contrast, the spectrum of the 4-nitrocatechol-pyrocatechase complex has a maximum at the same wavelength as that of a 1:1 solution of free Fe(II) and 4-nitrocatechol in the absence of enzyme after titration of the catecholic protons with base and the g equal 4.28 EPR signal is not resolved at liquid N-2 temperature. These changes are interpreted as resulting in part from a pronounced change in the ligand fields about the irons at the active sites which in the case of protocatechuate 3,4-dioxygenase leads to enzyme inactivation. The results also are the first indication that substrate analogues change their ionization form upon complexation with Fe (III) dioxygenases. The interaction of the probe with metapyrocatechase, an Fe(III) containing dioxygenase, and with several additional oxygenases and hydroperoxidases is also briefly examined. The probe is not specific

  5. Radiochemical decomposition of polychlorinated biphenyls in hexane

    International Nuclear Information System (INIS)

    Products of polychlorinated biphenyls (PCB) decomposition are analyzed with the aim of determining whether polychlorinated dibenzodioxins (PCDD) or dibenzafurans (PCDF) are formed during radition-chemical decomposition. It is shown that under irradiation of PCB Arochlor 1260 mixture with 10-2 mass % concentration decomposition degree equals 90.4 % at radiaion dose more than 6 Mrad. As the result of irradiation the content of relatively light PCB in the mixture increases and the content of irradiated mixture becomes close to the content of Arochlor 1242 mixture. Neitgher PCDD nor PCDE is detected on the products of PCB decomposition

  6. Novel Polyamides Containing Biphenyl-phthalazinone Moieties

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A novel diamine monomer 2H-(4-aminophenyl)-4-[4-(4-aminophenoxy) biphenyl]-phthalazinone 1 containing aza hetero cycle was synthesized and utilized for preparation of new high molecular weight aromatic polyamides with various aromatic dicarboxylic acids with the inherent viscosity of 0.50 ~ 1.62 g/dL. These polyamides had rather high glass transition temperatures of 327~356℃ and their structure was confirmed by IR, 1H NMR and MS. They are readily soluble in polar solvents such as NMP, DMF etc. and easily cast into tough, flexible films.

  7. 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.

  8. ADSORPTION OF POLYCHLORINATED BIPHENYLS BY SOILS

    Directory of Open Access Journals (Sweden)

    Mihaela Preda

    2010-01-01

    Full Text Available The behavior of polychlorinated biphenyls (PCBs in soil is determined by several factors including adsorption, mobility and degradation. Adsorption, directly or indirectly, influences the other factors. Adsorption process is generally evaluated by using adsorption isotherms representing the relationship between the quantity of substance adsorbed per unit weight and concentration of the substance in solution at equilibrium. They allow determination of the adsorption constant, which is directly proportional to the adsorption of PCBs in soil. PCBs are very insoluble in water, so they tend to accumulate in the lipids. This is the reason why polychlorinated biphenyls are more strongly adsorbed in soils with higher organic matter content. To obtain the adsorption isotherm were used standard solutions of PCB 101with initial concentrations: 0.05, 0.1, 0.5, 1 and 2 g/ml. The adsorption constants were in order: 3072 ml/g for chernozem, 2943 mg/l for chromic luvisol, 998 mg/l for aluviosol and 1443 mg/l for anthrosol. The values of adsorption constants depend on the organic matter and clay content.

  9. Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls concentrations.

    OpenAIRE

    Maroni, M; Colombi, A.; Cantoni, S; Ferioli, E; Foa, V

    1981-01-01

    Industrial exposure to polychlorinated biphenyls (PCBs) and internal dose were investigated in 80 worker exposed for many years to PCB mixtures with a 42% chlorine content (Pyralene 3010 and Apirolio). PCBs were determined by liquid gas chromatography on samples taken from workroom air, workroom surfaces and tools, the palms of the hand, and the blood of the workers. In the workroom air samples, PCB concentrations ranged from 48 to 275 micrograms/m3. All tested surfaces and tools were heavily...

  10. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase.

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2016-05-01

    Full Text Available Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO. Here we show that acute influenza A virus (IAV and chronic murine leukemia retrovirus (MuLV infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS tissues. Moreover, kynurenine (Kyn, a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19 and dendritic cell (CD11c markers (CD19+ DCs. CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC phenotypes, unlike conventional (CD19neg DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19

  11. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase.

    Science.gov (United States)

    Huang, Lei; Ou, Rong; Rabelo de Souza, Guilherme; Cunha, Thiago M; Lemos, Henrique; Mohamed, Eslam; Li, Lingqian; Pacholczyk, Gabriela; Randall, Janice; Munn, David H; Mellor, Andrew L

    2016-05-01

    Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO). Here we show that acute influenza A virus (IAV) and chronic murine leukemia retrovirus (MuLV) infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS) tissues. Moreover, kynurenine (Kyn), a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19) and dendritic cell (CD11c) markers (CD19+ DCs). CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg) DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC) phenotypes, unlike conventional (CD19neg) DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19+ DCs

  12. Tryptophan recycling is responsible for the interferon-gamma resistance of Chlamydia psittaci GPIC in indoleamine dioxygenase-expressing host cells.

    Science.gov (United States)

    Wood, Heidi; Roshick, Christine; McClarty, Grant

    2004-05-01

    Comparative genomics indicates that vast differences in Chlamydia sp. host range and disease characteristics can be traced back to subtle variations in gene content within a region of the chromosome termed the plasticity zone. Genes required for tryptophan biosynthesis are located in the plasticity zone; however, the complement of genes encoded varies depending on the chlamydial species examined. Of the sequenced chlamydia genomes, Chlamydia psittaci GPIC contains the most complete tryptophan biosynthesis operon, encoding trpRDCFBA. Immediately downstream of the trp operon are genes encoding kynureninase and ribose phosphate pyrophosphokinase. Here, we show that, in GPIC, these genes are transcribed as a single transcript, the expression of which is regulated by tryptophan. Complementation analyses, using various mutant Escherichia coli isolates, indicate that the tryptophan biosynthesis, kynureninase and ribose phosphate pyrophosphokinase gene products are functional. Furthermore, growth of C. psittaci GPIC in HeLa cells, cultured in tryptophan-free medium, could be rescued by the addition of anthranilate, kynurenine or indole. In total, our results indicate that this complement of genes enables GPIC to recycle tryptophan and thus accounts for the interferon-gamma resistant phenotype displayed in indoleamine-2,3-dioxygenase-expressing host cells. PMID:15101993

  13. 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.

  14. The carotenoid cleavage dioxygenase CCD2 catalysing the synthesis of crocetin in spring crocuses and saffron is a plastidial enzyme.

    Science.gov (United States)

    Ahrazem, Oussama; Rubio-Moraga, Angela; Berman, Judit; Capell, Teresa; Christou, Paul; Zhu, Changfu; Gómez-Gómez, Lourdes

    2016-01-01

    The apocarotenoid crocetin and its glycosylated derivatives, crocins, confer the red colour to saffron. Crocetin biosynthesis in saffron is catalysed by the carotenoid cleavage dioxygenase CCD2 (AIG94929). No homologues have been identified in other plant species due to the very limited presence of crocetin and its derivatives in the plant kingdom. Spring Crocus species with yellow flowers accumulate crocins in the stigma and tepals. Four carotenoid CCDs, namely CaCCD1, CaCCD2 and CaCCD4a/b and CaCCD4c were first cloned and characterized. CaCCD2 was localized in plastids, and a longer CCD2 version, CsCCD2L, was also localized in this compartment. The activity of CaCCD2 was assessed in Escherichia coli and in a stable rice gene function characterization system, demonstrating the production of crocetin in both systems. The expression of all isolated CCDs was evaluated in stigma and tepals at three key developmental stages in relation with apocarotenoid accumulation. CaCCD2 expression parallels crocin accumulation, but C14 apocarotenoids most likely are associated to the CaCCD1 activity in Crocus ancyrensis flowers. The specific CCD2 localization and its membrane interaction will contribute to the development of a better understanding of the mechanism of crocetin biosynthesis and regulation in the chromoplast. PMID:26377696

  15. Molecular cloning of hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger.

    Science.gov (United States)

    Matsuda, J; Okabe, S; Hashimoto, T; Yamada, Y

    1991-05-25

    Roots of several solanaceous plants produce anticholinergic alkaloids, hyoscyamine and scopolamine. Hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase (EC 1.14.11.11), catalyzes hydroxylation of hyoscyamine in the biosynthetic pathway leading to scopolamine. We report here on the isolation of cDNA clones encoding the hydroxylase from a cDNA library made from mRNA of the cultured roots of Hyoscyamus niger. The library was screened with three synthetic oligonucleotides that encode amino acid sequences of internal peptide fragments of the purified hydroxylase. Nucleotide sequence analysis of the cloned cDNA revealed an open reading frame that encodes 344 amino acids (Mr = 38,999). All 12 internal peptide fragments determined in the purified enzyme were found in the amino acid sequence deduced from the cDNA. With computer-aided comparison to other proteins we found that the hydroxylase is homologous to two synthases involved in the biosynthesis of beta-lactam antibiotics in some microorganisms and the gene products of tomato pTOM13 cDNA and maize A2 locus which had been proposed to catalyze oxidative reactions in the biosynthesis of ethylene and anthocyan, respectively. RNA blotting hybridization showed that mRNA of the hydroxylase is abundant in cultured roots and present in plant roots, but absent in leaves, stems, and cultured cells of H. niger. PMID:2033047

  16. Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation

    Directory of Open Access Journals (Sweden)

    Vera Levina

    2012-01-01

    Full Text Available The role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1, in tumor escape and metastasis formation was analyzed using two pairs of Ido1+ and Ido1− murine breast cancer cell lines. Ido1 expression in 4T1 cells was knocked down by shRNA, and Ido1 expression in NT-5 cells was upregulated by stable transfection. Growth of Ido1− tumors and spontaneous metastasis formation were inhibited in immunocompetent mice. A higher level of cytotoxic T lymphocytes was generated by spleen cells from mice bearing Ido1− tumors than Ido1+ tumors. Tumor and metastatic growth was enhanced in immunodeficient mice, confirming an intensified immune response in the absence of Ido1 expression. However, Ido1+ tumors grow faster than Ido1− tumors in immunodeficient SCID/beige mice (lacking T, B, and NK cells suggesting that some Ido1-controlled nonimmunological mechanisms may be involved in tumor cell growth regulation. In vitro experiments demonstrated that downregulation of Ido1 in tumor cells was associated with decreased cell proliferation, increased apoptosis, and changed expression of cell cycle regulatory genes, whereas upregulation of Ido1 in the cells had the opposite effects. Taken together, our findings indicate that Ido1 expression could exert immunological and nonimmunological effects in murine breast tumor cells.

  17. 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.

  18. 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.

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

    OpenAIRE

    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 i...

  20. 4-Hydroxyphenylpyruvate dioxygenase inhibitors in combination with safeners: solutions for modern and sustainable agriculture.

    Science.gov (United States)

    Ahrens, Hartmut; Lange, Gudrun; Müller, Thomas; Rosinger, Chris; Willms, Lothar; van Almsick, Andreas

    2013-09-01

    Inhibitors of 4-hydroxyphenylpyruvate dioxygenase (HPPD) prevent plant carotenoid pigment formation, which in turn leads to chlorophyll degradation. This "bleaching" herbicide mode of action provides weed-control products for various crops, such as rice, corn, and cereals. Combinations with suitable safeners allow the full exploitation of the potential of this compound class to selectively control major weed problems, including rapidly increasing cases of resistance against other important herbicide classes.

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

    OpenAIRE

    Luukkainen Annika; Karjalainen Jussi; Honkanen Teemu; Lehtonen Mikko; Paavonen Timo; Toppila-Salmi Sanna

    2011-01-01

    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 e...

  2. The Physcomitrella patens unique alpha-dioxygenase participates in both developmental processes and defense responses

    OpenAIRE

    Machado, Lucina; De Castro, Alexandra; Hamberg, Mats; Bannenberg, Gerard; Gaggero, Carina; Castresana, Carmen; León, Inés Ponce de

    2015-01-01

    Background Plant α-dioxygenases catalyze the incorporation of molecular oxygen into polyunsaturated fatty acids leading to the formation of oxylipins. In flowering plants, two main groups of α-DOXs have been described. While the α-DOX1 isoforms are mainly involved in defense responses against microbial infection and herbivores, the α-DOX2 isoforms are mostly related to development. To gain insight into the roles played by these enzymes during land plant evolution, we performed biochemical, ge...

  3. 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.

  4. Characterizations of Two Bacterial Persulfide Dioxygenases of the Metallo-β-lactamase Superfamily.

    Science.gov (United States)

    Sattler, Steven A; Wang, Xia; Lewis, Kevin M; DeHan, Preston J; Park, Chung-Min; Xin, Yufeng; Liu, Honglei; Xian, Ming; Xun, Luying; Kang, ChulHee

    2015-07-31

    Persulfide dioxygenases (PDOs), also known as sulfur dioxygenases (SDOs), oxidize glutathione persulfide (GSSH) to sulfite and GSH. PDOs belong to the metallo-β-lactamase superfamily and play critical roles in animals, plants, and microorganisms, including sulfide detoxification. The structures of two PDOs from human and Arabidopsis thaliana have been reported; however, little is known about the substrate binding and catalytic mechanism. The crystal structures of two bacterial PDOs from Pseudomonas putida and Myxococcus xanthus were determined at 1.5- and 2.5-Å resolution, respectively. The structures of both PDOs were homodimers, and their metal centers and β-lactamase folds were superimposable with those of related enzymes, especially the glyoxalases II. The PDOs share similar Fe(II) coordination and a secondary coordination sphere-based hydrogen bond network that is absent in glyoxalases II, in which the corresponding residues are involved instead in coordinating a second metal ion. The crystal structure of the complex between the Pseudomonas PDO and GSH also reveals the similarity of substrate binding between it and glyoxalases II. Further analysis implicates an identical mode of substrate binding by known PDOs. Thus, the data not only reveal the differences in metal binding and coordination between the dioxygenases and the hydrolytic enzymes in the metallo-β-lactamase superfamily, but also provide detailed information on substrate binding by PDOs. PMID:26082492

  5. Crystal structure of 2-nitropropane dioxygenase complexed with FMN and substrate. Identification of the catalytic base.

    Science.gov (United States)

    Ha, Jun Yong; Min, Ji Young; Lee, Su Kyung; Kim, Hyoun Sook; Kim, Do Jin; Kim, Kyoung Hoon; Lee, Hyung Ho; Kim, Hye Kyung; Yoon, Hye-Jin; Suh, Se Won

    2006-07-01

    Nitroalkane compounds are widely used in chemical industry and are also produced by microorganisms and plants. Some nitroalkanes have been demonstrated to be carcinogenic, and enzymatic oxidation of nitroalkanes is of considerable interest. 2-Nitropropane dioxygenases from Neurospora crassa and Williopsis mrakii (Hansenula mrakii), members of one family of the nitroalkane-oxidizing enzymes, contain FMN and FAD, respectively. The enzymatic oxidation of nitroalkanes by 2-nitropropane dioxygenase operates by an oxidase-style catalytic mechanism, which was recently shown to involve the formation of an anionic flavin semiquinone. This represents a unique case in which an anionic flavin semiquinone has been experimentally observed in the catalytic pathway for oxidation catalyzed by a flavin-dependent enzyme. Here we report the first crystal structure of 2-nitropropane dioxygenase from Pseudomonas aeruginosa in two forms: a binary complex with FMN and a ternary complex with both FMN and 2-nitropropane. The structure identifies His(152) as the proposed catalytic base, thus providing a structural framework for a better understanding of the catalytic mechanism. PMID:16682407

  6. 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) blue多sh collected in the vicinity...

  7. 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...

  8. Sphingobium fuliginis HC3: A Novel and Robust Isolated Biphenyl- and Polychlorinated Biphenyls-Degrading Bacterium without Dead-End Intermediates Accumulation

    OpenAIRE

    Hu, Jinxing; Qian, Mingrong; Zhang, Qian; Cui, Jinglan; Yu, Chunna; Su, Xiaomei; Shen, Chaofeng; Hashmi, Muhammad Z.; Shi, Jiyan

    2015-01-01

    Biphenyl and polychlorinated biphenyls (PCBs) are typical environmental pollutants. However, these pollutants are hard to be totally mineralized by environmental microorganisms. One reason for this is the accumulation of dead-end intermediates during biphenyl and PCBs biodegradation, especially benzoate and chlorobenzoates (CBAs). Until now, only a few microorganisms have been reported to have the ability to completely mineralize biphenyl and PCBs. In this research, a novel bacterium HC3, whi...

  9. Diversity of extradiol dioxygenases in aromatic-degrading microbial community explored using both culture-dependent and culture-independent approaches.

    Science.gov (United States)

    Suenaga, Hikaru; Mizuta, Shiori; Miyazaki, Kentaro; Yaoi, Katsuro

    2014-11-01

    Culture-dependent and culture-independent approaches were used for extensive retrieval of the extradiol dioxygenase (EDO) gene from the environment to investigate the relationship between the EDO genes from isolated bacteria and the metagenomic EDO genes from which they were isolated. In our previous study, we identified 91 fosmid clones showing EDO enzyme activity using a metagenomic approach. In the present study, we classified all these metagenome-derived EDOs and newly isolated 88 phenol-utilizing bacteria from the same sample and identified four EDO genes from them. Of these, two EDOs had amino acid sequences similar to those reported previously in aromatic-utilizing strains, and one EDO had a sequence almost identical to that of metagenomic EDOs identified in our previous study. Unexpectedly, one EDO showed no similarity to any class I EDOs and was categorized as class II, which has not been found in past metagenomic approaches. Quantitative polymerase chain reaction (PCR) assay indicated that the low-abundance class II EDO gene can be enriched by culturing approaches. We conclude that the combined use of the two approaches can explore the gene community more extensively than their individual use. PMID:25059259

  10. 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.

  11. ENANTIOMER SEPARATION OF POLYCHLORINATED BIPHENYL ATROPISOMERS AND POLYCHLORINATED BIPHENYL RETENTION BEHAVIOR ON MODIFIED CYCLODEXTRIN CAPILLARY GAS CHROMATOGRAPHY COLUMNS

    Science.gov (United States)

    Seven commercially-available chiral capillary gas chromatography columns containing modified cyclodextrins were evaluated for their ability to separate enantiomers of the 19 stable chiral polychlorinated biphenyl (PCB) atropisomers, and for their ability to separate these enantio...

  12. Biphenyl 4-Hydroxylases Involved in Aucuparin Biosynthesis in Rowan and Apple Are Cytochrome P450 736A Proteins.

    Science.gov (United States)

    Sircar, Debabrata; Gaid, Mariam M; Chizzali, Cornelia; Reckwell, Dennis; Kaufholdt, David; Beuerle, Till; Broggini, Giovanni A L; Flachowsky, Henryk; Liu, Benye; Hänsch, Robert; Beerhues, Ludger

    2015-06-01

    Upon pathogen attack, fruit trees such as apple (Malus spp.) and pear (Pyrus spp.) accumulate biphenyl and dibenzofuran phytoalexins, with aucuparin as a major biphenyl compound. 4-Hydroxylation of the biphenyl scaffold, formed by biphenyl synthase (BIS), is catalyzed by a cytochrome P450 (CYP). The biphenyl 4-hydroxylase (B4H) coding sequence of rowan (Sorbus aucuparia) was isolated and functionally expressed in yeast (Saccharomyces cerevisiae). SaB4H was named CYP736A107. No catalytic function of CYP736 was known previously. SaB4H exhibited absolute specificity for 3-hydroxy-5-methoxybiphenyl. In rowan cell cultures treated with elicitor from the scab fungus, transient increases in the SaB4H, SaBIS, and phenylalanine ammonia lyase transcript levels preceded phytoalexin accumulation. Transient expression of a carboxyl-terminal reporter gene construct directed SaB4H to the endoplasmic reticulum. A construct lacking the amino-terminal leader and transmembrane domain caused cytoplasmic localization. Functional B4H coding sequences were also isolated from two apple (Malus × domestica) cultivars. The MdB4Hs were named CYP736A163. When stems of cv Golden Delicious were infected with the fire blight bacterium, highest MdB4H transcript levels were observed in the transition zone. In a phylogenetic tree, the three B4Hs were closest to coniferaldehyde 5-hydroxylases involved in lignin biosynthesis, suggesting a common ancestor. Coniferaldehyde and related compounds were not converted by SaB4H.

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

    International Nuclear Information System (INIS)

    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. 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.

  15. Intron retention and rhythmic diel pattern regulation of carotenoid cleavage dioxygenase 2 during crocetin biosynthesis in saffron.

    Science.gov (United States)

    Ahrazem, Oussama; Rubio-Moraga, Angela; Argandoña-Picazo, Javier; Castillo, Raquel; Gómez-Gómez, Lourdes

    2016-06-01

    The carotenoid cleavage dioxygenase 2, a new member of the CCD family, catalyzes the conversion of zeaxanthin into crocetin-dialdehyde in Crocus. CCD2 is expressed in flowers, being responsible for the yellow, orange and red colorations displayed by tepals and stigma. Three CsCCD2 genes were identified in Crocus sativus, the longest contains ten exons and the shorter is a truncated copy with no introns and which lacks one exon sequence. Analysis of RNA-seq datasets of three developmental stages of saffron stigma allowed the determination of alternative splicing in CsCCD2, being intron retention (IR) the prevalent form of alternative splicing in CsCCD2. Further, high IR was observed in tissues that do not accumulate crocetin. The analysis of one CsCCD2 promoter showed cis-regulatory motifs involved in the response to light, temperature, and circadian regulation. The light and circadian regulation are common elements shared with the previously characterized CsLycB2a promoter, and these shared common cis-acting elements may represent binding sites for transcription factors responsible for co-regulation of these genes during the development of the stigma in saffron. A daily coordinated rhythmic regulation for CsCCD2 and CsLycB2a was observed, with higher levels of mRNA occurring at low temperatures during darkness, confirming the results obtained in the in silico promoter analysis. In addition, to the light and temperature dependent regulation of CsCCD2 expression, the apocarotenoid β-cyclocitral up-regulated CsCCD2 expression and could acts as a mediator of chromoplast-to-nucleus signalling, coordinating the expression of CsCCD2 with the developmental state of the chromoplast in the developing stigma. PMID:27071403

  16. New technologies for PCB [polychlorinated biphenyl] decontamination

    International Nuclear Information System (INIS)

    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

  17. Consolidated PCBs [polychlorinated biphenyls] improves waste control

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    Sastry, G. Narahari

    2012-01-01

    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 spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes [Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869–3882], hence the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)-superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)-oxo complex with a bound sulfenato group. After reorganization the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron-oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic CDO center are highlighted. PMID:22091701

  19. 75 FR 34076 - Polychlorinated Biphenyls (PCBs); Reassessment of Use Authorizations; Extension of Comment Period...

    Science.gov (United States)

    2010-06-16

    ... AGENCY 40 CFR Part 761 RIN 2070-AJ38 Polychlorinated Biphenyls (PCBs); Reassessment of Use Authorizations..., Hazardous substances, Labeling, Polychlorinated biphenyls (PCBs), Reporting and recordkeeping requirements..., 2010, concerning the reassessment of the use authorizations for PCBs. This document extends the...

  20. Iron(III) complexes of certain tetradentate phenolate ligands as functional models for catechol dioxygenases

    Indian Academy of Sciences (India)

    Mallayan Palaniandavar; Marappan Velusamy; Ramasamy Mayilmurugan

    2006-11-01

    Catechol 1,2-dioxygenase (CTD) and protocatechuate 3,4-dioxygenase (PCD) are bacterial non-heme iron enzymes, which catalyse the oxidative cleavage of catechols to cis, cis-muconic acids with the incorporation of molecular oxygen via a mechanism involving a high-spin ferric centre. The iron(III) complexes of tripodal phenolate ligands containing N3O and N2O2 donor sets represent the metal binding region of the iron proteins. In our laboratory iron(III) complexes of mono- and bisphenolate ligands have been studied successfully as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The single crystal X-ray crystal structures of four of the complexes have been determined. One of the bis-phenolato complexes contains a FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. The Fe-O-C bond angle of 136.1° observed for one of the iron(III) complex of a monophenolate ligand is very similar to that in the enzymes. The importance of the nearby sterically demanding coordinated -NMe2 group has been established and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133, 148°). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features, FeIII/FeII redox potentials and catechol cleavage activity of the complexes. Upon interacting with catecholate anions, two catecholate to iron(III) charge transfer bands appear and the low energy band is similar to that of catechol dioxygenase-substrate complex. Four of the complexes catalyze the oxidative cleavage of H2DBC by molecular oxygen to yield intradiol cleavage products. Remarkably, the more basic N-methylimidazole ring in one of the complexes facilitates the rate-determining productreleasing phase of the catalytic reaction. The present

  1. Trichloroethylene removal and oxidation toxicity mediated by toluene dioxygenase of Pseudomonas putida.

    OpenAIRE

    Heald, S.; Jenkins, R. O.

    1994-01-01

    Whole cells of Pseudomonas putida containing toluene dioxygenase were able to remove all detectable trichloroethylene (TCE) from assay mixtures. The capacity of cells to remove TCE was 77 microM/mg of protein with an initial rate of removal of 5.2 nmol/min/ng of protein. TCE oxidation resulted in a decrease in the growth rate of cultures and caused rapid cell death. Addition of dithiothreitol to assay mixtures increased the TCE removal capacity of cells by up to 67% but did not prevent TCE-me...

  2. Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators

    DEFF Research Database (Denmark)

    Sørensen, Rikke Bæk; Hadrup, Sine Reker; Svane, Inge Marie;

    2011-01-01

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We......, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-alpha while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosine-phosphate- guanosine, soluble cytotoxic T lymphocyte-associated antigen 4...

  3. Compound-Specific Isotope Analysis of Nitroaromatic Contaminant Transformations by Nitroarene Dioxygenases

    Science.gov (United States)

    Pati, Sarah G.; Kohler, Hans-Peter E.; Hofstetter, Thomas B.

    2014-05-01

    Dioxygenation is an important biochemical reaction that often initiates the mineralization of recalcitrant organic contaminants such as nitroaromatic explosives, chlorinated benzenes, and polycyclic aromatic hydrocarbons. However, to assess the extent of dioxygenation in contaminated environments is difficult because of competing transformation processes and further reactions of the dioxygenation products. Compound-specific isotope analysis (CSIA) offers a new approach to reliably quantify biodegradation initiated by dioxygenation based on changes in stable isotope ratios of the pollutant. For CSIA it is essential to know the kinetic isotope effects (KIEs) pertinent to the dioxygenation mechanism of organic contaminants. Unfortunately, the range of KIEs of such reactions is poorly constrained although many dioxygenase enzymes with a broad substrate specificity have been reported. Dioxygenase enzymes usually exhibit complex reaction kinetics involving multiple substrates and substrate-specific binding modes which makes the determination of KIEs challenging. The goal of this study was to explore the magnitude and variability of 13C-, 2H-, and 15N-KIEs for the dioxygenation of one contaminant class, that is nitroaromatic contaminants (NACs). To this end, we investigated the C, H, and N isotope fractionation during the dioxygenation of nitrobenzene (NB), 2-nitrotoluene (2-NT), and 3-nitrotoluene (3-NT) by pure cultures, E. coli clones, cell extracts, and purified enzymes. From isotope fractionations measured in the substrates and reaction products, we determined dioxygenation KIEs for different combinations of the three substrates with nitrobenzene dioxygenase (NBDO) and 2-nitrotoluene dioxygenase (2NTDO). The 13C-, 2H-, and 15N-KIEs for the dioxygenation of NB by NBDO were consistent for all experimental systems considered (i.e., Comamonas sp. Strain JS765, E. coli clones, cell extracts of E. coli clones, and purified NBDO). This observation suggests that the isotope

  4. 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

  5. Estrogenicity of selected biphenyls evaluated using a recombinant yeast assay

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, T.W.; Kraut, D.H.; Sayler, G.S.; Layton, A.C. [Univ. of Tennessee, Knoxville, TN (United States)

    1998-09-01

    The estrogenic activity of biphenyl and 4-hydroxylated derivatives with varied levels of chloro- and/or hydroxyl substitution was measured in a Saccharomyces cerevisiae-based lac-Z ({beta}-galactosidase) reporter assay, {beta}-Galactosidase activity was compared with competitive binding to soluble mouse uterine estrogen receptor protein. The comparison of relative potency for biphenyls hydroxylated on one ring and chlorinated on the other ring (n = 5) revealed excellent correlation between the two systems (r{sup 2} = 0.995). However, estrogenicities of biphenyls hydroxylated and chlorinated on the same ring were not in agreement. Although weak ligand binding was demonstrated for these compounds, {beta}-galactosidase activity was not observed. Rather, these compounds were shown to be cytotoxic to yeast. The results of this study further support the hypothesis that both an unhindered phenolic ring and molecular symmetry are structural features associated with estrogenicity.

  6. Role of 9-Lipoxygenase and α-Dioxygenase Oxylipin Pathways as Modulators of Local and Systemic Defense

    Institute of Scientific and Technical Information of China (English)

    Jorge Vicente; Tomás Cascón; Begonya Vicedo; Pilar García-Agustín; Mats Hamberg; Carmen Castresana

    2012-01-01

    Plant 9-lipoxygenases(9-LOX)and α-dioxygenases(α-DOX)initiate the synthesis of oxylipins after bacterial infection.Here,the role of these enzymes in plants' defense was investigated using individual Arabidopsis thaliana lox1 and dox1 mutants and a double lox1 dox1 mutant.Studies with Pseudomonas syringae pv.tomato(Pst)revealed the enhanced susceptibility of lox1 to the virulent strain Pst DC3000 and the partial impairment of lox1 and dox1 mutants to activate systemic acquired resistance.Notably,both defects were enhanced in the lox1 dox1 plants as compared with individual mutants.We found that pre-treatment with 9-LOX- and α-DOX-generated oxylipins protected plant tissues against bacterial infection.The strongest effect in this respect was exerted by 9-ketooctadecatrienoic acid(9-KOT),which is produced from linolenic acid by 9-LOX.Quantification of 9-KOT revealed its accumulation after bacterial infection.The levels were reduced in lox1 and lox1 dox1 plants but strongly increased in the dox1 mutant due to metabolic interaction of the two pathways.Transcriptional analyses indicated that 9-KOT pre-treatment modifies hormone homeostasis during bacterial infection.The nature of the changes detected suggested that 9-KOT interferes with the hormonal changes caused by bacterial effectors.This notion was substantiated by the finding that 9-KOT failed to reduce the growth of PstDC3000hrpA,a mutant compromised in effector secretion,and of the avirulent strain Pst DC3000 avrRpm1.Further support for the action of the 9-LOX- and α-DOX-oxylipin pathways as modulators of hormone homeostasis was the observation that lox1 dox1 seedlings are hypersensitive to the growth-inhibitory effect of ABA and showed enhanced activation of ABA-inducible marker genes as compared with wild-type plants.

  7. Purification and Characterization of Catechol 1,2-Dioxygenase from Acinetobacter sp. Y64 Strain and Escherichia coli Transformants.

    Science.gov (United States)

    Lin, J; Milase, R N

    2015-12-01

    This study intends to purify and characterize catechol 1,2-dioxygenase (C1,2O) of phenol-degrading Acinetobacter sp. Y64 and of E. coli transformant. Acinetobacter sp. Y64 was capable of degrading 1000 mg/L of phenol within 14 ± 2 h at 30 °C, 160 rpm and pH of 7. One C1,2O of 36 kDa was purified using ammonium sulphate precipitation and Hitrap QFF column chromatograph with 49% recovery and a 10.6-fold increase in purity. Purified Y64 C1,2O had temperature and pH optimum at 37 °C and pH 7.7 respectively with the Michaelis constant of 17.53 µM and the maximal velocity of 1.95 U/mg, respectively. The presence of Fe(3+) or Fe(2+) enhanced the activity of Y64 C1,2O while other compounds such as Ca(2+), and EDTA had an inhibitory effect. 80% of C1,2O activity remained using 4-nitrocatechol as substrate while 2% remained using 3-methylcatechol compared with that using catechol. Y64 catA gene encoding C1,2O was amplified using PCR cloned into pET22b vector and expressed in Escherichia coli BL21 DE3 (pLysS) after transformation. Purified and cloned Y64 C1,2O show no significant differences in the biochemical properties. The phylogenetic tree based on the protein sequences indicates that these C1,2Os possess a common ancestry.

  8. Purification and Characterization of Catechol 1,2-Dioxygenase from Acinetobacter sp. Y64 Strain and Escherichia coli Transformants.

    Science.gov (United States)

    Lin, J; Milase, R N

    2015-12-01

    This study intends to purify and characterize catechol 1,2-dioxygenase (C1,2O) of phenol-degrading Acinetobacter sp. Y64 and of E. coli transformant. Acinetobacter sp. Y64 was capable of degrading 1000 mg/L of phenol within 14 ± 2 h at 30 °C, 160 rpm and pH of 7. One C1,2O of 36 kDa was purified using ammonium sulphate precipitation and Hitrap QFF column chromatograph with 49% recovery and a 10.6-fold increase in purity. Purified Y64 C1,2O had temperature and pH optimum at 37 °C and pH 7.7 respectively with the Michaelis constant of 17.53 µM and the maximal velocity of 1.95 U/mg, respectively. The presence of Fe(3+) or Fe(2+) enhanced the activity of Y64 C1,2O while other compounds such as Ca(2+), and EDTA had an inhibitory effect. 80% of C1,2O activity remained using 4-nitrocatechol as substrate while 2% remained using 3-methylcatechol compared with that using catechol. Y64 catA gene encoding C1,2O was amplified using PCR cloned into pET22b vector and expressed in Escherichia coli BL21 DE3 (pLysS) after transformation. Purified and cloned Y64 C1,2O show no significant differences in the biochemical properties. The phylogenetic tree based on the protein sequences indicates that these C1,2Os possess a common ancestry. PMID:26563518

  9. 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.

  10. 75 FR 4759 - Polychlorinated Biphenyls: Manufacturing (Import) Exemption for Veolia ES Technical Solutions, LLC

    Science.gov (United States)

    2010-01-29

    ... commerce of polychlorinated biphenyls (PCBs). Under TSCA section 3(7), ``manufacture'' is defined to... AGENCY 40 CFR Part 761 RIN 2050-AG42 Polychlorinated Biphenyls: Manufacturing (Import) Exemption for...'s request in the proposed rule, Polychlorinated Biphenyls: Manufacturing (Import) Exemption...

  11. 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...

  12. Incidence of thyroid disease following exposure to polybrominated biphenyls and polychlorinated biphenyls, Michigan, 1974-2006.

    Science.gov (United States)

    Yard, Ellen E; Terrell, Metrecia L; Hunt, Danielle Rentz; Cameron, Lorraine L; Small, Chanley M; McGeehin, Michael A; Marcus, Michele

    2011-08-01

    Thyroid hormones, which influence body metabolism and development, could be affected by persistent organic pollutants. We sought to examine the relationship between polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) and thyroid disease. We employed incidence density sampling to perform a nested case control analysis of the Michigan Long-Term PBB Cohort. Cohort members (n=3333) were exposed to PBBs through contaminated cattle feed in 1973-1974 and to PCBs through daily life. Those with detectable serum PBB and PCB concentrations at enrollment were categorized into tertiles of PBB and PCB exposure. Case-patients were cohort members answering "Yes" to "Has a healthcare provider ever told you that you had a thyroid problem?" during follow-up interviews; control-patients were cohort members answering "No". We used odds ratios (OR) with 95% confidence intervals (CI) to compare odds of thyroid disease by PBB and PCB exposure and by various risk factors. Total cumulative thyroid disease incidence after 33 years was 13.9% among women and 2.6% among men. After adjusting for body mass index, we found no statistically significant differences in odds of any type of thyroid disease among women or men with elevated PBB or PCB exposure. Compared to control-patients, women with thyroid disease had increased odds of being overweight/obese (OR=2.82, 95% CI: 1.94-4.11) and developing infertility (OR=1.71, 95% CI: 1.08-2.69), diabetes (OR=1.61, 95% CI: 1.04-2.51), or arthritis (OR=1.71, 95% CI: 1.18-2.50) during follow-up. Additional research should explore potential associations between PBBs/PCBs and thyroid disease among children exposed in utero. PMID:21737118

  13. Functional identification of gene cluster for the aniline metabolic pathway mediated by transposable element

    Institute of Scientific and Technical Information of China (English)

    LIANG Quanfeng; Takeo Masahiro; LIN Min; CHEN Ming; XU Yuquan; ZHANG Wei; PING Shuzhen; LU Wei; SONG Xianlong; WANG Weiwei; GENG Lizhao

    2005-01-01

    A convenient and widely applicable method has been developed to clone aniline metabolic gene cluster in this study. Three positive recombinant plasmids pDA1, pDB2 and pDB11 were cloned from genomic library of aniline degradation strain AD9. The result of aniline dioxygenase (AD) activity and catechol 2,3-oxygenase (C23O) activity assay showed that pDA1 and pDB11 contain aniline dioxygenase genes and catechol 2,3-dioxygenase genes, respectively. The sequence analysis of the total 24.7-kb region revealed that this region contains 25 ORFs, of which 17 genes involve metabolism of aniline. In the gene cluster, the first five genes (tadQTA1A2B) and the subsequent gene (tadR1) were predicted to encode a multi-component aniline dioxygenase and a LysR-type regulator, respectively, while the others (tadD1C1D2C2EFGIJKL) were expected to encode meta- cleavage pathway enzymes for catechol degradation. The gene cluster was surrounded by two IS1071 sequences.

  14. para-Nitrophenol 4-monooxygenase and hydroxyquinol 1,2-dioxygenase catalyze sequential transformation of 4-nitrocatechol in Pseudomonas sp. strain WBC-3.

    Science.gov (United States)

    Wei, Min; Zhang, Jun-Jie; Liu, Hong; Zhou, Ning-Yi

    2010-11-01

    Pseudomonas sp. strain WBC-3 utilizes para-nitrophenol (PNP) as a sole source of carbon, nitrogen and energy. PnpA (PNP 4-monooxygenase) and PnpB (para-benzoquinone reductase) were shown to be involved in the initial steps of PNP catabolism via hydroquinone. We demonstrated here that PnpA also catalyzed monooxygenation of 4-nitrocatechol (4-NC) to hydroxyquinol, probably via hydroxyquinone. It was the first time that a single-component PNP monooxygenase has been shown to catalyze this conversion. PnpG encoded by a gene located in the PNP degradation cluster was purified as a His-tagged protein and identified as a hydroxyquinol dioxygenase catalyzing a ring-cleavage reaction of hydroxyquinol. Although all the genes necessary for 4-NC metabolism seemed to be present in the PNP degradation cluster in strain WBC-3, it was unable to grow on 4-NC as a sole source of carbon, nitrogen and energy. This was apparently due to the substrate's inability to trigger the expression of genes involved in degradation. Nevertheless, strain WBC-3 could completely degrade both PNP and 4-NC when PNP was used as the inducer, demonstrating its potential in bioremediation of the environment polluted by both 4-NC and PNP.

  15. Oxidation of alkyl nitronates catalyzed by 2-nitropropane dioxygenase from Hansenula mrakii.

    Science.gov (United States)

    Mijatovic, Slavica; Gadda, Giovanni

    2008-05-01

    2-Nitropropane dioxygenase from Hansenula mrakii was expressed in Escherichia coli cells and purified in active and stable form using 60% saturation of ammonium sulfate and a single chromatographic step onto a DEAE column. MALDI-TOF mass spectrometric and spectrophotometric analyses of the flavin extracted by heat or acid denaturation of the enzyme indicated that FMN, and not FAD as erroneously reported previously, is present in a 1:1 stoichiometry with the protein. Inductively coupled plasma mass spectrometric analysis of the enzyme established that H. mrakii 2-nitropropane dioxygenase contains negligible amounts of iron, manganese, zinc, and copper ions, which are not catalytically relevant. Anaerobic substrate reduction and kinetic data using a Clark oxygen electrode to measure rates of oxygen consumption indicated that the enzyme is active on a broad range of alkyl nitronates, with a marked preference for unbranched substrates over propyl-2-nitronate. Interestingly, the enzyme reacts poorly, if at all, with nitroalkanes, as suggested by lack of both anaerobic reduction of the enzyme-bound flavin and consumption of oxygen with nitroethane, nitrobutane, and 2-nitropropane. Finally, both the tight binding of sulfite (K(d)=90 microM, at pH 8 and 15 degrees C) to the enzyme and the formation of the anionic flavosemiquinone upon anaerobic incubation with alkyl nitronates are consistent with the presence of a positively charged group in proximity of the N1-C2=O atoms of the FMN cofactor. PMID:18329375

  16. The Role of Indoleamine 2,3-Dioxygenase in a Mouse Model of Neuroinflammation-Induced Depression

    NARCIS (Netherlands)

    Dobos, Nikoletta; de Vries, Erik F. J.; Kema, Ido P.; Patas, Konstantinos; Prins, Marloes; Nijholt, Ingrid M.; Dierckx, Rudi A.; Korf, Jakob; den Boer, Johan A.; Luiten, Paul G. M.; Eisel, Ulrich L. M.; Borsello, Tiziana

    2012-01-01

    Indoleamine 2,3-dioxygenase (IDO), an enzyme which is activated by pro-inflammatory cytokines, has been suggested as a potential link between neuroinflammatory processes in neurodegenerative diseases (like Alzheimer's disease) and depression. The present study aimed to determine whether neuroinflamm

  17. Danish emission inventory for hexachlorobenzene and polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Nielsen, Ole-Kenneth; Plejdrup, Marlene Schmidt; Winther, Morten;

    This report documents the improved air emission inventories for hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs). The emission inventories now include all sources covered by the EMEP/EEA Guidebook. The completeness and accuracy of the inventories for these pollutants have been signifi...

  18. 77 FR 54818 - Polychlorinated Biphenyls (PCBs): Revisions to Manifesting Regulations

    Science.gov (United States)

    2012-09-06

    ... AGENCY 40 CFR Part 761 RIN 2050-AG71 Polychlorinated Biphenyls (PCBs): Revisions to Manifesting... manifesting requirements for PCBs under TSCA to the manifesting requirements for hazardous waste under RCRA... bring into alignment, as much as possible, the manifesting requirements for PCBs to those of...

  19. FIBER OPTIC FLUOROIMMUNOSENSOR FOR THE DETECTION OF POLYCHLORINATED BIPHENYLS

    Science.gov (United States)

    There currently exists a critical and growing need for cost-effective, real-time, and in situ methods for detection of environmental pollutants such as polychlorinated biphenyls (PCBs). erein reported is a evanescent wave Fluoroimmunosensor for measurement of PCBS. 2,4-5-Trichlor...

  20. Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment

    NARCIS (Netherlands)

    Longnecker, MP; Gladen, BC; Brock, JW; Grandjean, P; Jacobson, JL; Korrick, SA; Rogan, WJ; Weisglas-Kuperus, N; Hertz-Picciotto, [No Value; Ayotte, P; Stewart, P; Winneke, G; Charles, MJ; Jacobson, SW; Dewailly, E; Boersma, ER; Altshul, LM; Heinzow, B; Pagano, JJ; Jensen, AA

    2003-01-01

    Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Int

  1. Polychlorinated biphenyls (PCBs) in San Francisco Bay.

    Science.gov (United States)

    Davis, J A; Hetzel, F; Oram, J J; McKee, L J

    2007-09-01

    San Francisco Bay is facing a legacy of polychlorinated biphenyls (PCBs) spread widely across the land surface of the watershed, mixed deep into the sediment of the Bay, and contaminating the Bay food web to a degree that poses health risks to humans and wildlife. In response to this persistent problem, water quality managers are establishing a PCB total maximum daily load (TMDL) and implementation plan to accelerate the recovery of the Bay from decades of PCB contamination. This article provides a review of progress made over the past 15 years in managing PCBs and understanding their sources, pathways, fate, and effects in the Bay, and highlights remaining information needs that should be addressed in the next 10 years. The phaseout of PCBs during the 1970s and the 1979 federal ban on sale and production led to gradual declines from the 1970s to the present. However, 25 years after the ban, PCB concentrations in some Bay sport fish today are still more than ten times higher than the threshold of concern for human health. Without further management action it appears that the general recovery of the Bay from PCB contamination will take many more decades. PCB concentrations in sport fish were, along with mercury, a primary cause of a consumption advisory for the Bay and the consequent classification of the Bay as an impaired water body. Several sources of information indicate that PCB concentrations in the Bay may also be high enough to adversely affect wildlife, including rare and endangered species. The greater than 90% reduction in food web contamination needed to meet the targets for protection of human health would likely also generally eliminate risks to wildlife. PCB contamination in the Bay is primarily associated with industrial areas along the shoreline and in local watersheds. Strong spatial gradients in PCB concentrations persist decades after the release of these chemicals to Bay Area waterways. Through the TMDL process, attention is being more sharply

  2. DNA双加氧酶TET在中枢神经系统的研究进展%Research progress of DNA dioxygenase TET in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    刘洁; 米亚静

    2015-01-01

    DNA双加氧酶TET家族是新发现的一类表观遗传修饰蛋白,能够将DNA的5-甲基胞嘧啶氧化为5-羟甲基胞嘧啶,进而调控基因的表达。多项研究显示,TET1-3在中枢神经系统表达丰富,其潜在的生物功能也被广泛关注。本文从TET蛋白结构功能概述、TET蛋白在中枢神经系统的表达及功能以及针对TET家族的基因敲除小鼠实验三方面作一综述。%DNA dioxygenase TET family is a recently discovered proteins involved epigenetic modification, which can oxidize the 5-methylcytosine of DNA into 5-hydroxymethylcytosine and thereby regulate gene expression. Accumulative studies have shown that TET1-3 was abundantly expressed in the central nervous system, and its poten-tial functions were beginning to be studied. This paper gives an overview of the structure and functions of TET, its po-tential roles in the central nervous system, and also the TET gene knockout experiments.

  3. Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1.

    Science.gov (United States)

    Murakami, Yuki; Ishibashi, Takaaki; Tomita, Eiichi; Imamura, Yukio; Tashiro, Tomoyuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Takahashi, Yuki; Takakura, Yoshinobu; Mitani, Satoko; Fujigaki, Hidetsugu; Ohta, Yoshiji; Kubo, Hisako; Mamiya, Takayoshi; Nabeshima, Toshitaka; Kim, Hyoung-Chun; Yamamoto, Yasuko; Saito, Kuniaki

    2016-01-01

    Depression is known to occur frequently in chronic hepatitis C viral (HCV) patients receiving interferon (IFN)-α therapy. In this study, we investigated whether indoleamine 2,3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy. Increases in serum kynurenine (KYN) and 3-hydroxykynurenine (3-HK) concentrations and in the ratios of KYN/TRP and 3-HK/kynurenic acid (KA) were much larger in depressive HCV patients than in non-depressed patients following therapy. Furthermore, transfection of a plasmid continuously expressing murine IFN-γ into normal mice significantly increased depression-like behavior. IFN-γ gene transfer also resulted in a decrease in serum TRP levels in the mice while KYN and 3-HK levels were significantly increased in both serum and frontal cortex. Genetic deletion of IDO1 in mice abrogated both the increase in depression-like behavior and the elevation in TRP metabolites' levels, and the turnover of serotonin in the frontal cortex after IFN-γ gene transfer. These results indicate that the KYN pathway of IDO1-mediated TRP metabolism plays a critical role in depressive symptoms associated with IFN-α therapy. PMID:27436416

  4. 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. PMID:16618520

  5. Identification of 11 Novel Homogentisate 1,2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database.

    Science.gov (United States)

    Zatkova, Andrea; Sedlackova, Tatiana; Radvansky, Jan; Polakova, Helena; Nemethova, Martina; Aquaron, Robert; Dursun, Ismail; Usher, Jeannette L; Kadasi, Ludevit

    2012-01-01

    Enzymatic loss in alkaptonuria (AKU), an autosomal recessive disorder, is caused by mutations in the homogentisate 1,2 dioxygenase (HGD) gene, which decrease or completely inactivate the function of the HGD protein to metabolize homogentisic acid (HGA). AKU shows a very low prevalence (1:100,000-250,000) in most ethnic groups, but there are countries with much higher incidence, such as Slovakia and the Dominican Republic. In this work, we report 11 novel HGD mutations identified during analysis of 36 AKU patients and 41 family members from 27 families originating from 9 different countries, mainly from Slovakia and France. In Slovak patients, we identified two additional mutations, thus a total number of HGD mutations identified in this small country is 12. In order to record AKU-causing mutations and variants of the HGD gene, we have created a HGD mutation database that is open for future submissions and is available online ( http://hgddatabase.cvtisr.sk/ ). It is founded on the Leiden Open (source) Variation Database (LOVD) system and includes data from the original AKU database ( http://www.alkaptonuria.cib.csic.es ) and also all so far reported variants and AKU patients. Where available, HGD-haplotypes associated with the mutations are also presented. Currently, this database contains 148 unique variants, of which 115 are reported pathogenic mutations. It provides a valuable tool for information exchange in AKU research and care fields and certainly presents a useful data source for genotype-phenotype correlations and also for future clinical trials.

  6. Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

    Science.gov (United States)

    Becerra, Aniuska; Warke, Rajas V.; Xhaja, Kris; Evans, Barbara; Evans, James; Martin, Katherine; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    The depletion of l-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of L-Trp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of l-kynurenine in sera from DENV-infected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-γ) in DENV-infected DCs in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-γ against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo. PMID:19264674

  7. 1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).

    Science.gov (United States)

    Röhrig, Ute F; Majjigapu, Somi Reddy; Caldelari, Daniela; Dilek, Nahzli; Reichenbach, Patrick; Ascencao, Kelly; Irving, Melita; Coukos, George; Vogel, Pierre; Zoete, Vincent; Michielin, Olivier

    2016-09-01

    Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, soluble form of the enzyme. Starting from our previously discovered highly efficient 4-aryl-1,2,3-triazole IDO1 inhibitor scaffold, we used computational structure-based methods to design inhibitors of IDO2 which we then tested in cellular assays. Our approach yielded low molecular weight inhibitors of IDO2, the most active displaying an IC50 value of 51μM for mIDO2, and twofold selectivity over hIDO1. These compounds could be useful as molecular probes to investigate the biological role of IDO2, and could inspire the design of new IDO2 inhibitors. PMID:27469130

  8. Characterization of catechol 1,2-dioxygenase from cell extracts of Sphingomonas xenophaga QYY

    Institute of Scientific and Technical Information of China (English)

    M.Salah; Uddin

    2009-01-01

    Sphingomonas xenophaga QYY, capable of growing significantly on more than ten kinds of aromatic compounds as sole carbon source, was used to study characterization of catechol 1,2-dioxygenase (C12O) in cell extracts. Characterization of the crude C12O showed that the maximum activity was obtained at 40-70℃ and pH 7.8-8.8. Metal ions had different influences on the activity of crude C12O. It was suggested that strain QYY possessed an inducible and ferric-dependent C12O. Kinetic studies showed that the value of Vmax and Km was 0.25 μmol catechol/L/mg protein/min and 52.85 μmol/L, respectively. In addition, the partial purification of C12O was achieved by a HiTrap Q Sepharose column chromatography.

  9. Characterization of catechol 1,2-dioxygenase from cell extracts of Sphingomonas xenophaga QYY

    Institute of Scientific and Technical Information of China (English)

    GOU Min; QU YuanYuan; ZHOU JiTi; LI Ang; M.Salah Uddin

    2009-01-01

    Sphingomonas xenophaga QYY, capable of growing significantly on more than ten kinds of aromatic compounds as sole carbon source, was used to study characterization of catechol 1,2-dioxygenase (C120) in cell extracts. Characterization of the crude C120 showed that the maximum activity was obtained at 40-70℃ and pH 7.8-8.8. Metal ions had different influences on the activity of crude C120. It was suggested that strain QYY possessed an inducible and ferric-dependent C120. Kinetic studies showed that the value of Vmax and Km was 0.25 μmol catechol/L/mg protein/min and 52.85 μmol/L, respectively. In addition, the partial purification of C120 was achieved by a HiTrap Q Sepharose column chromatography.

  10. Linolenate 9R-dioxygenase and allene oxide synthase activities of Lasiodiplodia theobromae.

    Science.gov (United States)

    Jernerén, Fredrik; Eng, Felipe; Hamberg, Mats; Oliw, Ernst H

    2012-01-01

    Jasmonic acid (JA) is synthesized from linolenic acid (18:3n-3) by sequential action of 13-lipoxygenase, allene oxide synthase (AOS), and allene oxide cyclase. The fungus Lasiodiplodia theobromae can produce large amounts of JA and was recently reported to form the JA precursor 12-oxophytodienoic acid. The objective of our study was to characterize the fatty acid dioxygenase activities of this fungus. Two strains of L. theobromae with low JA secretion (~0.2 mg/L medium) oxygenated 18:3n-3 to 5,8-dihydroxy-9Z,12Z,15Z-octadecatrienoic acid as well as 9R-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid, which was metabolized by an AOS activity into 9-hydroxy-10-oxo-12Z,15Z-octadecadienoic acid. Analogous conversions were observed with linoleic acid (18:2n-6). Studies using [11S-(2)H]18:2n-6 revealed that the putative 9R-dioxygenase catalyzed stereospecific removal of the 11R hydrogen followed by suprafacial attack of dioxygen at C-9. Mycelia from these strains of L. theobromae contained 18:2n-6 as the major polyunsaturated acid but lacked 18:3n-3. A third strain with a high secretion of JA (~200 mg/L) contained 18:3n-3 as a major fatty acid and produced 5,8-dihydroxy-9Z,12Z,15Z-octadecatrienoic acid from added 18:3n-3. This strain also lacked the JA biosynthetic enzymes present in higher plants. PMID:22048860

  11. Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity

    DEFF Research Database (Denmark)

    Bonefeld-Jørgensen, E.C.; Andersen, H. R.; Rasmussen, T.H.;

    2001-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some...... pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17 beta -Estradiol. whereas the compounds inhibited cell growth significantly at 1 and 10 muM. In reporter gene (ERE......-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17 beta -estradiol induced MCF-7 cells. In addition, PCB # 138 elicited a dose-dependent antagonistic effect on androgen receptor activity...

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

    International Nuclear Information System (INIS)

    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

  13. Sonochemical Degradation of Polychlorinated Biphenyls in Aqueous Solution

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Polychlorinated biphenyl (PCB) is a kind of persistent and dangerous environmental pollutants. This paper presented the research result of sonochemical degradation of 2-chloro- biphenyl (2-CBP), 4-chlorobiphenyl (4-CBP) and 4,4'-dichlorobiphenyl (4,4'-CBP)in water. The ultrasonic degradation kinetics of 2-CBP, 4-CBP and 4,4'-CBP in water were found to be first-order and the degradation rate coefficients are 3.69×10-2, 3.19×10-2 and 2.06×10-2 at 25±1°C for 2-CBP, 4-CBP and 4,4'-CBP respectively. The influence of initial concentrations, reaction temperature on the ultrasonic decomposition of 2-CBP were also investigated.

  14. 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

  15. Dehalorespiration with Polychlorinated Biphenyls by an Anaerobic Ultramicrobacterium▿

    OpenAIRE

    May, Harold D.; Miller, Greg S.; Birthe V. Kjellerup; Sowers, Kevin R.

    2008-01-01

    Anaerobic microbial dechlorination is an important step in the detoxification and elimination of polychlorinated biphenyls (PCBs), but a microorganism capable of coupling its growth to PCB dechlorination has not been isolated. Here we describe the isolation from sediment of an ultramicrobacterium, strain DF-1, which is capable of dechlorinating PCBs containing double-flanked chlorines added as single congeners or as Aroclor 1260 in contaminated soil. The isolate requires Desulfovibrio spp. in...

  16. The Influence of Polychlorinated Biphenyls Contamination on Soil Protein Expression

    OpenAIRE

    Xi Zhang; Feng Li; Tingting Liu; Cheng Peng; Dechao Duan; Chen Xu; Shenhai Zhu; Jiyan Shi

    2013-01-01

    Polychlorinated biphenyls (PCBs) are typical representative of chlorinated organic pollutants. Given the toxicity of PCBs, there is an urgent need to select an appropriate indicator to monitor their biological effects on soil ecosystems. For this purpose, we investigated the impacts of PCBs on soil protein and the potential of using protein as a biological indicator to assess soil contamination due to PCBs. This study demonstrated that soil protein concentration and expression were negatively...

  17. 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) ...

  18. Toxicity mechanisms and interactions of polychlorinated biphenyls and polybrominated diphenylethers

    OpenAIRE

    Antonijević Biljana; Milovanović Vesna; Ćurčić Marijana; Janković Saša; Jaćević Vesna; Vučinić Slavica

    2012-01-01

    Polychlorinated biphenyls (PCBs) and brominated flame retardants, polybrominated diphenylethers (PBDEs), are widespread environmental contaminants as a result of anthropogenic activities and due to their persistency and resistance to degradation. Both groups of chemicals are placed on the list of persistent organic pollutants (POPs), covered by the Stockholm convention which is aimed to limit or ban the production, use, emission, import and export of POPs i...

  19. Analysis of polychlorinated biphenyls (PCBs) in human serum.

    OpenAIRE

    Luotamo, M; Järvisalo, J; Aitio, A

    1985-01-01

    Polychlorinated biphenyls (PCBs) are widely dispersed in the environment. Occupational exposure to PCBs takes place, e.g., in manufacture and repair of capacitors and transformers. A special type of exposure of workers to PCBs may occur in connection with accidents where capacitors or transformers containing PCBs products are damaged, as in the case of a fire or electric arcing. The quantitation of PCBs poses several problems: There are 209 different homologs and isomers of PCBs. The isomers ...

  20. Polychlorinated Biphenyl (PCB) carcinogenicity with special emphasis on airborne PCBs

    OpenAIRE

    Robertson, Larry W.; Ludewig, Gabriele

    2011-01-01

    Polychlorinated biphenyls (PCBs) are industrial chemicals used in various applications requiring chemical stabilityand have now become widely dispersed. Their characteristics of persistence, low water/higher lipid solubility, contribute to their ability to bioconcentrate and bioaccumulate. Traditionally PCBs have been regulated as food contaminants and the general population is primarily exposed by that route. PCBs in foodstuffs are generally higher chlorinated, resistant to metabolic breakdo...

  1. Binding of polychlorinated biphenyls to the aryl hydrocarbon receptor.

    OpenAIRE

    Kafafi, S A; Afeefy, H Y; A. H. Ali; Said, H K; Kafafi, A G

    1993-01-01

    A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that ...

  2. Gas chromatographic separation of methoxylated polychlorinated biphenyl atropisomers

    OpenAIRE

    Kania-Korwel, Izabela; Vyas, Sandhya M.; Song, Yang; Lehmler, Hans-Joachim

    2008-01-01

    Several polychlorinated biphenyls (PCBs) and their hydroxylated metabolites display axial chirality. Here we describe an enantioselective, gas chromatographic separation of methylated derivatives of hydroxylated (OH-)PCB atropisomers (MeO-PCB) using a chemically bonded β-cyclodextrin column (Chirasil-Dex). The atropisomers of several MeO-PCBs could be separated on this column with resolutions ranging from 0.42–0.87 under isothermal or temperature-programmed conditions. In addition, the enanti...

  3. Human Receptor Activation by Aroclor 1260, a Polychlorinated Biphenyl Mixture

    OpenAIRE

    Wahlang, Banrida; Falkner, K. Cameron; Clair, Heather B.; Al-Eryani, Laila; Prough, Russell A.; States, J. Christopher; Coslo, Denise M.; Omiecinski, Curtis J.; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of U.S. adults and dose-dependently associated with obesity and non-alcoholic fatty liver disease (NAFLD). PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), ...

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

    OpenAIRE

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

  5. Research progress of the endocrine disrupting activities of polychlorinated biphenyls

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jingming; QIN Zhanfen; CONG Lin; XU Xiaobai

    2004-01-01

    Polychlorinated biphenyls (PCBs) are global persistent organic pollutants. Almost all commercial PCBs mixtures, single PCB congener, and their metabolites possess endocrine disrupting activities. They can disrupt the estrogen/androgen system, thyroid hormone system and other endocrine systems by interfering with the synthesis, transport, storage, metabolism, and feedback regulation of hormones. The newest data related to the endocrine disrupting activities of PCBs and their mechanisms are reviewed and the research perspectives are also discussed.

  6. 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.

  7. 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.

  8. 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.

  9. Indoleamine 2,3-Dioxygenase 1 (Ido1) Is Involved in the Control of Mouse Caput Epididymis Immune Environment

    OpenAIRE

    Aicha Jrad-Lamine; Joelle Henry-Berger; Christelle Damon-Soubeyrand; Fabrice Saez; Ayhan Kocer; Laurent Janny; Hanae Pons-Rejraji; MUNN, DAVID H.; Mellor, Andrew L.; Najoua Gharbi; Rémi Cadet; Rachel Guiton; Aitken, Robert J.; Joël R Drevet

    2013-01-01

    The epididymis maintains a state of immune tolerance towards spermatozoa while also protecting them and itself against infection and acute inflammation. The immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (Ido1) participates in this delicate local equilibrium. Using the mouse Ido1(-/-) model, we show here that the absence of IDO1 expression leads in the epididymis but not in serum to (1) an increase in the inflammatory state as evidenced by changes in the content of cytokines and chemo...

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

    International Nuclear Information System (INIS)

    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

  11. Synthesis, structural, spectroscopic and thermal characteristics of disubstituted biphenyl derivative: Biphenyl-4,4‧-diacetic acid

    Science.gov (United States)

    Sienkiewicz-Gromiuk, Justyna; Głuchowska, Halina; Tarasiuk, Bogdan; Mazur, Liliana; Rzączyńska, Zofia

    2014-07-01

    A novel 4,4‧-disubstituted biphenyl derivative featuring two acetic acid side arms symmetrically attached to a biphenyl system, that is biphenyl-4,4‧-diacetic acid (H2bpda), has been successfully synthesized by means of the three-stage organic strategy. The synthesis product was characterized by elemental analysis, various spectroscopic techniques including FT-IR, Raman, 1H and 13C NMR as well as thermogravimetric and TG-FT-IR coupled measurements. The phase purity of material was verified on the basis of the X-ray powder diffraction. The studied compound crystallizes in the monoclinic P21/c space group with half of the molecule in the asymmetric unit. Structural studies indicate intermolecular Osbnd H⋯O hydrogen bonding between the carboxylic groups of the adjacent molecules of H2bpda. The occurrence of intermolecularly associated carboxylic groups can also be clearly seen in the vibrational spectra of the acid. On thermal analysis both in air and nitrogen an anhydrous compound demonstrates considerable thermal stability.

  12. Crystallization and preliminary crystallographic analysis of 2-aminophenol 1,6-dioxygenase complexed with substrate and with an inhibitor.

    Science.gov (United States)

    Li, De-Feng; Zhang, Jia-Yue; Hou, Yanjie; Liu, Lei; Liu, Shuang-Jiang; Liu, Wei

    2012-11-01

    Dioxygen activation implemented by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Extradiol dioxygenase is the archetypal member of this superfamily and catalyzes the oxygenolytic ring opening of catechol analogues. Here, the crystallization and preliminary X-ray analysis of 2-aminophenol 1,6-dioxygenase, an enzyme representing a minor subset of extradiol dioxygenases that catalyze the fission of 2-aminophenol rather than catecholic compounds, is reported. Crystals of the holoenzyme with FeII and of complexes with the substrate 2-aminophenol and the suicide inhibitor 4-nitrocatechol were grown using the cocrystallization method under the same conditions as used for the crystallization of the apoenzyme. The crystals belonged to space group C2 and diffracted to 2.3-2.7 Å resolution; the crystal that diffracted to the highest resolution had unit-cell parameters a=270.24, b=48.39, c=108.55 Å, β=109.57°. All X-ray data sets collected from diffraction-quality crystals were suitable for structure determination.

  13. 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.

  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 a chance…

  15. Biodegradation of biphenyl and 2-chlorobiphenyl by a Pseudomonas sp. KM-04 isolated from PCBs-contaminated coal mine soil.

    Science.gov (United States)

    Nam, In-Hyun; Chon, Chul-Min; Jung, Ka-Young; Kim, Jae-Gon

    2014-07-01

    The biphenyl-degrading strain, Pseudomonas sp. KM-04, was isolated from polychlorinated biphenyls-contaminated soil sample obtained from the vicinity of a former coal mine. We herein report that strain KM-04 can use biphenyl as a sole carbon source, and resting cells convert biphenyl to its corresponding metabolic intermediates. Incubation of KM-04 with autoclaved mining-contaminated soil for 10 days in a slurry system reduced the levels of biphenyl and 2-chlorobiphenyl by 98.5 % and 82.3 %, respectively. Furthermore, treatment of a mine-soil microcosm with strain KM-04 for 15 days in a composting system under laboratory conditions reduced the levels of biphenyl and 2-chlorobiphenyl by 87.1 % and 68.7 %, respectively. These results suggest that KM-04 is a potential candidate for the biological removal of biphenyl and its chlorinated derivatives from polychlorinated biphenyl-contaminated mining areas.

  16. The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin.

    Science.gov (United States)

    Ferreiro, Dardo N; Boechi, Leonardo; Estrin, Darío A; Martí, Marcelo A

    2013-02-01

    Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such as Escherichia coli, NOD activity is a defence mechanism against the NO release by the macrophages of the hosts' immune system during infection. Because of that, FHbs have been studied thoroughly and several drugs have been developed in an effort to fight infectious processes. Nevertheless, the protein's structural determinants involved in the NOD activity are still poorly understood. In this context, the aim of the present work is to unravel the molecular basis of FHbs structural dynamics-to-function relationship using state of the art computer simulation tools. In an effort to fulfill this goal, we studied three key processes that determine NOD activity, namely i) ligand migration into the active site ii) stabilization of the coordinated oxygen and iii) intra-protein electron transfer (ET). Our results allowed us to determine key factors related to all three processes like the presence of a long hydrophobic tunnel for ligand migration, the presence of a water mediated hydrogen bond to stabilize the coordinated oxygen and therefore achieve a high affinity, and the best possible ET paths between the FAD and the heme, where water molecules play an important role. Taken together the presented results close an important gap in our understanding of the wide and diverse globin structural-functional relationships. PMID:23220591

  17. Salmonella overcomes tumor immune tolerance by inhibition of tumor indoleamine 2, 3-dioxygenase 1 expression.

    Science.gov (United States)

    Kuan, Yu-Diao; Lee, Che-Hsin

    2016-01-01

    Over the past decades, Salmonella has been proven capable of inhibiting tumor growth. It can specifically target tumors and due to its facultative anaerobic property, can be more penetrative than other drug therapies. However, the molecular mechanism by which Salmonella inhibits tumor growth is still incompletely known. The antitumor therapeutic effect mediated by Salmonella is associated with an inflammatory immune response at the tumor site and a T cell-dependent immune response. Many tumors have been proven to have a high expression of indoleamine 2, 3-dioxygenase 1 (IDO), which is a rate-limiting enzyme that catalyzes tryptophan to kynurenine, thus causing immune tolerance within the tumor microenvironment. With decreased expression of IDO, increased immune response can be observed, which might be helpful when developing cancer immunotherapy. The expression of IDO was decreased after tumor cells were infected with Salmonella. In addition, Western blot analysis showed that the expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased after Salmonella infection. In conclusion, our results indicate that Salmonella inhibits IDO expression and plays a crucial role in anti-tumor therapy, which might be a promising strategy combined with other cancer treatments.

  18. 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

    2013-10-15

    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 26.5μM) and trachelogenin (IC50 of 57.4μM) showed higher activity than matairesinol (IC50 >200μM) 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, anticancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

  19. 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.

  20. Pyrazolone-quinazolone hybrids: a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.

    Science.gov (United States)

    Xu, Yu-Ling; Lin, Hong-Yan; Cao, Run-Jie; Ming, Ze-Zhong; Yang, Wen-Chao; Yang, Guang-Fu

    2014-10-01

    4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Ki values of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation. PMID:25182962

  1. 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. PMID:22264428

  2. The Immunoregulatory Function of Indoleamine 2, 3 Dioxygenase and Its Application in Allotransplantation

    Directory of Open Access Journals (Sweden)

    Reza B. Jalili

    2007-12-01

    Full Text Available Indolemine 2, 3-dioxygenase (IDO is a cytosolic monomeric hemoprotein enzyme that catalyses tryptophan, the least available essential amino acid in the human body, to N-formylkynurenine, which in turn rapidly degrades to give kynurenine. IDO is expressed in different tissues, especially and prominently in some subsets of antigen presenting cells (APCs of lymphoid organs and also in the placenta of human and other mammals. Expression of IDO by certain dendritic cells, monocytes and macrophages has a regulatory effect on T cells probably by providing a tryptophan-deficient microenvironment and/or accumulation of toxic metabolites of tryptophan. This immunomodulatory function of IDO plays an essential role in different physiological and pathological states. IDO was shown to prevent rejection of the fetus during pregnancy, possibly by inhibiting alloreactive T cells. Moreover, IDO expression in APCs was suggested to control autoreactive immune responses. In this review we discuss the molecular and biological characteristics of IDO and its function in immune system as well as the potential application of this enzyme in improving the outcome of allogeneic transplantation as a local immunosuppressive factor.

  3. Reaction mechanism of cobalt-substituted homoprotocatechuate 2,3-dioxygenase: a QM/MM study.

    Science.gov (United States)

    Cao, Lili; Dong, Geng; Lai, Wenzhen

    2015-04-01

    The reaction mechanisms of cobalt-substituted homoprotocatechuate 2,3-dioxygenase (Co-HPCD) with electron-rich substrate homoprotocatechuate (HPCA) and electron-poor substrate 4-nitrocatechol (4NC) were investigated by quantum mechanical/molecular mechanical (QM/MM) calculations. Our results demonstrated that the Co-O2 adducts has doublet ground state with a Co(III)-O2(•-) character when 4NC was used as the substrate, in good agreement with the EPR spectroscopic experiment. The reactive oxygen species is the doublet Co(III)-O2(•-) for Co-HPCD/4NC and the quartet SQ(•↑)-Co(II)-O2(•-↓) species for Co-HPCD/HPCA, indicating that the substrate plays important roles in the dioxygen activation by Co-HPCD. B3LYP was found to overestimate the rate-limiting barriers in Co-HPCD. TPSSh predicts barriers of 21.5 versus 12.0 kcal/mol for Co-HPCD/4NC versus Co-HPCD/HPCA, which is consistent with the fact that the rate of the reaction is decreased when the substrate was changed from HPCA to 4NC.

  4. Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts.

    Science.gov (United States)

    Gupta, S L; Carlin, J M; Pyati, P; Dai, W; Pfefferkorn, E R; Murphy, M J

    1994-01-01

    Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+ or Zn2+. The inhibition correlated with the level of INDO activity induced and could be reversed by the addition of excess tryptophan to the medium. The growth of Toxoplasma gondii was also strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+. Expression of Cd(2+)-induced INDO activity also inhibited thymidine incorporation and led to cytotoxicity in INDO +ve cells but not in INDO -ve cells. Thus, the induction of INDO activity by IFN-gamma may be an important factor in the antimicrobial and antiproliferative effects of IFN-gamma in human fibroblasts. Images PMID:8188349

  5. 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.

  6. Tissue distribution, intracellular localization and proteolytic processing of rat 4-hydroxyphenylpyruvate dioxygenase.

    Science.gov (United States)

    Neve, Søren; Aarenstrup, Lene; Tornehave, Ditte; Rahbek-Nielsen, Henrik; Corydon, Thomas Juhl; Roepstorff, Peter; Kristiansen, Karsten

    2003-01-01

    4-hydroxyphenylpyruvate dioxygenase (HPD) is an important enzyme involved in tyrosine catabolism. HPD was shown to be identical to a protein named the F-antigen, exploited by immunologists because of its unique immunological properties. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. Decreased expression of HPD is often observed in association with the severe type I tyrosinemia, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. In this study we present a comprehensive analysis of tissue specific expression and intracellular localization of HPD in the rat. By combined use of in situ hybridization and immunohistochemistry we confirm previously known sites of expression in liver and kidney. In addition, we show that HPD is abundantly expressed in neurons in the cortex, cerebellum and hippocampus. By using immunoelectron microscopy and confocal laser scanning microscopy, we provide evidence that HPD contrary to earlier assumptions specifically localizes to membranes of the endoplasmic reticulum and the Golgi apparatus. Detailed mass spectrometric analyses of HPD purified from rat liver revealed N-terminal and C-terminal processing of HPD, and expression of recombinant HPD suggested that C-terminal processing enhances the enzymatic activity.

  7. Emerging concepts on inhibitors of indoleamine 2,3-dioxygenase in rheumatic diseases.

    Science.gov (United States)

    Filippini, P; Del Papa, N; Sambataro, D; Del Bufalo, A; Locatelli, F; Rutella, S

    2012-01-01

    The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis. PMID:22963664

  8. The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Jacques C. Mbongue

    2015-09-01

    Full Text Available Indoleamine 2, 3-dioxygenase (IDO is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called “kynurenines” that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells.

  9. Indoleamine 2, 3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines

    Institute of Scientific and Technical Information of China (English)

    Shih Ling HWANG; Nancy Pei-Yee CHUNG; Jacqueline Kwai-Yi CHAN; Chen-Lung Steve LIN

    2005-01-01

    Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs),and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC functions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflammatory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regulated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.

  10. Substrate Recognition and Catalysis by the Cofactor-Independent Dioxygenase DpgC+

    Energy Technology Data Exchange (ETDEWEB)

    Fielding,E.; Widboom, P.; Bruner, S.

    2007-01-01

    The enzyme DpgC belongs to a small class of oxygenases not dependent on accessory cofactors for activity. DpgC is in the biosynthetic pathway for the nonproteinogenic amino acid 3, 5-dihydroxyphenylglycine in actinomycetes bacteria responsible for the production of the vancomycin/teicoplanin family of antibiotic natural products. The X-ray structure of DpgC confirmed the absence of cofactors and defined a novel hydrophobic dioxygen binding pocket adjacent to a bound substrate analogue. In this paper, the role specific amino acids play in substrate recognition and catalysis is examined through biochemical and structural characterization of site-specific enzyme mutations and alternate substrates. The results establish the importance of three amino acids, Arg254, Glu299, and Glu189, in the chemistry of DpgC. Arg254 and Glu189 join to form a specific contact with one of the phenolic hydroxyls of the substrate, and this interaction plays a key role in both substrate recognition and catalysis. The X-ray crystal structure of Arg254Lys was determined to address the role this residue plays in the chemistry. In addition, characterization of alternate substrate analogues demonstrates the presence and position of phenol groups are necessary for both enzyme recognition and downstream oxidation chemistry. Overall, this work defines the mechanism of substrate recognition and specificity by the cofactor-independent dioxygenase DpgC.

  11. Fluorescent biphenyl derivatives of phenylalanine suitable for protein modification.

    Science.gov (United States)

    Chen, Shengxi; Fahmi, Nour Eddine; Bhattacharya, Chandrabali; Wang, Lin; Jin, Yuguang; Benkovic, Stephen J; Hecht, Sidney M

    2013-11-26

    In a recent study, we demonstrated that structurally compact fluorophores incorporated into the side chains of amino acids could be introduced into dihydrofolate reductase from Escherichia coli (ecDHFR) with minimal disruption of protein structure or function, even when the site of incorporation was within a folded region of the protein. The modified proteins could be employed for FRET measurements, providing sensitive monitors of changes in protein conformation. The very favorable results achieved in that study encouraged us to prepare additional fluorescent amino acids of potential utility for studying protein dynamics. Presently, we describe the synthesis and photophysical characterization of four positional isomers of biphenyl-phenylalanine, all of which were found to exhibit potentially useful fluorescent properties. All four phenylalanine derivatives were used to activate suppressor tRNA transcripts and incorporated into multiple positions of ecDHFR. All phenylalanine derivatives were incorporated with good efficiency into position 16 of ecDHFR and afforded modified proteins that consumed NADPH at rates up to about twice the rate measured for wild type. This phenomenon has been noted on a number of occasions previously and shown to be due to an increase in the off-rate of tetrahydrofolate from the enzyme, altering a step that is normally rate limiting. When introduced into sterically accessible position 49, the four phenylalanine derivatives afforded DHFRs having catalytic function comparable to wild type. The four phenylalanine derivatives were also introduced into position 115 of ecDHFR, which is known to be a folded region of the protein less tolerant of structural alteration. As anticipated, significant differences were noted in the catalytic efficiencies of the derived proteins. The ability of two of the sizable biphenyl-phenylalanine derivatives to be accommodated at position 115 with minimal perturbation of DHFR function is attributed to rotational

  12. 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.

  13. 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,...

  14. Polychlorinated biphenyl exposure and effects in transformer repair workers.

    OpenAIRE

    Emmett, E A

    1985-01-01

    Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower....

  15. Prediction of the Aqueous Solubilities of Polychlorinated Biphenyls

    Institute of Scientific and Technical Information of China (English)

    Shu Shen LIU; Shi Hai CUI; Lian Sheng WANG

    2004-01-01

    Using the molecular electronegativity distance vector descriptors derived directly from the molecular topological structures, the aqueous solubilities of polychlorinated biphenyls(PCBs)were predicted. A three-variable regression equation with correlation coefficient of 0.9739 and the root mean square errors of 0.26 was developed. The descriptors included in the equation represent three interactions between three pairs of atomic types,I.e.,atom-C=and>C=,-C=and-Cl,and-Cland-Cl.It has been proved that the aqueous solubilities of 137 PCB congeners can be accurately predicted as long as there are more than 65 calibration compounds.

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

    International Nuclear Information System (INIS)

    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

  17. Plasma polychlorinated biphenyls in residents of 91 PCB-contaminated and 108 non-contaminated dwellings

    DEFF Research Database (Denmark)

    Meyer, Harald William; Frederiksen, Marie; Göen, Thomas;

    2013-01-01

    In the1950s-1970s polychlorinated biphenyls (PCBs) were used in several countries as plasticizers in elastic sealants in buildings.......In the1950s-1970s polychlorinated biphenyls (PCBs) were used in several countries as plasticizers in elastic sealants in buildings....

  18. Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung.

    Science.gov (United States)

    Harmer, Christopher J; Wynn, Matthew; Pinto, Rachel; Cordwell, Stuart; Rose, Barbara R; Harbour, Colin; Triccas, James A; Manos, Jim

    2015-01-01

    Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hypoxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1. PMID:26252386

  19. Recombinant adenovirus with human indoleamine-2,3-dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Yong-bing; SHI Xian-jie; LU Gang; NIE Hong-feng; SHEN Xiao-qing; YU Cong-hui; GONG Jian-ping

    2011-01-01

    Background Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments.Methods The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hlDO gene and HBVpreS gene was packaged and amplified in 293 cells.Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hlDO and HBVpreS was detected by RT-PCR and Western blotting respectively.Results The recombinant adenovirus was produced successfully. Its titer was 2.5x109 efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells.Conclusion The transfer of hlDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hlDO and HBVpreS would provide the experimental basis for future studies.

  20. Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase.

    Science.gov (United States)

    Fuertig, René; Azzinnari, Damiano; Bergamini, Giorgio; Cathomas, Flurin; Sigrist, Hannes; Seifritz, Erich; Vavassori, Stefano; Luippold, Andreas; Hengerer, Bastian; Ceci, Angelo; Pryce, Christopher R

    2016-05-01

    Psychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immune-inflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity to aversive stimuli. The present mouse study investigated effects of psychosocial stress as chronic social defeat (CSD) versus control-handling (CON) on: Pavlovian tone-shock fear conditioning, activation of the kynurenine pathway, and efficacy of a specific inhibitor (IDOInh) of the tryptophan-kynurenine catabolising enzyme indoleamine 2,3-dioxygenase (IDO1), in reversing CSD effects on the kynurenine pathway and fear. CSD led to excessive fear learning and memory, whilst repeated oral escitalopram (antidepressant and anxiolytic) reversed excessive fear memory, indicating predictive validity of the model. CSD led to higher blood levels of TNF-α, IFN-γ, kynurenine (KYN), 3-hydroxykynurenine (3-HK) and kynurenic acid, and higher KYN and 3-HK in amygdala and hippocampus. CSD was without effect on IDO1 gene or protein expression in spleen, ileum and liver, whilst increasing liver TDO2 gene expression. Nonetheless, oral IDOInh reduced blood and brain levels of KYN and 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyper-activity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders. PMID:26724575

  1. 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.

  2. Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 2. X-ray absorption studies of native enzyme and anaerobic complexes with the substrates quercetin and myricetin

    NARCIS (Netherlands)

    Steiner, Roberto A.; Meyer-Klaucke, Wolfram; Dijkstra, Bauke W.

    2002-01-01

    Quercetin 2,3-dioxygenase (2,3QD) is a mononuclear copper-dependent dioxygenase which catalyzes the cleavage of the heterocyclic ring of the flavonol quercetin (5,7,3',4'-tetrahydroxy flavonol) to produce 2-protocatechuoyl-phloroglucinol carboxylic acid and carbon monoxide. In this study, X-ray abso

  3. Study of tritium labeling of complex mixture of polychlorinated biphenyls

    International Nuclear Information System (INIS)

    The method for tritium labeling of technical mixture (commercial mark - SOVOL, USSR) of polychlorinated biphenyls (PCBs) was developed. The influence of procedure of labeling by thermally activated tritium on the nativity of polychlorinated biphenyls (PCBs) was studied. The method of labeling by thermally activated tritium has some factors, which are able to destroy organic compounds - photodegradation, thermo-degradation and degradation caused by reaction of substitution of organic compounds hydrogen atoms by activated tritium atoms. To develop a method of labeling of every organic compound by thermally activated tritium it is necessary to determine and optimize the conditions of labeling. In our case procedure of labeling is complicated because of technical mixture of PCBs consist from more than 20 isomers, chlorinated with different degree. We studied the dependence of appearance of products of degradation PCBs from duration of labeling procedure. It was found that some part of PCBs and product of its degradation were evaporated under vacuum and were collected on the glass flask cooled by liquid nitrogen. It was found that correlation between labeled of PCBs and products of degradation did not changed with increasing time of labeling, and radiochemical yield of tritium labeled of PCBs was stable - about 15-20 %. The optimum regime of labeling was selected. It was found that purification of labeled PCBs by TLC on silica gel with hexane allows obtaining tritium-labeled PCBs purified from by-products. Thus, TLC purification seems inexpensive, fast and suitable for purification of tritium-labeled PCBs

  4. Levels of polychlorinated biphenyls in 1,4-dichlorobenzene mothballs

    Institute of Scientific and Technical Information of China (English)

    LIU Wen-bin; ZHENG Ming-hui; XING Ying; WANG Dong-sheng; ZHAO Xing-ru; GAO Li-rong

    2005-01-01

    Although polychlorinated biphenyls(PCBs) are globally recognized pollutant, an understanding of their resources as by-products in chemical industry is poorly investigated. This paper presents data from a study that was conducted in order to determine the extent of PCBs in 1,4-dichlorobenzene(p-DCB) mothballs. Total PCBs and dioxin-like PCBs were detected in five mothball samples. Total PCB concentrations ranged from 328 ng/g to 1798 ng/g, while the levels of WHO-TEQ were between 0.16 pg/g and 13 pg/g. Mean concentrations of total PCBs and WHO-TEQ in the samples were 724 ng/g and 3.2 pg/g, respectively. The highest level of PCB congeners was that of trichlorinated biphenyls(537 ng/g), which maybe due to the relatively low chlorination in the process of p-DCB production. A mechanism of the formation of PCBs from polychlorinated benzene in the presence of chlorine is also suggested. The results suggested that re-estimation on the risk of p-DCB products, especially the products for daily use such as mothballs, is expected.

  5. Polychlorinated biphenyl residues in sandstorm depositions in Beijing, China.

    Science.gov (United States)

    Fu, Shan; Yang, Zhong-Zhi; Li, Ke; Xu, Xiao-Bai

    2008-10-01

    Sandstorms, which distribute many particles, are a special atmospheric occurrence and are frequent in northern China. We conducted this study to determine, for the first time, the concentration of polychlorinated biphenyls (PCBs) in sandstorm depositions. We collected 13 samples from urban areas of Beijing, and we measured a total of 144 PCB congeners. Thirteen samples all contained PCB residues. The total PCB concentration ranged from 1.6 to 15.6ngg(-1) (median, 4.8ngg(-1), dry weight), with trichlorinated biphenyls as the predominant homologue (>50.4%). Furthermore, we observed increasing PCB contamination from northwest to east Beijing. We later explored possible factors affecting contamination of the sandstorm depositions, which revealed a significant correlation between SigmaPCBs and the minimum particle size of the sandstorm deposition samples. Principal-component analysis revealed that the major source of PCBs in Beijing may be potentially associated with the number-one commercial PCB through the long-range transmission. In previous results, PCBs were not a severe component of contamination in sandstorm depositions of Beijing. However, this study suggested that sandstorm deposition may be a potential source of exposure to PCBs for the residents of Beijing, China. PMID:18674798

  6. Fate and Complex Pathogenic Effects of Dioxins and Polychlorinated Biphenyls in Obese Subjects before and after Drastic Weight Loss

    Science.gov (United States)

    Kim, Min-Ji; Marchand, Philippe; Henegar, Corneliu; Antignac, Jean-Philippe; Alili, Rohia; Poitou, Christine; Bouillot, Jean-Luc; Basdevant, Arnaud; Le Bizec, Bruno; Barouki, Robert; Clément, Karine

    2011-01-01

    Background In humans, persistent organic pollutants (POPs) are stored primarily in adipose tissue. Their total body burden and their contribution to obesity-associated diseases remain unclear. Objectives We characterized POP total body burden and their redistribution in obese individuals before and after drastic weight loss and compared these values with a variety of molecular, biological, and clinical parameters. Methods Seventy-one obese subjects were enrolled and underwent bariatric surgery. Blood and adipose tissue samples were obtained at different times from these individuals as well as from 18 lean women. Results POP content (17 dioxins/furans and 18 polychlorinated biphenyl congeners) in different adipose tissue territories was similar, allowing us to assess total POP body burden from a single biopsy. Total POP body burden was 2 to 3 times higher in obese than in lean individuals. We also found increased expression of some POP target genes in obese adipose tissue. Drastic weight loss led to increased serum POPs and, within 6–12 months, to a significant 15% decrease in total polychlorinated biphenyl body burden. Importantly, serum POP levels were positively correlated with liver toxicity markers and lipid parameters, independently of age and body mass index. Conclusions POP content in adipose tissue and serum correlate with biological markers of obesity-related dysfunctions. Drastic weight loss leads to a redistribution of POPs and to a moderate decrease of their total body burden. PMID:21156398

  7. An EXAFS study of the interaction of substrate with the ferric active site of protocatechuate 3,4-dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    True, A.E.; Orville, A.M.; Pearce, L.L.; Lipscomb, J.D.; Que, L. Jr. (Univ. of Minnesota, Minneapolis (USA))

    1990-12-01

    X-ray crystallographic studies of the intradiol cleaving protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa have shown that the enzyme has a trigonal bipyramidal ferric active site with two histidines, two tyrosines, and a solvent molecule as ligands. Fe K-edge EXAFS studies of the spectroscopically similar protocatechuate 3,4-dioxygenase from Brevibacterium fuscum are consistent with a pentacoordinate geometry of the iron active site with 3 O/N ligands at 1.90 {angstrom} and 2 O/N ligands at 2.08 {angstrom}. The 2.08-{angstrom} bonds are assigned to the two histidines, while the 1.90-{angstrom} bonds are associated with the two tyrosines and the coordinated solvent. The short Fe-O distance for the solvent suggests that it coordinates as hydroxide rather than water. When the inhibitor terephthalate is bound to the enzyme, the XANES data indicate that the ferric site becomes 6-coordinate and the EXAFS data show a beat pattern which can only be simulated with an additional Fe-O/N interaction at 2.46 {angstrom}. Together, the data suggest that the oxygens of the carboxylate group in terephthalate displace the hydroxide and chelate to the ferric site but in an asymmetric fashion. In contrast, protocatechuate 3,4-dioxygenase remains 5-coordinate upon the addition of the slow substrate homoprotocatechuic acid (HPCA). Previous EPR data have indicated that HPCA forms an iron chelate via the two hydroxyl functions. For the iron site to remain 5-coordinate and the HPCA to be chelated to the iron, the substrate must displace not only the hydroxide but also a ligand from the protein backbone, probably a histidine. The mechanistic implications of the displacement of hydroxide and a protein ligand in the active site are discussed.

  8. Swapping metals in Fe- and Mn-dependent dioxygenases: Evidence for oxygen activation without a change in metal redox state

    Energy Technology Data Exchange (ETDEWEB)

    Emerson, Joseph P.; Kovaleva, Elena G.; Farquhar, Erik R.; Lipscomb, John D.; Oue, Jr., Lawrence (UMM)

    2008-07-21

    Biological O{sub 2} activation often occurs after binding to a reduced metal [e.g., M(II)] in an enzyme active site. Subsequent M(II)-to-O{sub 2} electron transfer results in a reactive M(III)-superoxo species. For the extradiol aromatic ring-cleaving dioxygenases, we have proposed a different model where an electron is transferred from substrate to O{sub 2} via the M(II) center to which they are both bound, thereby obviating the need for an integral change in metal redox state. This model is tested by using homoprotocatechuate 2,3-dioxygenases from Brevibacterium fuscum (Fe-HPCD) and Arthrobacter globiformis (Mn-MndD) that share high sequence identity and very similar structures. Despite these similarities, Fe-HPCD binds Fe(II) whereas Mn-MndD incorporates Mn(II). Methods are described to incorporate the nonphysiological metal into each enzyme (Mn-HPCD and Fe-MndD). The x-ray crystal structure of Mn-HPCD at 1.7 {angstrom} is found to be indistinguishable from that of Fe-HPCD, while EPR studies show that the Mn(II) sites of Mn-MndD and Mn-HPCD, and the Fe(II) sites of the NO complexes of Fe-HPCD and Fe-MndD, are very similar. The uniform metal site structures of these enzymes suggest that extradiol dioxygenases cannot differentially compensate for the 0.7-V gap in the redox potentials of free iron and manganese. Nonetheless, all four enzymes exhibit nearly the same K{sub M} and V{sub max} values. These enzymes constitute an unusual pair of metallo-oxygenases that remain fully active after a metal swap, implicating a different way by which metals are used to promote oxygen activation without an integral change in metal redox state.

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

    International Nuclear Information System (INIS)

    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−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

  10. (-)-Epigallocatechin gallate inhibits the expression of indoleamine 2,3-dioxygenase in human colorectal cancer cells.

    Science.gov (United States)

    Ogawa, Kengo; Hara, Takeshi; Shimizu, Masahito; Nagano, Junji; Ohno, Tomohiko; Hoshi, Masato; Ito, Hiroyasu; Tsurumi, Hisashi; Saito, Kuniaki; Seishima, Mitsuru; Moriwaki, Hisataka

    2012-09-01

    Immune escape, the ability of tumor cells to avoid tumor-specific immune responses, occurs during the development and progression of several types of human malignancies, including colorectal cancer (CRC). Indoleamine 2,3-dioxygenase (IDO), the tryptophan catabolic enzyme, plays a significant role in regulating the immune response and provides tumor cells with a potent tool to evade the immune system. In the present study, we examined the effects of (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, on the inhibition of IDO expression induced by interferon (IFN)-γ in human CRC cells. We found that IFN-γ increased the expression levels of IDO protein and mRNA in HT29 and SW837 CRC cell lines. Treatment of SW837 cells with EGCG significantly decreased IFN-γ-induced expression of IDO protein and mRNA in a dose-dependent manner. Enzymatic activity of IDO, determined by the concentration of L-kynurenine in the culture medium, was also significantly inhibited by EGCG treatment. Phosphorylation of signal transducer and activator of transcription 1 (STAT1) induced by IFN-γ was also significantly inhibited by EGCG. Reporter assays indicated that EGCG inhibited the transcriptional activities of IDO promoters, IFN-stimulated response element and IFN-γ activation sequence, activated by STAT1 phosphorylation. These findings suggest that EGCG may exert antitumor effects on CRC, at least in part, by inhibiting the expression and function of IDO through the suppression of STAT1 activation. EGCG may, thus, serve as a potential agent for antitumor immunotherapy and be useful in the chemoprevention and/or treatment of CRC. PMID:23741252

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

    Directory of Open Access Journals (Sweden)

    Rikke Baek Sørensen

    Full Text Available 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 lymphocytes (CTL from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one 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, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general.

  12. Characteristics and function of sulfur dioxygenase in Echiuran worm Urechis unicinctus.

    Directory of Open Access Journals (Sweden)

    Litao Zhang

    Full Text Available BACKGROUND: Sulfide is a common toxin to animals and is abundant in coastal and aquatic sediments. Sulfur dioxygenase (SDO is thought to be the key enzyme involved in sulfide oxidation in some organisms. The echiuran worm, Urechis unicinctus, inhabits coastal sediment and tolerates high concentrations of sulfide. The SDO is presumably important for sulfide tolerance in U. unicinctus. RESULTS: The full-length cDNA of SDO from the echiuran worm U. unicinctus, proven to be located in the mitochondria, was cloned and the analysis of its sequence suggests that it belongs to the metallo-β-lactamase superfamily. The enzyme was produced using an E. coli expression system and the measured activity is approximately 0.80 U mg protein(-1. Furthermore, the expression of four sub-segments of the U. unicinctus SDO was accomplished leading to preliminary identification of functional domains of the enzyme. The identification of the conserved metal I (H113, H115, H169 and D188, metal II (D117, H118, H169 and H229 as well as the potential glutathione (GSH (R197, Y231, M279 and I283 binding sites was determined by enzyme activity and GSH affinity measurements. The key residues responsible for SDO activity were identified by analysis of simultaneous mutations of residues D117 and H118 located close to the metal II binding site. CONCLUSION: The recombinant SDO from U. unicinctus was produced, purified and characterized. The metal binding sites in the SDO were identified and Y231 recognized as the mostly important amino acid residue for GSH binding. Our results show that SDO is located in the mitochondria where it plays an important role in sulfide detoxification of U. unicinctus.

  13. Inflated kinetic isotope effects in the branched mechanism of Neurospora crassa 2-nitropropane dioxygenase.

    Science.gov (United States)

    Francis, Kevin; Gadda, Giovanni

    2009-03-24

    Catalytic turnover of Neurospora crassa 2-nitropropane dioxygenase with nitroethane as substrate occurs through both nonoxidative and oxidative pathways. The pH dependence of the kinetic isotope effects with [1,1-(2)H(2)]nitroethane as substrate was measured in the current study by monitoring the formation of the nitronate product in the nonoxidative pathway. The kinetic isotope effect on the second-order rate constant for nitronate formation, k(cat)/K(m), decreased from an upper limiting value of 23 +/- 1 at low pH to a lower limiting value of 11 +/- 1 at high pH. These kinetic isotope effects are three times larger than those determined previously through measurements of oxygen consumption that occurs in the oxidative pathway of the enzyme [(2006) Biochemistry 45, 13889]. Analytical expressions for the k(cat)/K(m) values determined in each study show that the difference in the kinetic isotope effects arises from the branching of an enzyme-ethylnitronate reaction intermediate through oxidative and nonoxidative turnover. This branching is isotope sensitive due to a kinetic isotope effect on nitronate release rather than on flavin reduction as indicated by the pH-independent (D)k(red) value of 0.99 +/- 0.06 with ethylnitronate as substrate. The kinetic isotope effect on ethylnitronate release arises from the deprotonation of histidine 196, which provides electrostatic interactions with the nitronate to keep it bound in the active site for oxidation. The isotope effect on branching results in an inflation of the kinetic isotope observed for the nonoxidative pathway to values that are larger than the intrinsic values associated with CH bond cleavage. PMID:19199786

  14. Adjuvant indoleamine 2,3-dioxygenase enzyme inhibition for comprehensive management of epilepsy and comorbid depression.

    Science.gov (United States)

    Singh, Tanveer; Goel, Rajesh Kumar

    2016-08-01

    Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. Alteration of tryptophan metabolism towards kynurenine pathway may be one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme (responsible for shifting tryptophan metabolism) employing minocycline with valproic acid for comprehensive management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive dose (35mg/kg, i.p.) at an interval of 48±2h. Kindled animals were treated with saline, valproate (300mg/kg/day i.p.), valproate in combination with different doses of minocycline (10mg/kg; 20mg/kg; 40mg/kg)/day i.p. and minocycline per se (40mg/kg/day i.p.) for 15 days. Except naïve, all the groups were challenged with pentylenetetrazole (35mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using tail suspension and forced swim test on days 1, 5, 10 and 15, 2h after pentylenetetrazole challenge. Results suggested that saline treated kindled animals were significantly associated with depression. Chronic valproate treatment significantly reduced seizure severity score but unable to ameliorate the associated depression. Minocycline supplementation with valproic acid dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of IDO enzyme inhibitors with valproic acid could be explored further for comprehensive management of epilepsy and associated depression. PMID:27189423

  15. Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

    OpenAIRE

    Hashimoto, Hideharu; Pais, June E.; Dai, Nan; Corrêa, Ivan R; Zhang, Xing; Zheng, Yu; Cheng, Xiaodong

    2015-01-01

    The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and α-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be...

  16. Structural Basis for Substrate and Oxygen Activation in Homoprotocatechuate 2,3-Dioxygenase: Roles of Conserved Active Site Histidine-200

    OpenAIRE

    Kovaleva, Elena G.; Rogers, Melanie S.; Lipscomb, John D.

    2015-01-01

    Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady state kinetics, pH dependence, and X-ray crystal structures of the FeHPCD position 200 variants His200Asn, His200Gln, and His200Glu alone and in complex with three catecholic substrates (homo...

  17. Internal Reorganization Energy Contributed by Torsional Motion in Electron Transfer Reaction between Biphenyl and Biphenyl Anion Radical

    Institute of Scientific and Technical Information of China (English)

    MIN,Wei(闵玮); SUN,Lin(孙琳)

    2002-01-01

    Concerning the theoretical estimation of internal reorganization energy contributed by the tortional motion between biphenyl and biphenyl anion radical, direct calculation of self-exchange electron transfer reaction was investigated. With the introduction of a proper average bond length and angle parameters < bond Bp > , a multiple step relaxation Nelson method was developed to deal with the torsional reoganization energy.Based on the above model, an estimation of pure torsional reorganization energy λt,p with an approximation of λt,1 was achieved. The results of 0.140 and 0.125 eV of torsional reorganization energy for a cross-reaction at the levels of 4-31G and HP/DZP, respectively, are in good agreement with the value of 0.13 eV obtained by Miller et al. from the rate measurements. This implies the efficiency and validity of our method to estinate the reorganization energy contributed by pure torsional motion of Bp.

  18. Mechanistic insights on the hydrodesulfurization of biphenyl-2-thiol with nickel compounds.

    Science.gov (United States)

    Torres-Nieto, Jorge; Brennessel, William W; Jones, William D; García, Juventino J

    2009-03-25

    The reactivity of the nickel(I) dimer [(dippe)Ni(mu-H)](2) (1) with biphenyl-2-thiol was explored with the aim of clarifying the key step of sulfur extrusion during the hydrodesulfurization process using dibenzothiophene (DBT). These reactions were monitored by variable temperature NMR experiments which allowed the complete characterization and isolation of [(dippe)(2)Ni(2)(mu-H)(mu-S-2-biphenyl)] (3). The latter compound evolves to the terminal nickel-hydride [(dippe)Ni (eta(1)-C-2-biphenyl)(H)] (4) and transient [(dippe)NiS] (5), to ultimately yield [(dippe)(2)Ni(2)(mu-S)] (2) and biphenyl as the resulting HDS products. The reactivity of 1 and biphenyl-2-thiol was examined using different ratios of reactants, which allowed preparation of [(dippe)Ni(eta(1)-S-biphenyl-2-thiolate)(2)] (6) when using an excess of this substrate. The reactivity of 6 with 1 was addressed, yielding compound 2 and an equivalent amount of biphenyl. PMID:19292493

  19. Overexpression of Crocus carotenoid cleavage dioxygenase, CsCCD4b, in Arabidopsis imparts tolerance to dehydration, salt and oxidative stresses by modulating ROS machinery.

    Science.gov (United States)

    Baba, Shoib Ahmad; Jain, Deepti; Abbas, Nazia; Ashraf, Nasheeman

    2015-09-15

    Apocarotenoids modulate vital physiological and developmental processes in plants. These molecules are formed by the cleavage of carotenoids, a reaction catalyzed by a family of enzymes called carotenoid cleavage dioxygenases (CCDs). Apocarotenoids like β-ionone and β-cyclocitral have been reported to act as stress signal molecules during high light stress in many plant species. In Crocus sativus, these two apocarotenoids are formed by enzymatic cleavage of β-carotene at 9, 10 and 7, 8 bonds by CsCCD4 enzymes. In the present study three isoforms of CsCCD4 were subjected to molecular modeling and docking analysis to determine their substrate specificity and all the three isoforms displayed high substrate specificity for β-carotene. Further, expression of these three CsCCD4 isoforms investigated in response to various stresses revealed that CsCCD4a and CsCCD4b exhibit enhanced expression in response to dehydration, salt and methylviologen, providing a clue towards their role in mediating plant defense response. This was confirmed by overexpressing CsCCD4b in Arabidopsis. The transgenic plants developed longer roots and possessed higher number of lateral roots. Further, overexpression of CsCCD4b imparted enhanced tolerance to salt, dehydration and oxidative stresses as was evidenced by higher survival rate, increased relative root length and biomass in transgenic plants as compared to wild type. Transgenic plants also displayed higher activity and expression of reactive oxygen species (ROS) metabolizing enzymes. This indicates that β-ionone and β-cyclocitral which are enzymatic products of CsCCD4b may act as stress signals and mediate reprogramming of stress responsive genes which ultimately leads to plant defense.

  20. The tryptophan derivative, tranilast, and conditioned medium with indoleamine 2,3-dioxygenase-expressing cells inhibit the proliferation of lymphoid malignancies.

    Science.gov (United States)

    Suwa, Shihoko; Kasubata, Aya; Kato, Miyu; Iida, Megumi; Watanabe, Ken; Miura, Osamu; Fukuda, Tetsuya

    2015-03-01

    Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan degradation and induces immunosuppression. Although IDO is an important factor that allows tumors to escape from immunological attack, its effect on lymphoid malignancies has not been fully revealed. We evaluated the expression of IDO in samples from patients with B-cell malignancies. The IDO expression in the tumor samples was comparable to those in peripheral blood mononuclear cells from healthy donors and had mainly originated from non-B cell populations. We introduced IDO gene into Chinese hamster ovary (CHO) cells. We then cultured various cell lines using CHO- or CHO-IDO-conditioned medium. Compared with the CHO medium (CHO-CM), the CHO-IDO medium (IDO-CM) decreased the viability of lymphoid cell lines but not those of the non-lymphoid lines. Next, we examined the effects of tryptophan metabolites on lymphoid tumors, and revealed that the drug N-[3',4'-dimethoxycinnamoyl] anthranilic acid (tranilast), a synthetic derivative of the tryptophan metabolite, was able to repress proliferation and dose-dependently induce cell death of lymphoid cell lines. Tranilast induced the activation of the c-Jun N-terminal kinase, which is activated by cellular stress, in lymphoid cells. The effect of tranilast on lymphoid cells was independent of the aryl hydrocarbon receptor (AhR) although tranilast has been reported to be an AhR agonist. Finally, the administration of tranilast decreased murine lymphoid tumor progression in vivo. These results indicated that IDO and tryptophan derivatives, particularly tranilast, can be tools for the therapy for lymphoid malignancies.

  1. Synthesis of P,N-2,2’-biphenyl derivatives with central chirality

    Institute of Scientific and Technical Information of China (English)

    JEAN; Ludovic; POULIQUEN; Michael; BLANCHET; Jér?me; LASNE; Marie-Claire; ROUDEN; Jacques

    2010-01-01

    Enantiopure 2-(dicyclohexylphosphino)-1,1’-biphenyl derivatives substituted in the 2’-position by a chiral amino group were prepared.For the compound bearing an acyclic chiral chain,the key step was a Suzuki coupling between bromobenzeneboronic acid and N-Boc-iodoaniline whereas an aromatic nucleophilic substitution allowed the introduction of a chiral pyrrolidine in the 2’-position of the biphenyl backbone.The efficiency of the P,N-biphenyl pyrrolidine derivatives as ligands in Pd-catalyzed arylaminations compares well with that of DavePhos ligand.

  2. Determination of polychlorinated biphenyls (PCBs) in insulating oil

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, S.; Goda, Y.; Hirobe, M. [Japan EnvironChemicals Ltd., Tokyo (Japan); Tomita, J.; Nishikiori, M.; Nakajima, T. [Tokyo Electric Power Environmental Engineering Co. Inc., Tokyo (Japan); Rubio, F. [Abraxis LLC, Warminster, PA (United States); Takigami, H. [National Inst. for Environmental Studies, Tsukuba (Japan); Sakai, S. [Kyoto Univ., Kyoto (Japan); Ike, M.; Fujita, M. [Osaka Univ., Osaka (Japan)

    2005-07-01

    This paper described a newly developed cocktail polychlorinated biphenyl (PCB) enzyme-linked immunosorbent assay (ELISA) designed as a pretreatment method for determining levels of PCBs in insulating oils. Standard and pretreated PCBs were dissolved in dimethyl sulfoxide (DMSO) and mixed. The diluted mixture was then combined with a horseradish peroxidase conjugate combined with an anti-PCB antibody coupled with magnetic particles. A comparison of the method with standard ELISA processes indicated that the cocktail showed that cross reactivity patterns were improved. Twenty-six insulating oil samples contaminated with PCBs were then analyzed using the method. Values obtained using the cocktail method correlated with gas chromatography (GC) and mass spectroscopy (MS) analyses conducted on the same samples. It was concluded that the cocktail ELISA technique is a reliable and simple analytical method for determining PCBs in insulating oils. 3 refs., 4 tabs., 2 figs.

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

    International Nuclear Information System (INIS)

    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 cm2, 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

  4. Fluorescence characteristics of polychlorinated biphenyl isomers in cyclodextrin media

    Energy Technology Data Exchange (ETDEWEB)

    Femia, R.A.; Scypinski, S.; Love, L.J.C.

    1985-01-01

    The fluorescence characteristics of several polychlorinated biphenyl (PCB) isomers in ..cap alpha..- and ..beta..-cyclodextrin (CD) are discussed and contrasted. The steric hindrance of PCBs imposed by the positions of the chlorine atoms on the rings determines the overall stability of the resulting inclusion complexes with cyclodextrin which is reflected in the fluorescence intensities. Less substituted homologues include into the CD cavity equally well in both cyclodextrins, but very heavily substituted molecules show drastic differences between their fluorescence intensities in the ..cap alpha..- and ..beta..-cyclodextrin solutions. This behavior can be employed as a method for spectral fractionation of PCB isomers. Spectral separation is demonstrated here for two variably substituted molecules, and the photophysical limitations of this approach are discussed.

  5. Bis(4-carbamoylpiperidinium biphenyl-4,4′-disulfonate

    Directory of Open Access Journals (Sweden)

    Graham Smith

    2010-12-01

    Full Text Available In the title isonipecotamide salt 2C6H13N2O+·C12H8O6S22−, the asymmetric unit comprises one biphenyl-4,4′-disulfonate dianion which lies across a crystallographic inversion centre and another in a general position [dihedral angle between the two phenyl rings is 37.1 (1°], together with three isonipecotamide cations. Two of these cations give a cyclic homomeric amide–amide dimer interaction [graph set R22(8], the other giving a similar dimeric interaction but across an inversion centre, both dimers then forming lateral cyclic R42(8 pyrimidinium–amide N—H...O interactions. These units are linked both laterally and longitudinally to the sulfonate groups of the dianions through piperidinium N—H...O hydrogen bonds, giving a three-dimensional framework structure.

  6. Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases.

    Science.gov (United States)

    Wahlang, Banrida; Petriello, Michael C; Perkins, Jordan T; Shen, Shu; Hennig, Bernhard

    2016-09-01

    Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) is correlated with multiple vascular complications including endothelial cell dysfunction and atherosclerosis. PCB-induced activation of the vasculature subsequently leads to oxidative stress and induction of pro-inflammatory cytokines and adhesion proteins. Gene expression of these cytokines/proteins is known to be regulated by small, endogenous oligonucleotides known as microRNAs that interact with messenger RNA. MicroRNAs are an acknowledged component of the epigenome, but the role of environmentally-driven epigenetic changes such as toxicant-induced changes in microRNA profiles is currently understudied. The objective of this study was to determine the effects of PCB exposure on microRNA expression profile in primary human endothelial cells using the commercial PCB mixture Aroclor 1260. Samples were analyzed using Affymetrix GeneChip® miRNA 4.0 arrays for high throughput detection and selected microRNA gene expression was validated (RT-PCR). Microarray analysis identified 557 out of 6658 microRNAs that were changed with PCB exposure (p<0.05). In-silico analysis using MetaCore database identified 21 of these microRNAs to be associated with vascular diseases. Further validation showed that Aroclor 1260 increased miR-21, miR-31, miR-126, miR-221 and miR-222 expression levels. Upregulated miR-21 has been reported in cardiac injury while miR-126 and miR-31 modulate inflammation. Our results demonstrated evidence of altered microRNA expression with PCB exposure, thus providing novel insights into mechanisms of PCB toxicity. PMID:27288564

  7. 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.

  8. Multistep conversion of para-substituted phenols by phenol hydroxylase and 2,3-dihydroxybiphenyl 1,2-dioxygenase.

    Science.gov (United States)

    Qu, Yuanyuan; Shi, Shengnan; Ma, Qiao; Kong, Chunlei; Zhou, Hao; Zhang, Xuwang; Zhou, Jiti

    2013-04-01

    A multistep conversion system of para-substituted phenols by recombinant phenol hydroxylase (PH(IND)) and 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC(LA-4)) was constructed in this study. Docking studies with different para-substituted phenols and corresponding catechols inside of the active site of PH(IND) and BphC(LA-4) predicted that all the substrates should be transformed. High-performance liquid chromatography-mass spectrometry analysis showed that the products of multistep conversion were the corresponding para-substituted catechols and semialdehydes. For the first-step conversion, the formation rate of 4-fluorocatechol (0.39 μM/min/mg dry weight) by strain PH(IND) hydroxylation was 1.15, 6.50, 3.00, and 1.18-fold higher than the formation of 4-chlorocatechol, 4-bromocatechol, 4-nitrocatechol, and 4-methylcatechol, respectively. For the second-step conversion, the formation rates of semialdehydes by strain BphC(LA-4) were as follows: 5-fluoro-HODA>5-chloro-HODA>2-hydroxy-5-nitro-ODA>5-bromo-HODA>2-hydroxy-5-methyl-ODA. The present study suggested that the multistep conversion by both ring hydroxylase and cleavage dioxygenase should be potential in the synthesis of industrial precursors and provide a novel avenue in the wastewater recycling treatment.

  9. Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase

    Science.gov (United States)

    Lewis-Ballester, Ariel; Forouhar, Farhad; Kim, Sung-Mi; Lew, Scott; Wang, YongQiang; Karkashon, Shay; Seetharaman, Jayaraman; Batabyal, Dipanwita; Chiang, Bing-Yu; Hussain, Munif; Correia, Maria Almira; Yeh, Syun-Ru; Tong, Liang

    2016-01-01

    Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes. Here we report the crystal structure of human TDO (hTDO) in a ternary complex with the substrates L-Trp and O2 and in a binary complex with the product N-formylkynurenine (NFK), defining for the first time the binding modes of both substrates and the product of this enzyme. The structure indicates that the dioxygenation reaction is initiated by a direct attack of O2 on the C2 atom of the L-Trp indole ring. The structure also reveals an exo binding site for L-Trp, located ~42 Å from the active site and formed by residues conserved among tryptophan-auxotrophic TDOs. Biochemical and cellular studies indicate that Trp binding at this exo site does not affect enzyme catalysis but instead it retards the degradation of hTDO through the ubiquitin-dependent proteasomal pathway. This exo site may therefore provide a novel L-Trp-mediated regulation mechanism for cellular degradation of hTDO, which may have important implications in human diseases. PMID:27762317

  10. 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.

  11. 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

  12. NO binding to Mn-substituted homoprotocatechuate 2,3-dioxygenase: relationship to O₂ reactivity.

    Science.gov (United States)

    Hayden, Joshua A; Farquhar, Erik R; Que, Lawrence; Lipscomb, John D; Hendrich, Michael P

    2013-10-01

    Iron(II)-containing homoprotocatechuate 2,3-dioxygenase (FeHPCD) activates O2 to catalyze the aromatic ring opening of homoprotocatechuate (HPCA). The enzyme requires Fe(II) for catalysis, but Mn(II) can be substituted (MnHPCD) with essentially no change in the steady-state kinetic parameters. Near simultaneous O2 and HPCA activation has been proposed to occur through transfer of an electron or electrons from HPCA to O2 through the divalent metal. In O2 reactions with MnHPCD-HPCA and the 4-nitrocatechol (4NC) complex of the His200Asn (H200N) variant of FeHPCD, this transfer has resulted in the detection of a transient M(III)-O2 (·-) species that is not observed during turnover of the wild-type FeHPCD. The factors governing formation of the M(III)-O2 (·-) species are explored here by EPR spectroscopy using MnHPCD and nitric oxide (NO) as an O2 surrogate. Both the HPCA and the dihydroxymandelic substrate complexes of MnHPCD bind NO, thus representing the first reported stable MnNO complexes of a nonheme enzyme. In contrast, the free enzyme, the MnHPCD-4NC complex, and the MnH200N and MnH200Q variants with or without HPCA bound do not bind NO. The MnHPCD-ligand complexes that bind NO are also active in normal O2-linked turnover, whereas the others are inactive. Past studies have shown that FeHPCD and the analogous variants and catecholic ligand complexes all bind NO, and are active in normal turnover. This contrasting behavior may stem from the ability of the enzyme to maintain the approximately 0.8-V difference in the solution redox potentials of Fe(II) and Mn(II). Owing to the higher potential of Mn, the formation of the NO adduct or the O2 adduct requires both strong charge donation from the bound catecholic ligand and additional stabilization by interaction with the active-site His200. The same nonoptimal electronic and structural forces that prevent NO and O2 binding in MnHPCD variants may lead to inefficient electron transfer from the catecholic substrate to

  13. NO Binding to Mn-Substituted Homoprotocatechuate 2,3-Dioxygenase: Relationship to O2 Reactivity

    Science.gov (United States)

    Hayden, Joshua A.; Farquhar, Erik R.; Que, Lawrence; Lipscomb, John D.; Hendrich, Michael P.

    2014-01-01

    Homoprotocatechuate 2,3-dioxygenase (FeHPCD) activates O2 to catalyze the aromatic ring opening of 3,4-dihydroxyphenylacetic acid (HPCA). The enzyme requires FeII for catalysis, but MnII can be substituted (MnHPCD) with essentially no change in the steady-state kinetic parameters. Near simultaneous O2 and HPCA activation has been proposed to occur through transfer of an electron(s) from HPCA to O2 through the divalent metal. In O2 reactions with MnHPCD-HPCA and the 4-nitrocatechol (4NC) complex of the His200Asn (H200N) variant of FeHPCD, this transfer has resulted in the detection of a transient MIII-O2•− species not observed during turnover of the wild type FeHPCD. The factors governing formation of the MIII-O2•− species are explored here with EPR spectroscopy using MnHPCD and nitric oxide (NO) as an O2 surrogate. Both the HPCA and dihydroxymandelic substrate complexes of MnHPCD bind NO, thus representing the first reported stable MnNO complexes of a nonheme enzyme. In contrast, the free enzyme, the MnHPCD-4NC complex, and the MnH200N and MnH200Q variants with or without HPCA bound do not bind NO. The MnHPCD-ligand complexes that bind NO are also active in normal O2-linked turnover, whereas the others are inactive. Past studies have shown that FeHPCD and the analogous variants and catecholic ligand complexes all bind NO, and are active in normal turnover. This contrasting behavior may stem from ability of the enzyme to maintain the ~0.8 V difference in the solution redox potentials of FeII and MnII. Due to the higher potential of Mn, the formation of the NO or O2 adduct requires both strong charge donation from the bound catecholic ligand and additional stabilization by interaction with the active site His200. The same non-optimal electronic and structural forces that prevent NO and O2 binding in MnHPCD variants may lead to inefficient electron transfer from the catecholic substrate to the metal center in variants of FeHPCD during O2-linked turnover

  14. 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...

  15. COMPARING POLYCHLORINATED BIPHENYLS IN FARM-RAISED AND WILD-CAUGHT CATFISH FROM SOUTHERN MISSISSIPPI

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) are among the most thermally stable organic chemicals known. This characteristic has historically made them useful in a wide array of applications including use in electrical transformers and capacitors, varnishes, waxes, synthetic resins, epoxy ...

  16. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children

    NARCIS (Netherlands)

    N. Weisglas-Kuperus (Nynke); S. Patandin (Svati); G.A. Berbers; T.C.J. Sas (Theo); P.J.J. Sauer (Pieter); H. Hooijkaas (Herbert); P.G.H. Mulder (Paul)

    2000-01-01

    textabstractPrenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to P

  17. Polychlorinated biphenyl (PCB) removal from the Kenai National Wildlife Refuge, Alaska, October 1984 and 1988

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report covers the removal of polychlorinated biphenyl (PCB) from Kenai National Wildlife Refuge in Alaska during October 1984 and 1985. Atlantic Ritchfield...

  18. 78 FR 20640 - Polychlorinated Biphenyls (PCBs); Recycling Plastics from Shredder Residue

    Science.gov (United States)

    2013-04-05

    ... AGENCY Polychlorinated Biphenyls (PCBs); Recycling Plastics from Shredder Residue AGENCY: Environmental... will generally allow for the recycling of plastic separated from shredder residue under the conditions described in the Voluntary Procedures for Recycling Plastics from Shredder Residue, relying principally...

  19. METHODS FOR DETERMINING THE POLYCHLORINATED BIPHENYL EMISSIONS FROM INCINERATION AND CAPACITOR AND TRANSFORMER FILLING PLANTS

    Science.gov (United States)

    Described are methods to measure the polychlorinated biphenyl (PCB) emissions from the stacks of municipal waste, industrial waste, and sewage sludge incinerators and from capacitor and transformer filling plants. The PCB emissions from the incineration plants are collected by im...

  20. POLYCHLORINATED BIPHENYLS IN HOUSE DUST AND YARD SOIL NEAR A SUPERFUND SITE. (R825173)

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) were measured in house dust and yard soil at 34 homes surrounding New Bedford Harbor during dredging of highly contaminated harbor sediments. PCBs can volatilize from sediments and seawater and subsequently deposit on surrounding soil, resulting i...

  1. Synthesis of the Reported Pyranonaphthoquinone Structure of the Indoleamine-2,3-dioxygenase Inhibitor Annulin B by Regioselective Diels-Alder Reaction.

    Science.gov (United States)

    Inman, Martyn; Carvalho, Catarina; Lewis, William; Moody, Christopher J

    2016-09-01

    Annulin B, isolated from the marine hydroid isolated from Garveia annulata, is a potent inhibitor of the tryptophan catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). A synthesis of the reported pyranonaphthoquinone structure is described, in which the key step is a regioselective Diels-Alder reaction between a pyranobenzoquinone dienophile and a silyl ketene acetal diene. PMID:27513176

  2. Modeling the 2-His-1-Carboxylate Facial Triad: Iron-Catecholato Complexes as Structural and Functional Models of the Extradiol Cleaving Dioxygenases

    NARCIS (Netherlands)

    Bruijnincx, P.C.A.; Lutz, M.; Spek, A.L.; Hagen, W.R.; Weckhuysen, B.M.; van Koten, G.; Klein Gebbink, R.J.M.

    2007-01-01

    Mononuclear iron(II)- and iron(III)-catecholato complexes with three members of a new 3,3-bis(1-alkylimidazol-2-yl)propionate ligand family have been synthesized as models of the active sites of the extradiol cleaving catechol dioxygenases. These enzymes are part of the superfamily of dioxygen-activ

  3. Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review

    OpenAIRE

    Ribas-Fito, N; Sala, M.; Kogevinas, M; Sunyer, J.

    2001-01-01

    BACKGROUND—Polychlorinated biphenyls (PCBs) are complex mixtures of persistent contaminants that are widespread in the environment. Newborns are exposed across the placenta and through breast feeding. Experimental animal studies have indicated that PCBs are neurotoxic. The neurological effects of these compounds on children are not clear. Methods—A systematic review of literature on the relation between neurological development in children and exposure to polychlorinated biphenyls.
RESULTS—Se...

  4. Novel Ring Cleavage Products in the Biotransformation of Biphenyl by the Yeast Trichosporon mucoides

    OpenAIRE

    Sietmann, Rabea; Hammer, Elke; Specht, Michael; Carl E Cerniglia; Schauer, Frieder

    2001-01-01

    The yeast Trichosporon mucoides, grown on either glucose or phenol, was able to transform biphenyl into a variety of mono-, di-, and trihydroxylated derivatives hydroxylated on one or both aromatic rings. While some of these products accumulated in the supernatant as dead end products, the ortho-substituted dihydroxylated biphenyls were substrates for further oxidation and ring fission. These ring fission products were identified by high-performance liquid chromatography, gas chromatography-m...

  5. Investigation of mechanisms of formation of biphenyls and benzonaphthothiophenes by simulation experiment

    Institute of Scientific and Technical Information of China (English)

    XIA; Yanqing(夏燕青); ZHANG; Gengxin(张更新)

    2002-01-01

    The formation mechanisms of biphenyl series and benzonaphthothiophene series are investigated by means of simulation experiment. Biphenyl series are likely formed in two ways: one is the aromatization of the chain compounds containing conjugated C== C double bonds or the compounds with such a kind of sidechains, and the other is the reaction of sulfur with ordinary chain compounds, in which sulphur acts on ordinary sidechain compounds by seizing some hydrogens and forming (H2S and) the intermediates with conjugated C== C double bonds first, and then the intermediates are aromatized. One of the basic precursors of benzonaphthothiophenes is likely the phenylnaphthalenes which may originate from the chain compounds containing conjugated C== C double bonds, the compounds with such sidechains and saturate or unsaturate chain compounds. Thermal stability of biphenyls is high, but they can become dibenzothiophenes and polycyclic aromatic hydrocarbons or dibenzofurans and polycyclic aromatic hydrocarbons respectively in the presence of sulphur or oxygen. The ratio of biphenyl and m-biphenyl to biphenyls may be employed to indicate the depositional environment in the mild to medium maturation, of which the higher value indicates a fresh water depositional environment and the lower indicates a saline depositional environment. The relative high content of benzonaphthothiophenes in the crude oil indicates that the crude oil has undergone an intense sulfurization in the source rock or reservoir.

  6. Investigation of saponification for determination of polychlorinated biphenyls in marine sediments.

    Science.gov (United States)

    Numata, Masahiko; Yarita, Takashi; Aoyagi, Yoshie; Yamazaki, Misako; Takatsu, Akiko

    2005-02-01

    The effects of saponification conditions (temperature and water content of saponifying solution) on the determination of chlorinated biphenyls (CBs) in marine sediments were investigated. Although highly chlorinated biphenyls (nona- to deca-CBs) decomposed during high-temperature saponification, the degree of degradation was reduced by adding water to the ethanolic potassium hydroxide saponifying solution. Room-temperature saponification yielded quantitative recovery of highly chlorinated biphenyl surrogates but low extraction efficiencies of lightly chlorinated biphenyls (mono- to di-CBs). The same samples were analyzed by other extraction techniques, for example, pressurized liquid extraction, and analytical results were compared. The mono- and di-CB concentrations were correlated with the extraction temperatures of various extraction techniques. In particular, the concentrations of some CB congeners (CB11, CB14) were higher with saponification. The low degree of degradation of highly chlorinated biphenyls and the high recovery of lightly chlorinated biphenyls were compatible when room-temperature and high-temperature saponification were combined. Except for the anomalies of CB11 and CB14, the combined method gave satisfactory results for analysis of PCBs.

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

    Science.gov (United States)

    Shuai, Jianjun; Yu, Xurun; Zhang, Jing; Xiong, Ai-Sheng; Xiong, Fei

    2016-01-01

    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. PMID:27140507

  8. Structure-activity relationships for interaction with multidrug resistance protein 2 (ABCC2/MRP2): the role of torsion angle for a series of biphenyl-substituted heterocycles.

    Science.gov (United States)

    Lai, Yurong; Xing, Li; Poda, Gennadiy I; Hu, Yiding

    2007-06-01

    Multidrug resistance protein 2 (ABCC2/MRP2) is an ATP-binding cassette transporter involved in the absorption, distribution, and excretion of drugs and xenobiotics. Identifying compounds that are ABCC2/MRP2 substrates and/or inhibitors and understanding their structure-activity relationships (SARs) are important considerations in the selection and optimization of drug candidates. In the present study, the interactions between ABCC2/MRP2 and a series of biphenyl-substituted heterocycles were evaluated using Caco-2 cells and human ABCC2/MRP2 gene-transfected Madin-Darby canine kidney cells. It was observed that ABCC2/MRP2 transport and/or inhibition profile, both in nature and in magnitude, depends strongly on the substitution patterns of the biphenyl system. In particular, different ortho-substitutions cause various degrees of twisting between the two-phenyl rings, resulting in changing interactions between the ligands and ABCC2/MRP2. The compounds with small ortho functions (hydrogen, fluorine, and oxygen) and, thus, the ones displaying the smallest torsion angles of biphenyl (37-45 degrees) are neither substrates nor inhibitors of human ABCC2/MRP2. The transporter interactions increase as the steric bulkiness of the ortho-substitutions increase. When the tested compounds are 2-methyl substituted biphenyls, they exhibit moderate torsion angles (54-65 degrees) and behave as ABCC2/MRP2 substrates as well as mild inhibitors [10-40% compared with 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethyl-sulfanyl)methylsulfanyl] propionic acid (MK571)]. For the 2,2'-dimethyl substituted biphenyls, the torsions are enhanced (78-87 degrees) and so is the inhibition of ABCC2/MRP2. This class of compounds behaves as strong inhibitors of ABCC2/MRP2. These results can be used to define the three-dimensional structural requirements of ABCC2/MRP2 interaction with their substrates and inhibitors, as well as to provide SAR guidance to support drug discovery.

  9. The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

    Energy Technology Data Exchange (ETDEWEB)

    Gopal, B.; Madan, Lalima L.; Betz, Stephen F.; Kossiakoff, Anthony A. (Indian); (UC); (GeneFormatics)

    2010-11-10

    Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s), whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.

  10. Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase.

    Science.gov (United States)

    Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

    2013-01-01

    Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect. PMID:24251110

  11. Indoleamine 2,3-dioxygenase 1 (ido1 is involved in the control of mouse caput epididymis immune environment.

    Directory of Open Access Journals (Sweden)

    Aicha Jrad-Lamine

    Full Text Available The epididymis maintains a state of immune tolerance towards spermatozoa while also protecting them and itself against infection and acute inflammation. The immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (Ido1 participates in this delicate local equilibrium. Using the mouse Ido1(-/- model, we show here that the absence of IDO1 expression leads in the epididymis but not in serum to (1 an increase in the inflammatory state as evidenced by changes in the content of cytokines and chemokines, (2 the engagement of a Th1-driven inflammatory response as evidenced by changes in the Th17/Treg as well as Th1/Th2 equilibria, as well as (3 differences in the content of lipid intermediates classically involved in inflammation. Despite this more pronounced inflammatory state, Ido1(-/- animals succeed in preserving the local epididymal immune situation due to the activation of compensatory mechanisms that are discussed.

  12. Indoleamine 2,3-dioxygenase 1 (ido1) is involved in the control of mouse caput epididymis immune environment.

    Science.gov (United States)

    Jrad-Lamine, Aicha; Henry-Berger, Joelle; Damon-Soubeyrand, Christelle; Saez, Fabrice; Kocer, Ayhan; Janny, Laurent; Pons-Rejraji, Hanae; Munn, David H; Mellor, Andrew L; Gharbi, Najoua; Cadet, Rémi; Guiton, Rachel; Aitken, Robert J; Drevet, Joël R

    2013-01-01

    The epididymis maintains a state of immune tolerance towards spermatozoa while also protecting them and itself against infection and acute inflammation. The immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (Ido1) participates in this delicate local equilibrium. Using the mouse Ido1(-/-) model, we show here that the absence of IDO1 expression leads in the epididymis but not in serum to (1) an increase in the inflammatory state as evidenced by changes in the content of cytokines and chemokines, (2) the engagement of a Th1-driven inflammatory response as evidenced by changes in the Th17/Treg as well as Th1/Th2 equilibria, as well as (3) differences in the content of lipid intermediates classically involved in inflammation. Despite this more pronounced inflammatory state, Ido1(-/-) animals succeed in preserving the local epididymal immune situation due to the activation of compensatory mechanisms that are discussed. PMID:23840489

  13. Molecular modeling of 2-nitropropane dioxygenase domain of Mycobacterium tuberculosis H37Rv and docking of herbal ligands.

    Science.gov (United States)

    Ramesh, K V; Akhila, B N; Deshmukh, Sudha

    2011-06-01

    The 3D structure of enoyl reductase (ER) domain generated by the SWISS MODEL server contains the 2-nitropropane dioxygenase (2NPD) structure displaying the TIM barrel fold. Though TIM barrel fold is made up of both main and inserted domains, in our study, we could only predict the structure of the main domain, which had central barrel of eight beta-strands surrounded by eight alpha-helices. Superimposition of the 2NPD region of ER domain of Mycobacterium tuberculosis H37Rv on to the corresponding region of 2UVA_G revealed a good structural alignment between the two, suggesting this template to be a good structural homologue. Among various herbal ligands that were screened as inhibitors, daucosterol was found to bind in closest proximity to the flavin mono nucleotide (FMN) binding site with the lowest docking energy. PMID:21793307

  14. Atmospheric emission of polychlorinated biphenyls from multiple industrial thermal processes.

    Science.gov (United States)

    Liu, Guorui; Zheng, Minghui; Cai, Mingwei; Nie, Zhiqiang; Zhang, Bing; Liu, Wenbin; Du, Bing; Dong, Shujun; Hu, Jicheng; Xiao, Ke

    2013-03-01

    In this study, field measurements were conducted to estimate and characterize the atmospheric emission levels and profiles of polychlorinated biphenyls (PCBs) from multiple industrial thermal processes. The emission levels and profiles of PCBs from five types of thermal processes at twenty-three plants were studied and compared with eight processes reported in our previous studies. Correlation analysis was preformed to identify a marker congener for emission of ΣPCB. A significant correlation was observed between congener CB-118 and ΣPCB (R(2)=0.65 and pprocesses were compared, and this information could be used for studying source-receptor relationships and identifying the specific sources of PCBs. To prioritize the sources for control, the concentrations of PCBs from thirteen industrial thermal sources were compared. The PCB concentrations from secondary zinc smelting and thermal wire reclamation were about one to three order magnitude higher than those of other sources, which suggests that these two sources be given priority in PCB source control. Finally, the atmospheric emission factors of PCBs from the thirteen industrial sources were summarized, and these data will be useful for developing an integrated emission inventory of PCBs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Fung-Chi, E-mail: ko@nmmba.gov.tw [National Dong Hwa University, Institute of Marine Biodiversity and Evolutionary Biology, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Baker, Joel E. [The Center for Urban Waters, University of Washington, Tacoma, WA 98402 (United States); Tew, Kwee S. [National Dong Hwa University, Institute of Marine Biodiversity and Evolutionary Biology, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China)

    2012-02-01

    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{sub 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{sub ow}, and was instead related to the molecular structure of the compound.

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

    Science.gov (United States)

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

    2012-02-01

    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 15min, second, a first order process reaching the maximum concentration within 48h 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.

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

    International Nuclear Information System (INIS)

    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. Accumulation and efflux of polychlorinated biphenyls in Escherichia coli.

    Science.gov (United States)

    Geng, Shen; Fang, Jun; Turner, Kendrick B; Daunert, Sylvia; Wei, Yinan

    2012-06-01

    Polychlorinated biphenyls (PCBs) are environmental pollutants that have been associated with numerous adverse health effects in human and animals. Hydroxylated PCBs (HPCBs) are the product of the oxidative metabolism of PCBs. The presence of hydroxyl groups in HPCBs makes these compounds more hydrophilic than the parent PCBs. One of the best approaches to break down and remove these contaminants is bioremediation; an environmentally friendly process that uses microorganisms to degrade hazardous chemicals into non-toxic ones. In this study, we investigated the cellular accumulation and toxicity of selected PCBs and HPCBs in Gram-negative bacteria, using Escherichia coli as a model organism. We found that none of the five PCBs tested were toxic to E. coli, presumably due to their limited bioavailability. Nevertheless, different HPCBs tested showed different levels of toxicity. Furthermore, we demonstrated that the primary multidrug efflux system in E. coli, AcrAB-TolC, facilitated the efflux of HPCBs out of the cell. Since AcrAB-TolC is constitutively expressed in E. coli and is conserved in all sequenced Gram-negative bacterial genomes, our results suggest that the efflux activities of multidrug resistant pumps may affect the accumulation and degradation of PCBs in Gram-negative bacteria.

  19. 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.

  20. Reproduction success of American kestrels exposed to dietary polychlorinated biphenyls.

    Science.gov (United States)

    Fernie, K J; Smits, J E; Bortolotti, G R; Bird, D M

    2001-04-01

    While reproduction of wild birds is adversely affected by multiple environmental contaminants, we determined that polychlorinated biphenyls (PCBs) alone alter reproduction. Captive American kestrels (Falco sparverius), fed PCB-spiked (Aroclor 1248:1254:1260) food (7 mg/kg body weight/d) prior to and during the first breeding season only (100 d) laid eggs with environmentally relevant levels of total PCBs (34.0 microg/g whole egg wet wt vs 0 microg/g for controls). Reproduction changed during, not after, PCB exposure in this two-year study. The PCB-exposed pairs laid smaller clutches later in the season and laid more totally infertile clutches. Hatching success was reduced in PCB-exposed pairs, and 50% of PCB nestlings died within 3 d of hatching. Nearly 60% of PCB-exposed pairs with hatchlings failed to produce fledglings. Higher levels of total PCB residues and congeners were associated with later clutch initiation and fewer fertile eggs, hatchlings, and fledglings. We suggest that nonpersistent PCB congeners have a greater influence on reproduction than do persistent congeners. PMID:11345453

  1. Organochlorine pesticides and polychlorinated biphenyls in California sea lions

    International Nuclear Information System (INIS)

    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

  2. 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.

  3. The internal barriers of rotation for the 209 polychlorinated biphenyls.

    Science.gov (United States)

    Andersson, P L; Haglund, P; Tysklind, M

    1997-01-01

    The internal barrier of rotation (Erot) was calculated for all 209 polychlorinated biphenyls (PCBs) by using a semi-empirical method, viz. the Austin Model 1 (AMI) Hamiltonian. The difference in total energy between a forced planar state and an optimised twisted structure was defined as Erot. The Erot values were in the range of 8.33 to 483 kJ/mol, and were significantly influenced by the number of chlorine atoms in ortho position. An additional structural characteristic of the PCBs influencing Erot of ortho substituted congeners was substitution by chlorine atoms in vicinal meta positions, which is assumed to prevent outward bending of ortho substituents. This so-called buttressing effect contributed with 4 to 31 kJ/mol per added chlorine atom. In conclusion, the internal barrier of rotation, calculated for all 209 PCBs, provides an important structure dependent physico-chemical parameter for multivariate modelling of future quantitative structure-activity and structure-property relationships (QSARs/QSPRs). PMID:19005788

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

    International Nuclear Information System (INIS)

    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

  5. Toxicity mechanisms and interactions of polychlorinated biphenyls and polybrominated diphenylethers

    Directory of Open Access Journals (Sweden)

    Antonijević Biljana

    2012-01-01

    Full Text Available Polychlorinated biphenyls (PCBs and brominated flame retardants, polybrominated diphenylethers (PBDEs, are widespread environmental contaminants as a result of anthropogenic activities and due to their persistency and resistance to degradation. Both groups of chemicals are placed on the list of persistent organic pollutants (POPs, covered by the Stockholm convention which is aimed to limit or ban the production, use, emission, import and export of POPs in order to protect human health and the environment. Taking into account the structural similarity between PCBs and PBDEs, and the known effects of PCBs, these two groups of chemicals could have similar mechanisms of action. Also, because of real simultaneous exposure to these compounds, an examination of possible interactions is of great importance. Interactions of the compounds from these groups are likely at the system level of hormones, particularly thyroid and reproductive ones. As there are mechanisms of adverse effects of both groups of chemicals on the nervous system, including functional, neurological and behavioral changes, there are influences on neurotransmiters, changes in signal transduction and apoptosis. There are interactions affecting the occurrence of metabolic disorders as well. Data on the toxicity of mixtures of PCBs and PBDEs, as well as interactions of these chemicals would contribute to the processes of risk evaluation and risk characterisation. [Projekat Ministarstva nauke Republike Srbije, br. III 46009

  6. A comprehensive approach to actual polychlorinated biphenyls environmental contamination.

    Science.gov (United States)

    Risso, F; Magherini, A; Ottonelli, M; Magi, E; Lottici, S; Maggiolo, S; Garbarino, M; Narizzano, R

    2016-05-01

    Worldwide polychlorinated biphenyls (PCBs) pollution is due to complex mixtures with high number of congeners, making the determination of total PCBs in the environment an open challenge. Because the bulk of PCBs production was made of Aroclor mixtures, this analysis is usually faced by the empirical mixture identification via visual inspection of the chromatogram. However, the identification reliability is questionable, as patterns in real samples are strongly affected by the frequent occurrence of more than one mixture. Our approach is based on the determination of a limited number of congeners chosen to enable objective criteria for Aroclor identification, summing up the advantages of congener-specific analysis with the ones of total PCBs determination. A quantitative relationship is established between congeners and any single mixture, or mixtures combination, leading to the identification of the actual contamination composition. The approach, due to its generality, allows the use of different sets of congeners and any technical mixture, including the non-Aroclor ones. The results confirm that PCB environmental pollution in northern Italy is based on Aroclor. Our methodology represents an important tool to understand the source and fate of the PCBs contamination.

  7. Properties of catechol 1,2-dioxygenase in the cell free extract and immobilized extract of Mycobacterium fortuitum

    Directory of Open Access Journals (Sweden)

    A.S. Silva

    2013-01-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAH are carcinogenic compounds which contaminate water and soil, and the enzymes can be used for bioremediation of these environments. This study aimed to evaluate some environmental conditions that affect the production and activity of the catechol 1,2-dioxygenase (C12O by Mycobacterium fortuitum in the cell free and immobilized extract in sodium alginate. The bacterium was grown in mineral medium and LB broth containing 250 mg L-1 of anthracene (PAH. The optimum conditions of pH (4.0-9.0, temperature (5-70 ºC, reaction time (10-90 min and the effect of ions in the enzyme activity were determined. The Mycobacterium cultivated in LB shown higher growth and the C12O activity was two-fold higher to that in the mineral medium. To both extracts the highest enzyme activity was at pH 8.0, however, the immobilized extract promoted the increase in the C12O activity in a pH range between 4.0 and 8.5. The immobilized extract increased the enzymatic activity time and showed the highest C12O activity at 45 ºC, 20 ºC higher than the greatest temperature in the cell free extract. The enzyme activity in both extracts was stimulated by Fe3+, Hg2+ and Mn2+ and inhibited by NH4+ and Cu2+, but the immobilization protected the enzyme against the deleterious effects of K+ and Mg2+ in tested concentrations. The catechol 1,2-dioxygenase of Mycobacterium fortuitum in the immobilized extract has greater stability to the variations of pH, temperature and reaction time, and show higher activity in presence of ions, comparing to the cell free extract.

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

    International Nuclear Information System (INIS)

    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. Dietary uptake of polychlorinated biphenyls (PCBs) by rainbow trout

    Science.gov (United States)

    Carline, Robert F.; Barry, Patrick M.; Ketola, H. George

    2004-01-01

    The presence of detectable levels of polychlorinated biphenyls (PCBs) in commercially produced fish feed has raised a concern about the degree of biomagnification of these contaminants in hatchery-reared trout. Our objectives were to (1) define the relationship between concentrations of PCBs in fish feed and in fish tissue and (2) estimate the relative contributions of feed and hatchery supply water to PCB concentrations in fish. We conducted a 6-month feeding trial with fingerling rainbow trout Oncorhynchus mykiss fed commercial diets with four concentrations of PCBs: a low-PCB diet (69 ng/g); a typical commercial diet (126 ng/g); and the typical diet spiked with PCBs at two levels (220 and 280 ng/g). The concentrations of PCBs in fillets after 1 month were commensurate with those in the feeds and remained relatively stable for the next 5 months; mean PCB concentrations in fillets ranged from 54 to 94 ng/g. Low levels of PCBs were detected in the hatchery supply water. We used the concentrations of PCBs in the feeds, absorption rates of PCBs, and two different rates of PCB depuration to estimate the potential uptake of PCBs from supply water. When we used a low depuration rate (half-life = 219 d), the computed body burdens of PCBs could be entirely attributed to the feeds. When a high depuration rate (half-life = 66 d) was used, some uptake of PCBs from the supply water was likely, but most of the total body burden originated from the feeds. We concluded that rainbow trout fed a diet with 126 ng/g PCBs would have a PCB concentration of about 60 ng/g in their fillets, which is high enough to warrant issuance of a consumption advisory (no more than one meal of fish per week) under a protocol adopted by some Great Lakes states.

  10. Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture.

    Science.gov (United States)

    Wahlang, Banrida; Falkner, K Cameron; Clair, Heather B; Al-Eryani, Laila; Prough, Russell A; States, J Christopher; Coslo, Denise M; Omiecinski, Curtis J; Cave, Matthew C

    2014-08-01

    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of U.S. adults and dose-dependently associated with obesity and non-alcoholic fatty liver disease (NAFLD). PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor (LXRα), and farnesoid-X-receptor (FXR). This study evaluates Aroclor 1260, a PCB mixture with congener composition mimicking that of human adipose tissue, and selected congeners, as potential ligands for these receptors utilizing human hepatoma-derived (HepG2) and primate-derived (COS-1) cell lines, and primary human hepatocytes. Aroclor 1260 (20 μg/ml) activated AhR, and PCB 126, a minor component, was a potent inducer. Aroclor 1260 activated PXR in a simple concentration-dependent manner at concentrations ≥10 μg/ml. Among the congeners tested, PCBs 138, 149, 151, 174, 183, 187, and 196 activated PXR. Aroclor 1260 activated CAR2 and CAR3 variants at lower concentrations and antagonize CAR2 activation by the CAR agonist, CITCO, at higher concentrations (≥20 μg/ml). Additionally, Aroclor 1260 induced CYP2B6 in primary hepatocytes. At subtoxic doses, Aroclor 1260 did not activate LXR or FXR and had no effect on LXR- or FXR-dependent induction by the agonists T0901317 or GW4064, respectively. Aroclor 1260 (20 μg/ml) suppressed PPARα activation by the agonist nafenopin, although none of the congeners tested demonstrated significant inhibition. The results suggest that Aroclor 1260 is a human AhR, PXR and CAR3 agonist, a mixed agonist/antagonist for CAR2, and an antagonist for human PPARα. PMID:24812009

  11. 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.

  12. 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.

  13. Ecotoxicology of polychlorinated biphenyls in fish--a critical review.

    Science.gov (United States)

    Henry, T B

    2015-01-01

    Polychlorinated biphenyls (PCBs) are widespread persistent anthropogenic contaminants that can accumulate in tissues of fish. The toxicity of PCBs and their transformation products has been investigated for nearly 50 years, but there is a lack of consensus regarding the effects of these environmental contaminants on wild fish populations. The objective of this review is to critically examine these investigations and evaluate publicly available databases for evidence of effects of PCBs in wild fish. Biological activity of PCBs is limited to a small proportion of PCB congeners [e.g., dioxin-like PCBs (DL-PCBs)] and occurs at concentrations that are typically orders of magnitude higher than PCB levels detected in wild fish. Induction of biomarkers consistent with PCB exposure (e.g., induction of cytochrome P450 monooxygenase system) has been evaluated frequently and shown to be induced in fish from some environments, but there does not appear to be consistent reports of damage (i.e., biomarkers of effect) to biomolecules (i.e., oxidative injury) in these fish. Numerous investigations of endocrine system dysfunction or effects on other organ systems have been conducted in wild fish, but collectively there is no consistent evidence of PCB effects on these systems in wild fish. Early life stage toxicity of DL-PCBs does not appear to occur at concentrations reported in wild fish embryos, and results do not support an association between PCBs and decreased survival of early life stages of wild fish. Overall, there appears to be little evidence that PCBs have had any widespread effect on the health or survival of wild fish.

  14. Formation and stability of polychlorinated biphenyl Pickering emulsions

    Science.gov (United States)

    Roy-Perreault, Andréanne; Kueper, Bernard H.; Rawson, Jim

    2005-03-01

    An emulsion stabilized by colloidal suspensions of finely divided solids is known as a Pickering emulsion. The potential for polychlorinated biphenyls (PCBs) to form Pickering emulsions ex situ when in contact with powdered solids, such as clays and metal oxides, is investigated here. Bentonite, iron oxide and magnesium oxide dispersions proved to be robust Pickering emulsion stabilizers, whereas manganese oxide dispersions were not. Batch experiments revealed that emulsions can be formed using a moderately low energy input and can be stabilized with solid concentrations as low as 0.5 wt.%. For the base conditions (volumetric oil fraction ( ϕoil)=30 vol.%; solid concentration ( χ)=2 wt.%), the formed emulsions were indefinitely stable and the initial average droplet diameters varied from 80 to 258 μm, depending on the solid used in the colloidal dispersion. The average droplet size varied at early time, but for most conditions stabilized to a steady-state value 1 week after preparation. The effect of Ostwald ripening was limited. At greater than 0.5 wt.% concentration, the efficiency of the solid dispersion as a stabilizer was dependant on the volumetric oil fraction but not on the solid concentration. Generally, systems with volumetric oil fractions outside of the 20-70 vol.% range were unstable. The emulsions' droplet stability, average droplet size and size distribution were observed to vary as a function of the amount of energy provided to the system, the volumetric oil fraction, and the concentration of the solid in the aqueous dispersion. It is hypothesized that drilling through fractured rock in the immediate vicinity of dense, non-aqueous phase liquid (DNAPL) PCBs may provide both the energy and solid material necessary to form Pickering emulsions.

  15. Polychlorinated biphenyl quinone induces endoplasmic reticulum stress, unfolded protein response, and calcium release.

    Science.gov (United States)

    Xu, Demei; Su, Chuanyang; Song, Xiufang; Shi, Qiong; Fu, Juanli; Hu, Lihua; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-06-15

    Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is an organelle responsible for protein folding and calcium storage. ER stress leads to the accumulation of unfolded proteins in the ER lumen. To be against or respond to this effect, cells have a comprehensive signaling system, called unfolded protein response (UPR), to restore homeostasis and normal ER function or activate the cell death program. Therefore, it is critical to understand how environmental insult regulates the ingredients of ER stress and UPR signalings. Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2 cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress, UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed PCB29-pQ induced ER morphological defects by using transmission electron microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and calpain activity, which were significantly inhibited by the pretreatment of BAPTA-AM (Ca(2+) chelator). These results were correlated with the outcome that PCB29-pQ induces ER stress-related apoptosis through caspase family gene 12, while salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS formation and consequently alleviated PCB29-pQ-induced expression of ER stress-related genes. In conclusion, our result demonstrated for the first time that PCB quinone leads to ROS-dependent induction of ER stress, and UPR and calcium release in HepG2 cells, and the

  16. 2,2,6,6-Tetrakis(biphenyl-2-yl-4,4,8,8-tetramethylcyclotetrasiloxane

    Directory of Open Access Journals (Sweden)

    Erik P. A. Couzijn

    2009-09-01

    Full Text Available The title compound, [–Si(C12H92OSi(CH32O–]2, was obtained unintentionally as the product of an attempted crystallization of caesium bis(biphenyl-2,2′-diylfluorosilicate from dimethylformamide. In the crystal, the molecule is located on an inversion center and the siloxane ring adopts a twist-chair conformation with the two dimethyl-substituted Si atoms lying 0.7081 (5 Å out of the plane defined by the two bis(biphenyl-2-yl-substituted Si atoms and the four O atoms. In each Si(C12H92 unit, the orientation of one terminal phenyl ring relative to the phenylene ring of the other biphenyl moiety suggests a parallel displaced π–π stacking interaction [centroid distance = 4.2377 (11 Å and dihedral angle = 15.40 (9°].

  17. 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.

  18. 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....

  19. Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase

    OpenAIRE

    Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

    2013-01-01

    Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geom...

  20. A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia.

    Science.gov (United States)

    Endo, F; Katoh, H; Yamamoto, S; Matsuda, I

    1991-04-01

    We have characterized a new mutant strain of mouse that has hypertyrosinemia. The blood tyrosine level was persistently high, and increased amounts of 4-hydroxyphenylpyruvic acid and its derivatives were excreted into the urine. Succinylacetone was not detected in urine samples from these mice. All the animals were apparently healthy, and there was no evidence of hepatorenal dysfunction. The hypertyrosinemia was transmitted through an autosomal recessive inheritance. Analyses of hepatic enzymes related to tyrosine metabolism revealed that 4-hydroxyphenylpyruvic acid dioxygenase activity was virtually absent, while fumarylacetoacetase and tyrosine aminotransferases (cytosolic and mitochondrial forms) were normal in these mutant mice. Immunoblot analysis of 4-hydroxyphenylpyruvic acid dioxygenase protein in the liver indicated that the subunit protein of the enzyme was absent. It would appear that hypertyrosinemia in this mutant strain was caused by a genetic defect in 4-hydroxyphenylpyruvic acid dioxygenase. These features are similar to type III tyrosinemia in humans. Analysis of this mutant strain of mouse is expected to provide valuable information on the pathogenesis of human type III tyrosinemia and can also serve as a useful system for studies on tyrosine metabolism.

  1. The mitochondrial sulfur dioxygenase ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 is required for amino acid catabolism during carbohydrate starvation and embryo development in Arabidopsis.

    Science.gov (United States)

    Krüßel, Lena; Junemann, Johannes; Wirtz, Markus; Birke, Hannah; Thornton, Jeremy D; Browning, Luke W; Poschet, Gernot; Hell, Rüdiger; Balk, Janneke; Braun, Hans-Peter; Hildebrandt, Tatjana M

    2014-05-01

    The sulfur dioxygenase ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 (ETHE1) catalyzes the oxidation of persulfides in the mitochondrial matrix and is essential for early embryo development in Arabidopsis (Arabidopsis thaliana). We investigated the biochemical and physiological functions of ETHE1 in plant metabolism using recombinant Arabidopsis ETHE1 and three transfer DNA insertion lines with 50% to 99% decreased sulfur dioxygenase activity. Our results identified a new mitochondrial pathway catalyzing the detoxification of reduced sulfur species derived from cysteine catabolism by oxidation to thiosulfate. Knockdown of the sulfur dioxygenase impaired embryo development and produced phenotypes of starvation-induced chlorosis during short-day growth conditions and extended darkness, indicating that ETHE1 has a key function in situations of high protein turnover, such as seed production and the use of amino acids as alternative respiratory substrates during carbohydrate starvation. The amino acid profile of mutant plants was similar to that caused by defects in the electron-transfer flavoprotein/electron-transfer flavoprotein:ubiquinone oxidoreductase complex and associated dehydrogenases. Thus, in addition to sulfur amino acid catabolism, ETHE1 also affects the oxidation of branched-chain amino acids and lysine.

  2. Long-time measurements of polychlorinated dibenzodioxins (PCDD), dibenzofurans (PCDF) and biphenyls (PCB) in deposition

    International Nuclear Information System (INIS)

    Dioxins, furans and polychlorinated biphenyls from one and the same sample were first separated by chromatography, then determined by mass spectroscopy. Sampling was in accordance with VDI method No. 2119, sheet 2, for the measurement of particulate precipitations. The annual means of PCDD/PCDF deposition ranged from 10 to 83 pg TE/(m2.d). The annual means of the deposition of polychlorinated biphenyls (tri and decachlorobiphenyls combined) varied between 23 and 257 ng/(m2.d). The annual mean for coplanar PCBs No. 77, 126 and 169 was less than 1 ng/(m2.d). (orig./DG)

  3. Synthesis and Characterization of Nonsymmetric Liquid Crystal Dimer Containing Biphenyl and Azobenzene Moiety

    Directory of Open Access Journals (Sweden)

    S. Sandy Subala

    2013-01-01

    Full Text Available Calamitic liquid crystalline dimer containing azobenzene moiety and a decyloxy biphenyl linked by flexible spacers {4-[7-(4′-decyloxy-biphenyl-4-yloxy-alkyloxy]-phenyl}-(4-decyl-phenyl-diazene has been synthesized and characterized by spectroscopic methods. The transition temperatures and phase behaviours were studied by Differential Scanning Calorimeter (DSC and Polarizing Optical Microscope (POM. The synthesized compounds exhibited enantiotropic liquid crystal phase with higher spacer display nematic and smectic C phases while lower spacer shows nematic and smectic A phases.

  4. Bacterial degradation of polychlorinted biphenyls in sludge from an industrial sewer lagoon

    Science.gov (United States)

    Kim, W. S.; Takacs, A. M.; Kuivinen, D. E.

    1983-01-01

    A laboratory experiment was conducted to determine if polychlorinated biphenyls (PCB's) found in an industrial sewer sludge can be effectively degraded by mutant bacteria. The aerated sludge was inoculated daily with mutant bacteria in order to augment the existing bacteria with bacteria that were considered to be capable of degrading PCB's. The pH, nitrogen, and phosphorus levels were monitored daily to maintain an optimum growing medium for the bacteria. A gas chromatographic method was used to determine the PCB concentrations of the sludge initially and also throughout the experiment. Results and discussion of the bacterial treatment of polychlorinated biphenyls are presented.

  5. Alcaligenes eutrophus JMP134 "2,4-dichlorophenoxyacetate monooxygenase" is an alpha-ketoglutarate-dependent dioxygenase.

    OpenAIRE

    Fukumori, F; Hausinger, R P

    1993-01-01

    The Alcaligenes eutrophus JMP134 tfdA gene, encoding the enzyme responsible for the first step in 2,4-dichlorophenoxyacetic acid (2,4-D) biodegradation, was overexpressed in Escherichia coli, and several enzymatic properties of the partially purified gene product were examined. Although the tfdA-encoded enzyme is typically referred to as 2,4-D monooxygenase, we were unable to observe any reductant-dependent activity. Rather, we demonstrate that this enzyme is a ferrous ion-dependent dioxygena...

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 14C-labelled and in equimolar doses (2.0 μmol/kg body wt.)). CB-77 resulted in the comparatively strongest foetal 14C-accumulation, when measured in plasma or whole body homogenate four days after administration (day 17 of pregnancy); the plasma 14C-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 14C-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

  8. 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

  9. Unity in diversity, a systems approach to regulating plant cell physiology by 2-oxoglutarate-dependent dioxygenases.

    Science.gov (United States)

    Kundu, Siddhartha

    2015-01-01

    Could a disjoint group of enzymes synchronize their activities and execute a complex multi-step, measurable, and reproducible response? Here, I surmise that the alpha-ketoglutarate dependent superfamily of non-haem iron (II) dioxygenases could influence cell physiology as a cohesive unit, and that the broad spectra of substrates transformed is an absolute necessity to this portrayal. This eclectic group comprises members from all major taxa, and participates in pesticide breakdown, hypoxia signaling, and osmotic stress neutralization. The oxidative decarboxylation of 2-oxoglutarate to succinate is coupled with a concomitant substrate hydroxylation and, in most cases, is followed by an additional specialized conversion. The domain profile of a protein sequence was used as an index of miscellaneous reaction chemistry and interpreted alongside existent kinetic data in a linear model of integrated function. Statistical parameters were inferred by the creation of a novel, empirically motivated flat-file database of over 3800 sequences (DB2OG) with putative 2-oxoglutarate dependent activity. The collated information was categorized on the basis of existing annotation schema. The data suggests that 2OG-dependent enzymes incorporate several desirable features of a systems level player. DB2OG, is free, accessible without a login to all users, and available at the following URL (http://comp-biol.theacms.in/DB2OG.html).

  10. Structure prediction of Fe(II) 2-oxoglutarate dioxygenase from a psychrophilic yeast Glaciozyma antarctica PI12

    Science.gov (United States)

    Yusof, Nik Yusnoraini; Bakar, Farah Diba Abu; Mahadi, Nor Muhammad; Raih, Mohd Firdaus; Murad, Abdul Munir Abdul

    2015-09-01

    A cDNA encoding Fe(II) 2-oxoglutarate (2OG) dependent dioxygenases was isolated from psychrophilic yeast, Glaciozyma antarctica PI12. We have successfully amplified 1,029 bp cDNA sequence that encodes 342 amino acid with predicted molecular weight 38 kDa. The prediction protein was analysed using various bioinformatics tools to explore the properties of the protein. Based on a BLAST search analysis, the Fe2OX amino acid sequence showed 61% identity to the sequence of oxoglutarate/iron-dependent oxygenase from Rhodosporidium toruloides NP11. SignalP prediction showed that the Fe2OX protein contains no putative signal peptide, which suggests that this enzyme most probably localised intracellularly.The structure of Fe2OX was predicted by homology modelling using MODELLER9v11. The model with the lowest objective function was selected from hundred models generated using MODELLER9v11. Analysis of the structure revealed the longer loop at Fe2OX from G.antarctica that might be responsible for the flexibility of the structure, which contributes to its adaptation to low temperatures. Fe2OX hold a highly conserved Fe(II) binding HXD/E…H triad motif. The binding site for 2-oxoglutarate was found conserved for Arg280 among reported studies, however the Phe268 was found to be different in Fe2OX.

  11. 4-hydroxyphenylpyruvate dioxygenase catalysis: identification of catalytic residues and production of a hydroxylated intermediate shared with a structurally unrelated enzyme.

    Science.gov (United States)

    Raspail, Corinne; Graindorge, Matthieu; Moreau, Yohann; Crouzy, Serge; Lefèbvre, Bertrand; Robin, Adeline Y; Dumas, Renaud; Matringe, Michel

    2011-07-22

    4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxyphenylpyruvate (HPP) into homogentisate. HPPD is the molecular target of very effective synthetic herbicides. HPPD inhibitors may also be useful in treating life-threatening tyrosinemia type I and are currently in trials for treatment of Parkinson disease. The reaction mechanism of this key enzyme in both plants and animals has not yet been fully elucidated. In this study, using site-directed mutagenesis supported by quantum mechanical/molecular mechanical theoretical calculations, we investigated the role of catalytic residues potentially interacting with the substrate/intermediates. These results highlight the following: (i) the central role of Gln-272, Gln-286, and Gln-358 in HPP binding and the first nucleophilic attack; (ii) the important movement of the aromatic ring of HPP during the reaction, and (iii) the key role played by Asn-261 and Ser-246 in C1 hydroxylation and the final ortho-rearrangement steps (numbering according to the Arabidopsis HPPD crystal structure 1SQD). Furthermore, this study reveals that the last step of the catalytic reaction, the 1,2 shift of the acetate side chain, which was believed to be unique to the HPPD activity, is also catalyzed by a structurally unrelated enzyme.

  12. Reaction mechanism of homoprotocatechuate 2,3-dioxygenase with 4-nitrocatechol: implications for the role of substrate.

    Science.gov (United States)

    Dong, Geng; Lai, Wenzhen

    2014-02-20

    The reaction mechanism of the dioxygen activation by homoprotocatechuate 2,3-dioxygenase (HPCD) with the substrate 4-nitrocatechol was investigated by quantum mechanical/molecular mechanical calculations. Our results demonstrated that the experimentally determined side-on iron-oxygen complex in crystallo is a semiquinone substrate radical (SQ(•))-Fe(III)-hydroperoxo species, which could not act as the reactive species. In fact, the Fe(III)-superoxo species with a hydrogen bond between His200 and the proximal oxygen is the reactive oxygen species. The second-sphere His200 residue was found to play an important role in manipulating the orientation of the superoxide in the Fe-O2 adduct for the further reaction. The rate-limiting step is the attack of the superoxo group on the substrate with a barrier of 17.2 kcal/mol, in good agreement with the experimental value of 16.8 kcal/mol. The reaction mechanism was then compared with the one for HPCD with its native substrate homoprotocatechuate studied recently by the same methods, in which a hybrid SQ(•)-Fe(II)-O2(•-)/Fe(III)-O2(•-) was suggested to be the reactive species. Therefore, our studies suggested that the substrate plays important roles in the dioxygen activation by HPCD.

  13. Scavenging properties of neutrophil 4-hydroxyphenylpyruvate dioxygenase are based on a hypothesis that does not stand up to scrutiny.

    Science.gov (United States)

    Salerno, Costantino; Zicari, Alessandra; Mari, Emanuela; D'Eufemia, Patrizia

    2014-10-01

    It was previously reported by D'Eufemia et al. [9] that neutrophil preparations from a patient with tyrosinemia type III, i.e. with inherited deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPPD), exhibited a far higher NO release than controls, when NO was estimated in terms of nitrite content in the suspending media. It was hypothesized that HPPD might participate to NO sequestration in neutrophils and that excessive NO release might reflect the lack of the scavenging action in defective cells. In recent control experiments, we found that HPPD activity in neutrophils preparations from healthy subjects is below the detection limit of the enzymatic assay (less than 3nmol product/h per mg protein). This indicates that HPPD concentration in neutrophils is very low, if any, confirming what was already suggested in literature, and rules out the possibility of a prominent role of HPPD as NO scavenger in these cells. Moreover, we found that 500μM l-tyrosine increases nitrite release and accumulation in suspending media of U-937 cells, a human monoblast-like lymphoma cell line which displays many characteristics of macrophages, including the expression of inducible and endothelial nitric oxide synthases. We hypothesize that the increase of nitrite release by patient's neutrophils might be related to the presence of high l-tyrosine concentrations in the blood samples (426μmol/L instead of 52.1±10.9μmol/L as healthy subjects), rather than to HPPD deficiency of in these cells.

  14. Unity in diversity, a systems approach to regulating plant cell physiology by 2-oxoglutarate-dependent dioxygenases

    Directory of Open Access Journals (Sweden)

    Siddhartha eKundu

    2015-03-01

    Full Text Available Could a disjoint group of enzymes synchronize their activities and execute a complex multi-step, measurable, and reproducible response ? Here, I surmise that the alpha-ketoglutarate dependent superfamily of non-haem iron (II dioxygenases could influence cell physiology as a cohesive unit, and that the broad spectra of substrates transformed is an absolute necessity to this portrayal.This eclectic group comprises members from all major taxa, and participates in pesticide breakdown, hypoxia signaling, and osmotic stress neutralization. The oxidative decarboxylation of 2-oxoglutarate to succinate is coupled with a concomitant substrate hydroxylation and, in most cases, is followed by an additional specialized conversion. The domain profile of a protein sequence was used as an index of miscellaneous reaction chemistry and combined with available kinetic data to form a linear model of integrated function. Statistical parameters were inferred by the creation of a novel, empirically motivated flat-file database of over 3800 sequences (DB2OG with putative 2-oxoglutarate dependent activity. The collated information was categorized on the basis of existing annotation schema. The data suggests that the 2OG-dependent superfamily incorporates several desirable features of a systems level player. DB2OG, is free, accessible without a login to all users, and available at the following URL (http://comp-biol.theacms.in/DB2OG.html.

  15. 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. PMID:25176248

  16. The nonoxidative conversion of nitroethane to ethylnitronate in Neurospora crassa 2-nitropropane dioxygenase is catalyzed by histidine 196.

    Science.gov (United States)

    Francis, Kevin; Gadda, Giovanni

    2008-09-01

    The deprotonation of nitroethane catalyzed by Neurospora crassa 2-nitropropane dioxygenase was investigated by measuring the formation and release of ethylnitronate formed in turnover as a function of pH and through mutagenesis studies. Progress curves for the enzymatic reaction obtained by following the increase in absorbance at 228 nm over time were visibly nonlinear, requiring a logarithmic approximation of the initial reaction rates for the determination of the kinetic parameters of the enzyme. The pH dependence of the second-order rate constant k cat/ K m with nitroethane as substrate implicates the presence of a group with a p K a of 8.1 +/- 0.1 that must be unprotonated for nitronate formation. Mutagenesis studies suggest that this group is histidine 196 as evident from the inability of a H196N variant form of the enzyme to catalyze the formation of ethylnitronate from nitroethane. Replacement of histidine 196 with asparagine resulted in an approximately 15-fold increase in the k cat/ K m with ethylnitronate as compared to the wild-type, which results from the inability of the mutant enzyme to undergo nonoxidative turnover. The results presented herein are consistent with a branched catalytic mechanism for the enzyme in which the ethylnitronate intermediate formed from the H196-catalyzed deprotonation of nitroethane partitions between release from the active site and oxidative denitrification to yield acetaldehyde and nitrite. PMID:18690716

  17. Eosinophil Granulocytes Account for Indoleamine 2,3-Dioxygenase-Mediated Immune Escape in Human Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Simonetta Astigiano

    2005-04-01

    Full Text Available Indoleamine 2,3-dioxygenase (IDO, a catabolizing enzyme of tryptophan, is supposed to play a role in tumor immune escape. Its expression in solid tumors has not yet been well elucidated: IDO can be expressed by the tumor cells themselves, or by ill-defined infiltrating cells, possibly depending on tumor type. We have investigated IDO expression in 25 cases of non small cell lung cancer (NSCLC. Using histochemistry and immunohistochemistry, we found that IDO was expressed not by tumor cells, but by normal cells infiltrating the peritumoral stroma. These cells were neither macrophages nor dendritic cells, and were identified as eosinophil granulocytes. The amount of IDO-positive eosinophils varied in different cases, ranging from a few cells to more than 50 per field at x200 magnification. IDO protein in NSCLC was enzymatically active. Therefore, at least in NSCLC cases displaying a large amount of these cells in the inflammatory infiltrate, IDO-positive eosinophils could exert an effective immunosuppressive action. On analyzing the 17 patients with adequate follow-up, a significant relationship was found between the amount of IDO-positive infiltrate and overall survival. This finding suggests that the degree of IDO-positive infiltrate could be a prognostic marker in NSCLC.

  18. 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.

  19. Determination of Polychlorinated Biphenyls in Soil and Sediment by Selective Pressurized Liquid Extraction with Immunochemical Detection

    Science.gov (United States)

    A selective liquid pressurized extraction (SPLE) method was developed as a streamlined sample preparation/cleanup procedure for determining Aroclors and coplanar polychlorinated biphenyls (PCBs) in soil and sediment matrices. The SPLE method was coupled with an enzyme-linked imm...

  20. Genomic characterization of three unique Dehalococcoides that respire on persistent polychlorinated biphenyls

    OpenAIRE

    Wang, Shanquan; Chng, Kern Rei; Wilm, Andreas; Zhao, Siyan; Yang, Kun-Lin; Nagarajan, Niranjan; HE, Jianzhong

    2014-01-01

    Polychlorinated biphenyls (PCBs) as persistent organic pollutants are widespread in the sediments of lakes, rivers, and harbors. Although the PCB detoxification through microbial reductive dechlorination has been extensively studied for more than 20 y, the difficulty in cultivating PCB dechlorinators in pure culture impedes further characterization, optimization, and application in in situ bioremediation. By combining traditional culture techniques with next-generation sequencing technology, ...

  1. Commentary on Polychlorinated Biphenyls (PCBs), Toxins, and Neuropsychological Deficits: Good Science is the Antidote

    Science.gov (United States)

    Hebben, Nancy

    2004-01-01

    The seven cohort studies of the relation between prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) to cognitive, neuropsychological and behavioral development have suggested that exposure to PCBs can cause persistent changes in cognitive functioning. D.V. Cicchetti, A.S. Kaufman, and S.S. Sparrow (this issue) apply six scientific…

  2. A method for the chemical modification of polychlorinated biphenyls for improved affinity towards noble metal surfaces

    DEFF Research Database (Denmark)

    2015-01-01

    The present application discloses a method for the modification and analysis of a field sample suspected of containing contaminant(s) like polychlorinated biphenyls (PCBs). The invention also relates to a corresponding kit for the modification of samples suspected of containing such contaminant(s)....

  3. Polychlorinated Biphenyl Exposure and Glucose Metabolism in 9-Year-Old Danish Children

    DEFF Research Database (Denmark)

    Jensen, Tina K.; Timmermann, Amalie G.; Rossing, Laura I.;

    2014-01-01

    Context: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. Objectives: To determine whether concurrent serum PCB concentration was associated with markers of glucose metabolism in healthy children. Design: Cross-sectional study. Settings and part...

  4. 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 concentra

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

    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)

  6. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children

    NARCIS (Netherlands)

    Weisglas-Kuperus, N; Patandin, S; Berbers, GAM; Sas, TCJ; Mulder, PGH; Sauer, PJJ; Hooijkaas, H

    2000-01-01

    Prenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to PCBs and dioxins is associated with the pre

  7. Dermal toxicity studies of technical polychlorinated biphenyls and fractions thereof in rabbits

    NARCIS (Netherlands)

    Vos, J.G.; Beems, R.B.

    1971-01-01

    A significant difference in toxicity between 3 polychlorinated biphenyl (PCB) preparations was found in a prior study: Clophen A 60 and Phenoclor DP6 showing the highest, Aroclor 1260 the lowest, toxicity (Vos and Koeman, 1970). A subsequent study revealed the presence of tetra- and pentachlorodiben

  8. Biphenyl Phytoalexin in Sorbus pohuashanensis Suspension Cell Induced by Yeast Extract

    Directory of Open Access Journals (Sweden)

    Liangyun Zhou

    2016-09-01

    Full Text Available Biphenyls are unique phytoalexins de novo synthesized in plants in response to pathogen attack. These compounds are found in Maloideae, a subfamily of the Rosaceae. The anti-microbial activities of biphenyls have been reported in a number of studies and they appear to represent an important defense strategy against pathogens common in the Maloideae, such as species in Malus, Pyrus, Sorbus, and Chaenomeles. Here, cell suspension cultures of Sorbus pohuashanensis were established to study biphenyl phytoalexins formation after yeast extract (YE treatment. An ultra-performance liquid chromatography (UPLC method coupled with quadrupole time of flight mass spectrometry (Q-TOF-MS LC−MS/MS was applied to determine the time course of these biphenyl biomarkers accumulation in YE-treated S. pohuashanensis suspension cells. The results of quantitative analyses show the content of Noraucuparin, 2′-Hydroxyaucuparin, and their glycosides initially increased, then decreased over time. The Noraucuparin content reached its highest (225.76 μg·g−1 at 18 h after treatment, 6 hours earlier than that of Noraucuparin 5-O-β-d-glucopyranoside. The content of 2′-Hydroxyaucuparin reached its highest (422.75 μg·g−1 at 30 h after treatment, also earlier than that of its glycoside. The understanding of phytoalexin metabolism in this study may provide a basis for improving Maloideae resistance to pathogens.

  9. Polychlorinated biphenyls-induced alterations of thyroid hormone homeostasis and brain development in the rat.

    NARCIS (Netherlands)

    Morse, D.C.

    1995-01-01

    IntroductionThe 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 be in part responsibl

  10. Modelling the impact of room temperature on concentrations of polychlorinated biphenyls (PCBs) in indoor air

    DEFF Research Database (Denmark)

    Lyng, Nadja; Clausen, Per Axel; Lundsgaard, Claus;

    2016-01-01

    Buildings contaminated with polychlorinated biphenyls (PCBs) are a health concern for the building occupants. Inhalation exposure is linked to indoor air concentrations of PCBs, which are known to be affected by indoor temperatures. In this study, a highly PCB contaminated room was heated to six ...

  11. Effects of sedimentary soot-like materials on bioaccumulation and sorption of polychlorinated biphenyls

    NARCIS (Netherlands)

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

    2004-01-01

    Bioaccumulation of hydrophobic organic chemicals from sediments containing soot or sootlike materials has been hypothesized to be limited by strong sorption of the chemicals to the soot matrixes. To test this hypothesis, we quantified bioaccumulation of 11 polychlorinated biphenyls (PCBs) into the a

  12. An efficient synthesis, X-ray and spectral characterization of biphenyl derivatives

    Indian Academy of Sciences (India)

    Ravindra R Kamble; Dharesh B Biradar; Gangadhar Y Meti; Tasneem Taj; Tegginamath Gireesh; Imthiyaz Ahmed M Khazi; Sundar T Vaidyanathan; Raju Mohandoss; Balasubramanian Sridhar; Viraraghav Parthasarathi

    2011-07-01

    Derivatives of 1,3-thiazolidin-2,4-dione appended to biphenyl ring viz., 7-9, 16-18 were prepared. The newly synthesized compounds were confirmed by IR, NMR (1H and 13C) MS and elemental analyses. Single crystal X-ray diffraction study was carried out for one of the final compounds 9.

  13. 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...

  14. Assessment of polychlorinated biphenyls and organochlorine pesticides in water samples from the Yamuna River

    OpenAIRE

    Bhupander Kumar; Satish Kumar Singh; Meenu Mishra; Sanjay Kumar; Chandra Shekhar Sharma

    2012-01-01

    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 ...

  15. 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

    1998-01-01

    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. 118

  16. EXPRESSION AND POST-TRANSLATIONAL MODIFICATION OF HUMAN 4-HYDROXY-PHENYLPYRUVATE DIOXYGENASE

    DEFF Research Database (Denmark)

    Aarenstrup, Lene; Falch, Anne-Marie; Jakobsen, Kirsten K.;

    2002-01-01

    12q24¿qter. In the present study high-resolution chromosome mapping localized the HPD gene to 12q24.31. DNase I footprinting, revealed that four regions of the HPD promoter were protected by rat liver nuclear proteins. Computer-assisted analyses suggested that these elements might bind Sp1/AP2, HNF4...... provided evidence that HPD is subject to phosphorylation, and furthermore, allowed mapping of the HPD protein in the human keratinocyte 2D database....

  17. Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization-induced configuration transformation.

    Science.gov (United States)

    Wang, Limin; Cheng, Senxiang; Chen, Rongfeng; Chang, Junbiao

    2010-08-01

    Axially chiral biphenyls such as (M,S)-3k have been conveniently obtained by crystallization of their diastereomeric mixtures, which were synthesized from racemic 4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2-carboxylester-2'-carboxyl-biphenyls 4 and chiral amino alcohols (R)-alaninol, (S)-alaninol, (S)-valinol, and (S)-phenylalaninol. A crystallization-induced configuration transformation of the biphenyls was thus achieved. It was found that amide formation of an (S)-valinol or (S)-phenylalaninol at the 2'-position of the biphenyl usually induced the deposition of crystals with the (M)-configuration from ethanol in yields higher than 50%. The absolute configurations (ACs) of two crystalline biphenyls have been determined by X-ray crystallographic analysis. The ACs of nine biphenyls have been assigned based on their CD spectra. Further, stability investigation of these axially chiral biphenyls revealed that the ACs could revert upon redissolution. The energy barrier to epimerization between (P,R)-3b and (M,R)-3b was measured as DeltaG(#) = 21.45 kcal/mol and the half-life in ethanol at 301 K was 17.1 h. PMID:20623583

  18. 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

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

    Science.gov (United States)

    Cheung, Michael B.; Sampayo-Escobar, Viviana; Green, Ryan; Moore, Martin L.; Mohapatra, Subhra; Mohapatra, Shyam S.

    2016-01-01

    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. PMID:27695127

  20. Structural Basis for Substrate and Oxygen Activation in Homoprotocatechuate 2,3-Dioxygenase: Roles of Conserved Active Site Histidine 200.

    Science.gov (United States)

    Kovaleva, Elena G; Rogers, Melanie S; Lipscomb, John D

    2015-09-01

    Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady-state kinetics, pH dependence, and X-ray crystal structures of the FeHPCD position 200 variants His200Asn, His200Gln, and His200Glu alone and in complex with three catecholic substrates (homoprotocatechuate, 4-sulfonylcatechol, and 4-nitrocatechol) possessing substituents with different inductive capacity. Structures determined at 1.35-1.75 Å resolution show that there is essentially no change in overall active site architecture or substrate binding mode for these variants when compared to the structures of the wild-type enzyme and its analogous complexes. This shows that the maximal 50-fold decrease in kcat for ring cleavage, the dramatic changes in pH dependence, and the switch from ring cleavage to ring oxidation of 4-nitrocatechol by the FeHPCD variants can be attributed specifically to the properties of the altered second-sphere residue and the substrate. The results suggest that proton transfer is necessary for catalysis, and that it occurs most efficiently when the substrate provides the proton and His200 serves as a catalyst. However, in the absence of an available substrate proton, a defined proton-transfer pathway in the protein can be utilized. Changes in the steric bulk and charge of the residue at position 200 appear to be capable of altering the rate-limiting step in catalysis and, perhaps, the nature of the reactive species. PMID:26267790

  1. The cystine/glutamate antiporter regulates indoleamine 2,3-dioxygenase protein levels and enzymatic activity in human dendritic cells.

    Science.gov (United States)

    Mattox, Mildred L; D'Angelo, June A; Grimes, Zachary M; Fiebiger, Edda; Dickinson, Bonny L

    2012-11-30

    Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the tryptophan-catabolizing pathway and a key regulator of peripheral immune tolerance. As the suppressive effects of IDO are predominantly mediated by dendritic cells (DCs) and IDO-competent DCs promote long-term immunologic tolerance, a detailed understanding of how IDO expression and activity is regulated in these cells is central to the rational design of therapies to induce robust immune tolerance. We previously reported that the cystine/glutamate antiporter modulates the functional expression of IDO in human monocyte-derived DCs. Specifically, we showed that blocking antiporter uptake of cystine significantly increased both IDO mRNA and IDO enzymatic activity and that this correlated with impaired DC presentation of exogenous antigen to T cells via MHC class II and the cross-presentation pathway. The antiporter regulates intracellular and extracellular redox by transporting cystine into the cell in exchange for glutamate. Intracellular cystine is reduced to cysteine to support biosynthesis of the major cellular antioxidant glutathione and cysteine is exported from the cell where it functions as an extracellular antioxidant. Here we show that antiporter control of IDO expression in DCs is reversible, independent of interferon-γ, regulated by redox, and requires active protein synthesis. These findings highlight a role for antiporter regulation of cellular redox as a critical control point for modulating IDO expression and activity in DCs. Thus, systemic disease and aging, processes that perturb redox homeostasis, may adversely affect immunity by promoting the generation of IDO-competent DCs.

  2. Structural Basis for Substrate and Oxygen Activation in Homoprotocatechuate 2,3-Dioxygenase: Roles of Conserved Active Site Histidine-200

    Science.gov (United States)

    Kovaleva, Elena G.; Rogers, Melanie S.; Lipscomb, John D.

    2015-01-01

    Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady state kinetics, pH dependence, and X-ray crystal structures of the FeHPCD position 200 variants His200Asn, His200Gln, and His200Glu alone and in complex with three catecholic substrates (homoprotocatechuate, 4-sulfonylcatechol, and 4-nitrocatechol) possessing substituents with different inductive capacity. Structures solved at 1.35 –1.75 Å resolution show that there is essentially no change in overall active site architecture or substrate binding mode for these variants when compared to the structures of the wild type enzyme and its analogous complexes. This shows that the maximal 50-fold decrease in kcat for ring cleavage, the dramatic changes in pH dependence, and the switch from ring cleavage to ring oxidation of 4-nitrocatechol by the FeHPCD variants can be attributed specifically to the properties of the altered second sphere residue and the substrate. The results suggest that proton transfer is necessary for catalysis, and that it occurs most efficiently when the substrate provides the proton and His200 serves as a catalyst. However, in the absence of an available substrate proton, a defined proton-transfer pathway in the protein can be utilized. Changes in steric bulk and charge of the residue at position 200 appear capable of altering the rate-limiting step in catalysis, and perhaps, the nature of the reactive species. PMID:26267790

  3. Structural Basis for Substrate and Oxygen Activation in Homoprotocatechuate 2,3-Dioxygenase: Roles of Conserved Active Site Histidine 200.

    Science.gov (United States)

    Kovaleva, Elena G; Rogers, Melanie S; Lipscomb, John D

    2015-09-01

    Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady-state kinetics, pH dependence, and X-ray crystal structures of the FeHPCD position 200 variants His200Asn, His200Gln, and His200Glu alone and in complex with three catecholic substrates (homoprotocatechuate, 4-sulfonylcatechol, and 4-nitrocatechol) possessing substituents with different inductive capacity. Structures determined at 1.35-1.75 Å resolution show that there is essentially no change in overall active site architecture or substrate binding mode for these variants when compared to the structures of the wild-type enzyme and its analogous complexes. This shows that the maximal 50-fold decrease in kcat for ring cleavage, the dramatic changes in pH dependence, and the switch from ring cleavage to ring oxidation of 4-nitrocatechol by the FeHPCD variants can be attributed specifically to the properties of the altered second-sphere residue and the substrate. The results suggest that proton transfer is necessary for catalysis, and that it occurs most efficiently when the substrate provides the proton and His200 serves as a catalyst. However, in the absence of an available substrate proton, a defined proton-transfer pathway in the protein can be utilized. Changes in the steric bulk and charge of the residue at position 200 appear to be capable of altering the rate-limiting step in catalysis and, perhaps, the nature of the reactive species.

  4. 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

  5. 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.

  6. Draft Genome Sequence of Polychlorinated Biphenyl-Dechlorinating Dehalococcoides mccartyi Strain SG1, Which Carries a Circular Putative Plasmid

    OpenAIRE

    Wang, Shanquan; Chng, Kern Rei; Wu, Chen; Wilm, Andreas; Nagarajan, Niranjan; HE, Jianzhong

    2014-01-01

    Dehalococcoides mccartyi strain SG1, isolated from digester sludge, dechlorinates polychlorinated biphenyls (PCBs) to lower congeners. Here we report the draft genome sequence of SG1, which carries a 22.65 kbp circular putative plasmid.

  7. Environmental exposure to polychlorinated biphenyls (PCBs) and dioxins : Consequences for longterm neurological and cognitive development of the child lactation

    NARCIS (Netherlands)

    Boersma, ER; Lanting, Caren; Koletzko, B; Michaelsen, KF; Hernell, O

    2000-01-01

    Polychlorinated biphenyls (PCBs) and dioxins are environmental pollutants. 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 developmental neurotoxicity, we investigated

  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...

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

    International Nuclear Information System (INIS)

    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

  10. Long-lasting Disease Stabilization in the Absence of Toxicity in Metastatic Lung Cancer Patients Vaccinated with an Epitope Derived from Indoleamine 2,3 Dioxygenase

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg; Engell-Noerregaard, Lotte; Ellebaek, Eva;

    2014-01-01

    PURPOSE: To investigate targeting of indoleamine 2,3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In a clinical phase I study, we treated 15 HLA-A2-positive patients with stage III...... significant improved OS (P = 0.03) when compared with the group of patients excluded because of HLA-A2 negativity. IDO-specific CD8(+) T-cell immunity was demonstrated by IFN-γ Elispot and Tetramer staining. Fluorescence-activated cell sorting analyses demonstrated a significant reduction of the Treg...

  11. Polychlorinated biphenyls, cytochrome P450 1A1 (CYP1A1) polymorphisms, and breast cancer risk among African American women and white women in North Carolina: a population-based case-control study

    OpenAIRE

    Li, Yu; Millikan, Robert C.; Douglas A Bell; Cui, Lisa; Tse, Chiu-Kit J; Newman, Beth; Conway, Kathleen

    2004-01-01

    Introduction Epidemiologic studies have not shown a strong relationship between blood levels of polychlorinated biphenyls (PCBs) and breast cancer risk. However, two recent studies showed a stronger association among postmenopausal white women with the inducible M2 polymorphism in the cytochrome P450 1A1 (CYP1A1) gene. Methods In a population-based case-control study, we evaluated breast cancer risk in relation to PCBs and the CYP1A1 polymorphisms M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C),...

  12. Identification of PAHX, a Refsum disease gene.

    Science.gov (United States)

    Mihalik, S J; Morrell, J C; Kim, D; Sacksteder, K A; Watkins, P A; Gould, S J

    1997-10-01

    Refsum disease is an autosomal recessive disorder characterized by retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia and increased cerebrospinal fluid protein. Biochemically, the disorder is defined by two related properties: pronounced accumulation of phytanic acid and selective loss of the peroxisomal dioxygenase required for alpha-hydroxylation of phytanoyl-CoA2. Decreased phytanic-acid oxidation is also observed in human cells lacking PEX7, the receptor for the type-2 peroxisomal targetting signal (PTS2; refs 3,4), suggesting that the enzyme defective in Refsum disease is targetted to peroxisomes by a PTS2. We initially identified the human PAHX and mouse Pahx genes as expressed sequence tags (ESTs) capable of encoding PTS2 proteins. Human PAHX is targetted to peroxisomes, requires the PTS2 receptor for peroxisomal localization, interacts with the PTS2 receptor in the yeast two-hybrid assay and has intrinsic phytanoyl-CoA alpha-hydroxylase activity that requires the dioxygenase cofactor iron and cosubstrate 2-oxoglutarate. Radiation hybrid data place PAHX on chromosome 10 between the markers D10S249 and D10S466, a region previously implicated in Refsum disease by homozygosity mapping. We find that both Refsum disease patients examined are homozygous for inactivating mutations in PAHX, demonstrating that mutations in PAHX can cause Refsum disease.

  13. Rapid Detection of Polychlorinated Biphenyls at Trace Levels in Real Environmental Samples by Surface-Enhanced Raman Scattering

    OpenAIRE

    Zhengjun Zhang; Yu Huang; Zhengcao Li; Xian Zhang; Qin Zhou

    2011-01-01

    Detection of trace levels of persistent pollutants in the environment is difficult but significant. Organic pollutant homologues, due to their similar physical and chemical properties, are even more difficult to distinguish, especially in trace amounts. We report here a simple method to detect polychlorinated biphenyls (PCBs) in soil and distilled spirit samples by the surface-enhanced Raman scattering technique using Ag nanorod arrays as substrates. By this method, polychlorinated biphenyls ...

  14. A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2'-hydroxylase activity (C2'H): a missing step in the synthesis of umbelliferone in plants.

    Science.gov (United States)

    Vialart, Guilhem; Hehn, Alain; Olry, Alexandre; Ito, Kyoko; Krieger, Celia; Larbat, Romain; Paris, Cedric; Shimizu, Bun-Ichi; Sugimoto, Yukihiro; Mizutani, Masaharu; Bourgaud, Frederic

    2012-05-01

    Coumarins are important compounds that contribute to the adaptation of plants to biotic or abiotic stresses. Among coumarins, umbelliferone occupies a pivotal position in the plant phenylpropanoid network. Previous studies indicated that umbelliferone is derived from the ortho-hydroxylation of p-coumaric acid by an unknown biochemical step to yield 2,4-dihydroxycinnamic acid, which then undergoes spontaneous lactonization. Based on a recent report of a gene encoding a 2-oxoglutarate-dependent dioxygenase from Arabidopsis thaliana that exhibited feruloyl CoA 6'-hydroxylase activity (Bourgaud et al., 2006), we combined a bioinformatic approach and a cDNA library screen to identify an orthologous ORF (Genbank accession number JF799117) from Ruta graveolens L. This ORF shares 59% amino acid identity with feruloyl CoA 6'-hydroxylase, was functionally expressed in Escherichia coli, and converted feruloyl CoA into scopoletin and p-coumaroyl CoA into umbelliferone with equal activity. Its bi-functionality was further confirmed in planta: transient expression of JF799117 in Nicotiana benthamiana yielded plants with leaves containing high levels of umbelliferone and scopoletin when compared to control plants, which contained barely detectable traces of these compounds. The expression of JF799117 was also tightly correlated to the amount of umbelliferone that was found in UV-elicited R. graveolens leaves. Therefore, JF799117 encodes a p-coumaroyl CoA 2'-hydroxylase in R. graveolens, which represents a previously uncharacterized step in the synthesis of umbelliferone in plants. Psoralen, which is an important furanocoumarin in R. graveolens, was found to be a competitive inhibitor of the enzyme, and it may exert this effect through negative feedback on the enzyme at an upstream position in the pathway.

  15. Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males

    Science.gov (United States)

    Gallo, Mia V.; Deane, Glenn D.; Nelder, Kyrie R.; DeCaprio, Anthony P.; Jacobs, Agnes

    2013-01-01

    Background: Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized. Objectives: In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 to DeCaprio AP, Jacobs A; Akwesasne Task Force on the Environment. 2014. Relationships of polychlorinated biphenyls and dichlorodiphenyldichloroethylene (p,p´-DDE) with testosterone levels in adolescent males. Environ Health Perspect 122:304–309; http://dx.doi.org/10.1289/ehp.1205984 PMID:24398050

  16. Torsion sensitivity in NMR of aligned molecules: study on various substituted biphenyls.

    Science.gov (United States)

    Sahakyan, Aleksandr B; Shahkhatuni, Aleksan G; Shahkhatuni, Astghik A; Panosyan, Henry A

    2008-02-01

    To estimate the torsion sensitivity of dipolar coupling, biphenylic molecules were chosen as probes due to their relatively simple structure and the surprisingly high ambiguity of the only flexible parameter-the interring torsion angle. Solution structures of 4,4'-dibromobiphenyl and 4,4'-diiodobiphenyl are reported for the first time in two liquid crystals I52 and ZLI 1695. The comparison of NMR structures of various para-substituted biphenyls (BPs), calculated by the additive potential maximum entropy (APME) approach, shows that the small spread of torsion angle values in case of different solvents and para-substituents is in good agreement with theoretical expectations from hybrid density functional theory (DFT) methods. Furthermore, the real structural changes of interring torsion and the prevalence of solvent effects over para-halosubstitution can be correctly revealed from these small fluctuations. PMID:18095265

  17. Synthesis and biological evaluation of nitric oxide-releasing sixalkoxyl biphenyl derivatives as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Xiang Wen Kong; Yi Hua Zhang; Li Dai; Hui Ji; Yi Sheng Lai; Si Xun Peng

    2008-01-01

    A series of novel nitric oxide-donating sixalkoxyl biphenyl derivatives (14a-i)were synthesized by coupling furoxan with alkoxyl biphenyl skeleton using amino acids as the spacers,and their cytotoxicity against HepG2 cells in vitro were evaluated by MTr method.It was found that 14c,14d,14f,14i,14j and 14k showed more potent cytotoxic activities than control 5-fluorouracil.NO release assay of target compounds indicated that the maximum amount of NO released by most active compounds 14c and 14j was about 6 x 10-2μmol/L,whereas 14a and 14h with very weak activity only released NO of 1 x 10-μmol/L.

  18. Studies on the transformation of selected polychlorinated biphenyl congeners by Pseudomonas strain LB 400

    International Nuclear Information System (INIS)

    Some of the main factors influencing the degradation of certain PCB congeners by resting cells of Pseudomonas strain LB 400 were characterized. The significance of the carbon source used for growth was studied by comparison of rates of PCB transformation by cells grown on biphenyl and other carbon sources. PCB transformation was studied in resting cells grown on glucose and glycerol. Supplementation of the degradation medium with biphenyl significantly decreased the rate of PCB congener transformation. The presence of glycerol or glucose did not affect PCB transformation rates. The study showed that in the treatment of contaminated soils, resting cells lose their viability and PCB transforming ability, such that, in the absence of a growth substrate, soil would have to be reinoculated to maintain PCB biodegradation. 15 refs., 2 tabs., 5 figs

  19. 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.

  20. Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis

    OpenAIRE

    Arsenescu, Violeta; Arsenescu, Razvan I; King, Victoria; Swanson, Hollie; Cassis, Lisa A.

    2008-01-01

    Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effect...

  1. Plant compounds that induce polychlorinated biphenyl biodegradation by Arthrobacter sp. strain B1B.

    OpenAIRE

    Gilbert, E S; Crowley, D. E.

    1997-01-01

    Plant compounds that induced Arthrobacter sp. strain B1B to cometabolize polychlorinated biphenyls (PCBs) were identified by a screening assay based on the formation of a 4,4'-dichlorobiphenyl ring fission product. A chemical component of spearmint (Mentha spicata), l-carvone, induced Arthrobacter sp. strain B1B to cometabolize Aroclor 1242, resulting in significant degradation of 26 peaks in the mixture, including selected tetra- and pentachlorobiphenyls. Evidence for PCB biodegradation incl...

  2. Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males

    OpenAIRE

    Schell, Lawrence M.; Gallo, Mia V.; Deane, Glenn D.; Nelder, Kyrie R.; DeCaprio, Anthony P; Jacobs, Agnes; ,

    2013-01-01

    Background: Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized. Objectives: In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 ...

  3. Polychlorinated biphenyls in serum of the Siberian Yupik people from St. Lawrence Island, Alaska

    OpenAIRE

    Carpenter, David O.; DeCaprio, Anthony P; O’Hehir, David; Akhtar, Farooq; Johnson, Glenn.; Scrudato, Ronald J.; Apatiki, Lucy; Kava, Jane; Gologergen, Jesse; Miller, Pamela K.; Eckstein, Lorraine

    2005-01-01

    Objectives. To determine serum levels of polychlorinated biphenyls (PCBs) in Siberian Yupik adults from St. Lawrence Island, Alaska, and to determine the relative contribution of atmospheric transport of PCBs and local contamination to body burdens. Study Design. Siberian Yupiks of various ages were recruited from three populations: residents of the village of Gambell, residents of the village of Savoonga who did not have family hunting camps near the Northeast Cape (NEC), a Formerly Used Def...

  4. Plasma Levels of Polychlorinated Biphenyls, Non-Hodgkin Lymphoma, and Causation

    OpenAIRE

    Kohles, Sean S.; Freeman, Michael D

    2012-01-01

    Polychlorinated biphenyls (PCBs) are synthetic chlorinated hydrocarbons that have extensively polluted the environment and bioaccumulated in the food chain. PCBs have been deemed to be probable carcinogens by the Environmental Protection Agency, and exposure to high levels of PCBs has been consistently linked to increased risk of non-Hodgkin lymphoma (NHL). In the present article we present a forensic epidemiologic evaluation of the causal relationship between NHL and elevated PCB levels via ...

  5. Ship-source pollution by polychlorinated biphenyls and brominated flame retardants

    OpenAIRE

    ČULIN, Jelena; Bielić, Toni

    2015-01-01

    Polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) are groups of anthropogenic contaminants that have been routinely used in many applications for several decades. Prior to the discovery of their detrimental health effects and subsequent implementation of regulatory measures they were widely applied in shipbuilding. They are still found onboard active and inactive ships and pose a risk to human and environment. Therefore, it is important to continue to carry out preven...

  6. Effects of polychlorinated biphenyls on maternal odor conditioning in rat pups

    OpenAIRE

    Cromwell, Howard C.; Johnson, Asia; McKnight, Logan; Horinek, Maegan; Asbrock, Christina; Burt, Shannon; Jolous-Jamshidi, Banafsheh; Meserve, Lee A.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are pervasive environmental contaminants that can have damaging effects on physiologic, motoric and cognitive function. Results from studies on PCBs and behavior have shown that exposure can alter learning and memory processes and that these shifts in cognitive abilities can be related to changes in hormonal and neural function. Little experimentation has been done on the impact of exposure to PCBs on social and emotional development. Previous work has shown t...

  7. Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: a birth cohort study

    OpenAIRE

    Park Hye-Youn; Hertz-Picciotto Irva; Sovcikova Eva; Kocan Anton; Drobna Beata; Trnovec Tomas

    2010-01-01

    Abstract Background Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal ex...

  8. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls

    OpenAIRE

    Naveau, Elise; Pinson, Anneline; GERARD, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, Robert Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell...

  9. Polychlorinated Biphenyls and Leukocyte Telomere Length: An Analysis of NHANES 1999–2002

    OpenAIRE

    Franco Scinicariello; Buser, Melanie C.

    2015-01-01

    Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran wi...

  10. Effects of Developmental Exposure to Polychlorinated Biphenyls and/or Polybrominated Diphenyl Ethers on Cochlear Function

    OpenAIRE

    Poon, Emily; Powers, Brian E.; McAlonan, Ruth M.; Ferguson, Duncan C.; Schantz, Susan L

    2011-01-01

    Developmental exposure to polychlorinated biphenyls (PCBs) causes hearing loss that may be due to reduced thyroxine during cochlear development. Polybrominated diphenyl ethers (PBDEs) are structurally similar to PCBs and reduce thyroxine. This study utilized an environmental PCB mixture and a commercial PBDE mixture, DE-71, that represents the PBDEs found in humans to assess the potential for additive effects of PCBs and PBDEs on cochlear function. Female Long-Evans rats were dosed with corn ...

  11. Tissue damage after acute intoxication by polychlorinated biphenyls (PCBs) in cockroaches Blattella germanica

    OpenAIRE

    Lambiase, S; Zhang, Y.; P. Morbini; M. Fasola

    2009-01-01

    It is common knowledge that polychlorinated biphenyls (PCBs) represent a serious threat to the health of both vertebrates and invertebrates. As far as the former are concerned, especially as regards human beings, a broad literature describes the direct and indirect effects induced by the PCBs on their systems and organs. Among invertebrates, the information available is mostly related to arthropods and is, however, very scarce. The aim of this work was to evaluate the effects of polychlorinat...

  12. A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans

    OpenAIRE

    Eveline Dirinck; Dirtu, Alin C.; Govindan Malarvannan; Adrian Covaci; Jorens, Philippe G.; Van Gaal, Luc F.

    2016-01-01

    Background: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs) interfere with thyroid hormone action both in vitro and in vivo. However, epidemiologic studies on the link between PCB exposure and thyroid function have yielded discordant results, while very few data are available for HO-PCBs. Objectives: Our study aimed at investigating the relationship between clinically available markers of thyroid metabolism and serum levels of both PCBs and HO-PCBs. Subjects and ...

  13. Effects of Chinese domestic polychlorinated biphenyls (PCBs) on gonadal differentiation in Xenopus laevis.

    OpenAIRE

    Qin, Zhan-Fen; Zhou, Jing-Ming; Chu, Shao-Gang; Xu, Xiao-Bai

    2003-01-01

    To determine whether polychlorinated biphenyls (PCBs) influence gonadal differentiation in Xenopus laevis, tadpoles were exposed to two Chinese domestic PCBs (PCB3 and PCB5 from Nieuwkoop and Faber stage 46/47 to complete metamorphosis. Gonads were characterized using a dissecting microscope. The control X. laevis had normal ovaries or testes in gross morphology, whereas obviously abnormal testes including ovotestes were found in PCB3- and PCB5-exposed groups. Ovotestes were characterized by ...

  14. Prenatal Exposure to Polychlorinated Biphenyls and Postnatal Growth: A Structural Analysis

    OpenAIRE

    Lamb, Matthew R.; Taylor, Sylvia; Liu, Xinhua; Wolff, Mary S.; Borrell, Luisa; Matte, Thomas D; Susser, Ezra S.; Factor-Litvak, Pam

    2005-01-01

    Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have kno...

  15. Biomonitoring and Elimination of Perfluorinated Compounds and Polychlorinated Biphenyls through Perspiration: Blood, Urine, and Sweat Study

    OpenAIRE

    Stephen J. Genuis; Sanjay Beesoon; Detlef Birkholz

    2013-01-01

    Perfluorinated compounds (PFCs) are man-made organofluorine chemicals manufactured and marketed for their stain-resistant properties. Polychlorinated biphenyls (PCBs) are anthropogenic organochlorine compounds previously used in various industrial and chemical applications prior to being banned in the Western world in the 1970s. Both PFCs and PCBs are persistent contaminants within the human organism and both have been linked to adverse health sequelae. Data is lacking on effective means to f...

  16. Polychlorinated biphenyls fractioning assessment in aqueous bioremediation assy with phanerochaete chrysosporium

    OpenAIRE

    Sangely, Matthieu; Sablayrolles, Caroline; Vialle, Claire; Strehaiano, Pierre; Thannberger, Laurent; Vignoles, Mireille

    2009-01-01

    Thanks to growing environmental concerns in public opinion, bioremediation processes are more and more used to decontaminate soils from organic compounds. Polychlorinated biphenyls (PCBs) are known to be world wide spread persistent organic pollutants (POPs). The white rot fungus Phanerochaete chrysosporium is able to degrade PCBs in water, and soil As POPs, PCBs can also be adsorbed onto organic matter, such as Phanerochaete chrysosporium mycelium. This study aims at estimating the fractioni...

  17. Oculodermatological findings in workers with occupational exposure to polychlorinated biphenyls (PCBs).

    OpenAIRE

    Fischbein, A; Rizzo, J N; Solomon, S J; Wolff, M S

    1985-01-01

    Oculodermatological findings, such as hypersecretion of the Meibomian glands, swelling of the upper eyelids and hyperpigmentation of the conjunctivae are considered typical of "PCB poisoning." They were common clinical manifestations of yusho and yu-cheng, two epidemics in Japan and Taiwan caused by the ingestion of rice cooking oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans. To investigate the prevalence of such abnormalities in a population with lon...

  18. Prenatal and postnatal exposure to polychlorinated biphenyls and child size at 24 months of age

    OpenAIRE

    Jackson, Leila W.; Lynch, Courtney D.; Kostyniak, Paul J.; McGuinness, Bridget M; Buck Louis, Germaine M.

    2009-01-01

    Research suggests that exposure to polychlorinated biphenyls (PCBs) may result in decreased child growth, though the critical window(s) are unclear. We investigated the association between PCBs and child size at age 24 months (n=44). PCBs were measured in 1st trimester serum, breast milk, and child serum at age 24 months, and dichotomized at the median. Age- and gender-specific z-scores were calculated for anthropometric measures. Using linear regression, we observed no significant changes in...

  19. Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development

    OpenAIRE

    Huisman, Martijn; Koopman-Esseboom, Corine; Fidler, Vaclav; Hadders-Algra, Mijna; Paauw, Cornelis; Tuinstra, L.G.M.Th.; Weisglas-Kuperus, Nynke; Sauer, Pieter; Touwen, Bert C.; Boersma, Eric

    1995-01-01

    textabstractPolychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs)) are widespread environmental contaminants which are neurotoxic in animals. Perinatal exposure to PCBs, PCDDs, and PCDFs occurs prenatally via the placenta and postnatally via breast milk. To investigate whether such an exposure affects the neonatal neurological condition, the neurological optimality of 418 Dutch newborns was evaluated with the Prechtl neurological ex...

  20. 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...

  1. Evaluating Health Risks from Inhaled Polychlorinated Biphenyls: Research Needs for Addressing Uncertainty

    OpenAIRE

    Lehmann, Geniece M.; Christensen, Krista; Maddaloni, Mark; Phillips, Linda J.

    2014-01-01

    Background: Indoor air concentrations of polychlorinated biphenyls (PCBs) in some buildings are one or more orders of magnitude higher than background levels. In response to this, efforts have been made to assess the potential health risk posed by inhaled PCBs. These efforts are hindered by uncertainties related to the characterization and assessment of source, exposure, and exposure-response. Objectives: We briefly describe some common sources of PCBs in indoor air and estimate the contribut...

  2. Rhizospere Redox Cycling and Implications for Rhizosphere Biotransformation of Selected Polychlorinated Biphenyl (PCB) Congeners

    OpenAIRE

    Meggo, Richard E.; Schnoor, Jerald L.

    2013-01-01

    Theoretically, sequential cycles of dechlorination followed by aerobic bio-oxidation are desirable to achieve complete degradation of a mixture of higher and lower chlorinated PCBs. In this research, soil was artificially contaminated with polychlorinated biphenyls (PCBs) in mixture and as single congeners, aged, and planted with two different plant species. Alternating redox cycles were created in the root zone of plants by flooding and draining the soil. Over 32 weeks, switchgrass (Panicum ...

  3. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children.

    OpenAIRE

    Weisglas-Kuperus, Nynke; Patandin, Svati; Berbers, G A; Sas, Theo; Sauer, Pieter; Hooijkaas, Herbert; Mulder, Paul

    2000-01-01

    textabstractPrenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to PCBs and dioxins is associated with the prevalence of infectious or allergic diseases and humoral immunity at preschool age. The total study group consisted of 207 healthy mother-infant pairs. We estimated prenatal exposure to P...

  4. CONTAMINATION OF POLYCHLORINATED BIPHENYLS IN FISHES LEADING TO TOXICITY IN FISH CONSUMING POPULATION

    OpenAIRE

    Govind Pandey; Madhuri S.; A.B. Shrivastav

    2012-01-01

    The pollution of rivers and streams with chemical contaminants has become one of the most critical environmental problems. Similar to humans and other species of animals, fish have also been found to be polluted with a large number of pollutants/contaminants. Unintentionally added chemicals causing fish toxicity include organochlorine pesticides, polychlorinated biphenyls (PCBs) and other persistent chemicals in feed, chemicals in construction materials, and metabolites and degradation produc...

  5. (Biphenyl-2-yl)bromidobis(2-methyl-tetra-hydro-furan-κO)magnesium(II).

    Science.gov (United States)

    Nordschild, Simon; Wohlgemuth, D; Bolte, Michael

    2009-01-01

    In the title Grignard reagent, [MgBr(C(12)H(9))(C(5)H(10)O)(2)], the Mg centre adopts a distorted tetra-hedral MgCO(2)Br arrangement. The dihedral angle between the two aromatic rings of the biphenyl residue is 44.00 (14)°. Each mol-ecule incorporates one R- and one S-configured 2-methyl-tetra-hydro-furan mol-ecule. PMID:21583743

  6. Polychlorinated biphenyls-induced alterations of thyroid hormone homeostasis and brain development in the rat.

    OpenAIRE

    Morse, D.C.

    1995-01-01

    IntroductionThe 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 be in part responsible for the developmental neurotoxicity of these compounds in humans (Rogan et al. 1986). This is a logical hypothesis, given the well-described effects of PCBs on plasma thyroid hormone levels in adult animals, and ...

  7. Effect of Chemical Structure on the Isobaric and Isochoric Fragility in Polychlorinated Biphenyls

    OpenAIRE

    Roland, C. M.; Casalini, R.

    2005-01-01

    Pressure-volume-temperature data, along with dielectric relaxation measurements, are reported for a series of polychlorinated biphenyls (PCB), differing in the number of chlorine atoms on their phenyl rings. Analysis of the results reveals that with increasing chlorine content, the relaxation times of the PCB become governed to a greater degree by density, rho, relative to the effect of temperature, T. This result is consistent with the respective magnitudes of the scaling exponent, gamma, yi...

  8. Effects of polychlorinated biphenyls and environmental biotransformation products on aquatic nitrification.

    OpenAIRE

    Sayler, G S; Shiaris, M. P.; Beck, W.; Held, S.

    1982-01-01

    The effects of polychlorinated biphenyls (PCBs) on nitrification were examined for pure cultures and natural reservoir samples. PCBs at concentrations greater than 10 microgram liter-1 inhibited nitrification, principally ammonium oxidation, in one of two natural reservoir environments. However, this inhibition could not be reproduced in pure high-cell-density cultures or in previously contaminated reservoir waters. A PCB environmental biotransformation product, p-chlorophenylglyoxylic acid, ...

  9. Stimulatory effects of a microbially dechlorinated polychlorinated biphenyl (PCB) mixture on rat uterine contraction in vitro

    OpenAIRE

    Tsuneta, Taeko; Loch-Caruso, Rita; Quensen, John F.; Boyd, Stephen A.; Hanna, Mona; Grindatti, Carmen

    2008-01-01

    Microbially mediated reductive dechlorination has been advocated as the first part of a two-stage (anaerobic/aerobic) biotreatment process for polychlorinated biphenyls (PCBs) in sediments, and is generally viewed as a detoxication process. However, previous studies suggest that microbial dechlorination increases ability to stimulate uterine contractions compared with the original PCB mixtures. Here, we investigate the composition and uterotonic activity of the commercial PCB mixture Aroclor ...

  10. A stress tensor and QTAIM perspective on the substituent effects of biphenyl subjected to torsion.

    Science.gov (United States)

    Jiajun, D; Maza, J R; Xu, Y; Xu, T; Momen, R; Kirk, S R; Jenkins, S

    2016-10-30

    The Quantum Theory of Atoms in Molecules (QTAIM) defines quantities in 3D space that can be easily obtained from routine quantum chemical calculations. The present investigation shows that local properties can be related quantitatively to measures traditionally connected to experimental data, such as Hammett constants. We consider the specific case of substituted biphenyl to quantify the effects of a torsion φ, 0.0° ≤ φ ≤ 180.0°, of the C-C bond linking the two phenyl rings for C12 H9 -x, where x = N(CH3 )2 , NH2 , CH3 , CHO, CN, NO2, on the entire molecule. QTAIM interpreted Hammett constants, aΔH(rb ) are introduced and constructed using the difference between the H(rb ) value of C12 H9 -x and the C12 H9 -H, biphenyl which is the reference molecule, with a constant of proportionality a. This investigation unexpectedly yields very good or good agreement for the x groups with the Hammett para-, meta-, and ortho-substituent constants and is checked against para-substituted benzene. We then proceed to present the interpreted substituent constants of seven new biphenyl substituent groups, where tabulated Hammett substituent constant values are not available; y = SiH3 , ZnCl, COOCH3 , SO2 NH2 , SO2 OH, COCl, CB3 . Consistency is found for the QTAIM interpreted biphenyl substituent constants of the seven new groups y independently using the stress tensor polarizability Pσ . In addition, a selection of future applications is discussed that highlight the usefulness of this approach. © 2016 Wiley Periodicals, Inc. PMID:27546220

  11. 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.

  12. Field-derived Henry's law constants for polychlorinated biphenyls in oceanic waters

    OpenAIRE

    Gioia, Rosalinda; Dachs, Jordi; Lohmann, Rainer; Jones, Kevin C.; Nizzeto, Luca

    2010-01-01

    Accurate knowledge of Henry's law constants (Kaw) is very important for fate and transport studies of organic chemicals. Here field-derived Kaw values for polychlorinated biphenyl (PCB) congeners (PCBs 28, 49, 52, 118, 138, 149, and 153) were determined in the open Atlantic Ocean, at locations where air and seawater were assumed to be at equilibrium. Field-based Kaw values were derived from air and seawater samples simultaneously collected at these locations, and their relationship with tempe...

  13. Chlororganische Pestizide, polychlorierte Biphenyle und potentiell toxische Schwermetalle in Organproben von Seeadlern und Habichten

    OpenAIRE

    Kenntner, Norbert

    2010-01-01

    In the present study, we examined organs of 145 white-tailed eagles (Haliaeetus albicilla) from Germany and 5 specimen from Austria, as well as 62 northern goshawks (Accipiter gentilis) from different regions of Germany for their organ concentrations of chlorinated pesticides, polychlorinated biphenyls (PCB) and potentially toxic heavy metals. We proved a significant decline of DDT concentrations in livers of 127 white-tailed eagles (WTE) collected between 1990 and 2001. Considering the final...

  14. Hydroxylated and methylsulfonyl polychlorinated biphenyl metabolites in albatrosses from Midway Atoll, North Pacific Ocean

    Energy Technology Data Exchange (ETDEWEB)

    Klasson-Wehler, E.; Bergman, A.; Athanasiadou, M. [Stockholm Univ. (Sweden)] [and others

    1998-08-01

    Concentrations of hydroxylated metabolites of polychlorinated biphenyls (PCBs) (OH-PCBs) and methylsulfonyl metabolites of PCBs (MeSO{sub 2}-PCBs) were determined in plasma and liver of albatrosses collected from the Midway Atoll in the central North Pacific Ocean. The mean total concentrations of OH-PCBs in plasma of Laysan albatrosses (Diomedea immutabilis) and black-footed albatrosses (Diomedea nigripes) were 11.5 and 27.1 ng/g wet weight, respectively. Total concentrations of OH-PCBs were only one- to fivefold less than those of total PCBs. 4-hydroxy-2,2{prime},3,4{prime},5,5{prime},6-heptachlorinated biphenyl and 4-hydroxy-2,2{prime},3,4{prime},5,5{prime}-hexachlorinated biphenyl were the predominant polychlorinated biphenylols, constituting 70 to 90% of the total OH-PCBs. Concentrations of MeSO{sub 2}-PCBs in liver were between 10.6 and 77 ng/g, lipid weight, approximately 250 times less than those of total PCBs. The MeSO{sub 2}-PCBs congeners retained in the liver were dominated by those having the methylsulfonyl group in the 3-position.

  15. Polychlorinated biphenyls in eggs and chlorioallantoic membranes of American alligators (Alligator mississippiensis) from coastal South Carolina

    Energy Technology Data Exchange (ETDEWEB)

    Cobb, G.P.; Wood, P.D. [Clemson Univ., Pendleton, SC (United States); O`Quinn, M. [South Carolina Governor`s School for Science and Mathematics, Hartsville, SC (United States)

    1997-07-01

    Assessing chemical exposure in threatened or endangered wildlife species presents unique analytical problems. Chorioallantoic membranes (CAMs) have been proposed as surrogate tissues for evaluation of polychlorinated biphenyl (PCB) exposure in oviparous species. Research was undertaken to determine the extent of PCB accumulation in alligators (Alligator mississippiensis) at sites along the coast of South Carolina and to evaluate the utility of CAMs as surrogate tissues for determining PCB concentrations in whole alligator eggs. Polychlorinated biphenyls were found in eggs and CAMs of alligators from both sites examined. Concentrations of PCBs were higher in CAMs (p = 0.02) and eggs (p = 0.001) from sites known to contain chlorinated hydrocarbons than from more pristine sites. Total PCBs partitioned predictably (r{sup 2} > 0.59; p < 0.02) between egg and CAM tissues indicating the utility of CAMs to serve as surrogate tissues when comparing total PCB concentrations in whole eggs. Tetrachloro through octachloro biphenyl homologues and total PCBs in CAMs from reference areas were correlated with concentrations of these homologues in eggs. At contaminated sites, total PCB concentrations in CAMs were correlated with total PCB concentrations in eggs.

  16. Toxicity of hydroxylated polychlorinated biphenyls (HO-PCBs) using the bioluminescent assay Microtox(®).

    Science.gov (United States)

    Bhalla, Renu; Tehrani, Rouzbeh; Van Aken, Benoit

    2016-09-01

    Hydroxylated polychlorinated biphenyls (HO-PCBs) are toxic contaminants which are produced in the environment by biological or abiotic oxidation of PCBs. The toxicity of a suite of 23 mono-hydroxylated derivatives of PCBs and 12 parent PCBs was determined using the bacterial bioluminescent assay Microtox(®). All HO-PCBs tested exhibited higher toxicity than the corresponding parent PCB, with effect concentration 50 % (EC50) ranging from 0.07 to 133 mg L(-1). The highest toxicities were recorded with 4-hydroxylated derivatives of di-chlorinated biphenyls (EC50 = 0.07-0.36 mg L(-1)) and 2-hydroxylated derivatives of tri-chlorinated biphenyls carrying a chlorine substituent on the phenolic ring (EC50 = 0.34-0.48 mg L(-1)). The toxicity of HO-PCBs generally decreased when the degree of chlorination increased. Consistently with this observation, a significant positive correlation was measured between toxicity (measured by EC50) and octanol-water partition coefficient (pK ow) for the HO-PCBs under study (Pearson's correlation coefficient, r = 0.74), which may be explained by the lower solubility and bioavailability generally associated with higher hydrophobicity. This study is the first one which assessed the toxicity of a suite of PCBs and HO-PCBs using the bioluminescent assay Microtox(®), showing an inverse correlation between toxicity and hydrophobicity. PMID:27411941

  17. Role of tfdCIDIEIFI and tfdDIICIIEIIFII Gene Modules in Catabolism of 3-Chlorobenzoate by Ralstonia eutropha JMP134(pJP4)

    OpenAIRE

    Pérez-Pantoja, D.; L. Guzmán; Manzano, M.; Pieper, D. H.; González, B.

    2000-01-01

    The enzymes chlorocatechol-1,2-dioxygenase, chloromuconate cycloisomerase, dienelactone hydrolase, and maleylacetate reductase allow Ralstonia eutropha JMP134(pJP4) to degrade chlorocatechols formed during growth in 2,4-dichlorophenoxyacetate or 3-chlorobenzoate (3-CB). There are two gene modules located in plasmid pJP4, tfdCIDIEIFI (module I) and tfdDIICIIEIIFII (module II), putatively encoding these enzymes. To assess the role of both tfd modules in the degradation of chloroaromatics, each ...

  18. Non-chemical proton-dependent steps prior to O2-activation limit Azotobacter vinelandii 3-mercaptopropionic acid dioxygenase (MDO) catalysis.

    Science.gov (United States)

    Crowell, Joshua K; Sardar, Sinjinee; Hossain, Mohammad S; Foss, Frank W; Pierce, Brad S

    2016-08-15

    3-mercaptopropionate dioxygenase from Azotobacter vinelandii (Av MDO) is a non-heme mononuclear iron enzyme that catalyzes the O2-dependent oxidation of 3-mercaptopropionate (3mpa) to produce 3-sulfinopropionic acid (3spa). With one exception, the active site residues of MDO are identical to bacterial cysteine dioxygenase (CDO). Specifically, the CDO Arg-residue (R50) is replaced by Gln (Q67) in MDO. Despite this minor active site perturbation, substrate-specificity of Av MDO is more relaxed as compared to CDO. In order to investigate the relative timing of chemical and non-chemical events in Av MDO catalysis, the pH/D-dependence of steady-state kinetic parameters (kcat and kcat/KM) and viscosity effects are measured using two different substrates [3mpa and l-cysteine (cys)]. The pL-dependent activity of Av MDO in these reactions can be rationalized assuming a diprotic enzyme model in which three ionic forms of the enzyme are present [cationic, E((z+1)); neutral, E(z); and anionic, E((z-1))]. The activities observed for each substrate appear to be dominated by electrostatic interactions within the enzymatic active site. Given the similarity between MDO and the more extensively characterized mammalian CDO, a tentative model for the role of the conserved 'catalytic triad' is proposed. PMID:27311613

  19. 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)

    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 CO2. 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 P212121, with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 Å. The calculated Matthews coefficient (VM = 2.1 Å3 Da−1, 41% solvent content) suggested that the crystal contains two molecules per asymmetric unit

  20. 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

    2016-04-01

    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. PMID:26947423

  1. 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

    2016-04-01

    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.

  2. Spectroscopic and computational studies of NTBC bound to the non-heme iron enzyme (4-hydroxyphenyl)pyruvate dioxygenase: active site contributions to drug inhibition.

    Science.gov (United States)

    Neidig, Michael L; Decker, Andrea; Kavana, Michael; Moran, Graham R; Solomon, Edward I

    2005-12-01

    (4-Hydroxyphenyl)pyruvate dioxygenase (HPPD) is an alpha-keto-acid-dependent dioxygenase which catalyzes the conversion of (4-hydroxyphenyl)pyruvate (HPP) to homogentisate as part of tyrosine catabolism. While several di- and tri-ketone alkaloids are known as inhibitors of HPPD and used commercially as herbicides, one such inhibitor, [2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), has also been used therapeutically to treat type I tyrosinemia and alkaptonuria in humans. To gain further insight into the mechanism of inhibition by NTBC, a combination of CD/MCD spectroscopy and DFT calculations of HPPD/Fe(II)/NTBC has been performed to evaluate the contribution of the Fe(II)-NTBC bonding interaction to the high affinity of this drug for the enzyme. The results indicate that the bonding of NTBC to Fe(II) is very similar to that for HPP, both involving similar pi-backbonding interactions between NTBC/HPP and Fe(II). Combined with the result that the calculated binding energy of NTBC is, in fact, approximately 3 kcal/mol less than that for HPP, the bidentate coordination of NTBC to Fe(II) is not solely responsible for its extremely high affinity for the enzyme. Thus, the pi-stacking interactions between the aromatic rings of NTBC and two phenyalanine residues, as observed in the crystallography of the HPPD/Fe(II)/NTBC complex, appear to be responsible for the observed high affinity of drug binding.

  3. 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.

  4. 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)

    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.

  5. Enantiomer Separation of α-Dimethyl Dicarboxylate Biphenyl and Related Biphenyl Compounds by Normal Phase HPLC on Polysaccharide Based Chiral Stationary Phases

    Institute of Scientific and Technical Information of China (English)

    LIU,Yue-Qi(刘月启); HAN,Xiao-Qian(韩小茜); Qi,Bang-Feng(齐邦峰); LIU,Chun-Hui(柳春辉); LI,Yong-Min(李永民); CHEN,Li-Ren(陈立仁)

    2002-01-01

    Cellulose tris(4-methylphenylcarbamate), amylose tris(3,5-dimethylpphenylcarbamate) and amylose tris (phenylcarbamate)were prepared by the method reported by Okamoto and were coated onto an aminopropylated mesoporous spherical silica gel. These final products were used as chiral stationary phases of high performance liquid chromatography for the eighteen structurally related biphenyl conmpounds. The resolution was made using normal-phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, 2-propanol or 1-butanol). The effects of various aliphatic alcohols in the mobile phase were studied. The structural features of the solutes that influence their k'were discussed. A dominant effect of trifluoroaetic acid on chiral separation of aacidicdic solutes was noted.

  6. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice

    International Nuclear Information System (INIS)

    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.

  7. Polychlorinated biphenyl (PCB) load, lipid reserves and biotransformation activity in migrating Atlantic salmon from River Moerrum, Sweden

    International Nuclear Information System (INIS)

    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

  8. Polychlorinated biphenyls (PCBs) in the frame of the dismantling of nuclear facilities

    International Nuclear Information System (INIS)

    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.

  9. Polycyclic aromatic hydrocarbons (PAH) and polychlorinated biphenyls (PCB) in urban soils of Greater London, UK

    OpenAIRE

    Vane, Christopher H.; Kim, Alexander W.; Beriro, Darren J.; Cave, Mark R.; Knights, Katherine; Moss-Hayes, Vicky; Nathanail, Paul C.

    2014-01-01

    Surface soils from a 19 km2 area in east London, UK were analysed for polycyclic aromatic hydrocarbons (PAH) and polychlorinated biphenyls (PCB) (n = 76). ∑16 PAH ranged from 4 to 67 mg/kg (mean, 18 mg/kg) and ∑50 PAH ranged from 6 to 88 mg/kg (mean, 25 mg/kg). ∑7 PCB ranged from 1 to 750 μg/kg (mean, 22 μg/kg) and ∑tri-hepta PCB ranged 9 to 2600 μg/kg (mean, 120 μg/kg). Compared to other international cities concentrations were similar for PAH but higher for PCB. Normal background concentrat...

  10. Weakly faceted cellular patterns versus growth-induced plastic deformation in thin-sample directional solidification of monoclinic biphenyl.

    Science.gov (United States)

    Börzsönyi, Tamás; Akamatsu, Silvère; Faivre, Gabriel

    2009-11-01

    We present an experimental study of thin-sample directional solidification (T-DS) in impure biphenyl. The platelike growth shape of the monoclinic biphenyl crystals includes two low-mobility (001) facets and four high-mobility {110} facets. Upon T-DS, biphenyl plates oriented with (001) facets parallel to the sample plane can exhibit either a strong growth-induced plastic deformation (GID), or deformation-free weakly faceted (WF) growth patterns. We determine the respective conditions of appearance of these phenomena. GID is shown to be a long-range thermal-stress effect, which disappears when the growth front has a cellular structure. An early triggering of the cellular instability allowed us to avoid GID and study the dynamics of WF patterns as a function of the orientation of the crystal.

  11. trans-Tetraaquabis(nicotinamide-κNcadmium(II biphenyl-4,4′-disulfonate

    Directory of Open Access Journals (Sweden)

    Changlun Shao

    2008-02-01

    Full Text Available In the title compound, [Cd(C6H6N2O2(H2O4](C10H8O6S2, the CdII ion is located on a crystallographic inversion centre. An octahedral coordination geometry is defined by four water molecules in one plane, and two trans N-atom donors of the nicotinamide ligands. The biphenyl-4,4′-disulfonate anion also lies on a crystallographic inversion centre. In the crystal structure, the complex cations are connected to the counter-anions via N—H...O and O—H...O hydrogen bonds, forming a three-dimensional network.

  12. Isolation of bioactive biphenyl compounds from the twigs of Chaenomeles sinensis.

    Science.gov (United States)

    Kim, Chung Sub; Subedi, Lalita; Kwon, Oh Kil; Kim, Sun Yeou; Yeo, Eui-Ju; Choi, Sang Un; Lee, Kang Ro

    2016-01-15

    Investigation of the MeOH extract of Chaenomeles sinensis twigs resulted in the isolation of seven biphenyl compounds (1-7) including a new compound, chaenomin (1). The chemical structures of the isolated compounds were elucidated by extensive NMR data ((1)H and (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC), specific optical rotation, and chemical reaction. Compounds 2 and 6 showed potent cytotoxic activities against four cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15), and compound 7 exhibited potent anti-neuroinflammatory and NGF-potentiating activity. PMID:26706168

  13. 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...... 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...

  14. Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies

    Indian Academy of Sciences (India)

    Nellisara D Shashikumar; Ganganaika Krishnamurthy; Halehatti S Bhojyanaik; Mayasandra R Lokesh; Kaginalli S Jithendrakumara

    2014-01-01

    New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards -tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of -tubulin.

  15. Development and characterization of new polyclonal antibodies specific for three polychlorinated biphenyls

    Institute of Scientific and Technical Information of China (English)

    Han Yu Chen; Hui Sheng Zhuang; Chun Zhou

    2009-01-01

    Three polychlorinated biphenyls(PCBs)congeners and their corresponding haptens bearing four carbon length carboxylic groups that can be linked to a protein for raising antibodies were synthesized.The three resultant immunogens were fabricated and used to stimulate immune responses in rabbits to survey the characteristics of the haptens.Three of the resultant polyclonal antibodies(Pabs)were obtained.The antiserum exhibited relatively high antibody titres(1:32-64)in double agar diffusion.◎2008 Hui Sheng Zhuang.Published by Elsevier B.V.on behalf of Chinese Chemical Society.All rights reserved.

  16. Electrochemical and optical properties of biphenyl bridged-dicarbazole oligomer films: Electropolymerization and electrochromism

    Energy Technology Data Exchange (ETDEWEB)

    Koyuncu, Sermet [Department of Chemistry, Faculty of Sciences and Arts, Canakkale Onsekiz Mart University, 17020 Canakkale (Turkey); Can Vocational School, Canakkale Onsekiz Mart University, 17400 Canakkale (Turkey)], E-mail: sermetkoyuncu@hotmail.com; Gultekin, Burak [Solar Energy Institute, Ege University, 35100 Bornova, Izmir (Turkey); Zafer, Ceylan [Solar Energy Institute, Ege University, 35100 Bornova, Izmir (Turkey)], E-mail: ceylan.zafer@ege.edu.tr; Bilgili, Hakan; Can, Mustafa; Demic, Serafettin [Solar Energy Institute, Ege University, 35100 Bornova, Izmir (Turkey); Kaya, Ismet [Department of Chemistry, Faculty of Sciences and Arts, Canakkale Onsekiz Mart University, 17020 Canakkale (Turkey); Icli, Siddik [Solar Energy Institute, Ege University, 35100 Bornova, Izmir (Turkey)

    2009-10-01

    4,4'-Di(N-carbazoyl)biphenyl monomer (CBP) was synthesized and coated onto ITO-glass surface by electrochemical oxidative polymerization. Its CV shows two distinct one-electron and stepwise oxidation processes occurred at 1.29 and 1.61 V. By using this property, the monomer was electrochemically polymerized separately at these oxidation states and thus, two different oligomer films were obtained afterwards. Their spectro-electrochemical and electrochromic properties were also investigated. Switching ability of the oligomers was evaluated by kinetic studies upon measuring the percent transmittance (%T) at their maximum contrast point, indicating that these oligomers were found to be suitable material for electrochromic devices.

  17. Separation of Biphenyl Nitrile Compounds by Microemulsion Electrokinetic Chromatography with Mixed Surfactants

    Institute of Scientific and Technical Information of China (English)

    Su Xuan GONG; Tao BO; Lan HUANG; Ke An LI; Hu Wei LIU

    2004-01-01

    A mixture of nine biphenyl nitrile compounds with high hydrophobicity and similar structures was successfully separated by microemulsion electrokinetic chromatography (MEEKC) within 30 min. The buffer system contained 100 mmol/L sodium dodecyl sulfate (SDS), 80 mmol/L sodium cholate (SC), 0.81% heptane, 7.5% n-butanol, 10% acetonitrile and 10 mmol/L borate. The addition of SC, organic modifiers, sample preparation and temperature all showed remarkable effect on the separation. Meanwhile, the MEEKC method was briefly compared with micellar electrokinetic chromatography (MEKC) method.

  18. 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.

  19. The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma.

    Science.gov (United States)

    Pelak, Maciej J; Śnietura, Mirosław; Lange, Dariusz; Nikiel, Barbara; Pecka, Katarzyna M

    2015-12-01

    We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-βR1) and interferon gamma (IFN-γR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-βR1 and IFN-γR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-βR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-βR1 and IFN-γR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together. PMID:27003769

  20. Probing the chemical steps of nitroalkane oxidation catalyzed by 2-nitropropane dioxygenase with solvent viscosity, pH, and substrate kinetic isotope effects.

    Science.gov (United States)

    Francis, Kevin; Gadda, Giovanni

    2006-11-21

    Among the enzymes that catalyze the oxidative denitrification of nitroalkanes to carbonyl compounds, 2-nitropropane dioxygenase is the only one known to effectively utilize both the neutral and anionic (nitronate) forms of the substrate. A recent study has established that the catalytic pathway is common to both types of substrates, except for the initial removal of a proton from the carbon of the neutral substrates [Francis, K., Russell, B., and Gadda, G. (2005) J. Biol. Chem. 280, 5195-5204]. In the present study, the mechanistic properties of the enzyme have been investigated with solvent viscosity, pH, and kinetic isotope effects. With nitroethane or ethylnitronate, the kcat/Km and kcat values were independent of solvent viscosity, consistent with the substrate and product binding to the enzyme in rapid equilibrium. The abstraction of the proton from the alpha carbon of neutral substrates was investigated by measuring the pH dependence of the D(kcat/KNE) value with 1,1-[2H2]-nitroethane. The formation of the enzyme-bound flavosemiquinone formed during catalysis was examined by determining the pH dependence of the kcat/Km values with ethylnitronate and nitroethane and the inhibition by m-nitrobenzoate. Finally, alpha-secondary kinetic isotope effects with 1-[2H]-ethylnitronate were used to propose a non-oxidative tautomerization pathway, in which the enzyme catalyzes the interconversion of nitroalkanes between their anionic and neutral forms. The data presented suggest that enzymatic turnover of 2-nitropropane dioxygenase with neutral substrates is limited by the cleavage of the substrate CH bond at low pH, whereas that with anionic substrates is limited by the non-oxidative tautomerization of ethylnitroante to nitroethane at high pH. PMID:17105207

  1. Analysis the mixtures of polyphenyls by gas chromatrogaphie. 1.- Area response for biphenyl and terphenyls relative to triphenylmethane

    International Nuclear Information System (INIS)

    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

  2. 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)

    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)

  3. Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo 2,1-b thiazole in sodium/iodide sym-porter (NIS)-expressing cells

    Energy Technology Data Exchange (ETDEWEB)

    Lecat-Guillet, N.; Ambroise, Y. [CEA, DSV, Dept Bioorgan Chem andt IsotopLabelling, Inst Biol and Technol, iBiTecS, F-91191 Gif Sur Yvette (France)

    2008-07-01

    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)

  4. 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.

  5. Arbuscular Mycorrhizal Fungal Hyphae Alter Soil Bacterial Community and Enhance Polychlorinated Biphenyls Dissipation

    Science.gov (United States)

    Qin, Hua; Brookes, Philip C.; Xu, Jianming

    2016-01-01

    We investigated the role of arbuscular mycorrhizal fungal (AMF) hyphae in alternation of soil microbial community and Aroclor 1242 dissipation. A two-compartment rhizobox system with double nylon meshes in the central was employed to exclude the influence of Cucurbita pepo L. root exudates on hyphal compartment soil. To assess the quantitative effect of AMF hyphae on soil microbial community, we separated the hyphal compartment soil into four horizontal layers from the central mesh to outer wall (e.g., L1–L4). Soil total PCBs dissipation rates ranged from 35.67% of L4 layer to 57.39% of L1 layer in AMF inoculated treatment, which were significant higher than the 17.31% of the control (P biphenyls as well as the total PCBs were significantly correlated with soil hyphal length (P biphenyl dissipation, while taxa from the Oxalobacteraceae and Streptomycetaceae responded negatively to AMF and PCB congener dissipation. Our results suggested that the AMF hyphal exudates as well as the hyphae per se did have quantitative effects on shaping soil microbial community, and could modify the PCBs dissipation processes consequently. PMID:27379068

  6. Polychlorinated biphenyls (PCBs) in a benthic ecosystem in Gwangyang Bay, South Korea

    International Nuclear Information System (INIS)

    Highlights: ► PCBs are still detectable in Gwangyang Bay in spite of their ban in 1980s. ► PCBs in the benthic ecosystem is enriched in lower chlorinated biphenyls. ► PCBs are released from a nearby local steel industry. ► Distribution of PCBs to the bay arises mostly from atmospheric transfer. - Abstract: Benthic ecosystem in Gwangyang Bay, a fast developing industrial area with steel production, port container handling, petroleum and other chemical processing in South Korea was studied. The average levels of polychlorinated biphenyls (ΣPCB) in the benthic components were: seawater 2.99 ± 0.13 (ng/L); sediment 294 ± 118 (ng/g TOC); [biota = ng/g lipid] starfish 92; prawn 131 ± 2; mussels 127 ± 22; crab 182 ± 114; clam 187; polychaeta 215; sea cucumber 497 ± 90; squill 603 ± 38; fish 396 ± 159. Levels in the inner bay samples were higher than the outer bay samples suggesting land based pollution. Good correlation (r2 = 0.79; p < 0.05) existed between PCB concentration and lipid content indicating partitioning processes in action. PCB signature in the abiotic and biotic components shows enrichment of lower chlorinated congeners emitted by a unique source nearby, viz. steel manufacturing plant.

  7. Polychlorinated biphenyls in surface soil in urban and background areas of Mongolia

    International Nuclear Information System (INIS)

    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

  8. Tissue damage after acute intoxication by polychlorinated biphenyls (PCBs in cockroaches Blattella germanica

    Directory of Open Access Journals (Sweden)

    S Lambiase

    2009-06-01

    Full Text Available It is common knowledge that polychlorinated biphenyls (PCBs represent a serious threat to the health of both vertebrates and invertebrates. As far as the former are concerned, especially as regards human beings, a broad literature describes the direct and indirect effects induced by the PCBs on their systems and organs. Among invertebrates, the information available is mostly related to arthropods and is, however, very scarce. The aim of this work was to evaluate the effects of polychlorinated biphenyls (PCBs on tissues and organs of individuals belonging to a species of Blattaria (Blattella germanica treated with various doses of this toxic material. The pathologies found became more serious as the dosage increased and were present throughout the entire digestive system, in the fat body and in the male gonads: in these areas cell and tissue breakdown and severely damaged spermiogenesis were observed. In particular, the testicles, Malpighian tubules and fat body accumulated an amorphous basophilic PAS-positive substance. Furthermore, the NOS-dependent NADPH diaphorase activity pattern in the retina and optic lobes was more evident in the treated than in the control insects.

  9. 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.

  10. 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.

  11. Syntheses,Crystal Structures and Fluorescence Properties of Two Triazolyl Derivatives with Biphenyl Links

    Institute of Scientific and Technical Information of China (English)

    LING Yun; LI Jing; HU Ai-Xi; ZHANG Lei

    2009-01-01

    Two novel triazolyl derivatives with biphenyl links,namely 4,4-bis(1,2,4-triazol-1-yl-methyl)biphenylene 1 and 4,4-bis(3,5-dimethyl-1,2,4-triazol-1-ylmethyl)biphenylene 2,have been synthesized and structurally characterized by single-crystal X-ray diffraction.Compounds 1·H2O·HCl and 2·2H2O·2HCl crystallize in the monoclinic system with spacegroup C2/c and P21/c,respectively.he dihedral angles of the two phenyl rings are 30.26(6)° in 1·H2O·HCl,while co-planar(0.00(7)°)in 2·2H2O·2HCl.In 1'H2O·HCl,the N-H…O hydrogen bonds link 1 to form chain-like structures which are further connected by O-H…Cl,C-H…Cl,C-H…O and π-π supramolecular interactions.The hydrogen bonds of O-H…Cl in 2·2H2O·2HCl provide distinguishing P/M helical chains along the baxis,and these chains are further connected by N-H…O hydrogen bonds to generate a 2D structure.Compounds 1 and 2 in methanol solution show much stronger emission bands at 319 nm than biphenyl at 3 16 nm under excitation at 260 nm.

  12. Occurrence and congeners specific of polychlorinated biphenyls in agricultural soils from Southern Jiangsu, China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-ying; QIU Li-min; HE Jia; LIAO Yuan; LUO Yong-ming

    2007-01-01

    A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls(PCBs)in order to assess the levels of pollution,sources,area distribution,and potential risk for the environment.All methods were rigorously tested and an adequate quality control was ensured.Only one site had no PCBs residues,and the highest total PCBs concentration in the surface soils was 32.83 ng/g.The average concentration in all the soil samples was 4.13ng/g.signaling low-level pollution.Tetra-,penta-,and hexa-chlorinated biphenyls were dominant speoes in soil samples,accounnng for more than 75%of ΣPCBs in the soil samples.PCB118 was the most abundant congener in all the samples.The PCB118 Was about 20%of ΣPCBs.The soil organic matter content showed only a weak correlation with the levels of all PCB congeners,in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues.To a certain extent,the sources and land use seemed to influence the levels of PCBs.

  13. Ab initio study of long-range electron transfer between biphenyl anion radical and naphthalene

    Institute of Scientific and Technical Information of China (English)

    李象远; 肖顺清; 何福城

    1999-01-01

    After the separation of the donor, the aeceptor, and the σ-type bridge from the π-σ-π system, the geometries of biphenyl, biphenyl anion radical, naphthalene, and naphthalene anion radical are optimized, and then the reorganization energy for the intermolecular electron transfer (ET) at the levels of HF/4-31G and HF/DZP is calculated. The ET matrix elements of the self-exchange reactions of the π-σ-π systems have been calculated by means of both the direct calculation based on the variational principle, and the transition energy between the molecular orbitals at the linear coordinate R=0.5. For the cross reactions, the ET matrix element and the geometry of the transition state are determined by searching the minimum energy splitting △min along the reaction coordinate. In the evaluation of the solvent reorganization energy of the ET in solution, the Marcus’ two-sphere model has been invoked. A few of ET rate constants for the intramolecular ET reactions for the π-σ-π systems, which contain

  14. The proton nuclear magnetic shielding tensors in biphenyl: experiment and theory.

    Science.gov (United States)

    Schönborn, Frank; Schmitt, Heike; Zimmermann, Herbert; Haeberlen, Ulrich; Corminboeuf, Clémence; Grossmann, Gisbert; Heine, Thomas

    2005-07-01

    Line-narrowing multiple pulse techniques are applied to a spherical sample crystal of biphenyl. The 10 different proton shielding tensors in this compound are determined. The accuracy level for the tensor components is 0.3 ppm. The assignment of the measured tensors to the corresponding proton sites is given careful attention. Intermolecular shielding contributions are calculated by the induced magnetic point dipole model with empirical atom and bond susceptibilities (distant neighbours) and by a new quantum chemical method (near neighbours). Subtracting the intermolecular contributions from the (correctly assigned) measured shielding tensors leads to isolated-molecule shielding tensors for which there are symmetry relations. Compliance to these relations is the criterion for the correct assignment. The success of this program indicates that intermolecular proton shielding contributions can be calculated to better than 0.5 ppm. The isolated-molecule shielding tensors obtained from experiment and calculated intermolecular contributions are compared with isolated-molecule quantum chemical results. Expressed in the icosahedral tensor representation, the rms differences of the respective tensor components are below 0.5 ppm for all proton sites in biphenyl. In the isolated molecule, the least shielded direction of all protons is the perpendicular to the molecular plane. For the para proton, the intermediate principal direction is along the C-H bond. It is argued that these relations also hold for the protons in the isolated benzene molecule. PMID:15949748

  15. Assessing atmospheric concentration of polychlorinated biphenyls by evergreen Rhododendron maximum next to a contaminated stream.

    Science.gov (United States)

    Dang, Viet D; Walters, David M; Lee, Cindy M

    2016-09-01

    Conifers are often used as an air passive sampler, but few studies have focused on the implication of broadleaf evergreens to monitor atmospheric semivolatile organic compounds such as polychlorinated biphenyls (PCBs). In the present study, the authors used Rhododendron maximum (rhododendron) growing next to a contaminated stream to assess atmospheric PCB concentrations. The present study area was located in a rural setting and approximately 2 km downstream of a former capacitor plant. Leaves from the same mature shrubs were collected in late fall 2010 and winter and spring 2011. Polychlorinated biphenyls were detected in the collected leaves, suggesting that rhododendron can be used as air passive samplers in rural areas where active sampling is impractical. Estimated ΣPCB (47 congeners) concentrations in the atmosphere decreased from fall 2010 to spring 2011 with concentration means at 3990 pg m(-3) , 2850 pg m(-3) , and 931 pg m(-3) in fall 2010, winter 2011, and spring 2011, respectively. These results indicate that the atmospheric concentrations at this location continue to be high despite termination of active discharge from the former industrial source. Leaves had a consistent pattern of high concentrations of tetra-CBs and penta-CBs similar to the congener distribution in polyethylene passive samplers deployed in the water column, suggesting that volatilized PCBs from the stream were the primary source of contaminants in rhododendron leaves. Environ Toxicol Chem 2016;35:2192-2198. © 2016 SETAC. PMID:26889751

  16. Thermophysical properties of (diphenyl ether + biphenyl) mixtures for their use as heat transfer fluids

    International Nuclear Information System (INIS)

    Highlights: ► Densities at high pressure of mixtures of diphenyl ether and biphenyl were reported. ► The composition dependence on thermal conductivity and viscosity is very smooth. ► Crossing point in αp isotherms were detected around 38 MPa. ► MYEGA reproduces our experimental η(T) curves with deviations lower than 0.24%. ► The experimental devices were checked obtaining good agreements with literature. - Abstract: Experimental measurements of density, viscosity and thermal conductivity are reported for pure diphenyl ether and three different binary mixtures of diphenyl ether and biphenyl including the eutectic point. Density has been measured for the liquid phase at temperatures ranging from (298.15 to 363.15) K and for pressures up to 45 MPa using a high-pressure vibrating tube densimeter. A Tammann–Tait correlation of the experimental densities has been proposed for each composition. From these correlations, isothermal compressibility, isobaric thermal expansivity and internal pressure have been determined. Moreover, viscosity and thermal conductivity were experimentally determined at atmospheric pressure for several temperatures by using a rolling ball viscometer and a device based in the hot-wire technique, respectively. All the experimental devices used to determine the thermophysical properties were checked finding good agreements with previous literature data. The experimental viscosity values were correlated using the Vogel–Fulcher–Tammann, Avramov–Milchev and MYEGA equation.

  17. Assessment of exposure risk of polychlorinated biphenyls to interior least terns (Sterna antillarum).

    Science.gov (United States)

    Sanchez, Brian C; Caldwell, Colleen A

    2008-03-01

    Risk of polychlorinated biphenyl (PCB) exposure and effects were assessed for a colony of federally endangered interior least terns (Sterna antillarum) nesting on the Bitter Lake National Wildlife Refuge (NM, USA). The colony feeds from an area on the Refuge (Hunter Marsh/Oxbow Complex) wherein fish with elevated concentrations of total PCBs have been documented. Concentrations of total PCBs in whole fish averaged 0.94 mg/kg with a maximum concentration of 2.77 mg/kg, wet weight. Estimated daily PCB intake rates by adult birds throughout their 180-d breeding season ranged from <0.01 mg/kg/d to 0.98 mg/ kg/d, yielding hazard quotients that ranged from 0.01 to 21.68. Polychlorinated biphenyls pose a moderate risk to the colony of interior least terns that breed at the Bitter Lake National Wildlife Refuge, but the exposure rate is not likely to threaten their overall breeding success. PMID:17967068

  18. Polychlorinated biphenyls (PCBs) in indoor air originating from sealants in contaminated and uncontaminated apartments within the same housing estate

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Meyer, Harald William; Ebbehøj, Niels Erik;

    2012-01-01

    Twenty-four congeners of polychlorinated biphenyls (PCBs) were measured in 83 air samples and 20 elastic sealants samples of apartments with PCB-containing sealants. In addition, PCBs were measured in 21 air samples from reference apartments located in an uncontaminated section of the same estate...

  19. Levels of Polychlorinated Dibenzo-p-Dibenzofurans, and Biphenyls in Southern Mississippi Catfish and Estimation of Potential.

    Science.gov (United States)

    Fish consumption has been classified as one of the primary pathways of exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs). In this study, we evaluated tissue levels of the 17 laterally-substituted PCDD/Fs, 12 dioxin-like PCBs, and 97 non-...

  20. The Relationship between Prenatal and Postnatal Exposure to Polychlorinated Biphenyls (PCBs) and Cognitive, Neuropsychological, and Behavioral Deficits: A Critical Appraisal

    Science.gov (United States)

    Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.

    2004-01-01

    Our purpose in this report is to evaluate scientifically that body of literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants, children, and adults. The data derive from seven cohorts: six cohorts of mothers…

  1. 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 developmen

  2. (Biphenyl-2-yl)bromidobis(2-methyl­tetra­hydro­furan-κO)magnesium(II)

    OpenAIRE

    Michael Bolte; D. Wohlgemuth; Simon Nordschild

    2009-01-01

    In the title Grignard reagent, [MgBr(C12H9)(C5H10O)2], the Mg centre adopts a distorted tetrahedral MgCO2Br arrangement. The dihedral angle between the two aromatic rings of the biphenyl residue is 44.00 (14)°. Each molecule incorporates one R- and one S-configured 2-methyltetrahydrofuran molecule.

  3. USE OF PLANT AND EARTHWORM BIOASSAYS TO EVALUATE REMEDIATION OF SOIL FROM A SITE CONTAMINATED WITH POLYCHLORINATED BIPHENYLS

    Science.gov (United States)

    Soil from a site heavily contaminated with polychlorinated biphenyls (PCBs) was treated with a pilot-scale, solvent extraction technology. Bioassays in earthworms and plants were used to examine the efficacy of the remediation process for reducing the toxicity of the soil. The ...

  4. USE OF PLANT AND EARTHWORM BIOASSYS TO EVALUATE REMEDIATION OF SOIL FROM A SITE CONTAMINATED WITH POLYCHLORINATED BIPHENYLS

    Science.gov (United States)

    Soil from a site heavily contaminated with polychlorinated biphenyls (PCBs) was treated with a pilot-scale, solvent extraction tehnology. Bioassays in earthworms and plants were used to examine the efficacy of the remediation process for reducing the toxicity of the soil. The ear...

  5. ASSESSMENT OF PCDDS (POLYCHLORINATED DIBENZODIOXINS) AND PCDFS (POLYCHLORINATED DIBENZOFURANS) FROM PCB (POLYCHLORINATED BIPHENYL'S) TRANSFORMER AND CAPACITOR FIRES

    Science.gov (United States)

    The EPA, under the Toxic Substances Control Act, has been mandated to develop appropriate regulations for the control of exposure to polychlorinated biphenyls (PCBs). In light of this responsibility the EPA Office of Toxic Substances recently issued an Advance Notice of Proposed ...

  6. Nanosecond photochromic molecular switching of a biphenyl-bridged imidazole dimer revealed by wide range transient absorption spectroscopy

    NARCIS (Netherlands)

    T. Yamaguchi; M.F. Hilbers; P.P. Reinders; Y. Kobayashi; A.M. Brouwer; J. Abe

    2015-01-01

    We demonstrate that a biphenyl-bridged imidazole dimer exhibits fast photochromism with a thermal recovery time constant of similar to 100 ns, which is the fastest thermal back reaction in all reported imidazole dimers. Sub-ps transient absorption spectroscopy reveals that the generation process of

  7. Kinetics and conductivity parameters of uptake and transport of polychlorinated biphenyls in the Caco-2 intestinal cell line model

    NARCIS (Netherlands)

    Dulfer, W.J.; Govers, H.A.J.; Groten, J.P.

    1998-01-01

    Most of the accumulation of polychlorinated biphenyls (PCBs) over the food chain can be attributed to contaminant uptake from food. The effect of fatty acid absorption on net uptake and transport fluxes of a selection of 14 PCBs over the organismal gut epithelium has been determined in monolayers of

  8. Impact of polychlorinated biphenyl and polycyclic aromatic hydrocarbon sequestration in sediment on bioaccumulation in aquatic food webs

    NARCIS (Netherlands)

    Moermond, C.T.A.; Roessink, I.; Jonker, M.T.O.; Meijer, T.; Koelmans, A.A.

    2007-01-01

    It is not clear whether sequestration or aging of organic chemicals like polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) limits accumulation in higher levels of aquatic food chains. Therefore, the effect of aging on accumulation was studied in 1-m3 model ecosystems that

  9. Photochemistry treatment of polychlorinated biphenyls (PCB) in dielectric fluid; Tratamiento fotoquimico de bifenilos policlorados en fluidos dielectricos

    Energy Technology Data Exchange (ETDEWEB)

    Manzano Quinones, M. A. [Escuela Politecnica Superior de Algeciras (Spain)

    2000-07-01

    In this work a study of polychlorinated biphenyls (PCB) photodegradation in dielectric fluid have been done. The experiments has been carried out in a pilot scale photo rector with an ultraviolet light source. The results obtained showed a 92% elimination of PCB following a first kinetic order. In addition the photo reaction products have been identified. (Author) 6 refs.

  10. 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

    1999-01-01

    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

  11. Plasma polychlorinated biphenyl levels in Dutch preschool children either breast-fed or formula-fed during infancy

    NARCIS (Netherlands)

    Patandin, S; WeisglasKuperus, N; deRidder, MAJ; KoopmanEsseboom, C; vanStaveren, WA; vanderPaauw, CG; Sauer, PJJ

    1997-01-01

    Objectives. This study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children. Methods. Plasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy. Results. Medi

  12. 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

  13. Effect of Quercetin on Haematobiochemical and Histological Changes in the Liver of Polychlorined Biphenyls-Induced Adult Male Wistar Rats

    OpenAIRE

    Kandaswamy Selvakumar; Senthamilselvan Bavithra; Sekaran Suganya; Firdous Ahmad Bhat; Gunasekaran Krishnamoorthy; Jagadeesan Arunakaran

    2013-01-01

    Polychlorinated biphenyls exposure damages the rat liver cells. Hematological parameters such as hemoglobin, packed cell volume, red-blood cells, white-blood cells, neutrophils, platelet counts, and RBC indices were significantly decreased. Polymorphs, eosinophil counts, and erythrocyte sedimentation rate were significantly increased. Serum liver enzymes such as aspartate transaminase, alanine transaminase, alkaline phosphatase, and gamma-glutamyl transferase were increased by PCBs treatment....

  14. Determination of in vitro relative potency (REP) values for mono-ortho polychlorinated biphenyls after purification with active charcoal

    NARCIS (Netherlands)

    Peters, A.K.; Leonards, P.E.G.; Zhao, B.; Bergman, A.; Denison, M.S.; Berg, van den M.

    2006-01-01

    The TEF system for dioxin-like compounds has included assignment of TEF values for mono-ortho polychlorinated biphenyls (MO-PCBs). Small traces of aryl hydrocarbon receptor (AhR)-active impurities could result in artifactually higher relative potency (REP) values. MO-PCBs -105, -118, -156, and -167

  15. 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.

  16. 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 ...

  17. Cloning and characterisation of a maize carotenoid cleavage dioxygenase (ZmCCD1) and its involvement in the biosynthesis of apocarotenoids with various roles in mutualistic and parasitic interactions

    OpenAIRE

    Sun, Z.; Hans, J.; Walter, M H; Matusova, R.; Beekwilder, M.J.; Verstappen, F.W.A.; Ming, Z.; Echteld, van, C.J.A.; Strack, D; Bisseling, T.; Bouwmeester, H.J.

    2008-01-01

    Colonisation of maize roots by arbuscular mycorrhizal (AM) fungi leads to the accumulation of apocarotenoids (cyclohexenone and mycorradicin derivatives). Other root apocarotenoids (strigolactones) are involved in signalling during early steps of the AM symbiosis but also in stimulation of germination of parasitic plant seeds. Both apocarotenoid classes are predicted to originate from cleavage of a carotenoid substrate by a carotenoid cleavage dioxygenase (CCD), but the precursors and cleavag...

  18. Molecular perspectives and recent advances in microbial remediation of persistent organic pollutants.

    Science.gov (United States)

    Chakraborty, Jaya; Das, Surajit

    2016-09-01

    Nutrition and pollution stress stimulate genetic adaptation in microorganisms and assist in evolution of diverse metabolic pathways for their survival on several complex organic compounds. Persistent organic pollutants (POPs) are highly lipophilic in nature and cause adverse effects to the environment and human health by biomagnification through the food chain. Diverse microorganisms, harboring numerous plasmids and catabolic genes, acclimatize to these environmentally unfavorable conditions by gene duplication, mutational drift, hypermutation, and recombination. Genetic aspects of some major POP catabolic genes such as biphenyl dioxygenase (bph), DDT 2,3-dioxygenase, and angular dioxygenase assist in degradation of biphenyl, organochlorine pesticides, and dioxins/furans, respectively. Microbial metagenome constitutes the largest genetic reservoir with miscellaneous enzymatic activities implicated in degradation. To tap the metabolic potential of microorganisms, recent techniques like sequence and function-based screening and substrate-induced gene expression are proficient in tracing out novel catabolic genes from the entire metagenome for utilization in enhanced biodegradation. The major endeavor of today's scientific world is to characterize the exact genetic mechanisms of microbes for bioremediation of these toxic compounds by excavating into the uncultured plethora. This review entails the effect of POPs on the environment and involvement of microbial catabolic genes for their removal with the advanced techniques of bioremediation. PMID:27234838

  19. Expression, Function of the Human Androgen-Responsive Gene AD11 in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Shane W. Oram

    2007-08-01

    Full Text Available We have previously identified an androgen-responsive gene in rat prostate that shares homology with the acireductone dioxygenase (ARD/ARD′ family of metalbinding enzymes involved in methionine salvage. We found that the gene, aci-reductone dioxygenase 1 (ADI1, was downregulated in prostate cancer cells, whereas enforced expression of rat Adi1 in these cells caused apoptosis. Here we report the characterization of human ADI1 in prostate cancer. Androgens induced ADI1 expression in human prostate cancer LNCaP cells, which was not blocked by cycloheximide, indicating that ADI1 is a primary androgen-responsive gene. In human benign prostatic hyperplasia specimens, epithelial cells expressed ADI1. Immunohistochemistry of prostate tumor tissue microarrays showed that benign regions expressed more ADI1 than tumors, suggesting a suppressive role for ADI1 in prostate cancer. Bacterial lysates containing recombinant ADI1 produced a five-fold increase in aci-reductone decay over controls, demonstrating that ADI1 has ARD activity. We generated point mutations at key residues in the metal-binding site of ADI1 to disrupt ARD function, we found that these mutations did not affect intracellular localization, apoptosis, or colony formation suppression in human prostate cancer cells. Collectively, these observations argue that AD11 may check prostate cancer progression through apoptosis, that this activity does not require metal binding.

  20. Electro-optic and dynamic studies of biphenyl benzoate ferroelectric liquid crystals

    Energy Technology Data Exchange (ETDEWEB)

    Hemine, J., E-mail: hemine1@yahoo.f [Laboratoire de Physique de la Matiere Condensee, Universite Hassan II, Mohammedia-Casablanca, BP 146, F.S.T. Mohammedia (Morocco); Daoudi, A. [Universite Lille Nord de France, F-59000 Lille (France); ULCO, LDSMM, F-59140 Dunkerque (France); CNRS UMR8024, F-59140 Dunkerque (France); Legrand, C. [Universite Lille Nord de France, F-59000 Lille (France); ULCO, LEMCEL, F-62228 Calais (France); El kaaouachi, A.; Nafidi, A. [Laboratoire de Physique de la Matiere Condensee, Faculte des Sciences Ibnou Zohr, BP 28/S 80000 Agadir (Morocco); Ismaili, M.; Isaert, N. [Universite Lille Nord de France, F-59000 Lille (France); USTL, LDSMM, F-59655 Villeneuve d' Ascq (France); CNRS UMR8024, F-59655 Villeneuve d' Ascq (France); Nguyen, H.T. [Centre de Recherche Paul Pascal, Universite de Bordeaux 1, 33600 Pessac (France)

    2010-05-01

    We present electro-optic and dynamic properties on three homologous of biphenyl benzoate series of ferroelectric liquid crystals (FLCs) exhibiting the chiral smectic C phase (SmC*). The three compounds present high spontaneous polarization and show the SmC*-SmA*-N* phase sequence. Dielectric spectroscopy was used to provide the dynamics and dipolar ordering of the ferroelectric phase. The Goldstone relaxation mode was studied for sample cells on planar geometry without a DC bias voltage. The rotational viscosity corresponding to molecular motions in the SmC* phase was determined from dielectric measurements. The Arrhenius-type behavior of the rotational viscosity was found and the corresponding activation energies were evaluated.

  1. Biodegradation Of Persistent Organic Pollutants (POPs):I The Case Of Polychlorinated Biphenyls (PCB)

    International Nuclear Information System (INIS)

    Persistent organic pollutants are chemicals that are toxic to humans and wildlife, remain intact in the environment for long periods, accumulate in living organisms and can become widely distributed geographically by air, water or migrating species. As a result, these contaminants have been found all over the world including in places,such as the Polar Regions, which are very far from their application site. The Stockholm Convention was signed in 23/5/01 in order to cope with this international environmental problem. Although POPs were banned by most countries, there are still a lot of sites contaminated with these substances. The remediation of these sites is problematic and requires distinct considerations from those which are established for hydrocarbon remediation. This manuscript reviews the literature about anaerobic and aerobic biodegradation of polychlorinated biphenyls (PCB) and possible strategies to stimulate these processes. The degradation of the other POPs would be reviewed in additional texts.

  2. 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...... examined the possible association between PCB exposure and semen quality and reproductive hormones in fertile Faroese men. METHODS: Participants in this cross-sectional study include 266 proven fertile men residing in the Faroe Islands. PCB levels and hormone profiles were measured in serum samples taken...... at the clinical examination that included semen quality parameters. RESULTS: A significant positive association was seen between serum-PCB and the testosterone/estradiol ratio (p=0.04). In the unadjusted analyses, elevated PCB exposure was associated with increased serum concentrations of SHBG (p=0...

  3. Organochlorine Pesticides (OCs) and Polychlorinated Biphenyls (PCBs) in Tilapia zillii from Lake El-Manzala, Egypt

    International Nuclear Information System (INIS)

    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)

  4. Temperature of hydrogen radio frequency plasma under dechlorination process of polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Inada, Y., E-mail: inada@hvg.t.u-tokyo.ac.jp; Abe, K.; Kumada, A.; Hidaka, K. [Department of Electrical Engineering and Information Systems, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Amano, K.; Itoh, K.; Oono, T. [R and D Center, Tokyo Electric Power Company, 4-1 Egasaki-cho, Tsurumi-ku, Yokohama 230-8510 (Japan)

    2014-10-27

    It has been reported that RF (radio frequency) hydrogen plasmas promote the dechlorination process of PCBs (polychlorinated biphenyls) under irradiation of MW (microwave). A relative emission intensity spectroscope system was used for single-shot imaging of two-dimensional temperature distributions of RF hydrogen plasmas generated in chemical solutions with several mixing ratios of isopropyl alcohol (IPA) and insulation oil under MW irradiation. Our experimental results showed that the plasma generation frequencies for the oil-contaminating solutions were higher than that for the pure IPA solution. In addition, the plasma temperature in the compound liquids including both oil and IPA was higher than that in the pure IPA and oil solutions. A combination of the plasma temperature measurements and plasma composition analysis indicated that the hydrogen radicals generated in a chemical solution containing the equal volumes of IPA and oil were almost the same amounts of H and H{sup +}, while those produced in the other solutions were mainly H.

  5. 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.

  6. Studies on biphenyl disulphonic acid doped polyanilines: Synthesis, characterization and electrochemistry

    Indian Academy of Sciences (India)

    Chepuri R K Rao; R Muthukannan; M Vijayan

    2012-06-01

    In this article, we report on the results obtained for the efforts we made to bring processability to the conducting polyaniline and substituted polyanilines by designing and synthesizing a new disulphonic acid with a biphenyl moiety as spacer group, viz. 4,4'-biphenyldisulphonic acid (BPSA). When doped, the disulphonic acid acts as a spacer group between the polyaniline chains and facilitates increase in solubility and conductivity. The spacing effect is maximized when BPSA is used as doping agent in in situ polymerization reactions. The conductivity of polyaniline doped by BPSA is 4 S/cm and for the substituted polyanilines it ranged from 2 × 10-5 to 8 × 10-4 S/cm.

  7. Accumulation of polychlorinated biphenyls in turbot (Scophthalmus maximus) from seawater sediments and food

    Science.gov (United States)

    Courtney, W. A. M.; Langston, W. J.

    1980-03-01

    Juvenile turbot, Scophthalmus maximus (L.), were exposed to 0.58 µg 1-1 Aroclor 1254 in seawater, to sediments containing 100, 60 and 1 ppm or fed with cockle containing 20 ppm PCB (polychlorinated biphenyls). Concentration factors for liver and muscle were 104 and 103, respectively, for uptake of PCB from seawater. Contamination of muscle was similar to that of sediments containing 1 and 60 ppm PCB to which turbot were exposed, but less than the 20 ppm in their experimental diet. Contamination of flatfish in the North Sea area is compared with the levels of PCB in the flounder, Platichthys flesus (L.), in the River Thames and predictable values for uptake of PCB from different pathways discussed.

  8. Studies on the Quantitative Structure-activity Relationship of Substituted Biphenyls by Density Function Theory (DFT)

    Institute of Scientific and Technical Information of China (English)

    HAN Xiang-Yun; ZHENG Qing

    2007-01-01

    Geometrical configurations of 16 substituted biphenyls were computed at the B3LYP/6-311G** level with Gaussian 98 program. Based on linear solvation energy theory, lgKow as well as the structural and thermodynamic parameters obtained at this level was taken as theoretical descriptors, and corresponding equation predicting the toxicity of Daphnia magna (-lgEC50)was thus obtained, in which three parameters were contained, i.e., n-octanol/water partition coefficients (lgKow), dipole moment of the molecules (μ) and entropy (S°). For this equation, R2 =0.9582, q2 = 0.8921 and SD = 0.102. The absolute t-scores of three variables are larger than the standard one in the confidence range of 95%, which confirms the creditability and stability of this model.

  9. Relationships between polychlorinated biphenyls in molluscs, hydrological characteristics and human pressures, within Basque estuaries (northern Spain).

    Science.gov (United States)

    Solaun, O; Rodríguez, J G; Borja, A; Larreta, J; Valencia, V

    2015-01-01

    Interannual variability of polychlorinated biphenyls (PCBs), measured in the soft tissues of Mytilus galloprovincialis mussels and Crassostrea gigas oysters, collected from estuarine waters within the Basque Country (Bay of Biscay), are investigated. Samples were collected in the autumn, between 2002 and 2011. Sites located within the ports of Bilbao and Pasaia showed the highest PCBs concentrations in molluscs; the lowest were observed in the mouth of the Oka estuary, an area of low population and industrial activity. Congener profiles of PCBs in the tissues of molluscs reveal the predominance of hexachlorobiphenyls (CB153 and CB138). In addition, redundancy analysis has shown that residence time, river flow and a 'pressure index' explain 57% of the variability in the PCB congener concentrations (the higher the values of these variables, the higher the concentration). Finally, Σ7PCB median concentrations in molluscs and sediments, collected from nearby sampling sites, were found to be moderately correlated (r(2)=0.513, p<0.01).

  10. Accumulation and depletion of polychlorinated biphenyl (PCB) congeners in the housefly (musca domestica, L. )

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, L.G. (Univ. of Illinois, Urbana (United States)); Storr-Hansen, E. (National Environmental Research Inst., Soeborg (Denmark))

    1992-01-01

    Polychlorinated biphenyl (PCB) residues in food chains and in the environment are dynamic complex mixtures and there is considerable interest in the disposition as well as toxicities of individual congeners. The persistence and biological activities of PCBs are intimately associated with microsomal monooxygenases. The house fly, Musca domestica (L.), has long been a standard organism for studies of pesticide toxicology and has an active and well-defined microsomal monooxygenase system. These oxidases in the fly can be induced by PCBs. It was considered of interest to provide data which may indicate whether or not the relatively large and mobile biomass of insects in general may play a role in the global disposition of PCBs. It was also of interest to determine if the house fly could serve as a model for determining the relative accumulation, elimination, and toxicities of individual PCB congeners.

  11. Digestive tract absorption of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in a nursing infant

    Energy Technology Data Exchange (ETDEWEB)

    McLachlan, M.S. (Univ. of Bayreuth (Germany))

    1993-11-01

    The digestive tract absorption of environmental contaminants is an important but poorly understood parameter in contaminant is an important but poorly understood parameter in contaminant risk assessments. The net absorption of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in a nursing infant was measured under natural conditions over 12 days. The levels of the substances in the mother's milk were typical for Germany. It was found that for almost all congeners over 90% of the ingested compound was absorbed. This indicates that the common assumption of 100% absorption in nursing infants is reasonable. No firm conclusions could be drawn regarding the absorption of Cl7- and Cl8DD/F due to high blank levels in the cotton diapers used.

  12. [EVALUATION OF MIGRATION ABILITY OF POLYCHLORINATED BIPHENYLS IN THE "SOIL-PLANT" AND "SOIL-EARTHWORMS"].

    Science.gov (United States)

    Baeva, Yu I; Chernykh, N A

    2016-01-01

    In the article there is given a hygienic assessment ofpolychlorinated biphenyls (PCBs) contamination of soils of the city of Serpukhov of the Moscow region. For the first time there was investigated the PCB's ability to migrate in the system "soil-earthworms", and were calculated bioaccumulation factors at the different level of soil contamination. There was performed a comparative evaluation of the accumulation of given contaminants by higher terrestrial plants and representatives of soil paedobionts (Lumbricidae worms), and revealed clear differences in these processes. There was shown the possibility of the use of earthworms as a highly sensitive bio-indicators in monitoring for soil contamination by persistent organic pollutants, even at low concentrations. PMID:27430062

  13. [Application prospect about bioremediation of polychlorinated biphenyls-contaminated soil with immobilized microorganism technique: a review].

    Science.gov (United States)

    Hu, Jin-Xing; Su, Xiao-Mei; Han, Hui-Bo; Shen, Chao-Feng; Shi, Ji-Yan

    2014-06-01

    As one type of the persistent organic pollutants, polychlorinated biphenyls (PCBs) are tremendously harmful to organisms. These compounds are easily absorbed onto soil particles and able to accumulate in soil after they are released into the environment. Bioremediation technology of PCBs-contaminated soils has become a research hotspot in recent years, and immobilized microorganism technique has high developing and applying value because of its unique advantages in environmental remediation. This paper reviewed the chief remediation technology of PCBs-contaminated soils and then analyzed the characteristics of immobilized microorganism technique and its research progress in remediation of organic polluted soil. Finally, the feasibility and problems of this technique in remediation of PCBs-contaminated soil were also discussed.

  14. 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)

  15. Contamination of soil, leaves and vegetables by polychlorinated biphenyls in Xiamen region, China

    Institute of Scientific and Technical Information of China (English)

    MASKAOUI Khalid; ZHOU Jun-liang; HAN Ya-li; HU Zhong; ZHENG Tian-ling; HONG Hua-sheng

    2005-01-01

    The paper aimed to identify the primary of polychlorinated biphenyls(PCBs) in the diulong River Estuary, investigate the spatial distribution of PCBs contamination in the environment, localize the atmospheric source and evaluate ongoing PCBs emissions by analyzing soil samples collected along the Jiulong River region. In addition, the accumulation of PCBs in the human food chain was quantified by analyzing leaf of orange trees and vegetable samples collected along a gradient of soil/atmospheric contamination moving away from the source. Consequently, the impact on the human health and the ecosystem was quantified, different management options were proposedto reduce this impact and to carry out research on organic contaminants along the Jiulong River and Xiamen region.

  16. Polychlorinated biphenyl toxicity to Japanese quail as related to degree of chlorination

    Science.gov (United States)

    Hill, E.F.; Heath, R.G.; Spann, J.W.; Williams, J.D.

    1974-01-01

    To learn if the percentage of chlorine in a mixture of polychlorinated biphenyls (PCB's) alone determines toxicity, Japanese quail were fed diets containing Aroelor 1248, 1254, or 1260 at levels that added equal amounts of chlorine to the feed. The experiment comprised two consecutive 5-day periods; three sublethal concentrations of chlorine were evaluated during the first period and three lethal concentrations during the second period. Evaluations utilized comparisons of mortality, time to death, weight change, and food consumption. Sublethal concentrations produced no detectable effects. Lethal concentrations with equal Chlorine showed Aroelor 1248 to be less toxic at the highest chlorine concentrations, but at lower concentrations Aroelor 1254 was more toxic than Aroclor 1260. Although chlorine percentage of a PCB is positively correlated with its avian toxicity, PCB toxicity is apparently not simply a function of chlorination.

  17. Effect of polychlorinated biphenyls on spermatogenesis and testosterone secretion in adult cocks

    Institute of Scientific and Technical Information of China (English)

    张才乔; 乔惠理

    2004-01-01

    The effects ofpolychlorinated biphenyls (PCBs) on reproduction of adult cocks were studied by gavaging peanut oil or PCBs (Aroclor 1254, 50 mg/kg) once a week for six consecutive weeks. Physiological parameters were recorded and gonads were removed at the end of experiment for histological examination. The results showed that there was no significant difference between the control and treatment group in body weight, respiration rate, heart rate, body temperature, and the numbers of red and white blood cells. However, there was a marked decrease in the testicular weight and serum testosterone level after PCB treatment. Morphological studies manifested severe damage of the seminiferous tubules by PCB. The number of the germ cells at the different developmental stages was decreased and condensed nuclei were observed in most of these cells. This study revealed that the reproductive function of the adult cocks is sensitive to PCBs, which inhibited mainly spermatogenesis and testosterone secretion.

  18. 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.

  19. A new biphenyl from Clusia melchiorii and a new tocotrienol from C. obdeltifolia

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Josanaide S.R.; Moreira, Luciana de M.; Cruz, Frederico G. [Bahia Univ., Salvador, BA (Brazil). Inst. de Quimica]. E-mail: fguare@ufba.br; Guedes, Maria L. da S. [Bahia Univ., Salvador, BA (Brazil). Inst. de Biologia

    2006-08-15

    Chromatographic purification of the dichloromethane extract of Clusia melchiorii trunk leading to the isolation of a new biphenyl, 2,2-dimethyl-5-hydroxy-7-phenylchromene, along with the known compounds 2,2-dimethyl-5,10-dihydro-2H-benzo[g]chromene-5,10-dione (xyloidone), betulinic acid, friedelin, friedelinol, euphol, sitostenone, stigmastenone and a mixture of {beta}-sitosterol and stigmasterol. The hexane extract of Clusia obdeltifolia trunk yielded, after chromatographic fractionation, a new {delta}-tocotrienilic alcohol 2Z, 6E, 10E-13-(6-hydroxy- 2,8-dimethyl-3,4-dihydro-2H,2-chromenyl)-2,6,10-trimethyl- 2,6,10-tridecatrien-1-ol, along with 2Z and 2E-{delta}-tocotrienoloic acids, betulinic acid, betulonic acid, betunilic aldehyde, glutinol, friedelin, sitostenone and a mixture of {beta}-sitosterol and stigmasterol. Their structures were determined from spectral data and comparison with data from previously reported compounds. (author)

  20. Effects of pesticides, polychlorinated biphenyls and metals on the growth and reproduction of Acanthamoeba castellanii

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, L.M.; Kubovec, M.K.; Tryggestad, D.

    1977-07-01

    The effects of pollutants (pesticides, PCB and metals) were studied in the free-living amoeba, Acanthamoeba castellanii. Eight pesticides were used--the insecticides dieldrin, aldrin and sevin, and the herbicides linuron, stam F-34, IPC, atrazine and simazine. It was shown that the sensitivity of A. castellanii to pesticides varied greatly. The population growth was inhibited by linuron, stam F-34, IPC, sevin and atrazine at a level of 10 mg/l. The polychlorinated biphenyl, Arochor 1254, had no significant effect at a concentration of 0.01 mg/l (10 ppb). The studies with metal ions showed that A. castellanii was unaffected by moderately high levels of Cu and Zn, but was sensitive to the presence of Pb and mercuric ions.