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Volumn 58, Issue SUPPL. 1, 2009, Pages 29-40

Multiple roles of secretory lipocalins (Mup, Obp) in mice

Author keywords

Chemical communication; Urinary proteins

Indexed keywords

IMMUNE RESPONSE; IMMUNOASSAY; LIGAND; NATURAL SELECTION; PHYSIOLOGICAL RESPONSE; PROTEIN; RODENT;

EID: 72949090677     PISSN: 01397893     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article
Times cited : (22)

References (57)
  • 1
    • 0021815342 scopus 로고
    • Purification and characterisation of an odorant-binding protein from cow nasal tissue
    • DOI 10.1111/j.1432-1033.1985.tb08916.x
    • Bignetti E., Cavaggioni A., Pelosi P., Persaud K.C., Sorbi R.T. & Tirindelli R. 1985: Purification and characterization of an odorant-binding protein from cow nasal tissue. Eur. J. Biochem. 149:227-231. (Pubitemid 15015808)
    • (1985) European Journal of Biochemistry , vol.149 , Issue.2 , pp. 227-231
    • Bignetti, E.1    Cavaggioni, A.2    Pelosi, P.3
  • 2
    • 0034684162 scopus 로고    scopus 로고
    • The bacterial lipocalins
    • Bishop R.E. 2000: The bacterial lipocalins. Biochim. Biophys. Acta 1482: 73-83.
    • (2000) Biochim. Biophys. Acta , vol.1482 , pp. 73-83
    • Bishop, R.E.1
  • 3
    • 0034684231 scopus 로고    scopus 로고
    • Lipocalins and cancer
    • Bratt T. 2000: Lipocalins and cancer. Biochim. Biophys. Acta 1482: 318-326.
    • (2000) Biochim. Biophys. Acta , vol.1482 , pp. 318-326
    • Bratt, T.1
  • 4
    • 0034109042 scopus 로고    scopus 로고
    • Ligand-binding properties and structural characterization of a novel rat odorant-binding protein variant
    • DOI 10.1046/j.1432-1327.2000.01340.x
    • Briand L., Nespoulous C., Perez V., Rémy J.-J., Huet J.-C. & Pernollet J.-C. 2000a: Ligand binding properties and structural characterization of a novel rat odorant-binding protein variant. Eur. J. Biochem. 267: 3079-3089. (Pubitemid 30321357)
    • (2000) European Journal of Biochemistry , vol.267 , Issue.10 , pp. 3079-3089
    • Briand, L.1    Nespoulous, C.2    Perez, V.3    Remy, J.-J.4    Huet, J.-C.5    Pernollet, J.-C.6
  • 5
    • 0034617365 scopus 로고    scopus 로고
    • Odorant and pheromone binding by aphrodisin, a hamster aphrodisiac protein
    • DOI 10.1016/S0014-5793(00)01719-1, PII S0014579300017191
    • Briand L., Huet J.-C., Perez V., Lenoir G., Nespoulous C., Boucher Y., Trotier D. & Pernollet J.-C. 2000b: Odorant and pheromone binding by Aphrodisin, a hamster aphrodisiac protein. FEBS Letters 476: 179-185. (Pubitemid 30410813)
    • (2000) FEBS Letters , vol.476 , Issue.3 , pp. 179-185
    • Briand, L.1    Huet, J.-C.2    Perez, V.3    Lenoir, G.4    Nespoulous, C.5    Boucher, Y.6    Trotier, D.7    Pernollet, J.-C.8
  • 7
    • 36849029805 scopus 로고    scopus 로고
    • Identification of protein pheromones that promote aggressive behaviour
    • DOI 10.1038/nature05997, PII NATURE05997
    • Chamero P., Marton T. F., Logan D. W., Flanagan K., Cruz J. R., Saghatelian A., Cravatt B.F. & Stowers L. 2007: Identification of protein pheromones that promote aggressive behaviour. Nature 450:899- 902. (Pubitemid 350231315)
    • (2007) Nature , vol.450 , Issue.7171 , pp. 899-902
    • Chamero, P.1    Marton, T.F.2    Logan, D.W.3    Flanagan, K.4    Cruz, J.R.5    Saghatelian, A.6    Cravatt, B.F.7    Stowers, L.8
  • 8
    • 50849085145 scopus 로고    scopus 로고
    • The plant apolipoprotein D ortholog protects Arabidopsis against oxidative stress. BMC
    • Charron J.-B.F., Ouellet F., Houde M. & Sarhan F. 2008: The plant apolipoprotein D ortholog protects Arabidopsis against oxidative stress. BMC Plant Biol. 8: 86.
    • (2008) Plant Biol. , vol.8 , pp. 86
    • Charron, J.-B.F.1    Ouellet, F.2    Houde, M.3    Sarhan, F.4
  • 9
    • 0029826072 scopus 로고    scopus 로고
    • A 19 kDa protein secreted by the endometrium of the mare is a novel member of the lipocalin family
    • Crosset B., Allen W.R. & Stewart F. 1996: A 19 kDa protein secreted by the endometrium of the mare is a novel member of the lipocalin family. Biochem. J. 320: 137-143. (Pubitemid 26400171)
    • (1996) Biochemical Journal , vol.320 , Issue.1 , pp. 137-143
    • Crossett, B.1    Allen, W.R.2    Stewart, F.3
  • 10
    • 0025732668 scopus 로고
    • Purification and characterization of two odorant binding proteins from nasal tissue of rabbit and pig
    • Dal Monte M., Andreini I., Revoltella R. & Pelosi P. 1991: Purification and characterization of two odorant binding proteins from nasal tissue of rabbit and pig. Comp. Biochem. Physiol. 99B: 445-451.
    • (1991) Comp. Biochem. Physiol. , vol.99 B , pp. 445-451
    • Dal Monte, M.1    Andreini, I.2    Revoltella, R.3    Pelosi, P.4
  • 12
    • 0026347802 scopus 로고
    • Molecular cloning of putative odorant-binding and odorantmetabolizing proteins
    • Dear T.N., Campbell K. & Rabbitts T.H. 1991: Molecular cloning of putative odorant-binding and odorantmetabolizing proteins. Biochemistry 30:10376-10382.
    • (1991) Biochemistry , vol.30 , pp. 10376-10382
    • Dear, T.N.1    Campbell, K.2    Rabbitts, T.H.3
  • 13
    • 1842818734 scopus 로고    scopus 로고
    • Evolution and comparative genomics of odorant- and pheromone-associated genes in rodents
    • DOI 10.1101/gr.1940604
    • Emes R.D., Beatson S.A., Ponting C.P. & Goodstadt L. 2004: Evolution and comparative genomics of odorant- and pheromone-associated genes in rodents. Genome Research 14: 591-602. (Pubitemid 38500230)
    • (2004) Genome Research , vol.14 , Issue.4 , pp. 591-602
    • Emes, R.D.1    Beatson, S.A.2    Ponting, C.P.3    Goodstadt, L.4
  • 15
    • 0029790266 scopus 로고    scopus 로고
    • The lipocalin protein family: Structure and function
    • Flower D.R. 1996 : The lipocalin protein family: structure and function. Biochem. J. 318: 1-14.
    • (1996) Biochem. J. , vol.318 , pp. 1-14
    • Flower, D.R.1
  • 16
    • 4344596798 scopus 로고    scopus 로고
    • Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores
    • DOI 10.1128/AAC.48.9.3367-3372.2004
    • Fluckinger M., Haas H., Merschak P., Glasgow B.J. & Redi B. 2004: Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob. Agents Chemother. 48: 3367-3372. (Pubitemid 39129332)
    • (2004) Antimicrobial Agents and Chemotherapy , vol.48 , Issue.9 , pp. 3367-3372
    • Fluckinger, M.1    Haas, H.2    Merschak, P.3    Glasgow, B.J.4    Redl, B.5
  • 19
    • 0036865552 scopus 로고    scopus 로고
    • The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition
    • DOI 10.1016/S1097-2765(02)00708-6
    • Goetz D.H., Holmes M.A., Borregaard N., Bluhm M.E., Raymond K.N. & Strong R.K. 2002: The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10: 1033-1043. (Pubitemid 36001971)
    • (2002) Molecular Cell , vol.10 , Issue.5 , pp. 1033-1043
    • Goetz, D.H.1    Holmes, M.A.2    Borregaard, N.3    Bluhm, M.E.4    Raymond, K.N.5    Strong, R.K.6
  • 20
    • 33750567333 scopus 로고    scopus 로고
    • Odorant binding protein has the biochemical properties of a scavenger for 4-hydroxy-2-nonenal in mammalian nasal mucosa
    • DOI 10.1111/j.1742-4658.2006.05510.x
    • Grolli S., Merli E., Conti V., Scaltriti E. & Ramoni R. 2006: Odorant biding protein has the biochemical properties of a scavenger for 4-hydroxy-2-nonenal in mammalian nasal mucosa. FEBS Journal 273: 5131-5142. (Pubitemid 44673302)
    • (2006) FEBS Journal , vol.273 , Issue.22 , pp. 5131-5142
    • Grolli, S.1    Merli, E.2    Conti, V.3    Scaltriti, E.4    Ramoni, R.5
  • 22
    • 2042546096 scopus 로고    scopus 로고
    • Balancing acts: Molecular control of mammalian iron metabolism
    • Hentze M.W., Muckenthaler M.U. & Andrews N.C. 2004: Balancing acts: molecular control of mammalian iron metabolism. Cell. 117:285-297.
    • (2004) Cell. , vol.117 , pp. 285-297
    • Hentze, M.W.1    Muckenthaler, M.U.2    Andrews, N.C.3
  • 24
    • 72949100391 scopus 로고    scopus 로고
    • Mechanisms of chemical communication: The role of Major Urinary Proteins
    • Janotova K. & Stopka P. 2009: Mechanisms of chemical communication: the role of Major Urinary Proteins. Folia Zool. 58 (Suppl. 1): 41-55.
    • (2009) Folia Zool. , vol.58 , Issue.SUPPL. 1 , pp. 41-55
    • Janotova, K.1    Stopka, P.2
  • 27
    • 0033979907 scopus 로고    scopus 로고
    • A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: Differential expression in the oral and genital spheres
    • Lacazette E., Gachon A.-M. & Pitiot G. 2000: A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the oral and genital sphere. Human Mol. Genet. 9: 289-301. (Pubitemid 30052753)
    • (2000) Human Molecular Genetics , vol.9 , Issue.2 , pp. 289-301
    • Lacazette, E.1    Gachon, A.-M.2    Pitiot, G.3
  • 28
    • 0036786878 scopus 로고    scopus 로고
    • Molecular and functional characterization of an odorant binding protein of the Asian elephant, Elephas maximus: Implications for the role of lipocalins in mammalian olfaction
    • Lazar J., Greenwood D.R., Rasmussen L.E.L. & Prestwich G.D. 2002: Molecular and functional characterization of an odorant binding protein of the Asian elephant, Elephas maximus: Implications for the role of lipocalins in mammalian olfaction. Biochemistry 41: 11786-11794.
    • (2002) Biochemistry , vol.41 , pp. 11786-11794
    • Lazar, J.1    Greenwood, D.R.2    Rasmussen, L.E.L.3    Prestwich, G.D.4
  • 30
    • 0034876190 scopus 로고    scopus 로고
    • Identification of a third rat odorant-binding protein (OBP3)
    • Löbel D., Strotmann J., Jacob M. & Breer H. 2001: Identification of a third rat odorant-binding protein (Obp3). Chem. Senses 26: 673-680. (Pubitemid 32750519)
    • (2001) Chemical Senses , vol.26 , Issue.6 , pp. 673-680
    • Lobel, D.1    Strotmann, J.2    Jacob, M.3    Breer, H.4
  • 31
    • 54749096446 scopus 로고    scopus 로고
    • Species specificity in Major Urinary Proteins by parallel evolution
    • Logan D.W., Marton T.F. & Stowers L. 2008: Species specificity in Major Urinary Proteins by parallel evolution. PLoS ONE 3: e3280.
    • (2008) PLoS ONE , vol.3
    • Logan, D.W.1    Marton, T.F.2    Stowers, L.3
  • 35
    • 0022623249 scopus 로고
    • Adrenal-mediated endogenous metabolites inhibit puberty in female mice
    • Novotny M.V., Jemiolo B., Harvey S., Wiesler D. & Marchlewska-Koj A. 1986: Adre-nal-mediated endogenous metabolites inhibit puberty in female mice. Science 231: 722-725. (Pubitemid 16104041)
    • (1986) Science , vol.231 , Issue.4739 , pp. 722-725
    • Novotny, M.1    Jemiolo, B.2    Harvey, S.3
  • 36
    • 11944260592 scopus 로고
    • Chemistry of male dominance in the house mouse, Mus domesticus
    • Novotny M.V., Harvey S. & Jemiolo B. 1990: Chemistry of male dominance in the house mouse, Mus domesticus. Experientia 46: 109-113.
    • (1990) Experientia , vol.46 , pp. 109-113
    • Novotny, M.V.1    Harvey, S.2    Jemiolo, B.3
  • 37
    • 0033150478 scopus 로고    scopus 로고
    • A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice
    • DOI 10.1016/S1074-5521(99)80049-0
    • Novotny M.V, Jemiolo B., Wiesler D., Ma W., Harvey S., Xu F., Xie T. & Carmack M. 1999a: A unique urinary constituent, 6-hydroxy-6-methyl-3- heptanone, is a pheromone that accelerates puberty in female mice. Chem. Biol. 6: 377-383. (Pubitemid 29363170)
    • (1999) Chemistry and Biology , vol.6 , Issue.6 , pp. 377-383
    • Novotny, M.V.1    Jemiolo, B.2    Wiesler, D.3    Ma, W.4    Harvey, S.5    Fuqiang, X.6    Xie, T.-M.7    Carmack, M.8
  • 38
    • 0033533834 scopus 로고    scopus 로고
    • Positive identification of the puberty-accelerating pheromone of the house mouse: The volatile ligands associating with the major urinary protein
    • DOI 10.1098/rspb.1999.0880
    • Novotny M.V., Ma W., Wiesler D. & Zidek L. 1999b: Positive identification of the pu-berty-accelerating pheromone of the house mouse: the volatile ligands associating with the major urinary protein. Proc. R. Soc. Lond. B. 266:2017-2022. (Pubitemid 29479206)
    • (1999) Proceedings of the Royal Society B: Biological Sciences , vol.266 , Issue.1432 , pp. 2017-2022
    • Novotny, M.V.1    Ma, W.2    Wiesler, D.3    Zidek, L.4
  • 39
    • 0037326707 scopus 로고    scopus 로고
    • Pheromones, binding proteins and receptor responses in rodents
    • Novotný M.V. 2003: Pheromones, binding proteins and receptor responses in rodents. Bio-chem. Soc. Trans. 31: 117-122.
    • (2003) Bio-chem. Soc. Trans. , vol.31 , pp. 117-122
    • Novotný, M.V.1
  • 40
    • 0026464833 scopus 로고
    • Isolation of two odorant-binding proteins from mouse nasal tissue
    • Pes D., Dal Monte M., Ganni M. & Pelosi P. 1992: Isolation of two odorant-binding proteins from mouse nasal tissue. Comp. Biochem. Physiol. 103B: 1011-1017.
    • (1992) Comp. Biochem. Physiol. , vol.103 B , pp. 1011-1017
    • Pes, D.1    Dal Monte, M.2    Ganni, M.3    Pelosi, P.4
  • 41
    • 0028858417 scopus 로고
    • Odorant-binding proteins of the mouse
    • Pes D. & Pelosi P. 1995: Odorant-binding proteins of the mouse. Comp. Biochem. Physiol. 112B: 471-479.
    • (1995) Comp. Biochem. Physiol. , vol.112 B , pp. 471-479
    • Pes, D.1    Pelosi, P.2
  • 44
    • 0025358083 scopus 로고
    • Odorant-binding protein: Odorant transport function in the vertebrate nasal epithelium
    • Pevsner J. & Snyder S.H. 1990: Odorant-binding protein: odorant transport function in the vertebrate nasal epithelium. Chem. Senses 15: 217-222. (Pubitemid 20172840)
    • (1990) Chemical Senses , vol.15 , Issue.2 , pp. 217-222
    • Pevsner, J.1    Snyder, S.H.2
  • 45
    • 0032704543 scopus 로고    scopus 로고
    • Hormonal effects on hamster lacrimal gland female-specific major 20 kDa secretory protein and its immunological similarity with submandibular gland major male-specific proteins
    • DOI 10.1016/S0960-0760(99)00103-X, PII S096007609900103X
    • Ranganathan V., Jana N.R. & De P.K. 1999: Hormonal effects on hamster lacrimal gland female-specific major 20 kDa secretory protein and its immunological similarity with submandibular gland major male-specific proteins. J. Steroid Biochem. MoI. Biol. 70: 151-158. (Pubitemid 29528425)
    • (1999) Journal of Steroid Biochemistry and Molecular Biology , vol.70 , Issue.4-6 , pp. 151-158
    • Ranganathan, V.1    Jana, N.R.2    De, P.K.3
  • 46
    • 37549037152 scopus 로고    scopus 로고
    • A qualitative investigation of major urinary proteins in relation to the onset of aggressive behavior and dispersive motivation in male wild house mice (Mus musculus domesticus)
    • Rusu A.S., Krackow S., Jedelsky P.L., Stopka P. & Konig B. 2008: A qualitative investigation of major urinary proteins in relation to the onset of aggressive behavior and dispersive motivation in male wild house mice (Mus musculus domesticus). J. Ethol. 26: 127-135.
    • (2008) J. Ethol. , vol.26 , pp. 127-135
    • Rusu, A.S.1    Krackow, S.2    Jedelsky, P.L.3    Stopka, P.4    Konig, B.5
  • 47
    • 0034684196 scopus 로고    scopus 로고
    • Chromosomal location, exon/intron organization and evolution of lipocalin genes
    • Salier J.-P. 2000: Chromosomal location, exon/intron organization and evolution of lipocalin genes. Biochim. Biophys. Acta 1482: 25-34.
    • (2000) Biochim. Biophys. Acta , vol.1482 , pp. 25-34
    • Salier, J.-P.1
  • 48
    • 0037694045 scopus 로고    scopus 로고
    • Exon-intron structure and evolution of the lipocalin gene family
    • DOI 10.1093/molbev/msg079
    • Sánchez D., Ganfornina M.D., Gutiérrez G. & Marin A. 2003: Exon-intron structure and evolution of the lipocalin gene family. Mol. Biol. Evol. 20: 775-783. (Pubitemid 36539014)
    • (2003) Molecular Biology and Evolution , vol.20 , Issue.5 , pp. 775-783
    • Sanchez, D.1    Ganfornina, M.D.2    Gutierrez, G.3    Marin, A.4
  • 49
    • 0036668182 scopus 로고    scopus 로고
    • Glycodelin: A major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation
    • DOI 10.1210/er.2001-0026
    • Seppälä M., Taylor R.N., Koistinen H., Koistinen R. & Milgrom E. 2002: Glycodelin: A major lipocalin protein of the reproductive axis with diverse action in cell recognition and differentiation. Endocrine Reviews 23: 401-430. (Pubitemid 34925639)
    • (2002) Endocrine Reviews , vol.23 , Issue.4 , pp. 401-430
    • Seppala, M.1    Taylor, R.N.2    Koistinen, H.3    Koistinen, R.4    Milgrom, E.5
  • 50
    • 0022896208 scopus 로고
    • Purification and analysis of a proteinaceous aphrodisiac pheromone from hamster vaginal discharge
    • Singer A.G., Macrides F., Clancy A.N. & Agosta W.C. 1986: Purification and analysis of a proteinaceous aphrodisiac pheromone from hamster vaginal discharge. J. Biol. Chem. 261: 13323-13326.
    • (1986) J. Biol. Chem. , vol.261 , pp. 13323-13326
    • Singer, A.G.1    Macrides, F.2    Clancy, A.N.3    Agosta, W.C.4
  • 51
    • 34548242283 scopus 로고    scopus 로고
    • Iron metabolism at the host pathogen interface: Lipocalin 2 and the pathogen-associated iroA gene cluster
    • Smith K.D. 2007: Iron metabolism at the host pathogen interface: Lipocalin 2 and the pathogen-associated iroA gene cluster. Int. J. Biochem. Cell Biol. 39: 1776-1780.
    • (2007) Int. J. Biochem. Cell Biol. , vol.39 , pp. 1776-1780
    • Smith, K.D.1
  • 52
    • 21744434036 scopus 로고    scopus 로고
    • CDNA cloning and regulation of two sex-hormone-repressed hamster tear lipocalins having homology with odorant/pheromone-binding proteins
    • DOI 10.1016/j.bbaexp.2005.04.008, PII S0167478105001090
    • Srikantan S., Parekh V. & De P.K. 2005: cDNA cloning and regulation of two sex-hormone-repressed hamster tear lipocalins having homology with odorant/pheromone-binding proteins. Biochim. Biophys. Acta 1729: 154-165. (Pubitemid 40943499)
    • (2005) Biochimica et Biophysica Acta - Gene Structure and Expression , vol.1729 , Issue.3 , pp. 154-165
    • Srikantan, S.1    Parekh, V.2    De, P.K.3
  • 53
    • 34547841362 scopus 로고    scopus 로고
    • The advertisement role of major urinary proteins in mice
    • DOI 10.1016/j.physbeh.2007.03.030, PII S0031938407001230
    • Stopka P., Janotova K. & Heyrovsky D. 2007: The advertisement role of major urinary proteins in mice. Physiol. Behav. 91:667-670. (Pubitemid 47247795)
    • (2007) Physiology and Behavior , vol.91 , Issue.5 , pp. 667-670
    • Stopka, P.1    Janotova, K.2    Heyrovsky, D.3
  • 54
    • 33947503033 scopus 로고    scopus 로고
    • Species-specific expression of major urinary proteins in the house mice (Mus musculus musculus and Mus musculus domesticus)
    • Stopková R., Stopka P., Janotova K. & Jedelsky P.L. 2007: Species-specific expression of major urinary proteins in the house mice (Mus musculus musculus and Mus musculus domesticus). J. Chem. Ecol. 33: 861-869.
    • (2007) J. Chem. Ecol. , vol.33 , pp. 861-869
    • Stopková, R.1    Stopka, P.2    Janotova, K.3    Jedelsky, P.L.4
  • 55
    • 65349094296 scopus 로고    scopus 로고
    • Role of odorant binding proteins: Comparing hypothetical mechamisms with experimental data
    • Taylor A.J., Cook D.J. & Scott D.J. 2008: Role of odorant binding proteins: Comparing hypothetical mechamisms with experimental data. Chem. Percept. 1: 153-162.
    • (2008) Chem. Percept. , vol.1 , pp. 153-162
    • Taylor, A.J.1    Cook, D.J.2    Scott, D.J.3
  • 56
    • 34547781750 scopus 로고    scopus 로고
    • MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0
    • DOI 10.1093/molbev/msm092
    • Tamura K., Dudley J., Nei M. & Kumar S. 2007: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. MoI. Biol. Evol. 24: 1596-1599. (Pubitemid 47236692)
    • (2007) Molecular Biology and Evolution , vol.24 , Issue.8 , pp. 1596-1599
    • Tamura, K.1    Dudley, J.2    Nei, M.3    Kumar, S.4
  • 57
    • 0033485708 scopus 로고    scopus 로고
    • Abundant secretory lipocalins displaying male and lactation-specific expression in adult hamster submandibular gland
    • Thavathiru E., Jana N.R. & De P.K. 1999: Abundant secretory lipocalins displaying male and lactation-specific expression in adult hamster submandibular gland. Eur. J. Biochem. 266: 467-476.
    • (1999) Eur. J. Biochem. , vol.266 , pp. 467-476
    • Thavathiru, E.1    Jana, N.R.2    De, P.K.3


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