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Genetic diversification of Panstrongylus geniculatus (Reduviidae: Triatominae) in northern South America


Autoři: Valentina Caicedo-Garzón aff001;  Fabian C. Salgado-Roa aff002;  Melissa Sánchez-Herrera aff002;  Carolina Hernández aff001;  Luisa María Arias-Giraldo aff001;  Lineth García aff003;  Gustavo Vallejo aff004;  Omar Cantillo aff005;  Catalina Tovar aff006;  Joao Aristeu da Rosa aff007;  Hernán J. Carrasco aff008;  Maikell Segovia aff008;  Camilo Salazar aff002;  Juan David Ramírez aff001
Působiště autorů: Grupo de Investigaciones Microbiológicas–UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Cra. Bogotá D.C., Colombia aff001;  Grupo de Genética Evolutiva, Filogeografía y Ecología de la Biodiversidad Neotropical (GEUR), Departamento de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá D.C., Colombia aff002;  Universidad Nacional de San Simón, Cochabamba, Bolivia aff003;  Laboratorio de Investigaciones en Parasitología Tropical (LIPT), Universidad del Tolima, Ibagué, Colombia aff004;  Laboratorio de Referencia e Investigación en Enfermedades Tropicales, Dirección de Sanidad Ejército, Ejército Nacional de Colombia, Bogotá, Colombia aff005;  Grupo de investigación en Enfermedades Tropicales y Resistencia Bacteriana, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad del Sinú, Montería, Colombia aff006;  Laboratório de Parasitologia, Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Araraquara, SP, Brasil aff007;  Laboratorio de Biología Molecular de Protozoarios, Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas, Venezuela aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223963

Souhrn

Triatomines are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Although Triatoma and Rhodnius are the most-studied vector genera, other triatomines, such as Panstrongylus, also transmit T. cruzi, creating new epidemiological scenarios. Panstrongylus has at least 13 reported species but there is limited information about its intraspecific genetic variation and patterns of diversification. Here, we begin to fill this gap by studying populations of P. geniculatus from Colombia and Venezuela and including other epidemiologically important species from the region. We examined the pattern of diversification of P. geniculatus in Colombia using mitochondrial and nuclear ribosomal data. Genetic diversity and differentiation were calculated within and among populations of P. geniculatus. Moreover, we constructed maximum likelihood and Bayesian inference phylogenies and haplotype networks using P. geniculatus and other species from the genus (P. megistus, P. lignarius, P. lutzi, P. tupynambai, P. chinai, P. rufotuberculatus and P. howardi). Using a coalescence framework, we also dated the P. geniculatus lineages. The total evidence tree showed that P. geniculatus is a monophyletic species, with four clades that are concordant with its geographic distribution and are partly explained by the Andes orogeny. However, other factors, including anthropogenic and eco-epidemiological effects must be investigated to explain the existence of recent geographic P. geniculatus lineages. The epidemiological dynamics in structured vector populations, such as those found here, warrant further investigation. Extending our knowledge of P. geniculatus is necessary for the accurate development of effective strategies for the control of Chagas disease vectors.

Klíčová slova:

Genetic loci – Haplotypes – Mitochondria – Paleogenetics – Phylogenetic analysis – Phylogeography – Population genetics – Ribosomal RNA


Zdroje

1. Hernández C, Salazar C, Brochero H, Teherán A, Buitrago LS, Vera M, et al. Untangling the transmission dynamics of primary and secondary vectors of Trypanosoma cruzi in Colombia: parasite infection, feeding sources and discrete typing units. Parasit Vectors. 2016;9: 620. doi: 10.1186/s13071-016-1907-5 27903288

2. Coura JR, Borges-Pereira J. Chagas disease: 100 years after its discovery. A systemic review. Acta Trop. 2010;115(1–2): 5–13. doi: 10.1016/j.actatropica.2010.03.008 20382097

3. da Rosa JA, Justino HHG, Nascimento JD, Mendonça VJ, Rocha CS, de Carvalho DB, et al. A new species of Rhodnius from Brazil (Hemiptera, Reduviidae, Triatominae). ZooKeys. 2017;675(675): 1–25.

4. Galvão C, Carcavallo R, Rocha DDS, Jurberg J. A checklist of the current valid species of the subfamily Triatominae Jeannel, 1919 (Hemiptera, Reduviidae) and their geographical distribution, with nomenclatural and taxonomic notes. Zootaxa. 2003;202(1): 1.

5. Patterson JS, Barbosa SE, Feliciangeli MD. On the genus Panstrongylus Berg 1879: Evolution, ecology and epidemiological significance. Acta Trop. 2009;110(2–3): 187–199. doi: 10.1016/j.actatropica.2008.09.008 18929527

6. Molina JA, Gualdrón LE, Brochero HL, Olano V, Barrios D, Guhl F. Distribución actual e importancia epidemiológica de las especies de triatominos (Reduviidae: Triatominae) en Colombia. Biomédica. 2000;20: 344–360.

7. Valente VC, Valente SA, Noireau F, Carrasco HJ, Miles MA. Chagas disease in the Amazon Basin: association of Panstrongylus geniculatus (Hemiptera: Reduviidae) with domestic pigs. J Med Entomol. 1998;35(2): 99–103. doi: 10.1093/jmedent/35.2.99 9538568

8. Sampson-Ward L, Urdaneta-Morales S. Urban Trypanosoma cruzi: biological characterization of isolates from Panstrongylus geniculatus. Ann Soc Belg Med Trop. 1988;68(2):95–106. 3071279

9. Jácome-Pinilla D, Hincapie-Peñaloza E, Ortiz MI, Ramírez JD, Guhl F, Molina J. Risks associated with dispersive nocturnal flights of sylvatic Triatominae to artificial lights in a model house in the northeastern plains of Colombia. Parasit Vectors. 2015;8: 600. doi: 10.1186/s13071-015-1209-3 26582012

10. Carrasco HJ, Segovia M, Londoño JC, Ortegoza J, Rodríguez M, Martínez CE. Panstrongylus geniculatus and four other species of triatomine bug involved in the Trypanosoma cruzi enzootic cycle: high risk factors for Chagas’ disease transmission in the Metropolitan District of Caracas, Venezuela. Parasit Vectors. 2014;7: 602. doi: 10.1186/s13071-014-0602-7 25532708

11. Guhl F, Restrepo M, Angulo VM, Antunes CMF, Campbell-Lendrum D, Davies CR. Lessons from a national survey of Chagas disease transmission risk in Colombia. Trends Parasitol. 2005;21(6): 259–262. doi: 10.1016/j.pt.2005.04.011 15922243

12. Carrasco HJ, Torrellas A, García C, Segovia M, Feliciangeli MD. Risk of Trypanosoma cruzi I (Kinetoplastida: Trypanosomatidae) transmission by Panstrongylus geniculatus (Hemiptera: Reduviidae) in Caracas (metropolitan district) and neighboring states, Venezuela. Int J Parasitol. 2005;35(13): 1379–1384. doi: 10.1016/j.ijpara.2005.05.003 16019006

13. Guhl F, Aguilera G, Pinto NA, Vergara D. Actualización de la distribución geográfica y ecoepidemiología de la fauna de triatominos (Reduviidae: Triatominae) en Colombia. Biomédica. 2007;27: 143–162. 18154255

14. Aldana E, Heredia-Coronado E, Avendaño-Rangel F, Lizano E, Concepcióm JL, Bonfante-Cabarcas R, et al. Análisis morfométrico de Panstrongylus geniculatus de Caracas, Venezuela. Biomédica. 2011;31: 108–117. doi: 10.1590/S0120-41572011000100013 22159489

15. Avendaño-Rangel F, Sandoval CM, Aldana E, Aldana EJ. Descripción de setas cuticulares externas de cabeza, tórax, patas, abdomen y genitalias en cuatro especies de Triatominae. Biomédica. 2016;36(3): 354–358. doi: 10.7705/biomedica.v36i3.3122 27869382

16. Santos C, Jurberg J, Galvão C, Rocha D da S, Fernandez JIR. Morphometric study of the genus Panstrongylus Berg, 1879 (Hemiptera, Reduviidae, Triatominae). Mem Inst Oswaldo Cruz. 2003;98: 939–944. doi: 10.1590/s0074-02762003000700014 14762522

17. Lorosa ES, Dos Santos CM, Jurberg J. Foco de doença de Chagas em São Fidélis, no Estado do Rio de Janeiro. Rev Soc Bras Med Trop. 2008;41(4):419–20. doi: 10.1590/s0037-86822008000400020 18853020

18. Marcilla A, Bargues MD, Abad-Franch F, Panzera F, Carcavallo RU, Noireau F, et al. Nuclear rDNA ITS-2 sequences reveal polyphyly of Panstrongylus species (Hemiptera: Reduviidae: Triatominae), vectors of Trypanosoma cruzi. Infect Genet Evol. 2002;1(3): 225–235. 12798019

19. Justi SA, Russo CAM, Mallet JRDS, Obara MT, Galvão C. Molecular phylogeny of Triatomini (Hemiptera: Reduviidae: Triatominae). Parasit Vectors. 2014;7(1): 1–12.

20. Lent H, Wygodzinsky PW. Revision of the Triatominae (Hemiptera, Reduviidae), and their significance as vectors of Chagas disease. Bull Am Mus Nat Hist. 1979; 163:125–520.

21. Qiagen. DNeasy® Blood & Tissue Handbook. For purification of total DNA from animal blood animal tissue. DNeasy® Blood Tissue Handb Purif Total DNA from Anim blood Anim tissue. 2006; 1–59.

22. Díaz S, Panzera F, Jaramillo-O N, Pérez R, Fernández R, Vallejo G, et al. Genetic, cytogenetic and morphological trends in the evolution of the Rhodnius (Triatominae: Rhodniini) trans-Andean group. PLoS One. 2014;9(2): e87493. doi: 10.1371/journal.pone.0087493 24498330

23. Gómez-Palacio A, Triana O. Molecular evidence of demographic expansion of the Chagas disease vector Triatoma dimidiata (Hemiptera, Reduviidae, Triatominae) in Colombia. PLoS Negl Trop Dis. 2014;8(3): e2734. doi: 10.1371/journal.pntd.0002734 24625572

24. Monteiro FA, Barrett TV, Fitzpatrick S, Cordon-Rosales C, Feliciangeli D, Berad CD. Molecular Phylogeography of the Amazonian Chagas disease vectors Rhodnius prolixus and R. robustus. Mol Ecol 2003, 12:997–1006. doi: 10.1046/j.1365-294x.2003.01802.x 12753218

25. Patterson PS, Gaunt MW. Phylogenetic multilocus codon models and molecular clocks reveal the monophyly of hematophagous reduviid bugs and their evolution at the formation of South America. Mol Phyl Evol 2010, 56:608–621.

26. Geneious. Geneious 11.0.5 [software]. 2018 Jan 24. [cited 2018 Sep 17]. Available from: https://www.geneious.com

27. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23(21): 2947–2948. doi: 10.1093/bioinformatics/btm404 17846036

28. Librado P, Rozas J. DnaSP v5: A software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25(11): 1451–1452. doi: 10.1093/bioinformatics/btp187 19346325

29. Trifinopoulos J, Nguyen L-T, von Haeseler A, Minh BQ. W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis. Nucleic Acids Res. 2016;44: W232–235. doi: 10.1093/nar/gkw256 27084950

30. Berchtold A. Sequence analysis and transition models. Encycl Anim Behav. 2010: 139–145.

31. Minh BQ, Nguyen MAT, von Haeseler A. Ultrafast approximation for phylogenetic bootstrap. Mol Biol Evol. 2013;30(5): 1188–1195. doi: 10.1093/molbev/mst024 23418397

32. Bechara CCN, Londoño JC, Segovia M, Sanchez MAL, Martínez CE, Rodríguez MM, et al. Genetic variability of Panstrongylus geniculatus (Reduviidae: Triatominae) in the Metropolitan District of Caracas, Venezuela. Infect Genet Evol 2018; 66:236–244. doi: 10.1016/j.meegid.2018.09.011 30240833

33. Ronquist F, Teslenko M, van der Mark P, Ayres DL, Darling A, Höhna S, et al. MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst Biol. 2012;61(3): 539–542. doi: 10.1093/sysbio/sys029 22357727

34. Tracer. Tracer v1.7.1. [software]. 2018 May 1 [cited 2018 Sep 17]. Available from: http://tree.bio.ed.ac.uk/software/tracer/

35. Rambaut A. FigTree v1.4.4. [software]. 2018 Nov 25. [Cited 2019 Feb 12]. Available from: http://tree.bio.ed.ac.uk/software/figtree/.

36. Heled J, Drummond AJ. Bayesian inference of species trees from multilocus data. Mol Biol Evol. 2010;27(3): 570–580. doi: 10.1093/molbev/msp274 19906793

37. Bouckaert R, Heled J, Kühnert D, Vaughan T, Wu C-H, Xie D, et al. BEAST 2: A software platform for Bayesian evolutionary analysis. PLoS Comput Biol. 2014;10(4): e1003537. doi: 10.1371/journal.pcbi.1003537 24722319

38. Poinar G. Panstrongylus hispaniolae sp. n. (Hemiptera: Reduviidae: Triatominae), a new fossil triatomine in Dominican amber, with evidence of gut flagellates. Palaeodiversity. 2013;6:1–8.

39. Leigh JW, Bryant D. POPART: Full-feature software for haplotype network construction. Methods Ecol Evol. 2015;6(9): 1110–1116.

40. Wright S. The genetical structure of populations. Ann Eugen. 1949;15(1): 323–354.

41. Nei M, Miller JC. A simple method for estimating average number of nucleotide substitutions within and between populations from restriction data. Genet Soc Am. 1990. 125:873–879.

42. Mantel N. The detection of disease clustering and a generalized regression approach. Cancer Res. 1967;27(1): 209–220.

43. Dixon P. VEGAN, a package of R functions for community ecology. J Veg Sci. 2003;14:927–30.

44. Rousset F. GENEPOP’007: A complete re-implementation of the GENEPOP software for Windows and Linux. Mol Ecol Resour. 2008;8(1): 103–106. doi: 10.1111/j.1471-8286.2007.01931.x 21585727

45. Hijmans RJ. Spherical trigonometry: R package geosphere version 1.5–10 [software]. 2017 Nov 5 [cited 2018 Sep 17] Available from: https://cran.r-project.org/web/packages/geosphere/index.html

46. Legendre P, Fortin MJ. Comparison of the Mantel test and alternative approaches for detecting complex multivariate relationships in the spatial analysis of genetic data. Mol Ecol Resour. 2010;10(5): 831–844. doi: 10.1111/j.1755-0998.2010.02866.x 21565094

47. Crossa RP, Hernández M, Caraccio MN, Rose V, Valente SAS, Valente VC, et al. Chromosomal evolution trends of the genus Panstrongylus (Hemiptera, Reduviidae), vectors of Chagas disease. Infect Genet Evol. 2002;2(1): 47–56 12798000

48. Justi SA, Galvão C, Schrago CG. Geological changes of the Americas and their influence on the diversification of the neotropical kissing bugs (Hemiptera: Reduviidae: Triatominae). PLoS Negl Trop Dis. 2016;10(4): e0004527. doi: 10.1371/journal.pntd.0004527 27058599

49. Monteiro FA, Weirauch C, Felix M, Lazoski C, Abad-Franch F. Evolution, Systematics, and Biogeography of the Triatominae, Vectors of Chagas Disease. Adv Parasitol. 2018;99:265–344 doi: 10.1016/bs.apar.2017.12.002 29530308

50. Hypsa V, Tietz DF, Zrzavý J, Rego R, Galvao C, Jurberg J. Phylogeny and biogeography of Triatominae (Hemiptera: Reduviidae): molecular evidence of a New World origin of the Asiatic clade a clav Hyp. Mol Phylogenet Evol. 2002;23:447–57. 12099798

51. de Paula A, Diotaiuti L, John C. Testing the sister-group relationship of the Rhodniini and Triatomini (Insecta: Hemiptera: Reduviidae: Triatominae). Mol Phylogenet Evol. 2005;35:712–8. doi: 10.1016/j.ympev.2005.03.003 15878138

52. Zhang D-X, Hewitt GM. Nuclear DNA analyses in genetic studies of populations: practice, problems and prospects. Mol Ecol. 2003;12(3): 563–584. doi: 10.1046/j.1365-294x.2003.01773.x 12675814

53. Ballard JWO, Whitlock MC. The incomplete natural history of mitochondria. Mol Ecol. 2004;13(4): 729–744. doi: 10.1046/j.1365-294x.2003.02063.x 15012752

54. Eo SH, DeWoody JA. Evolutionary rates of mitochondrial genomes correspond to diversification rates and to contemporary species richness in birds and reptiles. Proc Biol Sci. 2010;277(1700): 3587–3592. doi: 10.1098/rspb.2010.0965 20610427

55. Justi SA, Galvão C. The evolutionary origin of diversity in Chagas disease vectors. Trends Parasitol. 2017;33(1): 42–52. doi: 10.1016/j.pt.2016.11.002 27986547

56. Justi SA, Cahan S, Stevens L, Monroy C, Lima-Cordón R, Dorn PL. Vectors of diversity: Genome wide diversity across the geographic range of the Chagas disease vector Triatoma dimidiata sensu lato (Hemiptera: Reduviidae). Mol Phylogenet Evol. 2018;120:144–50. doi: 10.1016/j.ympev.2017.12.016 29248626

57. Abad-Franch F, Monteiro FA. Biogeography and evolution of Amazonian triatomines (Heteroptera: Reduviidae): Implications for Chagas disease surveillance in humid forest ecoregions. Mem. Inst. Oswaldo Cruz.; 2007: 57–69. doi: 10.1590/s0074-02762007005000108 17906805

58. Cuervo AM. Evolutionary Assembly of the Neotropical Montane Avifauna [Internet]. LSU Doctoral Dissertations; 2013 [cited 2018 Sep 22]. Available from: https://digitalcommons.lsu.edu/gradschool_dissertations/275/

59. Cadena CD, Pedraza CA, Brumfield RT. Climate, habitat associations and the potential distributions of Neotropical birds: Implications for diversification across the Andes. Rev Acad Colomb Cienc Ex Fis Nat. 2016;40(155): 275–287.

60. Haffer J. In: Wolters H. E., editor. Avifauna of Northwestern Colombia, South America. Germany: Bonner Universitäts-Buchdruckerei;1975. p. 22–30

61. Chazot N, De-Silva DL, Willmott KR, Freitas AVL, Lamas G, Mallet J, et al. Contrasting patterns of Andean diversification among three diverse clades of Neotropical clearwing butterflies. Ecol Evol. 2018;8(8): 3965–3982. doi: 10.1002/ece3.3622 29721272

62. De-Silva DL, Elias M, Willmott K, Mallet J, Day JJ. Diversification of clearwing butterflies with the rise of the Andes. J Biogeogr. 2016;43(1): 44–58. doi: 10.1111/jbi.12611 27546953

63. De-Silva DL, Mota LL, Chazot N, Mallarino R, Silva-Brandão KL, Piñerez LMG, et al. North Andean origin and diversification of the largest ithomiine butterfly genus. Sci Rep. 2017;7: 45966. doi: 10.1038/srep45966 28387233

64. Dick CW, Roubik DW, Gruber KF, Bermingham E. Long-distance gene flow and cross-Andean dispersal of lowland rainforest bees (Apidae: Euglossini) revealed by comparative mitochondrial DNA phylogeography. Mol Ecol. 2004;13(12): 3775–3785. doi: 10.1111/j.1365-294X.2004.02374.x 15548290

65. Bargues MD, Klisiowicz DR, Gonzalez-Candelas F, Ramsey JM, Monroy C, Ponce C, et al. Phylogeography and genetic variation of Triatoma dimidiata, the main Chagas disease vector in Central America, and its position within the genus Triatoma. PLoS Negl Trop Dis. 2008;2(5): e233. doi: 10.1371/journal.pntd.0000233 18461141

66. Campos R, Torres-Pérez F, Botto-Mahan C, Coronado X, Solari A. High phylogeographic structure in sylvatic vectors of Chagas disease of the genus Mepraia (Hemiptera: Reduviidae). Infect Genet Evol. 2013;19: 280–286. doi: 10.1016/j.meegid.2013.04.036 23665465

67. Monteiro FA, Peretolchina T, Lazoski C, Harris K, Dotson EM, Abad-Franch F, et al. Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata. PLoS One. 2013;8(8): e70974. doi: 10.1371/journal.pone.0070974 23940678

68. Salgado-Roa FC, Pardo-Diaz C, Lasso E, Arias CF, Solferini VN, Salazar C. Gene flow and Andean uplift shape the diversification of Gasteracantha cancriformis (Araneae: Araneidae) in northern South America. Ecol Evol. 2018;8(14): 7131–7142. doi: 10.1002/ece3.4237 30073072

69. Dasmahapatra KK, Lamas G, Simpson F, Mallet J. The anatomy of a ‘suture zone’ in Amazonian butterflies: a coalescent-based test for vicariant geographic divergence and speciation. Mol Ecol. 2010;19(19): 4283–4301. doi: 10.1111/j.1365-294X.2010.04802.x 20819158

70. Nadeau NJ, Ruiz M, Salazar P, Counterman B, Medina JA, Ortiz-Zuazaga H, et al. Population genomics of parallel hybrid zones in the mimetic butterflies, H. melpomene and H. erato. Genome Res. 2014; 24(8): 1316–1333. doi: 10.1101/gr.169292.113 24823669

71. Dorn PL, de la Rúa NM, Axen H, Smith N, Richards BR, Charabati J, et al. Hypothesis testing clarifies the systematics of the main Central American Chagas disease vector, Triatoma dimidiata (Latreille, 1811), across its geographic range. Infect Genet Evol. 2016;44: 431–443. doi: 10.1016/j.meegid.2016.07.046 27496718

72. Ramírez CJ, Jaramillo CA, Delgado M del P, Pinto NA, Aguilera G, Guhl F. Genetic structure of sylvatic, peridomestic and domestic populations of Triatoma dimidiata (Hemiptera: Reduviidae) from an endemic zone of Boyacá, Colombia. Acta Trop. 2005;93(1): 23–29. doi: 10.1016/j.actatropica.2004.09.001 15589794

73. Gómez-Palacio A, Triana O, Jaramillo-O N, Dotson EM, Marcet PL. Eco-geographical differentiation among Colombian populations of the Chagas disease vector Triatoma dimidiata (Hemiptera: Reduviidae). Infect Genet Evol. 2013;20: 352–361. doi: 10.1016/j.meegid.2013.09.003 24035810

74. Gourbière S, Dorn P, Tripet F, Dumonteil E. Genetics and evolution of triatomines: From phylogeny to vector control. Heredity. 2012;108: 190–202. doi: 10.1038/hdy.2011.71 21897436

75. World Health Organization. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Weekly epidemiological record. 2015. 90(06),33–44.

76. Omahmaharaj I. Studies on vectors of Trypanosoma cruzi in Trinidad, West-Indies. Med Vet Entomol. 1992;6(2): 115–120. 1421480

77. McCoy KD. The population genetic structure of vectors and our understanding of disease epidemiology. Parasite. 2008;15(3): 444–448. doi: 10.1051/parasite/2008153444 18814720

78. Monteiro FA, Escalante AA, Beard CB. Molecular tools and triatomine systematics: a public health perspective. Trends Parasitol. 2001;17(7): 344–347. 11423378


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