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Volumn 50, Issue 1, 2011, Pages 37-47

The synucleins are a family of redox-active copper binding proteins

Author keywords

[No Author keywords available]

Indexed keywords

C-TERMINUS; COORDINATING LIGANDS; COPPER (II); COPPER CENTERS; COPPER-BINDING PROTEINS; HIGH AFFINITY; N-TERMINALS; NANOMOLAR AFFINITY; REDOX CYCLING; REDOX-ACTIVE; SYNUCLEIN; THERMODYNAMIC STUDIES;

EID: 78650872712     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi101582p     Document Type: Article
Times cited : (63)

References (65)
  • 1
    • 1642342857 scopus 로고    scopus 로고
    • Recent advances in research on Parkinson disease: Synuclein and parkin
    • Burke, R. E. (2004) Recent advances in research on Parkinson disease: synuclein and parkin Neurologist 10, 75-81
    • (2004) Neurologist , vol.10 , pp. 75-81
    • Burke, R.E.1
  • 3
    • 0034169203 scopus 로고    scopus 로고
    • Toxicity of non-abeta component of Alzheimer's disease amyloid, and N-terminal fragments thereof, correlates to formation of beta-sheet structure and fibrils
    • Bodles, A. M., Guthrie, D. J., Harriott, P., Campbell, P., and Irvine, G. B. (2000) Toxicity of non-abeta component of Alzheimer's disease amyloid, and N-terminal fragments thereof, correlates to formation of beta-sheet structure and fibrils Eur. J. Biochem. 267, 2186-2194
    • (2000) Eur. J. Biochem. , vol.267 , pp. 2186-2194
    • Bodles, A.M.1    Guthrie, D.J.2    Harriott, P.3    Campbell, P.4    Irvine, G.B.5
  • 4
    • 33645343557 scopus 로고    scopus 로고
    • Upregulation of alpha-synuclein in neurons and glia in inflammatory demyelinating disease
    • Papadopoulos, D., Ewans, L., Pham-Dinh, D., Knott, J., and Reynolds, R. (2006) Upregulation of alpha-synuclein in neurons and glia in inflammatory demyelinating disease Mol. Cell. Neurosci. 31, 597-612
    • (2006) Mol. Cell. Neurosci. , vol.31 , pp. 597-612
    • Papadopoulos, D.1    Ewans, L.2    Pham-Dinh, D.3    Knott, J.4    Reynolds, R.5
  • 11
    • 0034681471 scopus 로고    scopus 로고
    • Dopaminergic loss and inclusion body formation in alpha-synuclein mice: Implications for neurodegenerative disorders
    • Masliah, E., Rockenstein, E., Veinbergs, I., Mallory, M., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., and Mucke, L. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders Science 287, 1265-1269
    • (2000) Science , vol.287 , pp. 1265-1269
    • Masliah, E.1    Rockenstein, E.2    Veinbergs, I.3    Mallory, M.4    Hashimoto, M.5    Takeda, A.6    Sagara, Y.7    Sisk, A.8    Mucke, L.9
  • 12
    • 32344444326 scopus 로고    scopus 로고
    • Down-regulation of alpha-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson's disease rat model
    • Hayashita-Kinoh, H., Yamada, M., Yokota, T., Mizuno, Y., and Mochizuki, H. (2006) Down-regulation of alpha-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson's disease rat model Biochem. Biophys. Res. Commun. 341, 1088-1095
    • (2006) Biochem. Biophys. Res. Commun. , vol.341 , pp. 1088-1095
    • Hayashita-Kinoh, H.1    Yamada, M.2    Yokota, T.3    Mizuno, Y.4    Mochizuki, H.5
  • 13
    • 0028277520 scopus 로고
    • Identification of two distinct synucleins from human brain
    • Jakes, R., Spillantini, M. G., and Goedert, M. (1994) Identification of two distinct synucleins from human brain FEBS Lett. 345, 27-32
    • (1994) FEBS Lett. , vol.345 , pp. 27-32
    • Jakes, R.1    Spillantini, M.G.2    Goedert, M.3
  • 14
    • 0032540327 scopus 로고    scopus 로고
    • Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes
    • Davidson, W. S., Jonas, A., Clayton, D. F., and George, J. M. (1998) Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes J. Biol. Chem. 273, 9443-9449
    • (1998) J. Biol. Chem. , vol.273 , pp. 9443-9449
    • Davidson, W.S.1    Jonas, A.2    Clayton, D.F.3    George, J.M.4
  • 15
  • 16
    • 43049150678 scopus 로고    scopus 로고
    • Metals in Alzheimer's and Parkinson's diseases
    • Barnham, K. J. and Bush, A. I. (2008) Metals in Alzheimer's and Parkinson's diseases Curr. Opin. Chem. Biol. 12, 222-228
    • (2008) Curr. Opin. Chem. Biol. , vol.12 , pp. 222-228
    • Barnham, K.J.1    Bush, A.I.2
  • 20
    • 68849102707 scopus 로고    scopus 로고
    • Unique copper-induced oligomers mediate alpha-synuclein toxicity
    • Wright, J. A., Wang, X., and Brown, D. R. (2009) Unique copper-induced oligomers mediate alpha-synuclein toxicity FASEB J. 23, 2384-2393
    • (2009) FASEB J. , vol.23 , pp. 2384-2393
    • Wright, J.A.1    Wang, X.2    Brown, D.R.3
  • 21
    • 0033564726 scopus 로고    scopus 로고
    • Copper(II)-induced self-oligomerization of alpha-synuclein
    • Paik, S. R., Shin, H. J., Lee, J. H., Chang, C. S., and Kim, J. (1999) Copper(II)-induced self-oligomerization of alpha-synuclein Biochem. J. 340 (Part 3) 821-828
    • (1999) Biochem. J. , vol.340 , Issue.PART 3 , pp. 821-828
    • Paik, S.R.1    Shin, H.J.2    Lee, J.H.3    Chang, C.S.4    Kim, J.5
  • 23
    • 0036152892 scopus 로고    scopus 로고
    • Iron and Parkinson's disease
    • Wolozin, B. and Golts, N. (2002) Iron and Parkinson's disease Neuroscientist 8, 22-32
    • (2002) Neuroscientist , vol.8 , pp. 22-32
    • Wolozin, B.1    Golts, N.2
  • 24
    • 33746633380 scopus 로고    scopus 로고
    • Interaction of alpha-synuclein with divalent metal ions reveals key differences: A link between structure, binding specificity and fibrillation enhancement
    • Binolfi, A., Rasia, R. M., Bertoncini, C. W., Ceolin, M., Zweckstetter, M., Griesinger, C., Jovin, T. M., and Fernandez, C. O. (2006) Interaction of alpha-synuclein with divalent metal ions reveals key differences: a link between structure, binding specificity and fibrillation enhancement J. Am. Chem. Soc. 128, 9893-9901
    • (2006) J. Am. Chem. Soc. , vol.128 , pp. 9893-9901
    • Binolfi, A.1    Rasia, R.M.2    Bertoncini, C.W.3    Ceolin, M.4    Zweckstetter, M.5    Griesinger, C.6    Jovin, T.M.7    Fernandez, C.O.8
  • 26
    • 0037013194 scopus 로고    scopus 로고
    • Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein
    • Golts, N., Snyder, H., Frasier, M., Theisler, C., Choi, P., and Wolozin, B. (2002) Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein J. Biol. Chem. 277, 16116-16123
    • (2002) J. Biol. Chem. , vol.277 , pp. 16116-16123
    • Golts, N.1    Snyder, H.2    Frasier, M.3    Theisler, C.4    Choi, P.5    Wolozin, B.6
  • 27
    • 0035941201 scopus 로고    scopus 로고
    • Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure
    • Uversky, V. N., Li, J., and Fink, A. L. (2001) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure J. Biol. Chem. 276, 44284-44296
    • (2001) J. Biol. Chem. , vol.276 , pp. 44284-44296
    • Uversky, V.N.1    Li, J.2    Fink, A.L.3
  • 28
    • 33644847016 scopus 로고    scopus 로고
    • NMR mapping of copper binding sites in alpha-synuclein
    • Sung, Y. H., Rospigliosi, C., and Eliezer, D. (2006) NMR mapping of copper binding sites in alpha-synuclein Biochim. Biophys. Acta 1764, 5-12
    • (2006) Biochim. Biophys. Acta , vol.1764 , pp. 5-12
    • Sung, Y.H.1    Rospigliosi, C.2    Eliezer, D.3
  • 29
    • 28444447471 scopus 로고    scopus 로고
    • Coordination abilities of N-terminal fragments of alpha-synuclein towards copper(II) ions: A combined potentiometric and spectroscopic study
    • Kowalik-Jankowska, T., Rajewska, A., Wisniewska, K., Grzonka, Z., and Jezierska, J. (2005) Coordination abilities of N-terminal fragments of alpha-synuclein towards copper(II) ions: a combined potentiometric and spectroscopic study J. Inorg. Biochem. 99, 2282-2291
    • (2005) J. Inorg. Biochem. , vol.99 , pp. 2282-2291
    • Kowalik-Jankowska, T.1    Rajewska, A.2    Wisniewska, K.3    Grzonka, Z.4    Jezierska, J.5
  • 31
    • 0032533958 scopus 로고    scopus 로고
    • Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system
    • Buchman, V. L., Hunter, H. J., Pinon, L. G., Thompson, J., Privalova, E. M., Ninkina, N. N., and Davies, A. M. (1998) Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system J. Neurosci. 18, 9335-9341
    • (1998) J. Neurosci. , vol.18 , pp. 9335-9341
    • Buchman, V.L.1    Hunter, H.J.2    Pinon, L.G.3    Thompson, J.4    Privalova, E.M.5    Ninkina, N.N.6    Davies, A.M.7
  • 33
    • 0036121284 scopus 로고    scopus 로고
    • Purification and preparation of prion protein: Synaptic superoxide dismutase
    • Daniels, M. and Brown, D. R. (2002) Purification and preparation of prion protein: synaptic superoxide dismutase Methods Enzymol. 349, 258-267
    • (2002) Methods Enzymol. , vol.349 , pp. 258-267
    • Daniels, M.1    Brown, D.R.2
  • 34
    • 38749114643 scopus 로고    scopus 로고
    • Determining thermodynamic parameters from isothermal calorimetric isotherms of the binding of macromolecules to metal cations originally chelated by a weak ligand
    • Hong, L., Bush, W. D., Hatcher, L. Q., and Simon, J. (2008) Determining thermodynamic parameters from isothermal calorimetric isotherms of the binding of macromolecules to metal cations originally chelated by a weak ligand J. Phys. Chem. B 112, 604-611
    • (2008) J. Phys. Chem. B , vol.112 , pp. 604-611
    • Hong, L.1    Bush, W.D.2    Hatcher, L.Q.3    Simon, J.4
  • 35
    • 67650299008 scopus 로고    scopus 로고
    • Binding of Cu(II) to human alpha-synucleins: Comparison of wild type and the point mutations associated with the familial Parkinson's disease
    • Hong, L. and Simon, J. D. (2009) Binding of Cu(II) to human alpha-synucleins: comparison of wild type and the point mutations associated with the familial Parkinson's disease J. Phys. Chem. B 113, 9551-9561
    • (2009) J. Phys. Chem. B , vol.113 , pp. 9551-9561
    • Hong, L.1    Simon, J.D.2
  • 37
    • 65249118776 scopus 로고    scopus 로고
    • Thermodynamic and voltammetric characterization of the metal binding to the prion protein insights into pH dependence and redox chemistry
    • Davies, P., Marken, F., and Brown, D. (2009) Thermodynamic and voltammetric characterization of the metal binding to the prion protein insights into pH dependence and redox chemistry Biochemistry 48, 2610-2619
    • (2009) Biochemistry , vol.48 , pp. 2610-2619
    • Davies, P.1    Marken, F.2    Brown, D.3
  • 38
    • 0034631701 scopus 로고    scopus 로고
    • Isothermal titration calorimetry measurements of Ni(II) and Cu(II) binding to His, GlyGlyHis, HisGlyHis, and bovine serum albumin: A critical evaluation
    • Zhang, Y., Akilesh, S., and Wilcox, D. E. (2000) Isothermal titration calorimetry measurements of Ni(II) and Cu(II) binding to His, GlyGlyHis, HisGlyHis, and bovine serum albumin: a critical evaluation Inorg. Chem. 39, 3057-3064
    • (2000) Inorg. Chem. , vol.39 , pp. 3057-3064
    • Zhang, Y.1    Akilesh, S.2    Wilcox, D.E.3
  • 39
    • 0016369980 scopus 로고
    • Structural implications derived from the analysis of electron paramagnetic resonance spectra of natural and artificial copper proteins
    • Peisach, J. and Blumberg, W. E. (1974) Structural implications derived from the analysis of electron paramagnetic resonance spectra of natural and artificial copper proteins Arch. Biochem. Biophys. 165, 691-708
    • (1974) Arch. Biochem. Biophys. , vol.165 , pp. 691-708
    • Peisach, J.1    Blumberg, W.E.2
  • 40
    • 33846527387 scopus 로고    scopus 로고
    • Survey of the year 2005: Literature on applications of isothermal titration calorimetry
    • Ababou, A. and Ladbury, J. E. (2007) Survey of the year 2005: literature on applications of isothermal titration calorimetry J. Mol. Recognit. 20, 4-14
    • (2007) J. Mol. Recognit. , vol.20 , pp. 4-14
    • Ababou, A.1    Ladbury, J.E.2
  • 41
    • 31144454672 scopus 로고    scopus 로고
    • Survey of the year 2004: Literature on applications of isothermal titration calorimetry
    • Ababou, A. and Ladbury, J. E. (2006) Survey of the year 2004: literature on applications of isothermal titration calorimetry J. Mol. Recognit. 19, 79-89
    • (2006) J. Mol. Recognit. , vol.19 , pp. 79-89
    • Ababou, A.1    Ladbury, J.E.2
  • 42
    • 52649127984 scopus 로고    scopus 로고
    • A survey of the year 2007 literature on applications of isothermal titration calorimetry
    • Bjelic, S. and Jelesarov, I. (2008) A survey of the year 2007 literature on applications of isothermal titration calorimetry J. Mol. Recognit. 21, 289-312
    • (2008) J. Mol. Recognit. , vol.21 , pp. 289-312
    • Bjelic, S.1    Jelesarov, I.2
  • 43
    • 8444250720 scopus 로고    scopus 로고
    • A survey of the year 2003 literature on applications of isothermal titration calorimetry
    • Cliff, M. J., Gutierrez, A., and Ladbury, J. E. (2004) A survey of the year 2003 literature on applications of isothermal titration calorimetry J. Mol. Recognit. 17, 513-523
    • (2004) J. Mol. Recognit. , vol.17 , pp. 513-523
    • Cliff, M.J.1    Gutierrez, A.2    Ladbury, J.E.3
  • 44
    • 0842310293 scopus 로고    scopus 로고
    • A survey of the year 2002 literature on applications of isothermal titration calorimetry
    • Cliff, M. J. and Ladbury, J. E. (2003) A survey of the year 2002 literature on applications of isothermal titration calorimetry J. Mol. Recognit. 16, 383-391
    • (2003) J. Mol. Recognit. , vol.16 , pp. 383-391
    • Cliff, M.J.1    Ladbury, J.E.2
  • 45
    • 77956404669 scopus 로고    scopus 로고
    • Survey of the year 2008: Applications of isothermal titration calorimetry
    • (2010), (in press)
    • Falconer, R. J., Penkova, A., Jelesarov, I., and Collins, B. M. (2010) Survey of the year 2008: applications of isothermal titration calorimetry, J. Mol. Recognit. (in press).
    • J. Mol. Recognit.
    • Falconer, R.J.1    Penkova, A.2    Jelesarov, I.3    Collins, B.M.4
  • 47
    • 34249669709 scopus 로고    scopus 로고
    • Thermodynamics imprinting reveals differential binding of metals to alpha-synuclein: Relevance to Parkinson's disease
    • Bharathi and Rao, K. S. (2007) Thermodynamics imprinting reveals differential binding of metals to alpha-synuclein: relevance to Parkinson's disease Biochem. Biophys. Res. Commun. 359, 115-120
    • (2007) Biochem. Biophys. Res. Commun. , vol.359 , pp. 115-120
    • Bharathi1    Rao, K.S.2
  • 50
    • 33750359917 scopus 로고    scopus 로고
    • Copper(II) binding by fragments of alpha-synuclein containing M1-D2- and -H50-residues; A combined potentiometric and spectroscopic study
    • Kowalik-Jankowska, T., Rajewska, A., Jankowska, E., and Grzonka, Z. (2006) Copper(II) binding by fragments of alpha-synuclein containing M1-D2- and -H50-residues; a combined potentiometric and spectroscopic study Dalton Trans., 5068-5076
    • (2006) Dalton Trans. , pp. 5068-5076
    • Kowalik-Jankowska, T.1    Rajewska, A.2    Jankowska, E.3    Grzonka, Z.4
  • 51
    • 44449159424 scopus 로고    scopus 로고
    • Copper(II) binding to alpha-synuclein, the Parkinson's protein
    • Lee, J. C., Gray, H. B., and Winkler, J. R. (2008) Copper(II) binding to alpha-synuclein, the Parkinson's protein J. Am. Chem. Soc. 130, 6898-6899
    • (2008) J. Am. Chem. Soc. , vol.130 , pp. 6898-6899
    • Lee, J.C.1    Gray, H.B.2    Winkler, J.R.3
  • 52
    • 77952390443 scopus 로고    scopus 로고
    • Evidence for copper-dioxygen reactivity during alpha-synuclein fibril formation
    • Lucas, H. R., Debeer, S., Hong, M. S., and Lee, J. C. (2010) Evidence for copper-dioxygen reactivity during alpha-synuclein fibril formation J. Am. Chem. Soc. 132, 6636-6637
    • (2010) J. Am. Chem. Soc. , vol.132 , pp. 6636-6637
    • Lucas, H.R.1    Debeer, S.2    Hong, M.S.3    Lee, J.C.4
  • 53
    • 0034660568 scopus 로고    scopus 로고
    • Metal-catalyzed oxidation of alpha-synuclein in the presence of copper(II) and hydrogen peroxide
    • Paik, S. R., Shin, H. J., and Lee, J. H. (2000) Metal-catalyzed oxidation of alpha-synuclein in the presence of copper(II) and hydrogen peroxide Arch. Biochem. Biophys. 378, 269-277
    • (2000) Arch. Biochem. Biophys. , vol.378 , pp. 269-277
    • Paik, S.R.1    Shin, H.J.2    Lee, J.H.3
  • 54
    • 0031728689 scopus 로고    scopus 로고
    • Synthetic filaments assembled from C-terminally truncated alpha-synuclein
    • Crowther, R. A., Jakes, R., Spillantini, M. G., and Goedert, M. (1998) Synthetic filaments assembled from C-terminally truncated alpha-synuclein FEBS Lett. 436, 309-312
    • (1998) FEBS Lett. , vol.436 , pp. 309-312
    • Crowther, R.A.1    Jakes, R.2    Spillantini, M.G.3    Goedert, M.4
  • 55
    • 0034712918 scopus 로고    scopus 로고
    • Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation
    • Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., and Crowther, R. A. (2000) Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation Proc. Natl. Acad. Sci. U.S.A. 97, 4897-4902
    • (2000) Proc. Natl. Acad. Sci. U.S.A. , vol.97 , pp. 4897-4902
    • Serpell, L.C.1    Berriman, J.2    Jakes, R.3    Goedert, M.4    Crowther, R.A.5
  • 58
    • 34548021006 scopus 로고    scopus 로고
    • Copper- and iron-induced differential fibril formation in alpha-synuclein: TEM study
    • Bharathi, Indi, S. S., and Rao, K. S. (2007) Copper- and iron-induced differential fibril formation in alpha-synuclein: TEM study Neurosci. Lett. 424, 78-82
    • (2007) Neurosci. Lett. , vol.424 , pp. 78-82
    • Bharathi1    Indi, S.S.2    Rao, K.S.3
  • 60
    • 0037468467 scopus 로고    scopus 로고
    • Oxidized glutathione stimulated the amyloid formation of alpha-synuclein
    • Paik, S. R., Lee, D., Cho, H. J., Lee, E. N., and Chang, C. S. (2003) Oxidized glutathione stimulated the amyloid formation of alpha-synuclein FEBS Lett. 537, 63-67
    • (2003) FEBS Lett. , vol.537 , pp. 63-67
    • Paik, S.R.1    Lee, D.2    Cho, H.J.3    Lee, E.N.4    Chang, C.S.5
  • 61
    • 77149121411 scopus 로고    scopus 로고
    • Effect of dioxygen on copper(II) binding to alpha-synuclein
    • Lucas, H. R. and Lee, J. C. (2010) Effect of dioxygen on copper(II) binding to alpha-synuclein J. Inorg. Biochem. 104, 245-249
    • (2010) J. Inorg. Biochem. , vol.104 , pp. 245-249
    • Lucas, H.R.1    Lee, J.C.2
  • 62
    • 84871695420 scopus 로고    scopus 로고
    • Neuroprotective upregulation of endogenous alpha-synuclein precedes ubiquitination in cultured dopaminergic neurons
    • (2010), (in press)
    • Musgrove, R. E., King, A. E., and Dickson, T. C. (2010) Neuroprotective upregulation of endogenous alpha-synuclein precedes ubiquitination in cultured dopaminergic neurons, Neurotox. Res. (in press).
    • Neurotox. Res.
    • Musgrove, R.E.1    King, A.E.2    Dickson, T.C.3
  • 63
    • 0037192865 scopus 로고    scopus 로고
    • Alpha-synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells
    • Hashimoto, M., Hsu, L. J., Rockenstein, E., Takenouchi, T., Mallory, M., and Masliah, E. (2002) alpha-synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells J. Biol. Chem. 277, 11465-11472
    • (2002) J. Biol. Chem. , vol.277 , pp. 11465-11472
    • Hashimoto, M.1    Hsu, L.J.2    Rockenstein, E.3    Takenouchi, T.4    Mallory, M.5    Masliah, E.6
  • 64
    • 77950644314 scopus 로고    scopus 로고
    • Copper binding regulates intracellular alpha-synuclein localisation, aggregation and toxicity
    • Wang, X., Moualla, D., Wright, J. A., and Brown, D. R. (2010) Copper binding regulates intracellular alpha-synuclein localisation, aggregation and toxicity J. Neurochem. 113, 704-714
    • (2010) J. Neurochem. , vol.113 , pp. 704-714
    • Wang, X.1    Moualla, D.2    Wright, J.A.3    Brown, D.R.4
  • 65
    • 77956571912 scopus 로고    scopus 로고
    • Redox reactions of the alpha-synuclein-Cu(2+) complex and their effects on neuronal cell viability
    • Wang, C., Liu, L., Zhang, L., Peng, Y., and Zhou, F. (2010) Redox reactions of the alpha-synuclein-Cu(2+) complex and their effects on neuronal cell viability Biochemistry 49, 8134-8142
    • (2010) Biochemistry , vol.49 , pp. 8134-8142
    • Wang, C.1    Liu, L.2    Zhang, L.3    Peng, Y.4    Zhou, F.5


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