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The Peroxisomal β-Oxidation Systems: Characteristics and (Dys) Functions in Man

  • R. J. A. Wanders
  • C. W. T. Van Roermund
  • M. J. A. Van Wijland
  • R. B. H. Schutgens
  • H. Van Den Bosch
  • J. M. Tager
Conference paper

Abstract

Peroxisomes are now known to be present in virtually every mammalian cell except the mature erythrocyte. They were first described by Rhodin in 1954 as “spheric or oval bodies” present in the cytoplasm of mouse proximal kidney tubules [1]. Evidence that these “microbodies” were, indeed, different from the other subcellular organelles known at that time, came from cell fractionation experiments by de Duve and co-workers (see [2] for review). The identification of catalase and several Hb2O2-producing oxidases (D-aminoacid oxidase, urate oxidase, glycollate oxidase) within this organelle prompted de Duve and co-workers to introduce the name “peroxisome”.

Keywords

Zellweger Syndrome Hexacosanoic Acid Chain Fatty Acid Oxidation Zellweger Patient Thiolase Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Rhodin J (1954) Correlation of ultrastructural organisation and function in normal and experimentally changed proximal tubule cells of the mouse kidney. PhD Thesis, Aktiebolaget Godvil, StockholmGoogle Scholar
  2. 2.
    De Duve C, Baudhuin P (1966) Peroxisomes (microbodies) and related particles. Physiol Rev 46:323–357PubMedGoogle Scholar
  3. 3.
    Lazarow P, de Duve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes: enhancement by clofibrate, a hypolipidemic drug. Proe Natl Acad Sci USA 73:2043–2046CrossRefGoogle Scholar
  4. 4.
    Cooper TG, Beevers H (1969) β-oxidation in glyoxysomes from castor bean endosperm. J Biol Chem 244:3514–3520PubMedGoogle Scholar
  5. 5.
    Kunau WH, Kionka C, Ledebur A, Mateblowski M, Moreno de la Garza M, Schultz-Borchard U, Thieringer R, Veenhuis M (1987) β-oxidation systems in eukaryotic microorganisms. In: Fahimi HD, Sies H (eds) Peroxisomes in biology and medicine. Springer, Berlin Heidelberg New York Tokyo, pp 128–140CrossRefGoogle Scholar
  6. 6.
    Tanaka T, Hosaka T, Hoshimaru M, Numa S (1979) Purification and properties of long-chain acyl coenzyme A synthetase from rat liver. Eur J Biochem 98:165–172PubMedCrossRefGoogle Scholar
  7. 7.
    Shindo Y, Hashimoto T (1978) Acyl-coenzyme A synthetase and fatty acid oxidation in rat liver peroxisomes. J Biochem 84:1177–1181PubMedGoogle Scholar
  8. 8.
    Krisans SK, Mortensen RM, Lazarow PB (1980) Acyl-CoA synthetase in rat liver peroxisomes. J Biol Chem 255:9599–9607PubMedGoogle Scholar
  9. 9.
    Mannaerts GP, Van Veldhoven P, Van Broekhoven A, Van de Broek G, De Beer LJ (1982) Evidence that peroxisomal acyl-CoA synthetase is located at the cytoplasmic site of the peroxi-somal membrane. Biochem J 204:17–23PubMedGoogle Scholar
  10. 10.
    Miyazawa S, Hashimoto T, Yokota S (1985) Identity of long-chain acyl coenzyme A synthetase of microsomes, mitochondria, and peroxisomes in rat liver. J Biochem 98:723–733PubMedGoogle Scholar
  11. 11.
    Bremer J, Osmundsen H (1984) Fatty acid oxidation and its regulation. In: Numa S (ed) Fatty acid metabolism and its regulation. Elsevier, Amsterdam, pp 113–154CrossRefGoogle Scholar
  12. 12.
    Schulz H (1985) Oxidation of fatty acids. In: Vance DE, Vance FE (eds) Biochemistry of lipids and membranes. Benjamin/Cummings, Menlo Park, CA, pp 116–142Google Scholar
  13. 13.
    Middleton B (1973) The oxoacyl CoA thiolases of animal tissues. Biochem J 132:717–730PubMedGoogle Scholar
  14. 14.
    Staack H, Binstock JF, Schulz H (1978) Purification and properties of a pig heart thiolase with broad chain length specificity and comparison of thiolases from heart and Escherichia coli. J Biol Chem 253:1827–1831PubMedGoogle Scholar
  15. 15.
    Bhusnan A, Singh RP, Singh I (1986) Characterization of rat brain microsomal acyl-coenzyme A ligase: different enzymes for the synthesis of palmitoyl-CoA and lignoceroyl-CoA. Arch Biochem Biophys 246:374–380CrossRefGoogle Scholar
  16. 16.
    Wanders RJA, van Roermund CWT, van Wijland MJA, Schutgens RBH, Schram AW, van den Bosch H, Tager JM (1987) Studies on the peroxisomal oxidation of palmitate and lignocerate in rat liver. Biochim Biophys Acta 919:21–25PubMedGoogle Scholar
  17. 17.
    Singh H, Derwas N, Poulos A (1987) Very long chain fatty acid β-oxidation by rat liver mitochondria and peroxisomes. Arch Biochem Biophys 359:382–390CrossRefGoogle Scholar
  18. 18.
    Wanders RJA, van Roermund CWT, van Wijland MJA, Schutgens RBH, Heikoop J, van den Bosch H, Schräm AW, Tager JM (1987) Peroxisomal fatty acid β-oxidation in relation to the accumulation of very long chain fatty acids in peroxisomal disorders. J Clin Invest 80:1778–1783PubMedCrossRefGoogle Scholar
  19. 19.
    Wanders RJA, van Roermund CWT, van Wijland MJA, Schutgens RBH, van den Bosch H, Schräm AW, Tager JM (1988) Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids. Biochem Biophys Res Commun 153:618–624PubMedCrossRefGoogle Scholar
  20. 20.
    Osumi T, Hashimoto T (1978) Acyl-CoA oxidase of rat liver: a new enzyme for fatty acid oxidation. Biochem Biophys Res Commun 83:479–485PubMedCrossRefGoogle Scholar
  21. 21.
    Inestrosa NC, Bronfman M, Leighton F (1979) Detection of peroxisomal fatty acyl-coenzyme A oxidase activity. Biochem J 182:779–788PubMedGoogle Scholar
  22. 22.
    Osumi T, Hashimoto T, Ui N (1980) Acyl-CoA oxidase of rat liver: a new enzyme for fatty acid oxidation. J Biochem 87; 1735–1746PubMedGoogle Scholar
  23. 23.
    Inestrosa NC, Bronfman M, Leighton M (1980) Purification of the peroxisomal fatty acyl-Coa oxidase from rat liver. Biochem Biophys Res Commun 95:7–12PubMedCrossRefGoogle Scholar
  24. 24.
    Osumi T, Hashimoto T (1979) Peroxisomal β-oxidation system of rat liver. Copurification of enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. Biochem Biophys Res Commun 89:580–584PubMedCrossRefGoogle Scholar
  25. 25.
    Furuta S, Miyazawa S, Osumi T, Hashimoto T, Ui N (1980) Properties of mitochondrial and peroxisomal enoyl-CoA hydratase from rat liver. J Biochem 88; 1059–1070PubMedGoogle Scholar
  26. 26.
    Osumi T, Hashimoto T (1980) Purification and properties of mitochondrial and peroxisomal 3-hydroxyacyl-CoA dehydrogenase from rat liver. Arch Biochem Biophys 203:372–383PubMedCrossRefGoogle Scholar
  27. 27.
    Miyazawa S, Osumi T, Hashimoto T (1980) The presence of a new 3-oxoacyl-CoA thiolase in rat liver peroxisomes. Eur J Biochem 103:589–596PubMedCrossRefGoogle Scholar
  28. 28.
    Miyazawa S, Furuta S, Osumi T, Hashimoto T, Ui N (1981) Properties of peroxisomal 3-ketoacyl-Coa thiolase from rat liver. J Biochem 90:511–519PubMedGoogle Scholar
  29. 29.
    Markwell MAK, Tolbert NE, Bieber LL (1976) Comparison of the carnitine acyltransferase activities from rat liver peroxisomes and microsomes. Arch Biochem Biophys 176:479–488CrossRefGoogle Scholar
  30. 30.
    Miyazawa S, Ozasu H, Osumi T, Hashimoto T (1983) Purification and properties of carnitine octanoyltransferase and carnitine palmitoyltransferase from rat liver. J Biochem 94:529–542PubMedGoogle Scholar
  31. 31.
    Markwell MAK, McGroarty EJ, Bieber LL, Tolbert NE (1973) The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney. A new peroxisomal enzyme. J Biol Chem 248:3426–3452PubMedGoogle Scholar
  32. 32.
    Farrell SO, Bieber LL (1983) Carnitine octanoyltransferase of mouse liver peroxisomes: properties and effect of hypolipidemic drugs. Arch Biochem Biophys 222:123–132PubMedCrossRefGoogle Scholar
  33. 33.
    Stoffel W, Ditzer R, Caesar H (1964) Der Stoffwechsel der ungesättigten Fettsäuren III. Zur β-Oxidation der Mono-und Polyenfettsäuren. Der Mechanismus der enzymatischen Reaktionen an A3-cis-enoyl-CoA-Verbindungen. Hoppe-Seylers Z Physiol Chem 339:167–181PubMedCrossRefGoogle Scholar
  34. 34.
    Stoffel W, Caesar H (1965) Der Stoffwechsel der ungesättigten Fettsäuren V. Zur β-Oxidation der Mono-und Polyenfettsäuren. Der mechanismus der enzymatischen Reaktionen an A2-cis-en-oyl-CoA-Verbindungen. Hoppe-Seylers Z Physiol Chem 341:76–83PubMedCrossRefGoogle Scholar
  35. 35.
    Kunau WH, Schulz H (1987) β-oxidation of unsaturated fatty acids: a revised pathway. Trends Biochem Sci 12:403–406CrossRefGoogle Scholar
  36. 36.
    Dommes V, Kunau WH (1984) Purification and properties of acyl coenzyme A dehydrogenases from bovine liver. J Biol Chem 259:1789–1797PubMedGoogle Scholar
  37. 37.
    Kimura C, Kondo A, Koeda N, Yamanaka H, Mizugaki M (1984) Studies on the metabolism of unsaturated fatty acids. XV. Purification and properties of 2,4-dienoyl-CoA reductase from rat liver peroxisomes. J Biochem 96:1463–1469PubMedGoogle Scholar
  38. 38.
    Kärki T, Hakkola E, Hassinen IE, Hiltunen JK (1987) β-oxidation of polyunsaturated fatty acids in peroxisomes. Subcellular distribution of Δ3, Δ2-enoyl-CoA isomerase activity in rat liver. FEBS Lett 215:228–232PubMedCrossRefGoogle Scholar
  39. 39.
    Palosaari PM, Autio-Harmainen H, Sormunen R, Hassinen IE, Hiltunen JK (1988) β-oxidation of polyunsaturated fatty acids. Peroxisomal Δ32-enoyl-CoA isomerase in rat liver. In: IUB-Congr, Prague (Abstr)Google Scholar
  40. 40.
    Furuta S, Miyazawa S, Hashimoto T (1981) Purification and properties of rat liver acyl-CoA dehydrogenases and electron transfer flavoprotein. J Biochem 90:1739–1750PubMedGoogle Scholar
  41. 41.
    Osumi T, Hashimoto T (1980) Purification and properties of mitochondrial and peroxisomal 3-hydroxyacyl-CoA dehydrogenase from rat liver. Arch Biochem Biophys 203:372–383PubMedCrossRefGoogle Scholar
  42. 42.
    Miyazawa S, Ozasa H, Furuta S, Osumi T, Hashimoto T (1983) Purification and properties of carnitine acetyltransferase from rat liver. J Biochem 93:439–451PubMedGoogle Scholar
  43. 43.
    Ikeda Y, Dabrowski C, Tanaka K (1983) Separation and properties of five distinct acyl-CoA dehydrogenases from rat liver mitochondria. Identification of a new 2-methyl-branched chain acyl-CoA dehydrogenase. J Biol Chem 258:1066–1076Google Scholar
  44. 44.
    Neat CE, Thomassen MS, Osmundsen H (1981) Effects of high-fat diets on hepatic fatty acid oxidation in the rat. Biochem J 196:149–159PubMedGoogle Scholar
  45. 45.
    Horie S, Suga T (1985) Enhancement of peroxisomal β-oxidation in the liver of rats and mice treated with valproic acid. Biochem Pharmacol 34:1357–1362PubMedCrossRefGoogle Scholar
  46. 46.
    Van den Branden C, Vamecq J, Wijbo I, Roels F (1986) Phytol and peroxisome proliferation. Pediatr Res 20:411–415PubMedCrossRefGoogle Scholar
  47. 47.
    Just WW, Hartl FU (1983) Stimulation of peroxisomal fatty acid β-oxidation by thyroid hormones. Hoppe-Seylers Z Physiol Chem 264:1541–1547CrossRefGoogle Scholar
  48. 48.
    Reddy JK, Lalwani ND, Dabholkar AS, Reddy MK, Qureshi SA (1981) Proliferation of perox-isomes and vitamin E deficiency. Biochem Int 3:41–49Google Scholar
  49. 49.
    Nedergaard J, Alexson S, Cannon B (1980) Cold adaptation in the rat: increased brown fat peroxisomal β-oxidation relative to maximal mitochondrial oxidative capacity. Am j Physiol 239:C208–C216PubMedGoogle Scholar
  50. 50.
    Black VA, Russo JJ (1980) Hormone-dependent changes in peroxisomal enzyme activity in guinea pig adrenal. Am J Anat 159:85–120PubMedCrossRefGoogle Scholar
  51. 51.
    Mannaerts GP, De Beer LJ, Thomas J, De Schepper PJ ( 1979) Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates from control and clofibrate treated rats. J Biol Chem 254:4585–4595PubMedGoogle Scholar
  52. 52.
    Ide T, Ontko JA (1981) Increased secretion of very low density lipoprotein triglycéride following inhibition of long chain fatty acid oxidation in isolated rat liver. J Biol Chem 256:10247–10255PubMedGoogle Scholar
  53. 53.
    Foerster EC, Fuhrenkemper T, Rabe U, Graf P, Sies H (1981) Peroxisomal fatty acid oxidation as detected by H2O2 production in intact perfused liver. Biochem J 196:705–712PubMedGoogle Scholar
  54. 54.
    Tager JM, Ten Harmsen van de Beek WA, Wanders RJA, Hashimoto T, Heymans HSA, van den Bosch H, Schutgens RBH, Schräm AW (1985) Peroxisomal β-oxidation enzyme proteins in the Zellweger syndrome. Biochem Biophys Res Commun 126:1269–1275PubMedCrossRefGoogle Scholar
  55. 55.
    Lazarow PB, Black V, Shio H, Fujiki Y, Hajra AK, Datta NS, Bangaru BS, Dancis J (1985) Zellweger syndrome: biochemical and morphological studies on two patients treated with clofibrate. Pediatr Res 19:1356–1364PubMedCrossRefGoogle Scholar
  56. 56.
    Suzuki Y, Orii T, Mori M, Tatibana M, Hashimoto T (1986) Deficient activities and proteins of peroxisomal β-oxidation enzymes in infants with Zellweger syndrome. Clin Chim Acta 156:191–196PubMedCrossRefGoogle Scholar
  57. 57.
    Chen WW, Watkins PP, Osumi T, Hashimoto T, Moser HW (1987) Peroxisomal β-oxidation enzyme proteins in adrenoleukodystrophy: distinction between X-linked and neonatal adren-oleukodystrophy. Proc Natl Acad Sci USA 84:1425–1428PubMedCrossRefGoogle Scholar
  58. 58.
    Poll-Thé BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RBH, Wanders RJA, van Roermund CWT, van Wijland MJA, Schräm AW, Tager JM, Saudubray JM (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudoneonatal adrenoleukodystrophy). Am J Human Genet 42:422–434Google Scholar
  59. 59.
    Schräm AW, Goldfischer S, van Redmond CWT, Brouwer-Kelder EM, Collins J, Hashimoto T, Heymans HSA, van den Bosch H, Schutgens RBH, Tager JM, Wanders RJA (1987) Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci USA 84:2494–2497PubMedCrossRefGoogle Scholar
  60. 60.
    Wanders RJA, Heymans HSA, Schutgens RBH, Barth PG, van den Bosch H, Tager JM (1988) Peroxisomal disorders in neurology. J Neurol Sci 88:1–39PubMedCrossRefGoogle Scholar
  61. 61.
    Numa S (1981) Two long-chain acyl coenzyme A synthestases: their different roles in fatty acid metabolism and its regulation. Trends Biochem Sci 6:113–115CrossRefGoogle Scholar
  62. 62.
    Kawamura N, Moser HW, Kishimoto Y (1981) Very long chain fatty acid oxidation in rat liver. Biochem Biophys Res Commun 99:1216–1225PubMedCrossRefGoogle Scholar
  63. 63.
    Singh I, Moser AB, Goldfischer S, Moser HW (1984) Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebrohepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci USA 81:4203–4207PubMedCrossRefGoogle Scholar
  64. 64.
    Bremer J (1977) Carnitine and its role in fatty acid metabolism. Trends Biochem Sci 2:207–209Google Scholar
  65. 65.
    Singh H, Derwas N, Poulos a (1987) β-oxidation of very long chain fatty acids and their coenzyme A derivatives by human skin fibroblasts. Arch Biochem Biophys 254:526–533PubMedCrossRefGoogle Scholar
  66. 66.
    Christiansen RZ (1978) The effect of clofibrate feeding on hepatic fatty acid metabolism. Biochim Biophys Acta 530:314–324PubMedGoogle Scholar
  67. 67.
    Bremer J, Norum KR ( 1982) Metabolism of very long chain monounsaturated fatty acids (C22:1) and the adaptation to their presence in the diet. J Lipid Res 23:243–256PubMedGoogle Scholar
  68. 68.
    Dommes V, Baumgart C, Kunau WH (1981) Degradation of unsaturated fatty acids in peroxi-somes. J Biol Chem 256:8259–8262PubMedGoogle Scholar
  69. 69.
    Hiltunen JK, Kärki T, Hassinen IE, Osmundsen H (1986) β-oxidation of polyunsaturated fatty acids by rat liver peroxisomes. A role for 2,4-dienoyl-coenzyme A reductase in peroxisomal β-oxidation. J Biol Chem 261:16484–16493PubMedGoogle Scholar
  70. 70.
    Hovik R, Osmundsen H (1987) Peroxisomal β-oxidation of long-chain fatty acids possessing different extents of unsaturation. Biochem J 247:531–535PubMedGoogle Scholar
  71. 71.
    Kolvraa S, Gregersen N ( 1986) In vitro studies on the oxidation of medium chain dicarboxylic acids in rat liver. Biochim Biophys Acta 876:515–525PubMedGoogle Scholar
  72. 72.
    Vamecq J, Draye JP (1987) Interaction between the and β-oxidation of fatty acids. J Biochem 102:225–234PubMedGoogle Scholar
  73. 73.
    Vamecq J, de Hoffmann E, Van Hoof F (1985) The microsomal dicarboxylyl-CoA synthetase. Biochem J 230:683–693PubMedGoogle Scholar
  74. 74.
    Danielsson H, Sjövall J (1975) Bile acid metabolism. Annu Rev Biochem 44:233–253PubMedCrossRefGoogle Scholar
  75. 75.
    Masui T, Staple E (1966) The formation of bile acids from cholesterol. J Biol Chem 241:3889–3893PubMedGoogle Scholar
  76. 76.
    Pedersen JI, Gustafsson J (1980) Conversion of 3a, 7a, 12a-trihydroxy-5β-cholestanoic acid into cholic acid by rat liver peroxisomes. FEBS Lett 121:345–348PubMedCrossRefGoogle Scholar
  77. 77.
    Käse BF, Björkhem I, Pedersen JI (1983) Formation of cholic acid from 3α, 7α, 12α-trihydroxy-5β-eholestanoic acid by rat liver peroxisomes. J Lipid Res 24:1560–1567PubMedGoogle Scholar
  78. 78.
    Käse BF, Prydz K, Björkhem I, Pedersen JI (1986) In vitro formation of bile acids from di-and trihydroxy-5β-cholestanoic acid in human liver peroxisomes. Biochim Biophys Acta 877:37–42PubMedGoogle Scholar
  79. 79.
    Kase BF, Pedersen JI, Strandvik B, Björkhem I (1985) In vivo and in vitro studies on the formation of bile acids in patients with the Zellweger syndrome. Evidence that peroxisomes are of importance in the normal biosynthesis of both cholic acid and chenodeoxycholic acid. J Clin Invest 76:2393–2402PubMedCrossRefGoogle Scholar
  80. 80.
    Casteels M, Schepers L, Van Eldere J, Eyssen H, Mannaerts GP (1988) Inhibition of 3α, 7α, 12a-trihydroxy-5β-cholestanoic acid oxidation and of bile acid secretion in rat liver by fatty acids. J Biol Chem 263:4654–4661PubMedGoogle Scholar
  81. 81.
    Hamberg M (1968) Metabolism of prostaglandins in rat liver mitochondria. Eur J Biochem 6:135–146PubMedCrossRefGoogle Scholar
  82. 82.
    Diczfalusy U, Alexson SEH, Pedersen JI (1987) Chain-shortening of prostaglandin F2a by rat liver peroxisomes. Biochem Biophys Res Commun 144:1206–1215PubMedCrossRefGoogle Scholar
  83. 83.
    Schepers L, Casteels M, Vamecq J, Parmentier G, Van Veldhoven PP, Mannaerts GP (1988) β-oxidation of the carboxyl side chain of prostaglandin E2 in rat liver peroxisomes and mitochondria. J Biol Chem 263:2724–2731PubMedGoogle Scholar
  84. 84.
    Yamada J, Horie S, Watanabe T, Suga T (1984) Participation of peroxisomal β-oxidation system in the chain-shortening of a xenobiotic acyl compound. Biochem Biophys Res Commun 125:123–128PubMedCrossRefGoogle Scholar
  85. 85.
    Yamada J, Itoh S, Horie S, Watanabe T, Suga T (1986) Chain-shortening of a xenobiotic acyl compound by the peroxisomal β-oxidation system in rat liver. Biochem Pharmacol 35:4363–4368PubMedCrossRefGoogle Scholar
  86. 86.
    Simon EJ, Gross CS, Milhorat AT (1985) The metabolism of vitamin E. J Biol Chem 221:797–805Google Scholar
  87. 87.
    Stene DO, Murphy RC (1988) Metabolism of leukotriene E4 in isolated rat hepatocytes. J Biol Chem 263:2773–2778PubMedGoogle Scholar
  88. 88.
    Tsukamoto T, Ohno K, Yokota S, Fujiki Y (1987) Biogenesis of 15 kD integral membrane protein of rat liver peroxisomes, a common endomembrane protein. In: Tada K, Orii T, Hashimoto T, Fujiki Y (eds) 4th Int Congr Inborn errors of metabolism Abstr, p 20Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • R. J. A. Wanders
    • 1
  • C. W. T. Van Roermund
    • 1
  • M. J. A. Van Wijland
    • 1
  • R. B. H. Schutgens
    • 1
  • H. Van Den Bosch
    • 2
  • J. M. Tager
    • 3
  1. 1.Department of PediatricsUniversity Hospital AmsterdamAmsterdamThe Netherlands
  2. 2.Department of BiochemistryState University UtrechtUtrechtThe Netherlands
  3. 3.Department of BiochemistryUniversity of AmsterdamAmsterdamThe Netherlands

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