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Volumn 8, Issue 3, 2006, Pages 645-652

Borrelia burgdorferi sensu stricto invasiveness is correlated with OspC-plasminogen affinity

Author keywords

Borrelia burgdorferi sensu stricto; OspC; Plasminogen; Surface plasmon resonance

Indexed keywords

BACTERIAL ANTIGEN; CELL PROTEIN; MEMBRANE PROTEIN; OUTER SURFACE PROTEIN C; PLASMINOGEN; UNCLASSIFIED DRUG;

EID: 33646045625     PISSN: 12864579     EISSN: 1769714X     Source Type: Journal    
DOI: 10.1016/j.micinf.2005.08.017     Document Type: Article
Times cited : (100)

References (54)
  • 1
  • 2
    • 0027170535 scopus 로고
    • Monoclonal antibodies for identification of Borrelia afzelii sp. nov. associated with late cutaneous manifestations of Lyme borreliosis
    • Caniça M.M., Nato F., Du Merle L., Mazie J.C., Baranton G., and Postic D. Monoclonal antibodies for identification of Borrelia afzelii sp. nov. associated with late cutaneous manifestations of Lyme borreliosis. Scand. J. Infect. Dis. 25 (1993) 441-448
    • (1993) Scand. J. Infect. Dis. , vol.25 , pp. 441-448
    • Caniça, M.M.1    Nato, F.2    Du Merle, L.3    Mazie, J.C.4    Baranton, G.5    Postic, D.6
  • 4
    • 13444293534 scopus 로고    scopus 로고
    • The burgeoning molecular genetics of the Lyme disease spirochaete
    • Rosa P.A., Tilly K., and Stewart P.E. The burgeoning molecular genetics of the Lyme disease spirochaete. Nat. Rev. Microbiol. 3 (2005) 129-143
    • (2005) Nat. Rev. Microbiol. , vol.3 , pp. 129-143
    • Rosa, P.A.1    Tilly, K.2    Stewart, P.E.3
  • 5
    • 0037099692 scopus 로고    scopus 로고
    • Molecular adaptation of Borrelia burgdorferi in the murine host
    • Liang F.T., Nelson F.K., and Fikrig E. Molecular adaptation of Borrelia burgdorferi in the murine host. J. Exp. Med. 196 (2002) 275-280
    • (2002) J. Exp. Med. , vol.196 , pp. 275-280
    • Liang, F.T.1    Nelson, F.K.2    Fikrig, E.3
  • 6
    • 0030048119 scopus 로고    scopus 로고
    • Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease
    • Montgomery R.R., Malawista S.E., Feen K.J., and Bockenstedt L.K. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J. Exp. Med. 183 (1996) 261-269
    • (1996) J. Exp. Med. , vol.183 , pp. 261-269
    • Montgomery, R.R.1    Malawista, S.E.2    Feen, K.J.3    Bockenstedt, L.K.4
  • 7
    • 0033984294 scopus 로고    scopus 로고
    • Temporal changes in outer surface protein A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chains of infection in ticks and mice
    • Schwan T.G., and Piesman J. Temporal changes in outer surface protein A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chains of infection in ticks and mice. J. Clin. Microbiol. 38 (2000) 382-388
    • (2000) J. Clin. Microbiol. , vol.38 , pp. 382-388
    • Schwan, T.G.1    Piesman, J.2
  • 9
    • 0032950531 scopus 로고    scopus 로고
    • Influence of outer surface protein A antibody on Borrelia burgdorferi within feeding ticks
    • de Silva A.M., Zeidner N.S., Zhang Y., Dolan M.C., Piesman J., and Fikrig E. Influence of outer surface protein A antibody on Borrelia burgdorferi within feeding ticks. Infect. Immun. 67 (1999) 30-35
    • (1999) Infect. Immun. , vol.67 , pp. 30-35
    • de Silva, A.M.1    Zeidner, N.S.2    Zhang, Y.3    Dolan, M.C.4    Piesman, J.5    Fikrig, E.6
  • 10
    • 0343593690 scopus 로고    scopus 로고
    • Inhibition of Borrelia burgdorferi migration from the midgut to the salivary glands following feeding by ticks on OspC-immunized mice
    • Gilmore R.D., and Piesman J. Inhibition of Borrelia burgdorferi migration from the midgut to the salivary glands following feeding by ticks on OspC-immunized mice. Infect. Immun. 68 (2000) 411-414
    • (2000) Infect. Immun. , vol.68 , pp. 411-414
    • Gilmore, R.D.1    Piesman, J.2
  • 13
    • 0029000733 scopus 로고
    • Molecular analysis of genes encoding outer surface protein C (OspC) of Borrelia burgdorferi sensu lato: relationship to ospA genotype and evidence of lateral gene exchange of ospC
    • Jauris-Heipke S., Liegl G., Preac-Mursic V., Rossler D., Schwab E., Soutschek E., Will G., and Wilske B. Molecular analysis of genes encoding outer surface protein C (OspC) of Borrelia burgdorferi sensu lato: relationship to ospA genotype and evidence of lateral gene exchange of ospC. J. Clin. Microbiol. 33 (1995) 1860-1866
    • (1995) J. Clin. Microbiol. , vol.33 , pp. 1860-1866
    • Jauris-Heipke, S.1    Liegl, G.2    Preac-Mursic, V.3    Rossler, D.4    Schwab, E.5    Soutschek, E.6    Will, G.7    Wilske, B.8
  • 14
    • 0028785476 scopus 로고
    • Evidence for lateral transfer and recombination in OspC variation in Lyme disease Borrelia
    • Livey I., Gibbs C.P., Schuster R., and Dorner F. Evidence for lateral transfer and recombination in OspC variation in Lyme disease Borrelia. Mol. Microbiol. 18 (1995) 257-269
    • (1995) Mol. Microbiol. , vol.18 , pp. 257-269
    • Livey, I.1    Gibbs, C.P.2    Schuster, R.3    Dorner, F.4
  • 16
    • 0027362782 scopus 로고
    • Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen
    • Theisen M., Frederiksen B., Lebech A.-M., Vuust J., and Hansen K. Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen. J. Clin. Microbiol. 31 (1993) 2570-2576
    • (1993) J. Clin. Microbiol. , vol.31 , pp. 2570-2576
    • Theisen, M.1    Frederiksen, B.2    Lebech, A.-M.3    Vuust, J.4    Hansen, K.5
  • 18
    • 0032894835 scopus 로고    scopus 로고
    • Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto
    • Wang I.N., Dykhuizen D.E., Qui W., Dunn J.J., Bosler E.M., and Luft B.J. Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. Genetics 151 (1999) 15-30
    • (1999) Genetics , vol.151 , pp. 15-30
    • Wang, I.N.1    Dykhuizen, D.E.2    Qui, W.3    Dunn, J.J.4    Bosler, E.M.5    Luft, B.J.6
  • 19
    • 0035100181 scopus 로고    scopus 로고
    • Distinct levels of genetic diversity of Borrelia burgdorferi are associated with different aspects of pathogenicity
    • Baranton G., Seinost G., Theodore G., Postic D., and Dykhuizen D. Distinct levels of genetic diversity of Borrelia burgdorferi are associated with different aspects of pathogenicity. Res. Microbiol. (2001) 149-156
    • (2001) Res. Microbiol. , pp. 149-156
    • Baranton, G.1    Seinost, G.2    Theodore, G.3    Postic, D.4    Dykhuizen, D.5
  • 20
    • 0242425755 scopus 로고    scopus 로고
    • Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness
    • Lagal V., Postic D., Ruzic-Sabljic E., and Baranton G. Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness. J. Clin. Microbiol. 41 (2003) 5059-5065
    • (2003) J. Clin. Microbiol. , vol.41 , pp. 5059-5065
    • Lagal, V.1    Postic, D.2    Ruzic-Sabljic, E.3    Baranton, G.4
  • 22
    • 0036308535 scopus 로고    scopus 로고
    • Genetic diversity of the outer surface protein C gene of southern Borrelia isolates and its possible epidemiological, clinical, and pathogenetic implications
    • Lin T., Oliver J.H.J., and Gao L. Genetic diversity of the outer surface protein C gene of southern Borrelia isolates and its possible epidemiological, clinical, and pathogenetic implications. J. Clin. Microbiol. 40 (2002) 2572-2583
    • (2002) J. Clin. Microbiol. , vol.40 , pp. 2572-2583
    • Lin, T.1    Oliver, J.H.J.2    Gao, L.3
  • 23
    • 0033103020 scopus 로고    scopus 로고
    • Surface bound plasmin promotes migration of Streptococcus pneumoniae through reconstituted basement membranes
    • Eberhard T., Kronvall G., and Ullberg M. Surface bound plasmin promotes migration of Streptococcus pneumoniae through reconstituted basement membranes. Microb. Pathog. 26 (1999) 175-181
    • (1999) Microb. Pathog. , vol.26 , pp. 175-181
    • Eberhard, T.1    Kronvall, G.2    Ullberg, M.3
  • 25
    • 0027451350 scopus 로고
    • PAM, a novel plasminogen-binding protein from Streptococcus pyogenes
    • Berge A., and Sjöbring U. PAM, a novel plasminogen-binding protein from Streptococcus pyogenes. J. Biol. Chem. 268 (1993) 25417-25424
    • (1993) J. Biol. Chem. , vol.268 , pp. 25417-25424
    • Berge, A.1    Sjöbring, U.2
  • 26
    • 0030053039 scopus 로고    scopus 로고
    • Role of staphylokinase in the acquisition of plasmin(ogen)-dependent enzymatic activity by staphylococci
    • Christner R.B., and Boyle M.D.P. Role of staphylokinase in the acquisition of plasmin(ogen)-dependent enzymatic activity by staphylococci. J. Infect. Dis. 173 (1996) 104-112
    • (1996) J. Infect. Dis. , vol.173 , pp. 104-112
    • Christner, R.B.1    Boyle, M.D.P.2
  • 28
    • 0032769770 scopus 로고    scopus 로고
    • Plasmin-coated Borrelia burgdorferi degrades soluble and insoluble components of the mammalian extracellular matrix
    • Coleman J.L., Roemer E.J., and Benach J.L. Plasmin-coated Borrelia burgdorferi degrades soluble and insoluble components of the mammalian extracellular matrix. Infect. Immun. 67 (1999) 3929-3936
    • (1999) Infect. Immun. , vol.67 , pp. 3929-3936
    • Coleman, J.L.1    Roemer, E.J.2    Benach, J.L.3
  • 29
    • 0029039462 scopus 로고
    • Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers
    • Coleman J.L., Sellati T.J., Testa J.E., Kew R.R., Furie M.B., and Benach J.L. Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. Infect. Immun. 63 (1995) 2478-2484
    • (1995) Infect. Immun. , vol.63 , pp. 2478-2484
    • Coleman, J.L.1    Sellati, T.J.2    Testa, J.E.3    Kew, R.R.4    Furie, M.B.5    Benach, J.L.6
  • 30
    • 0028593448 scopus 로고
    • The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor
    • Fuchs H., Wallich R., Simon M.M., and Kramer M.D. The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 12594-12598
    • (1994) Proc. Natl. Acad. Sci. U.S.A. , vol.91 , pp. 12594-12598
    • Fuchs, H.1    Wallich, R.2    Simon, M.M.3    Kramer, M.D.4
  • 31
    • 0029084954 scopus 로고
    • Binding of human plasminogen to Borrelia burgdorferi
    • Hu L.T., Perides G., Noring R., and Klempner M.S. Binding of human plasminogen to Borrelia burgdorferi. Infect. Immun. 63 (1995) 3491-3496
    • (1995) Infect. Immun. , vol.63 , pp. 3491-3496
    • Hu, L.T.1    Perides, G.2    Noring, R.3    Klempner, M.S.4
  • 32
    • 84959806880 scopus 로고
    • Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi
    • Klempner M.S., Noring R., Epstein M.P., McCloud B., Hu R., Limentani S.A., and Rogers R.A. Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi. J. Infect. Dis. 171 (1995) 1258-1265
    • (1995) J. Infect. Dis. , vol.171 , pp. 1258-1265
    • Klempner, M.S.1    Noring, R.2    Epstein, M.P.3    McCloud, B.4    Hu, R.5    Limentani, S.A.6    Rogers, R.A.7
  • 34
    • 0034610332 scopus 로고    scopus 로고
    • Correlation between plasmid content and infectivity in Borrelia burgdorferi
    • Purser J.E., and Norris S.J. Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 13865-13870
    • (2000) Proc. Natl. Acad. Sci. U.S.A. , vol.97 , pp. 13865-13870
    • Purser, J.E.1    Norris, S.J.2
  • 35
    • 4644249919 scopus 로고    scopus 로고
    • Experimental assessment of the roles of linear plasmids lp25 and lp-28-1 of Borrelia burgdorferi throughout the infectious cycle
    • Grimm D., Eggers C.H., Caimano M.J., Tilly K., Stewart P.E., Elias A.F., Radolf J.D., and Rosa P.A. Experimental assessment of the roles of linear plasmids lp25 and lp-28-1 of Borrelia burgdorferi throughout the infectious cycle. Infect. Immun. 72 (2004) 5938-5946
    • (2004) Infect. Immun. , vol.72 , pp. 5938-5946
    • Grimm, D.1    Eggers, C.H.2    Caimano, M.J.3    Tilly, K.4    Stewart, P.E.5    Elias, A.F.6    Radolf, J.D.7    Rosa, P.A.8
  • 36
    • 0035168567 scopus 로고    scopus 로고
    • Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1
    • Labandeira-Rey M., and Skare J.T. Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect. Immun. 69 (2001) 446-455
    • (2001) Infect. Immun. , vol.69 , pp. 446-455
    • Labandeira-Rey, M.1    Skare, J.T.2
  • 39
    • 0031715109 scopus 로고    scopus 로고
    • The dominant epitope of Borrelia garinii outer surface protein C recognized by sera from patients with neuroborreliosis has a surface-exposed conserved structural motif
    • Mathiesen M.J., Holm A., Christiansen M., Blom J., Hansen K., Ostergaard S., and Theisen M. The dominant epitope of Borrelia garinii outer surface protein C recognized by sera from patients with neuroborreliosis has a surface-exposed conserved structural motif. Infect. Immun. 66 (1998) 4073-4079
    • (1998) Infect. Immun. , vol.66 , pp. 4073-4079
    • Mathiesen, M.J.1    Holm, A.2    Christiansen, M.3    Blom, J.4    Hansen, K.5    Ostergaard, S.6    Theisen, M.7
  • 40
    • 0033161361 scopus 로고    scopus 로고
    • 1H, 13C, and 15N NMR backbone assignments of 37 kDa surface antigen OspC from Borrelia burgdorferi
    • Huang X., Link K., Koide A., Dunn J.J., Luft B.J., and Koide S. 1H, 13C, and 15N NMR backbone assignments of 37 kDa surface antigen OspC from Borrelia burgdorferi. J. Biomol. NMR 14 (1999) 283-284
    • (1999) J. Biomol. NMR , vol.14 , pp. 283-284
    • Huang, X.1    Link, K.2    Koide, A.3    Dunn, J.J.4    Luft, B.J.5    Koide, S.6
  • 41
    • 0035283085 scopus 로고    scopus 로고
    • Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi
    • Kumaran D., Eswaramoorthy S., Luft B.J., Koide S., Dunn J.J., Lawson C.L., and Swaminathan S. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi. EMBO J. 20 (2001) 971-978
    • (2001) EMBO J. , vol.20 , pp. 971-978
    • Kumaran, D.1    Eswaramoorthy, S.2    Luft, B.J.3    Koide, S.4    Dunn, J.J.5    Lawson, C.L.6    Swaminathan, S.7
  • 42
    • 0035808379 scopus 로고    scopus 로고
    • Structural conservation of neurotropism-associated VspA within the variable Borrelia Vsp-OspC lipoprotein family
    • Zückert W.R., Kerentseva T.A., Lawson C.L., and Barbour A.G. Structural conservation of neurotropism-associated VspA within the variable Borrelia Vsp-OspC lipoprotein family. J. Biol. Chem. 276 (2001) 457-463
    • (2001) J. Biol. Chem. , vol.276 , pp. 457-463
    • Zückert, W.R.1    Kerentseva, T.A.2    Lawson, C.L.3    Barbour, A.G.4
  • 43
    • 0028965993 scopus 로고
    • Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype
    • Wilske B., Jauris-Heipke S., Lobentanzer R., Pradel I., Preacmursic V., Rossler D., Soutschek E., and Johnson R.C. Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype. J. Clin. Microbiol. 33 (1995) 103-109
    • (1995) J. Clin. Microbiol. , vol.33 , pp. 103-109
    • Wilske, B.1    Jauris-Heipke, S.2    Lobentanzer, R.3    Pradel, I.4    Preacmursic, V.5    Rossler, D.6    Soutschek, E.7    Johnson, R.C.8
  • 44
    • 0033856522 scopus 로고    scopus 로고
    • Interaction of the neurotoxic and non-toxic secretory phospholipases A2 with the crotoxin inhibitor from Crotalus serum
    • Faure G., Villela C., Perales J., and Bon C. Interaction of the neurotoxic and non-toxic secretory phospholipases A2 with the crotoxin inhibitor from Crotalus serum. Eur. J. Biochem. 267 (2000) 4799-4808
    • (2000) Eur. J. Biochem. , vol.267 , pp. 4799-4808
    • Faure, G.1    Villela, C.2    Perales, J.3    Bon, C.4
  • 45
    • 0030795295 scopus 로고    scopus 로고
    • Reliable determination of binding affinity and kinetics using surface plasmon resonance biosensors
    • Schuck P. Reliable determination of binding affinity and kinetics using surface plasmon resonance biosensors. Curr. Opin. Biotechnol. 8 (1997) 498-502
    • (1997) Curr. Opin. Biotechnol. , vol.8 , pp. 498-502
    • Schuck, P.1
  • 46
    • 0030561124 scopus 로고    scopus 로고
    • Co-feeding ticks: epidemiological significance for tick-borne pathogen transmission
    • Randolph S.E., Gern L., and Nuttall P.A. Co-feeding ticks: epidemiological significance for tick-borne pathogen transmission. Parasitol. Today 12 (1996) 472-479
    • (1996) Parasitol. Today , vol.12 , pp. 472-479
    • Randolph, S.E.1    Gern, L.2    Nuttall, P.A.3
  • 47
    • 0033016382 scopus 로고    scopus 로고
    • Access of antibody or trypsin to an integral outer membrane protein (P66) of Borrelia burgdorferi is hindered by Osp lipoproteins
    • Bunikis J., and Barbour A.G. Access of antibody or trypsin to an integral outer membrane protein (P66) of Borrelia burgdorferi is hindered by Osp lipoproteins. Infect. Immun. 67 (1999) 2874-2883
    • (1999) Infect. Immun. , vol.67 , pp. 2874-2883
    • Bunikis, J.1    Barbour, A.G.2
  • 48
    • 0342813129 scopus 로고    scopus 로고
    • Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors
    • Karlsson R., and Fält A. Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. J. Immunol. Methods 200 (1997) 121-133
    • (1997) J. Immunol. Methods , vol.200 , pp. 121-133
    • Karlsson, R.1    Fält, A.2
  • 49
    • 0028953918 scopus 로고
    • Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization
    • Sadziene A., Thomas D.D., and Barbour A.G. Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization. Infect. Immun. 63 (1995) 1573-1580
    • (1995) Infect. Immun. , vol.63 , pp. 1573-1580
    • Sadziene, A.1    Thomas, D.D.2    Barbour, A.G.3
  • 50
    • 0031587871 scopus 로고    scopus 로고
    • Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice
    • Coleman J.L., Gebbia J.A., Piesman J., Degen J.L., Bugge T.H., and Benach J.L. Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89 (1997) 1111-1119
    • (1997) Cell , vol.89 , pp. 1111-1119
    • Coleman, J.L.1    Gebbia, J.A.2    Piesman, J.3    Degen, J.L.4    Bugge, T.H.5    Benach, J.L.6
  • 51
    • 0037900067 scopus 로고    scopus 로고
    • Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks
    • Crippa M., Rais O., and Gern L. Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks. Vector Borne Zoonotic Dis. 2 (2002) 3-9
    • (2002) Vector Borne Zoonotic Dis. , vol.2 , pp. 3-9
    • Crippa, M.1    Rais, O.2    Gern, L.3
  • 53
    • 0023515556 scopus 로고
    • Characterization of Borrelia burgdorferi strains isolated from Ixodes pacificus ticks in California
    • Bissett M.L., and Hill W. Characterization of Borrelia burgdorferi strains isolated from Ixodes pacificus ticks in California. J. Clin. Microbiol. 25 (1987) 2296-2301
    • (1987) J. Clin. Microbiol. , vol.25 , pp. 2296-2301
    • Bissett, M.L.1    Hill, W.2
  • 54
    • 0022630551 scopus 로고
    • Involvement of birds in the epidemiology of the Lyme disease agent Borrelia burgdorferi
    • Anderson J.F., Johnson R.C., Magnarelli L.A., and Hyde F.W. Involvement of birds in the epidemiology of the Lyme disease agent Borrelia burgdorferi. Infect. Immun. 51 (1986) 394-396
    • (1986) Infect. Immun. , vol.51 , pp. 394-396
    • Anderson, J.F.1    Johnson, R.C.2    Magnarelli, L.A.3    Hyde, F.W.4


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