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Volumn 110, Issue 14, 2013, Pages 5683-5688

Mitogen-activated protein kinase modulates ethanol inhibition of cell adhesion mediated by the L1 neural cell adhesion molecule

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; LEUCINE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; NERVE CELL ADHESION MOLECULE L1;

EID: 84875837129     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1221386110     Document Type: Article
Times cited : (29)

References (51)
  • 1
    • 0022977191 scopus 로고
    • Fetal alcohol syndrome is now leading cause of mental retardation
    • Abel EL, Sokol RJ (1986) Fetal alcohol syndrome is now leading cause of mental retardation. Lancet 2(8517):1222.
    • (1986) Lancet , vol.2 , Issue.8517 , pp. 1222
    • Abel, E.L.1    Sokol, R.J.2
  • 2
    • 70149086044 scopus 로고    scopus 로고
    • Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies
    • May PA, et al. (2009) Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev 15(3):176-192.
    • (2009) Dev Disabil Res Rev , vol.15 , Issue.3 , pp. 176-192
    • May, P.A.1
  • 3
    • 38049161871 scopus 로고    scopus 로고
    • Computational selection and prioritization of candidate genes for fetal alcohol syndrome
    • Lombard Z, et al. (2007) Computational selection and prioritization of candidate genes for fetal alcohol syndrome. BMC Genomics 8:389.
    • (2007) BMC Genomics , vol.8 , pp. 389
    • Lombard, Z.1
  • 4
    • 77956565876 scopus 로고    scopus 로고
    • Genetic and epigenetic insights into fetal alcohol spectrum disorders
    • Ramsay M (2010) Genetic and epigenetic insights into fetal alcohol spectrum disorders. Genome Med 2(4):27.
    • (2010) Genome Med , vol.2 , Issue.4 , pp. 27
    • Ramsay, M.1
  • 5
    • 84860356723 scopus 로고    scopus 로고
    • Does moderate drinking harm the fetal brain? Insights from animal models
    • Valenzuela CF, Morton RA, Diaz MR, Topper L (2012) Does moderate drinking harm the fetal brain? Insights from animal models. Trends Neurosci 35(5):284-292.
    • (2012) Trends Neurosci , vol.35 , Issue.5 , pp. 284-292
    • Valenzuela, C.F.1    Morton, R.A.2    Diaz, M.R.3    Topper, L.4
  • 6
    • 79959284353 scopus 로고    scopus 로고
    • Strain differences in developmental vulnerability to alcohol exposure via embryo culture in mice
    • Chen Y, Ozturk NC, Ni L, Goodlett C, Zhou FC (2011) Strain differences in developmental vulnerability to alcohol exposure via embryo culture in mice. Alcohol Clin Exp Res 35(7):1293-1304.
    • (2011) Alcohol Clin Exp Res , vol.35 , Issue.7 , pp. 1293-1304
    • Chen, Y.1    Ozturk, N.C.2    Ni, L.3    Goodlett, C.4    Zhou, F.C.5
  • 7
    • 18244397174 scopus 로고    scopus 로고
    • Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders
    • Warren KR, Li TK (2005) Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders. Birth Defects Res A Clin Mol Teratol 73(4):195-203.
    • (2005) Birth Defects Res A Clin Mol Teratol , vol.73 , Issue.4 , pp. 195-203
    • Warren, K.R.1    Li, T.K.2
  • 8
    • 0027379593 scopus 로고
    • Fetal alcohol syndrome in twins of alcoholic mothers: Concordance of diagnosis and IQ
    • Streissguth AP, Dehaene P (1993) Fetal alcohol syndrome in twins of alcoholic mothers: Concordance of diagnosis and IQ. Am J Med Genet 47(6):857-861.
    • (1993) Am J Med Genet , vol.47 , Issue.6 , pp. 857-861
    • Streissguth, A.P.1    Dehaene, P.2
  • 9
    • 33845882730 scopus 로고    scopus 로고
    • Neural recognition molecules of the immunoglobulin superfamily: Signaling transducers of axon guidance and neuronal migration
    • Maness PF, Schachner M (2007) Neural recognition molecules of the immunoglobulin superfamily: Signaling transducers of axon guidance and neuronal migration. Nat Neurosci 10(1):19-26.
    • (2007) Nat Neurosci , vol.10 , Issue.1 , pp. 19-26
    • Maness, P.F.1    Schachner, M.2
  • 10
    • 0018092417 scopus 로고
    • The fetal alcohol syndrome
    • Clarren SK, Smith DW (1978) The fetal alcohol syndrome. N Engl J Med 298(19): 1063-1067.
    • (1978) N Engl J Med , vol.298 , Issue.19 , pp. 1063-1067
    • Clarren, S.K.1    Smith, D.W.2
  • 11
    • 79959922326 scopus 로고    scopus 로고
    • What does diffusion tensor imaging reveal about the brain and cognition in fetal alcohol spectrum disorders?
    • Wozniak JR, Muetzel RL (2011) What does diffusion tensor imaging reveal about the brain and cognition in fetal alcohol spectrum disorders? Neuropsychol Rev 21(2): 133-147.
    • (2011) Neuropsychol Rev , vol.21 , Issue.2 , pp. 133-147
    • Wozniak, J.R.1    Muetzel, R.L.2
  • 12
    • 79959966004 scopus 로고    scopus 로고
    • Magnetic resonance-based imaging in animal models of fetal alcohol spectrum disorder
    • O'Leary-Moore SK, Parnell SE, Lipinski RJ, Sulik KK (2011) Magnetic resonance-based imaging in animal models of fetal alcohol spectrum disorder. Neuropsychol Rev 21(2): 167-185.
    • (2011) Neuropsychol Rev , vol.21 , Issue.2 , pp. 167-185
    • O'Leary-Moore, S.K.1    Parnell, S.E.2    Lipinski, R.J.3    Sulik, K.K.4
  • 13
    • 0028876309 scopus 로고
    • CRASH syndrome: Clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1
    • Fransen E, et al. (1995) CRASH syndrome: Clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. Eur J Hum Genet 3(5):273-284.
    • (1995) Eur J Hum Genet , vol.3 , Issue.5 , pp. 273-284
    • Fransen, E.1
  • 14
    • 77955843976 scopus 로고    scopus 로고
    • L1 syndrome mutations impair neuronal L1 function at different levels by divergent mechanisms
    • Schäfer MK, et al. (2010) L1 syndrome mutations impair neuronal L1 function at different levels by divergent mechanisms. Neurobiol Dis 40(1):222-237.
    • (2010) Neurobiol Dis , vol.40 , Issue.1 , pp. 222-237
    • Schäfer, M.K.1
  • 15
    • 0036154050 scopus 로고    scopus 로고
    • Diseaseassociated mutations in L1 CAM interfere with ligand interactions and cell-surface expression
    • De Angelis E, Watkins A, Schäfer M, Brümmendorf T, Kenwrick S (2002) Diseaseassociated mutations in L1 CAM interfere with ligand interactions and cell-surface expression. Hum Mol Genet 11(1):1-12.
    • (2002) Hum Mol Genet , vol.11 , Issue.1 , pp. 1-12
    • De Angelis, E.1    Watkins, A.2    Schäfer, M.3    Brümmendorf, T.4    Kenwrick, S.5
  • 16
    • 0034639938 scopus 로고    scopus 로고
    • Neural cell recognition molecule L1: Relating biological complexity to human disease mutations
    • Kenwrick S, Watkins A, De Angelis E (2000) Neural cell recognition molecule L1: Relating biological complexity to human disease mutations. Hum Mol Genet 9(6): 879-886.
    • (2000) Hum Mol Genet , vol.9 , Issue.6 , pp. 879-886
    • Kenwrick, S.1    Watkins, A.2    De Angelis, E.3
  • 17
    • 0028289727 scopus 로고
    • Ethanol inhibits neural cell-cell adhesion
    • Charness ME, Safran RM, Perides G (1994) Ethanol inhibits neural cell-cell adhesion. J Biol Chem 269(12):9304-9309.
    • (1994) J Biol Chem , vol.269 , Issue.12 , pp. 9304-9309
    • Charness, M.E.1    Safran, R.M.2    Perides, G.3
  • 19
    • 0031742053 scopus 로고    scopus 로고
    • Characterization of ethanol-sensitive and insensitive fibroblast cell lines expressing human L1
    • Wilkemeyer MF, Charness ME (1998) Characterization of ethanol-sensitive and insensitive fibroblast cell lines expressing human L1. J Neurochem 71(6):2382-2391.
    • (1998) J Neurochem , vol.71 , Issue.6 , pp. 2382-2391
    • Wilkemeyer, M.F.1    Charness, M.E.2
  • 21
    • 18644365388 scopus 로고    scopus 로고
    • Peptide-mediated protection from ethanol-induced neural tube defects
    • Chen SY, Charness ME, Wilkemeyer MF, Sulik KK (2005) Peptide-mediated protection from ethanol-induced neural tube defects. Dev Neurosci 27(1):13-19.
    • (2005) Dev Neurosci , vol.27 , Issue.1 , pp. 13-19
    • Chen, S.Y.1    Charness, M.E.2    Wilkemeyer, M.F.3    Sulik, K.K.4
  • 22
    • 0037899135 scopus 로고    scopus 로고
    • Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity
    • Wilkemeyer MF, et al. (2003) Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. Proc Natl Acad Sci USA 100(14):8543-8548.
    • (2003) Proc Natl Acad Sci USA , vol.100 , Issue.14 , pp. 8543-8548
    • Wilkemeyer, M.F.1
  • 24
    • 0035040786 scopus 로고    scopus 로고
    • Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome
    • Spong CY, Abebe DT, Gozes I, Brenneman DE, Hill JM (2001) Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther 297(2):774-779.
    • (2001) J Pharmacol Exp Ther , vol.297 , Issue.2 , pp. 774-779
    • Spong, C.Y.1    Abebe, D.T.2    Gozes, I.3    Brenneman, D.E.4    Hill, J.M.5
  • 25
    • 12344328956 scopus 로고    scopus 로고
    • A neuroprotective peptide antagonizes fetal alcohol exposure-compromised brain growth
    • Zhou FC, Sari Y, Powrozek TA, Spong CY (2004) A neuroprotective peptide antagonizes fetal alcohol exposure-compromised brain growth. J Mol Neurosci 24(2): 189-199.
    • (2004) J Mol Neurosci , vol.24 , Issue.2 , pp. 189-199
    • Zhou, F.C.1    Sari, Y.2    Powrozek, T.A.3    Spong, C.Y.4
  • 26
    • 0030971118 scopus 로고    scopus 로고
    • Ethanol does not inhibit the adhesive activity of Drosophila neuroglian or human L1 in Drosophila S2 tissue culture cells
    • Vallejo Y, Hortsch M, Dubreuil RR (1997) Ethanol does not inhibit the adhesive activity of Drosophila neuroglian or human L1 in Drosophila S2 tissue culture cells. J Biol Chem 272(18):12244-12247.
    • (1997) J Biol Chem , vol.272 , Issue.18 , pp. 12244-12247
    • Vallejo, Y.1    Hortsch, M.2    Dubreuil, R.R.3
  • 27
    • 0033532157 scopus 로고    scopus 로고
    • Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells
    • Bearer CF, Swick AR, O'Riordan MA, Cheng G (1999) Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells. J Biol Chem 274(19): 13264-13270.
    • (1999) J Biol Chem , vol.274 , Issue.19 , pp. 13264-13270
    • Bearer, C.F.1    Swick, A.R.2    O'Riordan, M.A.3    Cheng, G.4
  • 28
    • 3142692818 scopus 로고    scopus 로고
    • The L1CAM extracellular region: A multi-domain protein with modular and cooperative binding modes
    • Haspel J, Grumet M (2003) The L1CAM extracellular region: A multi-domain protein with modular and cooperative binding modes. Front Biosci 8:s1210-s1225.
    • (2003) Front Biosci , vol.8
    • Haspel, J.1    Grumet, M.2
  • 29
    • 57649116073 scopus 로고    scopus 로고
    • Kinetic analysis of L1 homophilic interaction: Role of the first four immunoglobulin domains and implications on binding mechanism
    • Gouveia RM, Gomes CM, Sousa M, Alves PM, Costa J (2008) Kinetic analysis of L1 homophilic interaction: Role of the first four immunoglobulin domains and implications on binding mechanism. J Biol Chem 283(42):28038-28047.
    • (2008) J Biol Chem , vol.283 , Issue.42 , pp. 28038-28047
    • Gouveia, R.M.1    Gomes, C.M.2    Sousa, M.3    Alves, P.M.4    Costa, J.5
  • 30
    • 0035158040 scopus 로고    scopus 로고
    • Cell adhesion molecule L1 in folded (horseshoe) and extended conformations
    • Schürmann G, Haspel J, Grumet M, Erickson HP (2001) Cell adhesion molecule L1 in folded (horseshoe) and extended conformations. Mol Biol Cell 12(6):1765-1773.
    • (2001) Mol Biol Cell , vol.12 , Issue.6 , pp. 1765-1773
    • Schürmann, G.1    Haspel, J.2    Grumet, M.3    Erickson, H.P.4
  • 31
    • 79955540986 scopus 로고    scopus 로고
    • Two alcohol binding residues interact across a domain interface of the L1 neural cell adhesion molecule and regulate cell adhesion
    • Dou X, Menkari CE, Shanmugasundararaj S, Miller KW, Charness ME (2011) Two alcohol binding residues interact across a domain interface of the L1 neural cell adhesion molecule and regulate cell adhesion. J Biol Chem 286(18):16131-16139.
    • (2011) J Biol Chem , vol.286 , Issue.18 , pp. 16131-16139
    • Dou, X.1    Menkari, C.E.2    Shanmugasundararaj, S.3    Miller, K.W.4    Charness, M.E.5
  • 32
    • 33846479303 scopus 로고    scopus 로고
    • The role of cytoplasmic serine residues of the cell adhesion molecule L1 in neurite outgrowth, endocytosis, and cell migration
    • Schultheis M, Diestel S, Schmitz B (2007) The role of cytoplasmic serine residues of the cell adhesion molecule L1 in neurite outgrowth, endocytosis, and cell migration. Cell Mol Neurobiol 27(1):11-31.
    • (2007) Cell Mol Neurobiol , vol.27 , Issue.1 , pp. 11-31
    • Schultheis, M.1    Diestel, S.2    Schmitz, B.3
  • 33
    • 33748944502 scopus 로고    scopus 로고
    • Phosphorylation of L1-type cell-adhesion molecules - Ankyrins away
    • Nagaraj K, Hortsch M (2006) Phosphorylation of L1-type cell-adhesion molecules - ankyrins away! Trends Biochem Sci 31(10):544-546.
    • (2006) Trends Biochem Sci , vol.31 , Issue.10 , pp. 544-546
    • Nagaraj, K.1    Hortsch, M.2
  • 34
    • 33744764926 scopus 로고    scopus 로고
    • MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth
    • Whittard JD, Sakurai T, Cassella MR, Gazdoiu M, Felsenfeld DP (2006) MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth. Mol Biol Cell 17(6):2696-2706.
    • (2006) Mol Biol Cell , vol.17 , Issue.6 , pp. 2696-2706
    • Whittard, J.D.1    Sakurai, T.2    Cassella, M.R.3    Gazdoiu, M.4    Felsenfeld, D.P.5
  • 35
    • 77952382271 scopus 로고    scopus 로고
    • Inside-out regulation of L1 conformation, integrin binding, proteolysis, and concomitant cell migration
    • Chen MM, et al. (2010) Inside-out regulation of L1 conformation, integrin binding, proteolysis, and concomitant cell migration. Mol Biol Cell 21(10):1671-1685.
    • (2010) Mol Biol Cell , vol.21 , Issue.10 , pp. 1671-1685
    • Chen, M.M.1
  • 36
    • 0032514147 scopus 로고    scopus 로고
    • Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules
    • Hortsch M, et al. (1998) Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules. J Cell Biol 142(1):251-261.
    • (1998) J Cell Biol , vol.142 , Issue.1 , pp. 251-261
    • Hortsch, M.1
  • 37
    • 79953767777 scopus 로고    scopus 로고
    • Modification of the L1-CAM carboxyterminus in pancreatic adenocarcinoma cells
    • Chen MM, Lee CY, Leland HA, Silletti S (2011) Modification of the L1-CAM carboxyterminus in pancreatic adenocarcinoma cells. Tumour Biol 32(2):347-357.
    • (2011) Tumour Biol , vol.32 , Issue.2 , pp. 347-357
    • Chen, M.M.1    Lee, C.Y.2    Leland, H.A.3    Silletti, S.4
  • 38
    • 0032700871 scopus 로고    scopus 로고
    • Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells
    • Wilkemeyer MF, Pajerski M, Charness ME (1999) Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells. Alcohol Clin Exp Res 23(11):1711-1720.
    • (1999) Alcohol Clin Exp Res , vol.23 , Issue.11 , pp. 1711-1720
    • Wilkemeyer, M.F.1    Pajerski, M.2    Charness, M.E.3
  • 39
    • 0027363679 scopus 로고
    • Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells
    • Perides G, Hu G, Rueger DC, Charness ME (1993) Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells. J Biol Chem 268(33):25197-25205.
    • (1993) J Biol Chem , vol.268 , Issue.33 , pp. 25197-25205
    • Perides, G.1    Hu, G.2    Rueger, D.C.3    Charness, M.E.4
  • 40
    • 0033621478 scopus 로고    scopus 로고
    • Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization
    • Schaefer AW, et al. (1999) Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization. J Biol Chem 274(53):37965-37973.
    • (1999) J Biol Chem , vol.274 , Issue.53 , pp. 37965-37973
    • Schaefer, A.W.1
  • 41
    • 0028141496 scopus 로고
    • Transformation of mammalian cells by constitutively active MAP kinase kinase
    • Mansour SJ, et al. (1994) Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265(5174):966-970.
    • (1994) Science , vol.265 , Issue.5174 , pp. 966-970
    • Mansour, S.J.1
  • 42
    • 0029164688 scopus 로고
    • A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function
    • Catling AD, Schaeffer HJ, Reuter CW, Reddy GR, Weber MJ (1995) A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function. Mol Cell Biol 15(10):5214-5225.
    • (1995) Mol Cell Biol , vol.15 , Issue.10 , pp. 5214-5225
    • Catling, A.D.1    Schaeffer, H.J.2    Reuter, C.W.3    Reddy, G.R.4    Weber, M.J.5
  • 43
    • 66549103325 scopus 로고    scopus 로고
    • Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: Effects of acute insult on gestational day 8
    • Parnell SE, et al. (2009) Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: Effects of acute insult on gestational day 8. Alcohol Clin Exp Res 33(6):1001-1011.
    • (2009) Alcohol Clin Exp Res , vol.33 , Issue.6 , pp. 1001-1011
    • Parnell, S.E.1
  • 44
    • 38349162546 scopus 로고    scopus 로고
    • An alcohol binding site on the neural cell adhesion molecule L1
    • Arevalo E, et al. (2008) An alcohol binding site on the neural cell adhesion molecule L1. Proc Natl Acad Sci USA 105(1):371-375.
    • (2008) Proc Natl Acad Sci USA , vol.105 , Issue.1 , pp. 371-375
    • Arevalo, E.1
  • 46
    • 0029161504 scopus 로고
    • The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not essential for its homophilic adhesive properties in S2 cells
    • Hortsch M, Wang YM, Marikar Y, Bieber AJ (1995) The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not essential for its homophilic adhesive properties in S2 cells. J Biol Chem 270(32):18809-18817.
    • (1995) J Biol Chem , vol.270 , Issue.32 , pp. 18809-18817
    • Hortsch, M.1    Wang, Y.M.2    Marikar, Y.3    Bieber, A.J.4
  • 47
    • 39749174412 scopus 로고    scopus 로고
    • The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodies
    • Gast D, et al. (2008) The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodies. Oncogene 27(9): 1281-1289.
    • (2008) Oncogene , vol.27 , Issue.9 , pp. 1281-1289
    • Gast, D.1
  • 48
    • 3142733866 scopus 로고    scopus 로고
    • Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion
    • Silletti S, et al. (2004) Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem 279(28):28880-28888.
    • (2004) J Biol Chem , vol.279 , Issue.28 , pp. 28880-28888
    • Silletti, S.1
  • 49
    • 0035191129 scopus 로고    scopus 로고
    • System for cleavable Fc fusion proteins using tobacco etch virus (TEV) protease
    • 64-66
    • Haspel J, Blanco C, Jacob J, Grumet M (2001) System for cleavable Fc fusion proteins using tobacco etch virus (TEV) protease. Biotechniques 30(1):60-61, 64-66.
    • (2001) Biotechniques , vol.30 , Issue.1 , pp. 60-61
    • Haspel, J.1    Blanco, C.2    Jacob, J.3    Grumet, M.4
  • 51
    • 0022999802 scopus 로고
    • Ethanol induces the expression of functional delta-opioid receptors in the neuroblastoma-glioma hybrid NG108-15 cell line
    • Charness ME, Querimit LA, Diamond I (1986) Ethanol induces the expression of functional delta-opioid receptors in the neuroblastoma-glioma hybrid NG108-15 cell line. J Biol Chem 261:3164-3169.
    • (1986) J Biol Chem , vol.261 , pp. 3164-3169
    • Charness, M.E.1    Querimit, L.A.2    Diamond, I.3


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