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Volumn 22, Issue 24, 2003, Pages 6516-6525

Cooperation between the GATA and RUNX factors Serpent and Lozenge during Drosophila hematopoiesis

Author keywords

Drosophila; GATA; Hematopoiesis; RUNX

Indexed keywords

GENE PRODUCT; PROTEIN LOZENGE; PROTEIN SERPENT; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA; TRANSCRIPTION FACTOR RUNX; UNCLASSIFIED DRUG;

EID: 0346993689     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/cdg622     Document Type: Article
Times cited : (103)

References (44)
  • 1
    • 0036036446 scopus 로고    scopus 로고
    • gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila
    • Alfonso, T.B. and Jones, B.W. (2002) gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila. Dev. Biol., 248, 369-383.
    • (2002) Dev. Biol. , vol.248 , pp. 369-383
    • Alfonso, T.B.1    Jones, B.W.2
  • 2
    • 0031281656 scopus 로고    scopus 로고
    • glide/gcm is expressed and required in the scavenger cell lineage
    • Bernardoni, R., Vivancos, B. and Giangrande, A. (1997) glide/gcm is expressed and required in the scavenger cell lineage. Dev. Biol., 191, 118-130.
    • (1997) Dev. Biol. , vol.191 , pp. 118-130
    • Bernardoni, R.1    Vivancos, B.2    Giangrande, A.3
  • 3
    • 0035668437 scopus 로고    scopus 로고
    • A P-insertion screen identifying novel X-linked essential genes in Drosophila
    • Bourbon, H.M. et al. (2002) A P-insertion screen identifying novel X-linked essential genes in Drosophila. Mech. Dev., 110, 71-83.
    • (2002) Mech. Dev. , vol.110 , pp. 71-83
    • Bourbon, H.M.1
  • 4
    • 0038819114 scopus 로고    scopus 로고
    • RUNXI and GATA-1 coexpression and cooperation in megakaryocytic differentiation
    • Elagib, K.E., Racke, F.K., Mogass, M., Khetawat, R., Delehanty, L.L. and Goldfarb, A.N. (2003) RUNXI and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood, 101, 4333-4341.
    • (2003) Blood , vol.101 , pp. 4333-4341
    • Elagib, K.E.1    Racke, F.K.2    Mogass, M.3    Khetawat, R.4    Delehanty, L.L.5    Goldfarb, A.N.6
  • 5
    • 0038300342 scopus 로고    scopus 로고
    • Transcriptional regulation of hematopoiesis in Drosophila
    • Evans, C.J. and Banerjee, U. (2003) Transcriptional regulation of hematopoiesis in Drosophila. Blood Cells Mol. Dis., 30, 223-228.
    • (2003) Blood Cells Mol. Dis. , vol.30 , pp. 223-228
    • Evans, C.J.1    Banerjee, U.2
  • 6
    • 0035912754 scopus 로고    scopus 로고
    • The Friend of GATA proteins U-shaped, FOG-1 and FOG-2 function as negative regulators of blood, heart and eye development in Drosophila
    • Fossett, N., Tevosian, S.G., Gajewski, K., Zhang, Q., Orkin, S.H. and Schulz, R.A. (2001) The Friend of GATA proteins U-shaped, FOG-1 and FOG-2 function as negative regulators of blood, heart and eye development in Drosophila. Proc. Natl Acad. Sci. USA, 98, 7342-7347.
    • (2001) Proc. Natl. Acad. Sci. USA , vol.98 , pp. 7342-7347
    • Fossett, N.1    Tevosian, S.G.2    Gajewski, K.3    Zhang, Q.4    Orkin, S.H.5    Schulz, R.A.6
  • 7
    • 0030152160 scopus 로고    scopus 로고
    • Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells
    • Franc, N.C., Dimarcq, J.L., Lagueux, M., Hoffmann, J. and Ezekowitz, R.A. (1996) Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity, 4, 431-443.
    • (1996) Immunity , vol.4 , pp. 431-443
    • Franc, N.C.1    Dimarcq, J.L.2    Lagueux, M.3    Hoffmann, J.4    Ezekowitz, R.A.5
  • 8
    • 0029926485 scopus 로고    scopus 로고
    • Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1
    • Fujiwara, Y., Browne, C.P., Cunniff, K., Goff, S.C. and Orkin, S.H. (1996) Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc. Natl Acad. Sci. USA, 93, 12355-12358.
    • (1996) Proc. Natl. Acad. Sci. USA , vol.93 , pp. 12355-12358
    • Fujiwara, Y.1    Browne, C.P.2    Cunniff, K.3    Goff, S.C.4    Orkin, S.H.5
  • 9
    • 0030042980 scopus 로고    scopus 로고
    • Drosophila homologs of the proto-oncogene product PEBP2/CBFβ regulate the DNA-binding properties of Runt
    • Golling, G., Li, L., Pepling, M., Stebbins, M. and Gergen, J.P. (1996) Drosophila homologs of the proto-oncogene product PEBP2/CBFβ regulate the DNA-binding properties of Runt. Mol. Cell. Biol., 16, 932-942.
    • (1996) Mol. Cell. Biol. , vol.16 , pp. 932-942
    • Golling, G.1    Li, L.2    Pepling, M.3    Stebbins, M.4    Gergen, J.P.5
  • 10
    • 0037906527 scopus 로고    scopus 로고
    • Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder
    • Groet, J. et al. (2003) Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder. Lancet, 361, 1617-1620.
    • (2003) Lancet , vol.361 , pp. 1617-1620
    • Groet, J.1
  • 11
    • 0030709323 scopus 로고    scopus 로고
    • Transcriptional activity of Pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila
    • Haenlin, M., Cubadda, Y., Blondeau, F., Heitzler, P., Lutz, Y., Simpson, P. and Ramain, P. (1997) Transcriptional activity of Pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila. Genes Dev., 11, 3096-3108.
    • (1997) Genes Dev. , vol.11 , pp. 3096-3108
    • Haenlin, M.1    Cubadda, Y.2    Blondeau, F.3    Heitzler, P.4    Lutz, Y.5    Simpson, P.6    Ramain, P.7
  • 12
    • 7344251174 scopus 로고    scopus 로고
    • Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells
    • Harigae, H. et al. (1998) Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells. Genes Cells, 3, 39-50.
    • (1998) Genes Cells , vol.3 , pp. 39-50
    • Harigae, H.1
  • 13
    • 0030030943 scopus 로고    scopus 로고
    • Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: Demonstration by in situ hybridization
    • Jippo, T., Mizuno, H., Xu, Z., Nomura, S., Yamamoto, M. and Kitamura, Y. (1996) Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: demonstration by in situ hybridization. Blood, 87, 993-998.
    • (1996) Blood , vol.87 , pp. 993-998
    • Jippo, T.1    Mizuno, H.2    Xu, Z.3    Nomura, S.4    Yamamoto, M.5    Kitamura, Y.6
  • 14
    • 0034913919 scopus 로고    scopus 로고
    • Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development
    • Kaminker, J.S., Singh, R., Lebestky, T., Yan, H. and Banerjee, U. (2001) Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development. Development, 128, 2639-2648.
    • (2001) Development , vol.128 , pp. 2639-2648
    • Kaminker, J.S.1    Singh, R.2    Lebestky, T.3    Yan, H.4    Banerjee, U.5
  • 15
    • 0033559972 scopus 로고    scopus 로고
    • Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains
    • Kim, W.Y., Sieweke, M., Ogawa, E., Wee, H.J., Englmeier, U., Graf, T. and Ito, Y. (1999) Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. EMBO J., 18, 1609-1620.
    • (1999) EMBO J. , vol.18 , pp. 1609-1620
    • Kim, W.Y.1    Sieweke, M.2    Ogawa, E.3    Wee, H.J.4    Englmeier, U.5    Graf, T.6    Ito, Y.7
  • 16
    • 0034616310 scopus 로고    scopus 로고
    • Specification of Drosophila hematopoietic lineage by conserved transcription factors
    • Lebestky, T., Chang, T., Hartenstein, V. and Banerjee, U. (2000) Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science, 288, 146-149.
    • (2000) Science , vol.288 , pp. 146-149
    • Lebestky, T.1    Chang, T.2    Hartenstein, V.3    Banerjee, U.4
  • 17
    • 0037316602 scopus 로고    scopus 로고
    • A Serrate-expressing signaling center controls Drosophila hematopoiesis
    • Lebestky, T., Jung, S.H. and Banerjee, U. (2003) A Serrate-expressing signaling center controls Drosophila hematopoiesis. Genes Dev., 17, 348-353.
    • (2003) Genes Dev. , vol.17 , pp. 348-353
    • Lebestky, T.1    Jung, S.H.2    Banerjee, U.3
  • 18
    • 0034614616 scopus 로고    scopus 로고
    • The mammalian basic helix loop helix protein HES-1 binds to and modulates the transactivating function of the runt-related factor Cbfal
    • McLarren, K.W., Lo, R., Grbavec, D., Thirunavukkarasu, K., Karsenty, G. and Stifani, S. (2000) The mammalian basic helix loop helix protein HES-1 binds to and modulates the transactivating function of the runt-related factor Cbfal. J. Biol. Chem., 275, 530-538.
    • (2000) J. Biol. Chem. , vol.275 , pp. 530-538
    • McLarren, K.W.1    Lo, R.2    Grbavec, D.3    Thirunavukkarasu, K.4    Karsenty, G.5    Stifani, S.6
  • 19
    • 0037082499 scopus 로고    scopus 로고
    • In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: Implications for mechanisms of pathogenesis
    • Michaud, J. et al. (2002) In vitro analyses of known and novel RUNX1/ AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood, 99, 1364-1372.
    • (2002) Blood , vol.99 , pp. 1364-1372
    • Michaud, J.1
  • 21
    • 0035929608 scopus 로고    scopus 로고
    • The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds GATC motifs in DNA
    • Newton, A., Mackay, J. and Crossley, M. (2001) The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds GATC motifs in DNA. J. Biol. Chem., 276, 35794-35801.
    • (2001) J. Biol. Chem. , vol.276 , pp. 35794-35801
    • Newton, A.1    Mackay, J.2    Crossley, M.3
  • 22
    • 0030061554 scopus 로고    scopus 로고
    • AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis
    • Okuda, T., van Deursen, J., Hiebert, S.W., Grosveld, G. and Downing, J.R. (1996) AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell, 84, 321-330.
    • (1996) Cell , vol.84 , pp. 321-330
    • Okuda, T.1    Van Deursen, J.2    Hiebert, S.W.3    Grosveld, G.4    Downing, J.R.5
  • 23
    • 0036225224 scopus 로고    scopus 로고
    • Hematopoiesis and stem cells: Plasticity versus developmental heterogeneity
    • Orkin, S.H. and Zon, L.I. (2002) Hematopoiesis and stem cells: plasticity versus developmental heterogeneity. Nat. Immunol., 3, 323-328.
    • (2002) Nat. Immunol. , vol.3 , pp. 323-328
    • Orkin, S.H.1    Zon, L.I.2
  • 25
    • 0025977563 scopus 로고
    • Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1
    • Pevny, L., Simon, M.C., Robertson, E., Klein, W.H., Tsai, S.F., D'Agati, V., Orkin, S.H. and Costantini, F. (1991) Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature, 349, 257-260.
    • (1991) Nature , vol.349 , pp. 257-260
    • Pevny, L.1    Simon, M.C.2    Robertson, E.3    Klein, W.H.4    Tsai, S.F.5    D'Agati, V.6    Orkin, S.H.7    Costantini, F.8
  • 26
    • 0034967571 scopus 로고    scopus 로고
    • New members of the Drosophila Myc transcription factor subfamily revealed by a genome-wide examination for basic helix-loop-helix genes
    • Peyrefitte, S., Kahn, D. and Haenlin, M. (2001) New members of the Drosophila Myc transcription factor subfamily revealed by a genome-wide examination for basic helix-loop-helix genes. Mech. Dev., 104, 99-104.
    • (2001) Mech. Dev. , vol.104 , pp. 99-104
    • Peyrefitte, S.1    Kahn, D.2    Haenlin, M.3
  • 27
    • 0034287443 scopus 로고    scopus 로고
    • Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors
    • Querfurth, E., Schuster, M., Kulessa, H., Crispino, J.D., Doderlein, G., Orkin, S.H., Graf, T. and Nerlov, C. (2000) Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors. Genes Dev., 14, 2515-2525.
    • (2000) Genes Dev. , vol.14 , pp. 2515-2525
    • Querfurth, E.1    Schuster, M.2    Kulessa, H.3    Crispino, J.D.4    Doderlein, G.5    Orkin, S.H.6    Graf, T.7    Nerlov, C.8
  • 28
    • 0030451622 scopus 로고    scopus 로고
    • A molecular aspect of hematopoiesis and endoderm development common to vertebrates and Drosophila
    • Rehom, K.P., Thelen, H., Michelson, A.M. and Reuter, R. (1996) A molecular aspect of hematopoiesis and endoderm development common to vertebrates and Drosophila. Development, 122, 4023-4031.
    • (1996) Development , vol.122 , pp. 4023-4031
    • Rehom, K.P.1    Thelen, H.2    Michelson, A.M.3    Reuter, R.4
  • 29
    • 0000826497 scopus 로고
    • The circulatory system and associated tissues
    • Wright, T.R.F. (ed.). Academic Press, New York
    • Rizki, T.M. (1978) The circulatory system and associated tissues. In Wright, T.R.F. (ed.) The genetics and biology of Drosophila. Academic Press, New York, pp. 229-335.
    • (1978) The Genetics and Biology of Drosophila , pp. 229-335
    • Rizki, T.M.1
  • 30
    • 0018959836 scopus 로고
    • A mutant affecting the crystal cells in Drosophila melanogaster
    • Rizki, T.M., Rizki, R.M. and Grell, E. (1980) A mutant affecting the crystal cells in Drosophila melanogaster. Wilhelm Roux's Arch. Dev. Biol., 188, 91-99.
    • (1980) Wilhelm Roux's Arch. Dev. Biol. , vol.188 , pp. 91-99
    • Rizki, T.M.1    Rizki, R.M.2    Grell, E.3
  • 31
    • 0030473138 scopus 로고    scopus 로고
    • The serpent gene is necessary for progression through the early stages of fat-body development
    • Sam, S., Leise, W. and Hoshizaki, D.K. (1996) The serpent gene is necessary for progression through the early stages of fat-body development. Mech. Dev., 60, 197-205.
    • (1996) Mech. Dev. , vol.60 , pp. 197-205
    • Sam, S.1    Leise, W.2    Hoshizaki, D.K.3
  • 32
    • 0032830638 scopus 로고    scopus 로고
    • Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia
    • Song, W.J. et al. (1999) Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat. Genet., 23, 166-175.
    • (1999) Nat. Genet. , vol.23 , pp. 166-175
    • Song, W.J.1
  • 33
    • 0036636857 scopus 로고    scopus 로고
    • Core-binding factors in haematopoiesis and leukaemia
    • Speck, N.A. and Gilliland, D.G. (2002) Core-binding factors in haematopoiesis and leukaemia. Nat. Rev. Cancer, 2, 502-513.
    • (2002) Nat. Rev. Cancer , vol.2 , pp. 502-513
    • Speck, N.A.1    Gilliland, D.G.2
  • 34
    • 0028365963 scopus 로고
    • Embryonic origin of hemocytes and their relationship to cell death in Drosophila
    • Tepass, U., Fessler, L.I., Aziz, A. and Hartenstein, V. (1994) Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development, 120, 1829-1837.
    • (1994) Development , vol.120 , pp. 1829-1837
    • Tepass, U.1    Fessler, L.I.2    Aziz, A.3    Hartenstein, V.4
  • 35
    • 0030926190 scopus 로고    scopus 로고
    • Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation
    • Tsai, F.Y. and Orkin, S.H. (1997) Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood, 89, 3636-3643.
    • (1997) Blood , vol.89 , pp. 3636-3643
    • Tsai, F.Y.1    Orkin, S.H.2
  • 36
    • 0031472234 scopus 로고    scopus 로고
    • FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation
    • Tsang, A.P., Visvader, J.E., Turner, C.A., Fujiwara, Y., Yu, C., Weiss, M.J., Crossley, M. and Orkin, S.H. (1997) FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell, 90, 109-119.
    • (1997) Cell , vol.90 , pp. 109-119
    • Tsang, A.P.1    Visvader, J.E.2    Turner, C.A.3    Fujiwara, Y.4    Yu, C.5    Weiss, M.J.6    Crossley, M.7    Orkin, S.H.8
  • 37
    • 0032522474 scopus 로고    scopus 로고
    • Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG
    • Tsang, A.P., Fujiwara, Y., Hom, D.B. and Orkin, S.H. (1998) Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev., 12, 1176-1188.
    • (1998) Genes Dev. , vol.12 , pp. 1176-1188
    • Tsang, A.P.1    Fujiwara, Y.2    Hom, D.B.3    Orkin, S.H.4
  • 38
    • 0033134831 scopus 로고    scopus 로고
    • Consequences of GATA-1 deficiency in megakaryocytes and platelets
    • Vyas, P., Ault, K., Jackson, C.W., Orkin, S.H. and Shivdasani, R.A. (1999) Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood, 93, 2867-2875.
    • (1999) Blood , vol.93 , pp. 2867-2875
    • Vyas, P.1    Ault, K.2    Jackson, C.W.3    Orkin, S.H.4    Shivdasani, R.A.5
  • 39
    • 0037107443 scopus 로고    scopus 로고
    • Two isoforms of Serpent containing either one or two GATA zinc fingers have different roles in Drosophila haematopoiesis
    • Waltzer, L., Bataillé, L., Peyrefitte, S. and Haenlin, M. (2002) Two isoforms of Serpent containing either one or two GATA zinc fingers have different roles in Drosophila haematopoiesis. EMBO J., 21, 5477-5486.
    • (2002) EMBO J. , vol.21 , pp. 5477-5486
    • Waltzer, L.1    Bataillé, L.2    Peyrefitte, S.3    Haenlin, M.4
  • 40
    • 0029918597 scopus 로고    scopus 로고
    • Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis
    • Wang, Q., Stacy, T., Binder, M., Marin-Padilla, M., Sharpe, A.H. and Speck, N.A. (1996) Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl Acad. Sci. USA, 93, 3444-3449.
    • (1996) Proc. Natl. Acad. Sci. USA , vol.93 , pp. 3444-3449
    • Wang, Q.1    Stacy, T.2    Binder, M.3    Marin-Padilla, M.4    Sharpe, A.H.5    Speck, N.A.6
  • 41
    • 0036792665 scopus 로고    scopus 로고
    • Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: Role of Ets transcription factors
    • Wang, X., Crispino, J.D., Letting, D.L., Nakazawa, M., Poncz, M. and Blobel, G.A. (2002) Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors. EMBO J., 21, 5225-5234.
    • (2002) EMBO J. , vol.21 , pp. 5225-5234
    • Wang, X.1    Crispino, J.D.2    Letting, D.L.3    Nakazawa, M.4    Poncz, M.5    Blobel, G.A.6
  • 43
    • 0034730329 scopus 로고    scopus 로고
    • Overlapping activators and repressors delimit transcriptional response to receptor tyrosine kinase signals in the Drosophila eye
    • Xu, C., Kauffmann, R.C., Zhang, J., Kladny, S. and Carthew, R.W. (2000) Overlapping activators and repressors delimit transcriptional response to receptor tyrosine kinase signals in the Drosophila eye. Cell, 103, 87-97.
    • (2000) Cell , vol.103 , pp. 87-97
    • Xu, C.1    Kauffmann, R.C.2    Zhang, J.3    Kladny, S.4    Carthew, R.W.5
  • 44
    • 0033566366 scopus 로고    scopus 로고
    • C/EBPβ and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: Implication for C/EBPβ activity in eosinophil gene expression
    • Yamaguchi, Y., Nishio, H., Kishi, K., Ackerman, S.J. and Suda, T. (1999) C/EBPβ and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPβ activity in eosinophil gene expression. Blood, 94, 1429-1439.
    • (1999) Blood , vol.94 , pp. 1429-1439
    • Yamaguchi, Y.1    Nishio, H.2    Kishi, K.3    Ackerman, S.J.4    Suda, T.5


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