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The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse

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Abstract

Ticks and tick-borne diseases have a detrimental impact on livestock production causing estimated losses of around $200 million per year in Australia alone. Host resistance to ticks is heritable, within-breed heritability estimates being around 0.35, and with large differences between breeds. Previously a QTL for tick burden was detected on BTA14 at ~72 Mb distal to the centromere, near the gene receptor-interacting serine-threonine kinase 2 (RIPK2). To identify polymorphisms in this region, we sequenced all exons of the RIPK2 gene, identifying 46 single nucleotide polymorphism (SNP). Using SNP from RIPK2 as well as SNP from the bovine genome sequence, we genotyped two samples, one of 1,122 taurine dairy cattle and one of 761 zebu and zebu composite beef cattle. We confirmed that SNP and haplotypes from this region, including from RIPK2, were associated with tick burden in both dairy and beef cattle. To determine whether RIPK2 influences response to tick salivary gland extract (SGE), an immunisation experiment with tick SGE in a RIPK2 knockout (RIPK2 −/−) mouse strain was conducted. There was a significant (P < 0.05) reduction in IgG production in the RIPK2 −/− mouse in response to the SGE compared to its background strain C57BL/6 as well as the outbred CD1 mouse strain. In addition, antibodies generated by RIPK2 −/− mice recognised a different set of antigens within SGE when compared to parental-derived antibodies. In summary, the SNP association with tick burden at BTA14 was confirmed and quantitative and qualitative differences in antibody production were observed between RIPK2 −/− and wild-type mice.

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References

  • Adams S, Valchanova RS, Munz B (2010) RIP2: a novel player in the regulation of keratinocyte proliferation and cutaneous wound repair? Exp Cell Res 316(5):728–736. doi:10.1016/j.yexcr.2009.12.001

    Article  PubMed  CAS  Google Scholar 

  • Ajmone-Marsan P, Garcia JF, Lenstra JA, Globaldiv C (2010) On the origin of cattle: how aurochs became cattle and colonized the world. Evol Anthropol 19(4):148–157. doi:10.1002/evan20267

    Article  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic Local alignment search tool. J Mol Biol 215(3):403–410

    PubMed  CAS  Google Scholar 

  • Barendse W (2007) Assessing tick resistance in a bovine animal for selecting cattle for tick resistance by providing a nucleic acid from the bovine animal and assaying for the occurrence of a single nucleotide polymorphism (SNP). Patent application WO2007051248-A1

  • Barendse W, Harrison BE, Bunch RJ, Thomas MB, Turner LB (2009) Genome wide signatures of positive selection: the comparison of independent samples and the identification of regions associated to traits. BMC Genomics 10(1):178

    Article  PubMed  Google Scholar 

  • Battsetseg B, Mamiro K, Inoue N, Makala L, Nagasawa H, Iwakura Y, Toyoda Y, Mikami T, Fujisak K (2002) Immune responses of interferon gamma (IFN-gamma) knock out mice to repeated Haemaphysalis longicornis (Acari: Ixodidae) nymph infestations. J Med Entomol 39(1):173–176

    Article  PubMed  CAS  Google Scholar 

  • Beaumont MA, Nichols RA (1996) Evaluating loci for use in the genetic analysis of population structure. Proc R Soc Lond, B, Biol Sci 263(1377):1619–1626

    Article  Google Scholar 

  • Bertrand MJM, Doiron K, Labbe K, Korneluk RG, Barker PA, Saleh M (2009) Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity 30(6):789–801. doi:10.1016/j.immuni.2009.04.011

    Article  PubMed  CAS  Google Scholar 

  • Cavalli-Sforza LL (1966) Population structure and human evolution. Proc R Soc Lond, B, Biol Sci 164(995):362–379

    Article  PubMed  CAS  Google Scholar 

  • Chan EK, Hawken R, Reverter A (2009) The combined effect of SNP-marker and phenotype attributes in genome-wide association studies. Anim Genet 40(2):149–156

    Article  PubMed  CAS  Google Scholar 

  • Chin AI, Dempsey PW, Bruhn K, Miller JF, Xu Y, Cheng GH (2002) Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416(6877):190–194

    Article  PubMed  CAS  Google Scholar 

  • Constantinoiu CC, Jackson LA, Jorgensen WK, Lew-Tabor AE, Piper EK, Mayer DG, Venus B, Jonsson NN (2010) Local immune response against larvae of Rhipicephalus (Boophilus) microplus in Bos taurus indicus and Bos taurus taurus cattle. Int J Parasitol 40(7):865–875. doi:10.1016/j.ijpara.2010.01.004

    Article  PubMed  CAS  Google Scholar 

  • deCastro JJ (1997) Sustainable tick and tickborne disease control in Livestock improvement in developing countries. Vet Parasitol 71(2–3):77–97

    Article  CAS  Google Scholar 

  • den Dunnen JT, Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15(1):7–12

    Article  Google Scholar 

  • Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 8(3):186–194

    PubMed  CAS  Google Scholar 

  • Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8(3):175–185

    PubMed  CAS  Google Scholar 

  • Gasparin G, Miyata M, Coutinho LL, Martinez ML, Teodoro RL, Furlong J, Machado MA, Silva M, Sonstegard TS, Regitano LCA (2007) Mapping of quantitative trait loci controlling tick [Riphicephalus (Boophilus) microplus] resistance on bovine chromosomes 5, 7 and 14. Anim Genet 38(5):453–459

    Article  PubMed  CAS  Google Scholar 

  • Gibbs RA, Taylor JF, Van Tassell CP, Barendse W, Eversole KA, Gill CA, Green RD, Hamernik DL, Kappes SM, Lien S, Matukumalli LK, McEwan JC, Nazareth LV, Schnabel RD, Weinstock GM, Wheeler DA, Ajmone-Marsan P, Boettcher PJ, Caetano AR, Garcia JF, Hanotte O, Mariani P, Skow LC, Sonstegard TS, Williams JL, Diallo B, Hailemariam L, Martinez ML, Morris CA, Silva LO, Spelman RJ, Mulatu W, Zhao K, Abbey CA, Agaba M, Araujo FR, Bunch RJ, Burton J, Gorni C, Olivier H, Harrison BE, Luff B, Machado MA, Mwakaya J, Plastow G, Sim W, Smith T, Thomas MB, Valentini A, Williams P, Womack J, Woolliams JA, Liu Y, Qin X, Worley KC, Gao C, Jiang H, Moore SS, Ren Y, Song XZ, Bustamante CD, Hernandez RD, Muzny DM, Patil S, San Lucas A, Fu Q, Kent MP, Vega R, Matukumalli A, McWilliam S, Sclep G, Bryc K, Choi J, Gao H, Grefenstette JJ, Murdoch B, Stella A, Villa-Angulo R, Wright M, Aerts J, Jann O, Negrini R, Goddard ME, Hayes BJ, Bradley DG, Barbosa da Silva M, Lau LP, Liu GE, Lynn DJ, Panzitta F, Dodds KG (2009) Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science 324(5926):528–532

    Article  PubMed  CAS  Google Scholar 

  • Gilmour A, Gogel B, Cullis B, Welham S, Thompson R (2002) ASReml user guide release 1.0. VSN International Ltd, Hemel Hempstead

    Google Scholar 

  • Gordon D, Abajian C, Green P (1998) Consed: a graphical tool for sequence finishing. Genome Res 8(3):195–202

    PubMed  CAS  Google Scholar 

  • Greenstein RJ, Brown ST (2010) Genomewide Association study of leprosy. N Engl J Med 362(15):1447–1448

    PubMed  CAS  Google Scholar 

  • Hube F, Reverdiau P, Iochmann S, Gruel Y (2005) Improved PCR method for amplification of GC-Rich DNA sequences. Mol Biotechnol 31(1):81–84

    Article  PubMed  CAS  Google Scholar 

  • Inohara N, del Peso L, Koseki T, Chen S, Nunez G (1998) RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem 273(20):12296–12300

    Article  PubMed  CAS  Google Scholar 

  • Jackson LA, Opdebeeck JP (1989) The effect of antigen concentration and vaccine regimen on the immunity induced by membrane-antigens from midgut of Boophilus-microplus. Immunology 68(2):272–276

    PubMed  CAS  Google Scholar 

  • Jongejan F, Uilenberg G (2004) The global importance of ticks. Parasitology 129:S3–S14

    Article  PubMed  Google Scholar 

  • Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R, Flavell RA (2002) RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416(6877):194–199

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710):731–734. doi:10.1126/science.1104911

    Article  PubMed  CAS  Google Scholar 

  • Lewontin RC, Krakauer J (1973) Distribution of gene frequency as a test of theory of selective neutrality of polymorphisms. Genetics 74(1):175–195

    PubMed  CAS  Google Scholar 

  • Machado MA, Azevedo AL, Teodoro RL, Pires MD, Peixoto MG, de Freitas C, Prata MC, Furlong J, da Silva MV, Guimaraes SE, Regitano LC, Coutinho LL, Gasparin G, Verneque RS (2010) Genome wide scan for quantitative trait loci affecting tick resistance in cattle (Bos taurus x Bos indicus). BMC Genomics 11(1):280. doi:10.1186/1471-2164-11-280

    Article  PubMed  Google Scholar 

  • Magalhaes JG, Lee J, Geddes K, Rubino S, Philpott DJ, Girardin SE (2011) Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol 41(5):1445–1455. doi:10.1002/eji.201040827

    Article  PubMed  CAS  Google Scholar 

  • Matukumalli LK, Lawley CT, Schnabel RD, Taylor JF, Allan MF, Heaton MP, O’Connell J, Moore SS, Smith TP, Sonstegard TS, Van Tassell CP (2009) Development and characterization of a high density SNP genotyping assay for cattle. PLoS One 4(4):e5350

    Article  PubMed  Google Scholar 

  • McCarthy JV, Ni J, Dixit VM (1998) RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. J Biol Chem 273(27):16968–16975

    Article  PubMed  CAS  Google Scholar 

  • McCully ML, Fairhead T, Colmont CS, Beasley FC, Heinrichs DE, Blake PG, Topley N, Madrenas J (2008) Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during peritoneal dialysis-associated peritonitis. Am J Nephrol 28(6):879–889. doi:10.1159/000141041

    Article  PubMed  CAS  Google Scholar 

  • Nelson WA, Bell JF, Stewart SJ (1979) Polyplax serrata: cutaneous cytologic reactions in mice that do (CFW strain) and do not (C57BL strain) develop resistance. Exp Parasitol 48(2):259–264

    Article  PubMed  CAS  Google Scholar 

  • Netea MG, Kullberg BJ, van der Meer JWM (2010) Genomewide Association study of leprosy. N Engl J Med 362(15):1447–1447

    PubMed  CAS  Google Scholar 

  • Nickerson DA, Tobe VO, Taylor SL (1997) PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res 25(14):2745–2751

    Article  PubMed  CAS  Google Scholar 

  • Piper EK, Jackson LA, Bagnall NH, Kongsuwan KK, Lew AE, Jonsson NN (2008) Gene expression in the skin of Bos taurus and Bos indicus cattle infested with the cattle tick, Rhipicephalus (Boophilus) microplus. Vet Immunol Immunopathol 126(1–2):110–119. doi:10.1016/j.vetimm.2008.06.011

    Article  PubMed  CAS  Google Scholar 

  • Piper EK, Jackson LA, Bielefeldt-Ohmann H, Gondro C, Lew-Tabor AE, Jonsson NN (2010) Tick-susceptible Bos taurus cattle display an increased cellular response at the site of larval Rhipicephalus (Boophilus) microplus attachment, compared with tick-resistant Bos indicus cattle. Int J Parasitol 40(4):431–441. doi:10.1016/j.ijpara.2009.09.009

    Article  PubMed  Google Scholar 

  • Piper EK, Jonsson NN, Gondro C, Lew-Tabor AE, Moolhuijzen P, Vance ME, Jackson LA (2009) Immunological profiles of Bos taurus and Bos indicus cattle infested with the cattle tick, Rhipicephalus (Boophilus) microplus. Clin Vaccine Immunol 16(7):1074–1086. doi:10.1128/cvi.00157-09

    Article  PubMed  CAS  Google Scholar 

  • Playford M (2005) Review of research needs for cattle tick control Phases I and II. (AHW.054A):1–162

  • Porto Neto LR, Bunch R, Harrison BE, Barendse W (2011a) DNA variation in the gene ELTD1 is associated with tick burden in cattle. Anim Genet 42(1):50–55. doi:10.1111/j.1365-2052.2010.02120.x

    Article  PubMed  CAS  Google Scholar 

  • Porto Neto LR, Bunch RJ, Harrison BE, Prayaga KC, Barendse W (2010) Haplotypes that include the integrin alpha 11 gene are associated with tick burden in cattle. BMC Genet 11:55

    Article  PubMed  Google Scholar 

  • Porto Neto LR, Jonsson NN, D’Occhio MJ, Barendse W (2011b) Molecular genetic approaches for identifying the basis of variation in resistance to tick infestation in cattle. Vet Parasitol 180(3–4):165–172. doi:10.1016/j.vetpar.2011.05.048

    Article  PubMed  CAS  Google Scholar 

  • Prayaga KC, Corbet NJ, Johnston DJ, Wolcott ML, Fordyce G, Burrow HM (2009) Genetics of adaptive traits in heifers and their relationship to growth, pubertal and carcass traits in two tropical beef cattle genotypes. Anim Prod Sci 49(5–6):413–425. doi:10.1071/ea08247

    Article  Google Scholar 

  • Rabilloud T, Carpentier G, Tarroux P (1988) Improvement and simplification of low-background silver staining of proteins by using sodium dithionite. Electrophoresis 9(6):288–291

    Article  PubMed  CAS  Google Scholar 

  • Regitano LCA, Ibelli AMG, Gasparin G, Miyata M, Azevedo ALS, Coutinho LL, Teodoro RL, Machado MA, Silva M, Nakata LC, Zaros LG, Sonstegard TS, Silva AM, Alencar MM, Oliveira MCS (2008) On the Search for Markers of Tick Resistance in Bovines. In: Pinard MH, Gay C, Pastoret PP, Dodet B (eds) Animal genomics for animal health, vol 132. Developments in biologicals. Karger, Basel, pp 225–230

    Google Scholar 

  • Ruefli-Brasse AA, Lee WP, Hurst S, Dixit VM (2004) Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation. J Biol Chem 279(2):1570–1574

    Article  PubMed  CAS  Google Scholar 

  • Sackett D, Holmes P, Abbott K, Jephcott S, Barber M (2006) Assessing the economic cost of endemic disease on the profitability of Australian beef cattle and sheep producers. (AHW.087):1–133

  • Scheet P, Stephens M (2006) A fast and flexible statistical model for large-scale population genotype data: Applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78(4):629–644

    Article  PubMed  CAS  Google Scholar 

  • Shimada K, Chen S, Dempsey PW, Sorrentino R, Alsabeh R, Slepenkin AV, Peterson E, Doherty TM, Underhill D, Crother TR, Arditi M (2009) The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PloS Pathog 5(4):e1000379

    Article  PubMed  Google Scholar 

  • Thome M, Hofmann K, Burns K, Martinon F, Bodmer JL, Mattmann C, Tschopp J (1998) Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. Curr Biol 8(15):885–888

    Article  PubMed  CAS  Google Scholar 

  • Tigno-Aranjuez JT, Asara JM, Abbott DW (2010) Inhibition of RIP2’s tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev 24(23):2666–2677. doi:10.1101/gad.1964410

    Article  PubMed  CAS  Google Scholar 

  • Turner LB, Harrison BE, Bunch RJ, Porto Neto LR, Li Y, Barendse W (2010) A genome-wide association study of tick burden and milk composition in cattle. Anim Prod Sci 50(4):235–245. doi:10.1071/AN09135

    Article  Google Scholar 

  • Wang YH, Reverter A, Kemp D, McWilliam SM, Ingham A, Davis CK, Moore RJ, Lehnert SA (2007) Gene expression profiling of Hereford Shorthorn cattle following challenge with Boophilus microplus tick larvae. Aust J Exp Agr 47(12):1397–1407. doi:10.1071/ea07012

    Article  CAS  Google Scholar 

  • Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ (2009) Jalview Version 2-a multiple sequence alignment editor and analysis workbench. Bioinformatics 25(9):1189–1191. doi:10.1093/bioinformatics/btp033

    Article  PubMed  CAS  Google Scholar 

  • Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JRB, Stevens S, Hall AS, Samani NJ, Shields B, Prokopenko I, Farrall M, Dominiczak A, Johnson T, Bergmann S, Beckmann JS, Vollenweider P, Waterworth DM, Mooser V, Palmer CNA, Morris AD, Ouwehand WH, Caulfield M, Munroe PB, Hattersley AT, McCarthy MI, Frayling TM (2008) Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 40(5):575–583

    Article  PubMed  CAS  Google Scholar 

  • Weir BS (1996) Genetic data analysis II. Sinauer Associates, Inc, Sunderland

    Google Scholar 

  • Willadsen P (1980) Immunity to ticks. Adv Parasitol 18:293–311

    Article  PubMed  CAS  Google Scholar 

  • Willadsen P, Riding GA, McKenna RV, Kemp DH, Tellam RL, Nielsen JN, Lahnstein J, Cobon GS, Gough JM (1989) Immunological control of a parasitic arthropod—identification of a protective antigen from Boophilus-microplus. J Immunol 143(4):1346–1351

    PubMed  CAS  Google Scholar 

  • Wong SH, Hill AVS, Vannberg FO, India-Africa-United Kingdom L (2010) Genomewide Association study of leprosy. N Engl J Med 362(15):1446–1447

    Article  PubMed  CAS  Google Scholar 

  • Yang JA, Benyamin B, McEvoy BP, Gordon S, Henders AK, Nyholt DR, Madden PA, Heath AC, Martin NG, Montgomery GW, Goddard ME, Visscher PM (2010) Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42(7):565–569. doi:10.1038/ng.608

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Liu H, Chen S, Low H, Sun L, Cui Y, Chu T, Li Y, Fu X, Yu Y, Yu G, Shi B, Tian H, Liu D, Yu X, Li J, Lu N, Bao F, Yuan C, Liu J, Zhang L, Sun Y, Chen M, Yang Q, Yang H, Yang R, Wang Q, Zuo F, Zhang H, Khor CC, Hibberd ML, Yang S, Zhang X (2011) Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy. Nat Genet. doi:10.1038/ng.973

  • Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, Chu TS, Zhang C, Zhang L, Han JW, Yu GQ, Quan C, Yu YX, Zhang Z, Shi BQ, Zhang LH, Cheng H, Wang CY, Lin Y, Zheng HF, Fu XA, Zuo XB, Wang Q, Long H, Sun YP, Cheng YL, Tian HQ, Zhou FS, Liu HX, Lu WS, He SM, Du WL, Shen M, Jin QY, Wang Y, Low HQ, Erwin T, Yang NH, Li JY, Zhao X, Jiao YL, Mao LG, Yin G, Jiang ZX, Wang XD, Yu JP, Hu ZH, Gong CH, Liu YQ, Liu RY, Wang DM, Wei D, Liu JX, Cao WK, Cao HZ, Li YP, Yan WG, Wei SY, Wang KJ, Hibberd ML, Yang S, Zhang XJ, Liu JJ (2009) Genomewide Association study of leprosy. N Engl J Med 361(27):2609–2618. doi:10.1056/NEJMoa0903753

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Dr R. Flavell and Dr. K. Kobayashi for the kind donation of the RIPK2 knockout mice. We thank J.F. Garcia for donation of the zebu cattle samples. We thank L. Jackson and R. Pearson for guidance during the ELISA analysis and R. Pearson for guidance during the immunoblot experiment. We thank L. Jackson and E. Piper for providing the cattle ticks to produce the salivary gland extract. We thank the staff of the Otto Hirschfeld Animal House for looking after the mice. We thank A. Kotze for suggestions that improved the manuscript. LRPN was supported during his PhD by an Endeavour International Postgraduate Research Scholarship, a University of Queensland International Student Living Allowance and a Cooperative Research Centre for Beef Genetic Technologies (Beef CRC) Scholarship. This work was co-funded by the Beef CRC (WB).

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  1. CSIRO Livestock Industries, Queensland Bioscience Precinct, St Lucia, QLD, Australia

    Laercio R. Porto Neto, Aaron Ingham, Rowan J. Bunch, Blair E. Harrison & William Barendse

  2. School of Agriculture and Food Sciences, University of Queensland, Gatton, QLD, Australia

    Laercio R. Porto Neto

  3. School of Veterinary Science, University of Queensland, Gatton, QLD, 4343, Australia

    Laercio R. Porto Neto & Nicholas N. Jonsson

  4. College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

    Nicholas N. Jonsson

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  1. Laercio R. Porto Neto
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Correspondence to Laercio R. Porto Neto.

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Porto Neto, L.R., Jonsson, N.N., Ingham, A. et al. The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse. Immunogenetics 64, 379–388 (2012). https://doi.org/10.1007/s00251-012-0601-9

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