Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados
ilustraciones, diagramas, fotografías
- Autores:
-
Lasso Delgado, Jose Manuel
- Tipo de recurso:
- Fecha de publicación:
- 2024
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/86036
- Palabra clave:
- 590 - Animales::599 - Mamíferos
570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales
Patología animal
animal pathology
Oligodendroglía/patología
Moquillo/fisiopatología
Oligodendroglia/pathology
Distemper/physiopathology
Distemper canino
Oligodendrocitos
Desmielinización
Apoptosis
Caspasa 3
Caspasa 9
Canine distemper
Oligodendrocytes
Demyelination
Apoptosis
Caspase 3
Caspase 9
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
id |
UNACIONAL2_5930b174685847d25a52c2a86eb0a564 |
---|---|
oai_identifier_str |
oai:repositorio.unal.edu.co:unal/86036 |
network_acronym_str |
UNACIONAL2 |
network_name_str |
Universidad Nacional de Colombia |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
dc.title.translated.eng.fl_str_mv |
Evaluation of oligodendrocyte death caused by canine distemper virus in naturally infected animal brain |
title |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
spellingShingle |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados 590 - Animales::599 - Mamíferos 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales Patología animal animal pathology Oligodendroglía/patología Moquillo/fisiopatología Oligodendroglia/pathology Distemper/physiopathology Distemper canino Oligodendrocitos Desmielinización Apoptosis Caspasa 3 Caspasa 9 Canine distemper Oligodendrocytes Demyelination Apoptosis Caspase 3 Caspase 9 |
title_short |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
title_full |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
title_fullStr |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
title_full_unstemmed |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
title_sort |
Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectados |
dc.creator.fl_str_mv |
Lasso Delgado, Jose Manuel |
dc.contributor.advisor.spa.fl_str_mv |
Arboleda Bustos, Gonzalo Humberto Botero Espinosa, Lucia |
dc.contributor.author.spa.fl_str_mv |
Lasso Delgado, Jose Manuel |
dc.contributor.researchgroup.spa.fl_str_mv |
Muerte Celular |
dc.subject.ddc.spa.fl_str_mv |
590 - Animales::599 - Mamíferos 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales |
topic |
590 - Animales::599 - Mamíferos 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales Patología animal animal pathology Oligodendroglía/patología Moquillo/fisiopatología Oligodendroglia/pathology Distemper/physiopathology Distemper canino Oligodendrocitos Desmielinización Apoptosis Caspasa 3 Caspasa 9 Canine distemper Oligodendrocytes Demyelination Apoptosis Caspase 3 Caspase 9 |
dc.subject.agrovoc.spa.fl_str_mv |
Patología animal |
dc.subject.agrovoc.eng.fl_str_mv |
animal pathology |
dc.subject.decs.spa.fl_str_mv |
Oligodendroglía/patología Moquillo/fisiopatología |
dc.subject.decs.eng.fl_str_mv |
Oligodendroglia/pathology Distemper/physiopathology |
dc.subject.proposal.spa.fl_str_mv |
Distemper canino Oligodendrocitos Desmielinización Apoptosis Caspasa 3 Caspasa 9 |
dc.subject.proposal.eng.fl_str_mv |
Canine distemper Oligodendrocytes Demyelination Apoptosis Caspase 3 Caspase 9 |
description |
ilustraciones, diagramas, fotografías |
publishDate |
2024 |
dc.date.accessioned.none.fl_str_mv |
2024-05-06T20:50:34Z |
dc.date.available.none.fl_str_mv |
2024-05-06T20:50:34Z |
dc.date.issued.none.fl_str_mv |
2024-02-01 |
dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
status_str |
acceptedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/86036 |
dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
url |
https://repositorio.unal.edu.co/handle/unal/86036 https://repositorio.unal.edu.co/ |
identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
dc.language.iso.spa.fl_str_mv |
spa |
language |
spa |
dc.relation.references.spa.fl_str_mv |
Aige, V., & Morales, C. (2012). Neurología Canina y Felina. Arch. Med. Interna (Montevideo), 18(2), 83–89. Athanasiou, L. V., Kantere, M. C., Kyriakis, C. S., Pardali, D., Adamama Moraitou, K., & Polizopoulou, Z. S. (2018). Evaluation of a Direct Immunofluorescent Assay and/or Conjunctival Cytology for Detection of Canine Distemper Virus Antigen. Viral Immunology, 31(3), 272–275. https://doi.org/10.1089/vim.2017.0101 Atzeni, F., & Sarzi-Puttini, P. (2013). Tumor Necrosis Factor. In Brenner’s Encyclopedia of Genetics: Second Edition (pp. 229–231). Elsevier Inc. https://doi.org/10.1016/B978-0-12-374984-0.01594-1 Beineke, A., Puff, C., Seehusen, F., & Baumgärtner, W. (2009). Pathogenesis and immunopathology of systemic and nervous canine distemper. Veterinary Immunology and Immunopathology, 127(1–2), 1–18. https://doi.org/10.1016/j.vetimm.2008.09.023 Brenner, M., & Messing, A. (2021). Regulation of GFAP Expression. ASN Neuro, 13. https://doi.org/10.1177/1759091420981206 Campa, V. (2017). Análisis de Imágenes de Microscopía con ImageJ. Canene-Adams, K. (2013). Chapter Fifteen - Preparation of Formalin-fixed Paraffin-embedded Tissue for Immunohistochemistry. In J. Lorsch (Ed.), Methods in Enzymology (Vol. 533, pp. 225–233). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-420067-8.00015-5 Clarke, P., & Tyler, K. L. (2009). Apoptosis in animal models of virus-induced disease. Nature Reviews Microbiology, 7(2), 144–155. https://doi.org/10.1038/nrmicro2071 Cosby, S. L. (2012). Morbillivirus cross-species infection: Is there a risk for humans? Future Virology, 7(11), 1103–1113. https://doi.org/10.2217/fvl.12.103 D’Arcy, M. S. (2019). Cell death: a review of the major forms of apoptosis, necrosis and autophagy. In Cell Biology International (Vol. 43, Issue 6, pp. 582–592). Wiley-Blackwell Publishing Ltd. https://doi.org/10.1002/cbin.11137 Dawson, S. (2007). Guidelines for the vaccination of dogs and cats. Journal of Small Animal Practice, 48(9), 483. https://doi.org/10.1111/j.1748-5827.2007.00474.x de Lahunta, A., & Glass, E. (2009a). Chapter 2 - Neuroanatomy by Dissection (A. de Lahunta & E. B. T.-V. N. and C. N. (Third E. Glass, Eds.; pp. 6–22). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-7216-6706-5.00002-0 de Lahunta, A., & Glass, E. (2009b). Chapter 13 - Cerebellum (A. de Lahunta & E. B. T.-V. N. and C. N. (Third E. Glass, Eds.; pp. 348–388). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-7216-6706-5.00013-5 De Nardo, T. F. S., Bertolo, P. H. L., Bernardes, P. A., Munari, D. P., Machado, G. F., Jardim, L. S., Moreira, P. R. R., Rosolem, M. C., & Vasconcelos, R. O. (2020). Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated canine encephalitis caused by the distemper virus. Veterinary Immunology and Immunopathology, 221(March 2019), 110010. https://doi.org/10.1016/j.vetimm.2020.110010 DeBiasi, R. L., Robinson, B. A., Sherry, B., Bouchard, R., Brown, R. D., Rizeq, M., Long, C., & Tyler, K. L. (2004). Caspase Inhibition Protects against Reovirus-Induced Myocardial Injury In Vitro and In Vivo. Journal of Virology, 78(20), 11040–11050. https://doi.org/10.1128/jvi.78.20.11040-11050.2004 Del Puerto, H. L., Martins, A. S., Milsted, A., Souza-Fagundes, E. M., Braz, G. F., Hissa, B., Andrade, L. O., Alves, F., Rajão, D. S., Leite, R. C., & Vasconcelos, A. C. (2011). Canine distemper virus induces apoptosis in cervical tumor derived cell lines. Virology Journal, 8, 1–7. https://doi.org/10.1186/1743-422X-8-334 Del Puerto, H. L., Martins, A. S., Moro, L., Milsted, A., Alves, F., Braz, G. F., & Vasconcelos, A. C. (2010). Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus. Genetics and Molecular Research, 9(1), 151–161. https://doi.org/10.4238/vol9-1gmr717 Dewey, C. W., Davies, E. S., Xie, H., & Wakshlag, J. J. (2019). Canine Cognitive Dysfunction: Pathophysiology, Diagnosis, and Treatment. Veterinary Clinics of North America - Small Animal Practice, 49(3), 477–499. https://doi.org/10.1016/j.cvsm.2019.01.013 Duque-Valencia, J., Sarute, N., Olarte-Castillo, X. A., & Ruíz-Sáenz, J. (2019). Evolution and interspecies transmission of canine distemper virus—an outlook of the diverse evolutionary landscapes of a multi-host virus. In Viruses (Vol. 11, Issue 7). MDPI AG. https://doi.org/10.3390/v11070582 Echeverri-Zuluaga, M., Duque-García, Y. H., & Ruiz-Saenz, J. (2015). Morbillivirus de los delfines: Patógeno re-emergente en la población de cetáceos. Universitas Scientiarum, 20(1), 29–41. https://doi.org/10.11144/Javeriana.SC20-1.mdpr Galiano, M. R., Andrieux, A., Deloulme, J. C., Bosc, C., Schweitzer, A., Job, D., & Hallak, M. E. (2006). Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes. Journal of Neuroscience Research, 84(3), 534–541. https://doi.org/10.1002/jnr.20960 Garman, R. H. (2011). Histology of the Central Nervous System. Toxicologic Pathology, 39(1), 22–35. https://doi.org/10.1177/0192623310389621 Geiselhardt, F., Peters, M., Kleinschmidt, S., Chludzinski, E., Stoff, M., Ludlow, M., & Beineke, A. (2022). Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-19023-9 Gilbert, M., Miquelle, D. G., Goodrich, J. M., Reeve, R., Cleaveland, S., Matthews, L., & Joly, D. O. (2014). Estimating the potential impact of canine distemper virus on the Amur tiger population (Panthera tigris altaica) in Russia. PLoS ONE, 9(10). https://doi.org/10.1371/journal.pone.0110811 Gitler, A. D., Dhillon, P., & Shorter, J. (2017). Neurodegenerative disease: Models, mechanisms, and a new hope. DMM Disease Models and Mechanisms, 10(5), 499–502. https://doi.org/10.1242/dmm.030205 Graber, H. U., Müller, C. F., Vandevelde, M., & Zurbriggen, A. (1995). Restricted infection with canine distemper virus leads to down-regulation of myelin gene transcription in cultured oligodendrocytes. Acta Neuropathologica, 90(3), 312–318. https://doi.org/10.1007/BF00296516 Greene, C.E. and Appel, M. J. (2011). Canine distemper. pp 9-22. In: Infection Disease of the Dog and Cat (4th Ed). Griot, C., Vandevelde, M., Schobesberger, M., & Zurbriggen, A. (2003). Canine distemper, a re-emerging morbillivirus with complex neuropathogenic mechanisms. Animal Health Research Reviews, 4(1), 1–10. https://doi.org/10.1079/ahrr20047 Guillamón-Vivancos, T., Gómez-Pinedo, U., & Matías-Guiu, J. (2015). Astrocytes in neurodegenerative diseases (I): Function and molecular description. Neurologia, 30(2), 119–129. https://doi.org/10.1016/j.nrl.2012.12.007 Hopperton, K. E., Mohammad, D., Trépanier, M. O., Giuliano, V., & Bazinet, R. P. (2018). Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: A systematic review. Molecular Psychiatry, 23(2), 177–198. https://doi.org/10.1038/mp.2017.246 Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021). Beyond the GFAP-astrocyte protein markers in the brain. In Biomolecules (Vol. 11, Issue 9). MDPI. https://doi.org/10.3390/biom11091361 Kajita, M., Katayama, H., Murata, T., Kai, C., Hori, M., & Ozaki, H. (2006). Canine distemper virus induces apoptosis through caspase-3 and -8 activation in vero cells. Journal of Veterinary Medicine Series B: Infectious Diseases and Veterinary Public Health, 53(6), 273–277. https://doi.org/10.1111/j.1439-0450.2006.00963.x Kapil, S., & Yeary, T. J. (2011). Canine Distemper Spillover in Domestic Dogs from Urban Wildlife. Veterinary Clinics of North America - Small Animal Practice, 41(6), 1069–1086. https://doi.org/10.1016/j.cvsm.2011.08.005 Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, and D. (2002). The Human Genome Browser at UCSC. Genome Research, 12(6), 996–1006. https://doi.org/10.1101/gr.229102 Klemens, J., Ciurkiewicz, M., Chludzinski, E., Iseringhausen, M., Klotz, D., Pfankuche, V. M., Ulrich, R., Herder, V., Puff, C., Baumgärtner, W., & Beineke, A. (2019). Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis. Scientific Reports, 9(1), 1–16. https://doi.org/10.1038/s41598-019-48146-9 Koressaar, T., & Remm, M. (2007). Enhancements and modifications of primer design program Primer3. Bioinformatics, 23(10), 1289–1291. https://doi.org/10.1093/bioinformatics/btm091 Kubo, T., Kagawa, Y., Taniyama, H., & Hasegawa, A. (2007). Distribution of inclusion bodies in tissues from 100 dogs infected with canine distemper virus. Journal of Veterinary Medical Science, 69(5), 527–529. https://doi.org/10.1292/jvms.69.527 Kumagai, K., Yamaguchi, R., Uchida, K., & Tateyama, S. (2004). Lymphoid apoptosis in acute canine distemper. Journal of Veterinary Medical Science, 66(2), 175–181. https://doi.org/10.1292/jvms.66.175 Kumar, K., Oli, A., Hallikeri, K., Shilpasree, A. S., & Goni, M. (2022). An optimized protocol for total RNA isolation from archived formalin-fixed paraffin-embedded tissues to identify the long non-coding RNA in oral squamous cell carcinomas. MethodsX, 9(December 2021), 101602. https://doi.org/10.1016/j.mex.2021.101602 Lefkowitz, E. J., Dempsey, D. M., Hendrickson, R. C., Orton, R. J., Siddell, S. G., & Smith, D. B. (2018). Virus taxonomy: The database of the International Committee on Taxonomy of Viruses (ICTV). Nucleic Acids Research, 46(D1), D708–D717. https://doi.org/10.1093/nar/gkx932 Lempp, C., Spitzbarth, I., Puff, C., Cana, A., Kegler, K., Techangamsuwan, S., Baumgärtner, W., & Seehusen, F. (2014). New aspects of the pathogenesis of canine distemper leukoencephalitis. Viruses, 6(7), 2571–2601. https://doi.org/10.3390/v6072571 Lincoln, J. A., Hankiewicz, K., & Cook, S. D. (2008). Could Epstein-Barr Virus or Canine Distemper Virus Cause Multiple Sclerosis? Neurologic Clinics, 26(3), 699–715. https://doi.org/10.1016/j.ncl.2008.03.004 Lindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., Karlsson, E. K., Jaffe, D. B., Kamal, M., Clamp, M., Chang, J. L., Kulbokas, E. J., Zody, M. C., Mauceli, E., Xie, X., Breen, M., Wayne, R. K., Ostrander, E. A., Ponting, C. P., Galibert, F., Smith, D. R., deJong, P. J., … members, B. S. P. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 438(7069), 803–819. https://doi.org/10.1038/nature04338 Lorenz, M. D., Coates, J. R., & Kent, M. (2011). Neurologic History, Neuroanatomy, and Neurologic Examination. Handbook of Veterinary Neurology, 2–36. https://doi.org/10.1016/b978-1-4377-0651-2.10001-3 Machado, G. F., Melo, G. D., Souza, M. S., Machado, A. A., Migliolo, D. S., Moraes, O. C., Nunes, C. M., & Ribeiro, É. S. (2013). Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis. Veterinary Immunology and Immunopathology, 154(1–2), 68–74. https://doi.org/10.1016/j.vetimm.2013.04.006 Maganga, G. D., Labouba, I., Ngoubangoye, B., Nkili-Meyong, A. A., Obame Ondo, D., Leroy, E. M., & Berthet, N. (2018). Molecular characterization of complete genome of a canine distemper virus associated with fatal infection in dogs in Gabon, Central Africa. Virus Research, 247(January), 21–25. https://doi.org/10.1016/j.virusres.2018.01.012 Martella, V., Elia, G., & Buonavoglia, C. (2008). Canine Distemper Virus. Veterinary Clinics of North America - Small Animal Practice, 38(4), 787–797. https://doi.org/10.1016/j.cvsm.2008.02.007 Martinez-Gutierrez, M., & Ruiz-Saenz, J. (2016). Diversity of susceptible hosts in canine distemper virus infection: A systematic review and data synthesis. BMC Veterinary Research, 12(1), 1–11. https://doi.org/10.1186/s12917-016-0702-z Mifflin, L., Ofengeim, D., & Yuan, J. (2020). Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. In Nature Reviews Drug Discovery (Vol. 19, Issue 8, pp. 553–571). Nature Research. https://doi.org/10.1038/s41573-020-0071-y Mitchell, W. J., Summers, B. A., & Appel, M. J. G. (1991). Viral expression in experimental canine distemper demyelinating encephalitis. Journal of Comparative Pathology, 104(1), 77–87. https://doi.org/10.1016/S0021-9975(08)80090-4 Moro, L., De Sousa Martins, A., De Moraes Alves, C., De Araújo Santos, F. G., Dos Santos Nunes, J. E., Carneiro, R. A., Carvalho, R., & Vasconcelos, A. C. (2003). Apoptosis in canine distemper. Archives of Virology, 148(1), 153–164. https://doi.org/10.1007/s00705-002-0903-6 Moro, L., Martins, A. S., Alves, C. M., Santos, F. G. A., Del Puerto, H. L., & Vasconcelos, A. C. (2003). Apoptosis in the cerebellum of dogs with distemper. Journal of Veterinary Medicine, Series B, 50(5), 221–225. https://doi.org/10.1046/j.1439-0450.2003.00657.x Nova, L. A. C., & Manríquez, L. V. (2016). Moquillo Canino: Fisiopatología y signos clínicos. https://www.vanguardiaveterinaria.com.mx/moquillo-canino-fisiopatologia Nunes da Silva, P. H., De Fátima Dallo, B., Aguiar-Pesenti, A. C., Medeiros, J. M., Martins, A., & Pereira-Machado, L. (2021). Prueba inmunocromatográfica rápida en el diagnóstico del moquillo canino. Revista MVZ Córdoba, 27(1), e2046. https://doi.org/10.21897/rmvz.2046 Oberhaus, S. M., Smith, R. L., Clayton, G. H., Dermody, T. S., & Tyler, K. L. (1997). Reovirus Infection and Tissue Injury in the Mouse Central Nervous System Are Associated with Apoptosis. In JOURNAL OF VIROLOGY (Vol. 71, Issue 3). Of, I., Virulence, V., Resistance, H., Susceptibility, O. R., In, F., & Of, M. (2017). Pathogenesis of Viral Infections and Diseases. In Fenner’s Veterinary Virology. https://doi.org/10.1016/b978-0-12-800946-8.00003-9 Pan, Y. qian, Liu, X. you, Meng, L. ping, Zhu, G. rui, Xia, Y. ke, Chen, J. shan, & Takashi, Y. (2013). Pathogenesis of Demyelinating Encephalopathy in Dogs with Spontaneous Acute Canine Distemper. Journal of Integrative Agriculture, 12(2), 334–343. https://doi.org/10.1016/S2095-3119(13)60233-6 Pan, Y., Wang, S., Li, P., Yue, F., Zhang, Y., Pan, B., & Liu, X. (2021). Apoptotic investigation of brain tissue cells in dogs naturally infected by canine distemper virus. Virology Journal, 18(1), 1–10. https://doi.org/10.1186/s12985-021-01635-8 Panzera, Y., Sarute, N., Iraola, G., Hernández, M., & Pérez, R. (2015). Molecular phylogeography of canine distemper virus: Geographic origin and global spreading. Molecular Phylogenetics and Evolution, 92(July), 147–154. https://doi.org/10.1016/j.ympev.2015.06.015 Pimentel, J. M., Zhou, J. Y., & Wu, G. S. (2023). The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer. In Cancers (Vol. 15, Issue 10). MDPI. https://doi.org/10.3390/cancers15102752 Rendon-Marin, S., Da Fontoura Budaszewski, R., Canal, C. W., & Ruiz-Saenz, J. (2019). Tropism and molecular pathogenesis of canine distemper virus. Virology Journal, 16(1), 1–15. https://doi.org/10.1186/s12985-019-1136-6 Rentería-Solís, Z., Förster, C., Aue, A., Wittstatt, U., Wibbelt, G., & König, M. (2014). Canine distemper outbreak in raccoons suggests pathogen interspecies transmission amongst alien and native carnivores in urban areas from Germany. Veterinary Microbiology, 174(1–2), 50–59. https://doi.org/10.1016/j.vetmic.2014.08.034 Riascos Gómez, A. F. (2019). Prevalencia del virus del Distemper Canino en perros (Canis lupus familiaris) de Risaralda, Colombia. In Prevalencia del virus del Distemper Canino en perros (Canis lupus familiaris) de Risaralda, Colombia (Issue 2). Universidad Tecnológica de Pereira, Facultad de Ciencias de la Salud, Medicina Veterinaria y Zootecnia. Rohowsky-Kochan, C., Davidow, A., Dowling, P., & Cook, S. D. (2021). Increased frequency of canine distemper virus-specific antibodies in multiple sclerosis. Brain and Behavior, 11(1), 1–9. https://doi.org/10.1002/brb3.1920 Saito, T. B., Alfieri, A. A., Wosiacki, S. R., Negrão, F. J., Morais, H. S. A., & Alfieri, A. F. (2006). Detection of canine distemper virus by reverse transcriptase-polymerase chain reaction in the urine of dogs with clinical signs of distemper encephalitis. Research in Veterinary Science, 80(1), 116–119. https://doi.org/10.1016/j.rvsc.2005.03.002 Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative CT method. Nature Protocols, 3(6), 1101–1108. https://doi.org/10.1038/nprot.2008.73 Schneider, P., Bodmer, J. L., Holler, N., Mattmann, C., Scuderi, P., Terskikh, A., Peitsch, M. C., & Tschopp, J. (1997). Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. Journal of Biological Chemistry, 272(30), 18827–18833. https://doi.org/10.1074/jbc.272.30.18827 Song, K., Wu, Z. M., Peng, L. Y., Yuan, M., Huang, J. N., Zhang, C. L., Fu, B. D., Yi, P. F., & Shen, H. Q. (2019). Canine distemper virus increased the differentiation of CD4 + CD8 + T cells and mRNA expression of inflammatory cytokines in peripheral blood lymphocyte from canine. Microbial Pathogenesis, 131(April), 254–258. https://doi.org/10.1016/j.micpath.2019.04.025 Stein, V. M., Czub, M., Schreiner, N., Moore, P. F., Vandevelde, M., Zurbriggen, A., & Tipold, A. (2004). Microglial cell activation in demyelinating canine distemper lesions. Journal of Neuroimmunology, 153(1–2), 122–131. Sykes, J. E., & Vandevelde, M. (2021). 22 - Canine Distemper Virus Infection (J. E. B. T.-G. I. D. of the D. and C. (Fifth E. Sykes, Ed.; pp. 271–288). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-323-50934-3.00022-7 Ulrich, R., Puff, C., Wewetzer, K., Kalkuhl, A., Deschl, U., & Baumgar̈tner, W. (2014). Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination. PLoS ONE, 9(4). https://doi.org/10.1371/journal.pone.0095917 Untergasser, A., Cutcutache, I., Koressaar, T., Ye, J., Faircloth, B. C., Remm, M., & Rozen, S. G. (2012). Primer3-new capabilities and interfaces. Nucleic Acids Research, 40(15). https://doi.org/10.1093/nar/gks596 Vandevelde, M., & Zurbriggen, A. (2005). Demyelination in canine distemper virus infection: A review. Acta Neuropathologica, 109(1), 56–68. https://doi.org/10.1007/s00401-004-0958-4 Vandevelde, M., Zurbriggen, A., Dumas, M., & Palmer, D. (1985). Canine distemper virus does not infect oligodendrocytes in vitro. Journal of the Neurological Sciences, 69(3), 133–137. https://doi.org/10.1016/0022-510X(85)90128-5 Von Messling, V., Harder, T. C., Moennig, V., Rautenberg, P., Nolte, I., & Haas, L. (1999). Rapid and sensitive detection of immunoglobulin M (IgM) and IgG antibodies against canine distemper virus by a new recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay. Journal of Clinical Microbiology, 37(4), 1049–1056. https://doi.org/10.1128/jcm.37.4.1049-1056.1999 von Rüden, E. L., Avemary, J., Zellinger, C., Algermissen, D., Bock, P., Beineke, A., Baumgärtner, W., Stein, V. M., Tipold, A., & Potschka, H. (2012). Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis. Neuropathology and Applied Neurobiology, 38(5), 426–442. https://doi.org/10.1111/j.1365-2990.2011.01218.x Yuan, J., & Ofengeim, D. (2023). A guide to cell death pathways. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/s41580-023-00689-6 Zacarias, J., Dimande, A., Achá, S., Dias, P. T., Leonel, E. M., Messa, A., Macucule, B., Júnior, J. L., & Bila, C. G. (2016). Severe canine distemper outbreak in unvaccinated dogs in Mozambique. Journal of the South African Veterinary Association, 87(1), e1-2. https://doi.org/10.4102/jsava.v87i1.1350 Zaqout, S., Becker, L. L., & Kaindl, A. M. (2020). Immunofluorescence Staining of Paraffin Sections Step by Step. Frontiers in Neuroanatomy, 14(November), 1–11. https://doi.org/10.3389/fnana.2020.582218 Zhao, J., & Ren, Y. (2022). Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review. Viruses, 14(7). https://doi.org/10.3390/v14071520 Zurbriggen, A., Schmid, I., Graber, H. U., & Vandevelde, M. (1997). Oligodendroglial pathology in canine distemper. Acta Neuropathologica, 95(1), 71–77. https://doi.org/10.1007/s004010050767 Zurbriggen, A., Vandevelde, M., & Bollo, E. (1987). Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. Journal of the Neurological Sciences, 79(1–2), 33–41. https://doi.org/10.1016/0022-510X(87)90257-7 Zurbriggen, A., Vandevelde, M., & Bollo, E. (1987). Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. Journal of the Neurological Sciences, 79(1–2), 33–41. https://doi.org/10.1016/0022-510X(87)90257-7 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.license.spa.fl_str_mv |
Reconocimiento 4.0 Internacional |
dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Reconocimiento 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.format.extent.spa.fl_str_mv |
xiii, 81 páginas |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Universidad Nacional de Colombia |
dc.publisher.program.spa.fl_str_mv |
Bogotá - Medicina - Maestría en Neurociencias |
dc.publisher.faculty.spa.fl_str_mv |
Facultad de Medicina |
dc.publisher.place.spa.fl_str_mv |
Bogotá, Colombia |
dc.publisher.branch.spa.fl_str_mv |
Universidad Nacional de Colombia - Sede Bogotá |
institution |
Universidad Nacional de Colombia |
bitstream.url.fl_str_mv |
https://repositorio.unal.edu.co/bitstream/unal/86036/1/license.txt https://repositorio.unal.edu.co/bitstream/unal/86036/2/1085280935.2024.pdf https://repositorio.unal.edu.co/bitstream/unal/86036/3/1085280935.2024.pdf.jpg |
bitstream.checksum.fl_str_mv |
eb34b1cf90b7e1103fc9dfd26be24b4a 2605c8b335c978c1645a04894b8e0841 10b215a98ad82f6af53be9cf0e48d75a |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
repository.mail.fl_str_mv |
repositorio_nal@unal.edu.co |
_version_ |
1814090221277413376 |
spelling |
Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Arboleda Bustos, Gonzalo Humberto8d01100986b4e816de54bb4d3f52f1f0Botero Espinosa, Lucia9feb4b2c171f4e4975d9195bd3f56cf9600Lasso Delgado, Jose Manuel790e0f779ee73f31a856efabb12041ccMuerte Celular2024-05-06T20:50:34Z2024-05-06T20:50:34Z2024-02-01https://repositorio.unal.edu.co/handle/unal/86036Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramas, fotografíasEl Distemper Canino (CDV) es un virus de la familia Paramixoviridae y género Morbillivirus que afecta a caninos y otros mamíferos carnívoros, causando la enfermedad conocida como Distemper canino (DC) o "Moquillo canino". Este virus, se considera inmunosupresor y puede inducir la muerte de células inmunitarias, facilitando infecciones secundarias. En su fase neurológica, considerada terminal, provoca desmielinización en el sistema nervioso central (SNC) y periférico (SNP). Aunque la apoptosis se ha relacionado con la muerte celular en el SNC, se desconoce el mecanismo molecular de muerte celular específica en células mielinizantes (oligodendrocitos). Metodología: Se diseño un estudio descriptivo transversal cuyo objetivo fue dilucidar si la apoptosis participa como mecanismo de muerte de oligodendrocitos en la enfermedad desmielinizante causada por CDV en caninos infectados naturalmente. Se evaluaron muestras parafinadas cerebrales y cerebelares postmortem de 17 caninos positivos para CDV y 10 caninos control de la colección del Laboratorio de Patología Animal de la Universidad Nacional de Colombia. En estas, se buscó determinar: 1) la presencia y activación de proteínas proapoptóticas (Caspasa 3 clivada, Caspasa 9 clivada) en áreas desmielinizadas de cerebro y cerebelo a través de inmunofluorescencia. y 2) la presencia viral y expresión de genes proapoptóticos (Casp3, Casp9, BAX) y antiapoptóticos (BCL-2) mediante reacción en cadena de la polimerasa en tiempo real por transcriptasa inversa (RT-qPCR). Resultados: En la inmunofluorescencia se evidenció un aumento significativo de la activación y presencia de proteínas proapoptóticas (Caspasa 3 clivada: p = <0.0001, Caspasa 9 clivada: p = <0.0001) en áreas de desmielinización tanto en corteza como en cerebelo de los animales caso con respecto a animales control. Por otra parte, los resultados de los RT-qPCR arrojaron resultados significativos en la expresión de caspasa 3 (p = 0.0297), pero no mostraron cambios significativos en los demás genes proapoptóticos como caspasa 9 (p = 0.4437) y BAX (p = 0.6134), ni antiapoptóticos como BCL-2 (p = 0.3910). Estos hallazgos sugieren una asociación directa entre el virus del distemper canino y la apoptosis de los oligodendrocitos, destacando la complejidad de las respuestas celulares y genéticas involucradas en la patogénesis de esta enfermedad. Sin embargo existen limitantes en el estudio como el tamaño de la muestra que pueden afectar los resultados de forma significativa, además del uso de muestras parafinadas que pueden afectar la extracción y los índices de calidad de los ácidos nucleicos de la muestra de RNA para el RT-qPCR. (Texto tomado de la fuente).Canine Distemper (CDV) is a virus belonging to the Paramyxoviridae family and Morbillivirus genus that affects canines and other carnivorous mammals, causing the disease known as Canine Distemper (CD) or "Canine Distemper." This virus is considered immunosuppressive and can induce the death of immune cells, facilitating secondary infections. In its neurological phase, considered terminal, it causes demyelination in the central and peripheral nervous systems (CNS). Although apoptosis has been linked to cell death in the CNS, the specific molecular mechanism of cell death in myelinating cells (oligodendrocytes) is unknown. Methodology: A descriptive cross-sectional study was designed to elucidate whether apoptosis participates as a mechanism of oligodendrocyte death in the demyelinating disease caused by CDV in naturally infected canines. Postmortem brain and cerebellum paraffin samples from 17 CDV-positive canines and 10 control canines from the Animal Pathology Laboratory collection at the National University of Colombia were evaluated. The study aimed to determine: 1) the presence and activation of proapoptotic proteins (cleaved Caspase 3, cleaved Caspase 9) in demyelinated areas of the brain and cerebellum through immunofluorescence, and 2) the viral presence and expression of proapoptotic genes (Casp3, Casp9, Bax) and antiapoptotic genes (Bcl-2) through real-time reverse transcription polymerase chain reaction (RT-qPCR). Results: Immunofluorescence revealed a significant increase in the activation and presence of proapoptotic proteins (cleaved Caspase 3: p < 0.0001, cleaved Caspase 9: p < 0.0001) in demyelinated areas in both the cortex and cerebellum of case animals compared to control animals. On the other hand, RT-qPCR results showed significant outcomes in the expression of caspase 3 (p = 0.0297), but no significant changes in other proapoptotic genes such as caspase 9 (p = 0.4437) and BAX (p = 0.6134), nor in antiapoptotic gene BCL-2 (p = 0.3910). These findings suggest a direct association between the canine distemper virus and apoptosis of oligodendrocytes, highlighting the complexity of cellular and genetic responses involved in the pathogenesis of this disease. However, there are limitations in the study, such as the sample size, which could significantly impact results, and the use of paraffin samples, which may affect the extraction and purity of RNA for RT-qPCR.MaestríaMagíster en NeurocienciasSe diseñó un estudio descriptivo transversal en el cual se tomaron muestras de SNC (cerebrales y cerebelares) de necropsias de caninos con casos compatibles con DC, pertenecientes a la colección del Laboratorio de Patología Animal adscrito a la FMVZ-UNAL, para correlacionar los hallazgos histopatológicos y moleculares con procesos de muerte celular en la enfermedad desmielinizante causada por la infección del CDV, con el objetivo de analizar el mecanismo de muerte de oligodendrocitos que ocurre en la enfermedad desmielinizante del SNC en pacientes caninos naturalmente infectados por el virus y fallecidos por estas causas.Neurobiologia celular y molecularxiii, 81 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en NeurocienciasFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá590 - Animales::599 - Mamíferos570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animalesPatología animalanimal pathologyOligodendroglía/patologíaMoquillo/fisiopatologíaOligodendroglia/pathologyDistemper/physiopathologyDistemper caninoOligodendrocitosDesmielinizaciónApoptosisCaspasa 3Caspasa 9Canine distemperOligodendrocytesDemyelinationApoptosisCaspase 3Caspase 9Evaluación de la muerte de oligodendrocitos causada por el virus de distemper canino en cerebro de animales naturalmente infectadosEvaluation of oligodendrocyte death caused by canine distemper virus in naturally infected animal brainTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAige, V., & Morales, C. (2012). Neurología Canina y Felina. Arch. Med. Interna (Montevideo), 18(2), 83–89.Athanasiou, L. V., Kantere, M. C., Kyriakis, C. S., Pardali, D., Adamama Moraitou, K., & Polizopoulou, Z. S. (2018). Evaluation of a Direct Immunofluorescent Assay and/or Conjunctival Cytology for Detection of Canine Distemper Virus Antigen. Viral Immunology, 31(3), 272–275. https://doi.org/10.1089/vim.2017.0101Atzeni, F., & Sarzi-Puttini, P. (2013). Tumor Necrosis Factor. In Brenner’s Encyclopedia of Genetics: Second Edition (pp. 229–231). Elsevier Inc. https://doi.org/10.1016/B978-0-12-374984-0.01594-1Beineke, A., Puff, C., Seehusen, F., & Baumgärtner, W. (2009). Pathogenesis and immunopathology of systemic and nervous canine distemper. Veterinary Immunology and Immunopathology, 127(1–2), 1–18. https://doi.org/10.1016/j.vetimm.2008.09.023Brenner, M., & Messing, A. (2021). Regulation of GFAP Expression. ASN Neuro, 13. https://doi.org/10.1177/1759091420981206Campa, V. (2017). Análisis de Imágenes de Microscopía con ImageJ.Canene-Adams, K. (2013). Chapter Fifteen - Preparation of Formalin-fixed Paraffin-embedded Tissue for Immunohistochemistry. In J. Lorsch (Ed.), Methods in Enzymology (Vol. 533, pp. 225–233). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-420067-8.00015-5Clarke, P., & Tyler, K. L. (2009). Apoptosis in animal models of virus-induced disease. Nature Reviews Microbiology, 7(2), 144–155. https://doi.org/10.1038/nrmicro2071Cosby, S. L. (2012). Morbillivirus cross-species infection: Is there a risk for humans? Future Virology, 7(11), 1103–1113. https://doi.org/10.2217/fvl.12.103D’Arcy, M. S. (2019). Cell death: a review of the major forms of apoptosis, necrosis and autophagy. In Cell Biology International (Vol. 43, Issue 6, pp. 582–592). Wiley-Blackwell Publishing Ltd. https://doi.org/10.1002/cbin.11137Dawson, S. (2007). Guidelines for the vaccination of dogs and cats. Journal of Small Animal Practice, 48(9), 483. https://doi.org/10.1111/j.1748-5827.2007.00474.xde Lahunta, A., & Glass, E. (2009a). Chapter 2 - Neuroanatomy by Dissection (A. de Lahunta & E. B. T.-V. N. and C. N. (Third E. Glass, Eds.; pp. 6–22). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-7216-6706-5.00002-0de Lahunta, A., & Glass, E. (2009b). Chapter 13 - Cerebellum (A. de Lahunta & E. B. T.-V. N. and C. N. (Third E. Glass, Eds.; pp. 348–388). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-7216-6706-5.00013-5De Nardo, T. F. S., Bertolo, P. H. L., Bernardes, P. A., Munari, D. P., Machado, G. F., Jardim, L. S., Moreira, P. R. R., Rosolem, M. C., & Vasconcelos, R. O. (2020). Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated canine encephalitis caused by the distemper virus. Veterinary Immunology and Immunopathology, 221(March 2019), 110010. https://doi.org/10.1016/j.vetimm.2020.110010DeBiasi, R. L., Robinson, B. A., Sherry, B., Bouchard, R., Brown, R. D., Rizeq, M., Long, C., & Tyler, K. L. (2004). Caspase Inhibition Protects against Reovirus-Induced Myocardial Injury In Vitro and In Vivo. Journal of Virology, 78(20), 11040–11050. https://doi.org/10.1128/jvi.78.20.11040-11050.2004Del Puerto, H. L., Martins, A. S., Milsted, A., Souza-Fagundes, E. M., Braz, G. F., Hissa, B., Andrade, L. O., Alves, F., Rajão, D. S., Leite, R. C., & Vasconcelos, A. C. (2011). Canine distemper virus induces apoptosis in cervical tumor derived cell lines. Virology Journal, 8, 1–7. https://doi.org/10.1186/1743-422X-8-334Del Puerto, H. L., Martins, A. S., Moro, L., Milsted, A., Alves, F., Braz, G. F., & Vasconcelos, A. C. (2010). Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus. Genetics and Molecular Research, 9(1), 151–161. https://doi.org/10.4238/vol9-1gmr717Dewey, C. W., Davies, E. S., Xie, H., & Wakshlag, J. J. (2019). Canine Cognitive Dysfunction: Pathophysiology, Diagnosis, and Treatment. Veterinary Clinics of North America - Small Animal Practice, 49(3), 477–499. https://doi.org/10.1016/j.cvsm.2019.01.013Duque-Valencia, J., Sarute, N., Olarte-Castillo, X. A., & Ruíz-Sáenz, J. (2019). Evolution and interspecies transmission of canine distemper virus—an outlook of the diverse evolutionary landscapes of a multi-host virus. In Viruses (Vol. 11, Issue 7). MDPI AG. https://doi.org/10.3390/v11070582Echeverri-Zuluaga, M., Duque-García, Y. H., & Ruiz-Saenz, J. (2015). Morbillivirus de los delfines: Patógeno re-emergente en la población de cetáceos. Universitas Scientiarum, 20(1), 29–41. https://doi.org/10.11144/Javeriana.SC20-1.mdprGaliano, M. R., Andrieux, A., Deloulme, J. C., Bosc, C., Schweitzer, A., Job, D., & Hallak, M. E. (2006). Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes. Journal of Neuroscience Research, 84(3), 534–541. https://doi.org/10.1002/jnr.20960Garman, R. H. (2011). Histology of the Central Nervous System. Toxicologic Pathology, 39(1), 22–35. https://doi.org/10.1177/0192623310389621Geiselhardt, F., Peters, M., Kleinschmidt, S., Chludzinski, E., Stoff, M., Ludlow, M., & Beineke, A. (2022). Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-19023-9Gilbert, M., Miquelle, D. G., Goodrich, J. M., Reeve, R., Cleaveland, S., Matthews, L., & Joly, D. O. (2014). Estimating the potential impact of canine distemper virus on the Amur tiger population (Panthera tigris altaica) in Russia. PLoS ONE, 9(10). https://doi.org/10.1371/journal.pone.0110811Gitler, A. D., Dhillon, P., & Shorter, J. (2017). Neurodegenerative disease: Models, mechanisms, and a new hope. DMM Disease Models and Mechanisms, 10(5), 499–502. https://doi.org/10.1242/dmm.030205Graber, H. U., Müller, C. F., Vandevelde, M., & Zurbriggen, A. (1995). Restricted infection with canine distemper virus leads to down-regulation of myelin gene transcription in cultured oligodendrocytes. Acta Neuropathologica, 90(3), 312–318. https://doi.org/10.1007/BF00296516Greene, C.E. and Appel, M. J. (2011). Canine distemper. pp 9-22. In: Infection Disease of the Dog and Cat (4th Ed).Griot, C., Vandevelde, M., Schobesberger, M., & Zurbriggen, A. (2003). Canine distemper, a re-emerging morbillivirus with complex neuropathogenic mechanisms. Animal Health Research Reviews, 4(1), 1–10. https://doi.org/10.1079/ahrr20047Guillamón-Vivancos, T., Gómez-Pinedo, U., & Matías-Guiu, J. (2015). Astrocytes in neurodegenerative diseases (I): Function and molecular description. Neurologia, 30(2), 119–129. https://doi.org/10.1016/j.nrl.2012.12.007Hopperton, K. E., Mohammad, D., Trépanier, M. O., Giuliano, V., & Bazinet, R. P. (2018). Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: A systematic review. Molecular Psychiatry, 23(2), 177–198. https://doi.org/10.1038/mp.2017.246Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021). Beyond the GFAP-astrocyte protein markers in the brain. In Biomolecules (Vol. 11, Issue 9). MDPI. https://doi.org/10.3390/biom11091361Kajita, M., Katayama, H., Murata, T., Kai, C., Hori, M., & Ozaki, H. (2006). Canine distemper virus induces apoptosis through caspase-3 and -8 activation in vero cells. Journal of Veterinary Medicine Series B: Infectious Diseases and Veterinary Public Health, 53(6), 273–277. https://doi.org/10.1111/j.1439-0450.2006.00963.xKapil, S., & Yeary, T. J. (2011). Canine Distemper Spillover in Domestic Dogs from Urban Wildlife. Veterinary Clinics of North America - Small Animal Practice, 41(6), 1069–1086. https://doi.org/10.1016/j.cvsm.2011.08.005Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, and D. (2002). The Human Genome Browser at UCSC. Genome Research, 12(6), 996–1006. https://doi.org/10.1101/gr.229102Klemens, J., Ciurkiewicz, M., Chludzinski, E., Iseringhausen, M., Klotz, D., Pfankuche, V. M., Ulrich, R., Herder, V., Puff, C., Baumgärtner, W., & Beineke, A. (2019). Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis. Scientific Reports, 9(1), 1–16. https://doi.org/10.1038/s41598-019-48146-9Koressaar, T., & Remm, M. (2007). Enhancements and modifications of primer design program Primer3. Bioinformatics, 23(10), 1289–1291. https://doi.org/10.1093/bioinformatics/btm091Kubo, T., Kagawa, Y., Taniyama, H., & Hasegawa, A. (2007). Distribution of inclusion bodies in tissues from 100 dogs infected with canine distemper virus. Journal of Veterinary Medical Science, 69(5), 527–529. https://doi.org/10.1292/jvms.69.527Kumagai, K., Yamaguchi, R., Uchida, K., & Tateyama, S. (2004). Lymphoid apoptosis in acute canine distemper. Journal of Veterinary Medical Science, 66(2), 175–181. https://doi.org/10.1292/jvms.66.175Kumar, K., Oli, A., Hallikeri, K., Shilpasree, A. S., & Goni, M. (2022). An optimized protocol for total RNA isolation from archived formalin-fixed paraffin-embedded tissues to identify the long non-coding RNA in oral squamous cell carcinomas. MethodsX, 9(December 2021), 101602. https://doi.org/10.1016/j.mex.2021.101602Lefkowitz, E. J., Dempsey, D. M., Hendrickson, R. C., Orton, R. J., Siddell, S. G., & Smith, D. B. (2018). Virus taxonomy: The database of the International Committee on Taxonomy of Viruses (ICTV). Nucleic Acids Research, 46(D1), D708–D717. https://doi.org/10.1093/nar/gkx932Lempp, C., Spitzbarth, I., Puff, C., Cana, A., Kegler, K., Techangamsuwan, S., Baumgärtner, W., & Seehusen, F. (2014). New aspects of the pathogenesis of canine distemper leukoencephalitis. Viruses, 6(7), 2571–2601. https://doi.org/10.3390/v6072571Lincoln, J. A., Hankiewicz, K., & Cook, S. D. (2008). Could Epstein-Barr Virus or Canine Distemper Virus Cause Multiple Sclerosis? Neurologic Clinics, 26(3), 699–715. https://doi.org/10.1016/j.ncl.2008.03.004Lindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., Karlsson, E. K., Jaffe, D. B., Kamal, M., Clamp, M., Chang, J. L., Kulbokas, E. J., Zody, M. C., Mauceli, E., Xie, X., Breen, M., Wayne, R. K., Ostrander, E. A., Ponting, C. P., Galibert, F., Smith, D. R., deJong, P. J., … members, B. S. P. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 438(7069), 803–819. https://doi.org/10.1038/nature04338Lorenz, M. D., Coates, J. R., & Kent, M. (2011). Neurologic History, Neuroanatomy, and Neurologic Examination. Handbook of Veterinary Neurology, 2–36. https://doi.org/10.1016/b978-1-4377-0651-2.10001-3Machado, G. F., Melo, G. D., Souza, M. S., Machado, A. A., Migliolo, D. S., Moraes, O. C., Nunes, C. M., & Ribeiro, É. S. (2013). Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis. Veterinary Immunology and Immunopathology, 154(1–2), 68–74. https://doi.org/10.1016/j.vetimm.2013.04.006Maganga, G. D., Labouba, I., Ngoubangoye, B., Nkili-Meyong, A. A., Obame Ondo, D., Leroy, E. M., & Berthet, N. (2018). Molecular characterization of complete genome of a canine distemper virus associated with fatal infection in dogs in Gabon, Central Africa. Virus Research, 247(January), 21–25. https://doi.org/10.1016/j.virusres.2018.01.012Martella, V., Elia, G., & Buonavoglia, C. (2008). Canine Distemper Virus. Veterinary Clinics of North America - Small Animal Practice, 38(4), 787–797. https://doi.org/10.1016/j.cvsm.2008.02.007Martinez-Gutierrez, M., & Ruiz-Saenz, J. (2016). Diversity of susceptible hosts in canine distemper virus infection: A systematic review and data synthesis. BMC Veterinary Research, 12(1), 1–11. https://doi.org/10.1186/s12917-016-0702-zMifflin, L., Ofengeim, D., & Yuan, J. (2020). Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. In Nature Reviews Drug Discovery (Vol. 19, Issue 8, pp. 553–571). Nature Research. https://doi.org/10.1038/s41573-020-0071-yMitchell, W. J., Summers, B. A., & Appel, M. J. G. (1991). Viral expression in experimental canine distemper demyelinating encephalitis. Journal of Comparative Pathology, 104(1), 77–87. https://doi.org/10.1016/S0021-9975(08)80090-4Moro, L., De Sousa Martins, A., De Moraes Alves, C., De Araújo Santos, F. G., Dos Santos Nunes, J. E., Carneiro, R. A., Carvalho, R., & Vasconcelos, A. C. (2003). Apoptosis in canine distemper. Archives of Virology, 148(1), 153–164. https://doi.org/10.1007/s00705-002-0903-6Moro, L., Martins, A. S., Alves, C. M., Santos, F. G. A., Del Puerto, H. L., & Vasconcelos, A. C. (2003). Apoptosis in the cerebellum of dogs with distemper. Journal of Veterinary Medicine, Series B, 50(5), 221–225. https://doi.org/10.1046/j.1439-0450.2003.00657.xNova, L. A. C., & Manríquez, L. V. (2016). Moquillo Canino: Fisiopatología y signos clínicos. https://www.vanguardiaveterinaria.com.mx/moquillo-canino-fisiopatologiaNunes da Silva, P. H., De Fátima Dallo, B., Aguiar-Pesenti, A. C., Medeiros, J. M., Martins, A., & Pereira-Machado, L. (2021). Prueba inmunocromatográfica rápida en el diagnóstico del moquillo canino. Revista MVZ Córdoba, 27(1), e2046. https://doi.org/10.21897/rmvz.2046Oberhaus, S. M., Smith, R. L., Clayton, G. H., Dermody, T. S., & Tyler, K. L. (1997). Reovirus Infection and Tissue Injury in the Mouse Central Nervous System Are Associated with Apoptosis. In JOURNAL OF VIROLOGY (Vol. 71, Issue 3).Of, I., Virulence, V., Resistance, H., Susceptibility, O. R., In, F., & Of, M. (2017). Pathogenesis of Viral Infections and Diseases. In Fenner’s Veterinary Virology. https://doi.org/10.1016/b978-0-12-800946-8.00003-9Pan, Y. qian, Liu, X. you, Meng, L. ping, Zhu, G. rui, Xia, Y. ke, Chen, J. shan, & Takashi, Y. (2013). Pathogenesis of Demyelinating Encephalopathy in Dogs with Spontaneous Acute Canine Distemper. Journal of Integrative Agriculture, 12(2), 334–343. https://doi.org/10.1016/S2095-3119(13)60233-6Pan, Y., Wang, S., Li, P., Yue, F., Zhang, Y., Pan, B., & Liu, X. (2021). Apoptotic investigation of brain tissue cells in dogs naturally infected by canine distemper virus. Virology Journal, 18(1), 1–10. https://doi.org/10.1186/s12985-021-01635-8Panzera, Y., Sarute, N., Iraola, G., Hernández, M., & Pérez, R. (2015). Molecular phylogeography of canine distemper virus: Geographic origin and global spreading. Molecular Phylogenetics and Evolution, 92(July), 147–154. https://doi.org/10.1016/j.ympev.2015.06.015Pimentel, J. M., Zhou, J. Y., & Wu, G. S. (2023). The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer. In Cancers (Vol. 15, Issue 10). MDPI. https://doi.org/10.3390/cancers15102752Rendon-Marin, S., Da Fontoura Budaszewski, R., Canal, C. W., & Ruiz-Saenz, J. (2019). Tropism and molecular pathogenesis of canine distemper virus. Virology Journal, 16(1), 1–15. https://doi.org/10.1186/s12985-019-1136-6Rentería-Solís, Z., Förster, C., Aue, A., Wittstatt, U., Wibbelt, G., & König, M. (2014). Canine distemper outbreak in raccoons suggests pathogen interspecies transmission amongst alien and native carnivores in urban areas from Germany. Veterinary Microbiology, 174(1–2), 50–59. https://doi.org/10.1016/j.vetmic.2014.08.034Riascos Gómez, A. F. (2019). Prevalencia del virus del Distemper Canino en perros (Canis lupus familiaris) de Risaralda, Colombia. In Prevalencia del virus del Distemper Canino en perros (Canis lupus familiaris) de Risaralda, Colombia (Issue 2). Universidad Tecnológica de Pereira, Facultad de Ciencias de la Salud, Medicina Veterinaria y Zootecnia.Rohowsky-Kochan, C., Davidow, A., Dowling, P., & Cook, S. D. (2021). Increased frequency of canine distemper virus-specific antibodies in multiple sclerosis. Brain and Behavior, 11(1), 1–9. https://doi.org/10.1002/brb3.1920Saito, T. B., Alfieri, A. A., Wosiacki, S. R., Negrão, F. J., Morais, H. S. A., & Alfieri, A. F. (2006). Detection of canine distemper virus by reverse transcriptase-polymerase chain reaction in the urine of dogs with clinical signs of distemper encephalitis. Research in Veterinary Science, 80(1), 116–119. https://doi.org/10.1016/j.rvsc.2005.03.002Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative CT method. Nature Protocols, 3(6), 1101–1108. https://doi.org/10.1038/nprot.2008.73Schneider, P., Bodmer, J. L., Holler, N., Mattmann, C., Scuderi, P., Terskikh, A., Peitsch, M. C., & Tschopp, J. (1997). Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. Journal of Biological Chemistry, 272(30), 18827–18833. https://doi.org/10.1074/jbc.272.30.18827Song, K., Wu, Z. M., Peng, L. Y., Yuan, M., Huang, J. N., Zhang, C. L., Fu, B. D., Yi, P. F., & Shen, H. Q. (2019). Canine distemper virus increased the differentiation of CD4 + CD8 + T cells and mRNA expression of inflammatory cytokines in peripheral blood lymphocyte from canine. Microbial Pathogenesis, 131(April), 254–258. https://doi.org/10.1016/j.micpath.2019.04.025Stein, V. M., Czub, M., Schreiner, N., Moore, P. F., Vandevelde, M., Zurbriggen, A., & Tipold, A. (2004). Microglial cell activation in demyelinating canine distemper lesions. Journal of Neuroimmunology, 153(1–2), 122–131.Sykes, J. E., & Vandevelde, M. (2021). 22 - Canine Distemper Virus Infection (J. E. B. T.-G. I. D. of the D. and C. (Fifth E. Sykes, Ed.; pp. 271–288). W.B. Saunders. https://doi.org/https://doi.org/10.1016/B978-0-323-50934-3.00022-7Ulrich, R., Puff, C., Wewetzer, K., Kalkuhl, A., Deschl, U., & Baumgar̈tner, W. (2014). Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination. PLoS ONE, 9(4). https://doi.org/10.1371/journal.pone.0095917Untergasser, A., Cutcutache, I., Koressaar, T., Ye, J., Faircloth, B. C., Remm, M., & Rozen, S. G. (2012). Primer3-new capabilities and interfaces. Nucleic Acids Research, 40(15). https://doi.org/10.1093/nar/gks596Vandevelde, M., & Zurbriggen, A. (2005). Demyelination in canine distemper virus infection: A review. Acta Neuropathologica, 109(1), 56–68. https://doi.org/10.1007/s00401-004-0958-4Vandevelde, M., Zurbriggen, A., Dumas, M., & Palmer, D. (1985). Canine distemper virus does not infect oligodendrocytes in vitro. Journal of the Neurological Sciences, 69(3), 133–137. https://doi.org/10.1016/0022-510X(85)90128-5Von Messling, V., Harder, T. C., Moennig, V., Rautenberg, P., Nolte, I., & Haas, L. (1999). Rapid and sensitive detection of immunoglobulin M (IgM) and IgG antibodies against canine distemper virus by a new recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay. Journal of Clinical Microbiology, 37(4), 1049–1056. https://doi.org/10.1128/jcm.37.4.1049-1056.1999von Rüden, E. L., Avemary, J., Zellinger, C., Algermissen, D., Bock, P., Beineke, A., Baumgärtner, W., Stein, V. M., Tipold, A., & Potschka, H. (2012). Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis. Neuropathology and Applied Neurobiology, 38(5), 426–442. https://doi.org/10.1111/j.1365-2990.2011.01218.xYuan, J., & Ofengeim, D. (2023). A guide to cell death pathways. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/s41580-023-00689-6Zacarias, J., Dimande, A., Achá, S., Dias, P. T., Leonel, E. M., Messa, A., Macucule, B., Júnior, J. L., & Bila, C. G. (2016). Severe canine distemper outbreak in unvaccinated dogs in Mozambique. Journal of the South African Veterinary Association, 87(1), e1-2. https://doi.org/10.4102/jsava.v87i1.1350Zaqout, S., Becker, L. L., & Kaindl, A. M. (2020). Immunofluorescence Staining of Paraffin Sections Step by Step. Frontiers in Neuroanatomy, 14(November), 1–11. https://doi.org/10.3389/fnana.2020.582218Zhao, J., & Ren, Y. (2022). Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review. Viruses, 14(7). https://doi.org/10.3390/v14071520Zurbriggen, A., Schmid, I., Graber, H. U., & Vandevelde, M. (1997). Oligodendroglial pathology in canine distemper. Acta Neuropathologica, 95(1), 71–77. https://doi.org/10.1007/s004010050767Zurbriggen, A., Vandevelde, M., & Bollo, E. (1987). Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. Journal of the Neurological Sciences, 79(1–2), 33–41. https://doi.org/10.1016/0022-510X(87)90257-7Zurbriggen, A., Vandevelde, M., & Bollo, E. (1987). Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. Journal of the Neurological Sciences, 79(1–2), 33–41. https://doi.org/10.1016/0022-510X(87)90257-7EstudiantesInvestigadoresMaestrosPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86036/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1085280935.2024.pdf1085280935.2024.pdfTesis de Maestría en Neurocienciasapplication/pdf3147814https://repositorio.unal.edu.co/bitstream/unal/86036/2/1085280935.2024.pdf2605c8b335c978c1645a04894b8e0841MD52THUMBNAIL1085280935.2024.pdf.jpg1085280935.2024.pdf.jpgGenerated Thumbnailimage/jpeg4845https://repositorio.unal.edu.co/bitstream/unal/86036/3/1085280935.2024.pdf.jpg10b215a98ad82f6af53be9cf0e48d75aMD53unal/86036oai:repositorio.unal.edu.co:unal/860362024-05-06 23:04:44.767Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.coUEFSVEUgMS4gVMOJUk1JTk9TIERFIExBIExJQ0VOQ0lBIFBBUkEgUFVCTElDQUNJw5NOIERFIE9CUkFTIEVOIEVMIFJFUE9TSVRPUklPIElOU1RJVFVDSU9OQUwgVU5BTC4KCkxvcyBhdXRvcmVzIHkvbyB0aXR1bGFyZXMgZGUgbG9zIGRlcmVjaG9zIHBhdHJpbW9uaWFsZXMgZGUgYXV0b3IsIGNvbmZpZXJlbiBhIGxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhIHVuYSBsaWNlbmNpYSBubyBleGNsdXNpdmEsIGxpbWl0YWRhIHkgZ3JhdHVpdGEgc29icmUgbGEgb2JyYSBxdWUgc2UgaW50ZWdyYSBlbiBlbCBSZXBvc2l0b3JpbyBJbnN0aXR1Y2lvbmFsLCBiYWpvIGxvcyBzaWd1aWVudGVzIHTDqXJtaW5vczoKCgphKQlMb3MgYXV0b3JlcyB5L28gbG9zIHRpdHVsYXJlcyBkZSBsb3MgZGVyZWNob3MgcGF0cmltb25pYWxlcyBkZSBhdXRvciBzb2JyZSBsYSBvYnJhIGNvbmZpZXJlbiBhIGxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhIHVuYSBsaWNlbmNpYSBubyBleGNsdXNpdmEgcGFyYSByZWFsaXphciBsb3Mgc2lndWllbnRlcyBhY3RvcyBzb2JyZSBsYSBvYnJhOiBpKSByZXByb2R1Y2lyIGxhIG9icmEgZGUgbWFuZXJhIGRpZ2l0YWwsIHBlcm1hbmVudGUgbyB0ZW1wb3JhbCwgaW5jbHV5ZW5kbyBlbCBhbG1hY2VuYW1pZW50byBlbGVjdHLDs25pY28sIGFzw60gY29tbyBjb252ZXJ0aXIgZWwgZG9jdW1lbnRvIGVuIGVsIGN1YWwgc2UgZW5jdWVudHJhIGNvbnRlbmlkYSBsYSBvYnJhIGEgY3VhbHF1aWVyIG1lZGlvIG8gZm9ybWF0byBleGlzdGVudGUgYSBsYSBmZWNoYSBkZSBsYSBzdXNjcmlwY2nDs24gZGUgbGEgcHJlc2VudGUgbGljZW5jaWEsIHkgaWkpIGNvbXVuaWNhciBhbCBww7pibGljbyBsYSBvYnJhIHBvciBjdWFscXVpZXIgbWVkaW8gbyBwcm9jZWRpbWllbnRvLCBlbiBtZWRpb3MgYWzDoW1icmljb3MgbyBpbmFsw6FtYnJpY29zLCBpbmNsdXllbmRvIGxhIHB1ZXN0YSBhIGRpc3Bvc2ljacOzbiBlbiBhY2Nlc28gYWJpZXJ0by4gQWRpY2lvbmFsIGEgbG8gYW50ZXJpb3IsIGVsIGF1dG9yIHkvbyB0aXR1bGFyIGF1dG9yaXphIGEgbGEgVW5pdmVyc2lkYWQgTmFjaW9uYWwgZGUgQ29sb21iaWEgcGFyYSBxdWUsIGVuIGxhIHJlcHJvZHVjY2nDs24geSBjb211bmljYWNpw7NuIGFsIHDDumJsaWNvIHF1ZSBsYSBVbml2ZXJzaWRhZCByZWFsaWNlIHNvYnJlIGxhIG9icmEsIGhhZ2EgbWVuY2nDs24gZGUgbWFuZXJhIGV4cHJlc2EgYWwgdGlwbyBkZSBsaWNlbmNpYSBDcmVhdGl2ZSBDb21tb25zIGJham8gbGEgY3VhbCBlbCBhdXRvciB5L28gdGl0dWxhciBkZXNlYSBvZnJlY2VyIHN1IG9icmEgYSBsb3MgdGVyY2Vyb3MgcXVlIGFjY2VkYW4gYSBkaWNoYSBvYnJhIGEgdHJhdsOpcyBkZWwgUmVwb3NpdG9yaW8gSW5zdGl0dWNpb25hbCwgY3VhbmRvIHNlYSBlbCBjYXNvLiBFbCBhdXRvciB5L28gdGl0dWxhciBkZSBsb3MgZGVyZWNob3MgcGF0cmltb25pYWxlcyBkZSBhdXRvciBwb2Ryw6EgZGFyIHBvciB0ZXJtaW5hZGEgbGEgcHJlc2VudGUgbGljZW5jaWEgbWVkaWFudGUgc29saWNpdHVkIGVsZXZhZGEgYSBsYSBEaXJlY2Npw7NuIE5hY2lvbmFsIGRlIEJpYmxpb3RlY2FzIGRlIGxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhLiAKCmIpIAlMb3MgYXV0b3JlcyB5L28gdGl0dWxhcmVzIGRlIGxvcyBkZXJlY2hvcyBwYXRyaW1vbmlhbGVzIGRlIGF1dG9yIHNvYnJlIGxhIG9icmEgY29uZmllcmVuIGxhIGxpY2VuY2lhIHNlw7FhbGFkYSBlbiBlbCBsaXRlcmFsIGEpIGRlbCBwcmVzZW50ZSBkb2N1bWVudG8gcG9yIGVsIHRpZW1wbyBkZSBwcm90ZWNjacOzbiBkZSBsYSBvYnJhIGVuIHRvZG9zIGxvcyBwYcOtc2VzIGRlbCBtdW5kbywgZXN0byBlcywgc2luIGxpbWl0YWNpw7NuIHRlcnJpdG9yaWFsIGFsZ3VuYS4KCmMpCUxvcyBhdXRvcmVzIHkvbyB0aXR1bGFyZXMgZGUgZGVyZWNob3MgcGF0cmltb25pYWxlcyBkZSBhdXRvciBtYW5pZmllc3RhbiBlc3RhciBkZSBhY3VlcmRvIGNvbiBxdWUgbGEgcHJlc2VudGUgbGljZW5jaWEgc2Ugb3RvcmdhIGEgdMOtdHVsbyBncmF0dWl0bywgcG9yIGxvIHRhbnRvLCByZW51bmNpYW4gYSByZWNpYmlyIGN1YWxxdWllciByZXRyaWJ1Y2nDs24gZWNvbsOzbWljYSBvIGVtb2x1bWVudG8gYWxndW5vIHBvciBsYSBwdWJsaWNhY2nDs24sIGRpc3RyaWJ1Y2nDs24sIGNvbXVuaWNhY2nDs24gcMO6YmxpY2EgeSBjdWFscXVpZXIgb3RybyB1c28gcXVlIHNlIGhhZ2EgZW4gbG9zIHTDqXJtaW5vcyBkZSBsYSBwcmVzZW50ZSBsaWNlbmNpYSB5IGRlIGxhIGxpY2VuY2lhIENyZWF0aXZlIENvbW1vbnMgY29uIHF1ZSBzZSBwdWJsaWNhLgoKZCkJUXVpZW5lcyBmaXJtYW4gZWwgcHJlc2VudGUgZG9jdW1lbnRvIGRlY2xhcmFuIHF1ZSBwYXJhIGxhIGNyZWFjacOzbiBkZSBsYSBvYnJhLCBubyBzZSBoYW4gdnVsbmVyYWRvIGxvcyBkZXJlY2hvcyBkZSBwcm9waWVkYWQgaW50ZWxlY3R1YWwsIGluZHVzdHJpYWwsIG1vcmFsZXMgeSBwYXRyaW1vbmlhbGVzIGRlIHRlcmNlcm9zLiBEZSBvdHJhIHBhcnRlLCAgcmVjb25vY2VuIHF1ZSBsYSBVbml2ZXJzaWRhZCBOYWNpb25hbCBkZSBDb2xvbWJpYSBhY3TDumEgY29tbyB1biB0ZXJjZXJvIGRlIGJ1ZW5hIGZlIHkgc2UgZW5jdWVudHJhIGV4ZW50YSBkZSBjdWxwYSBlbiBjYXNvIGRlIHByZXNlbnRhcnNlIGFsZ8O6biB0aXBvIGRlIHJlY2xhbWFjacOzbiBlbiBtYXRlcmlhIGRlIGRlcmVjaG9zIGRlIGF1dG9yIG8gcHJvcGllZGFkIGludGVsZWN0dWFsIGVuIGdlbmVyYWwuIFBvciBsbyB0YW50bywgbG9zIGZpcm1hbnRlcyAgYWNlcHRhbiBxdWUgY29tbyB0aXR1bGFyZXMgw7puaWNvcyBkZSBsb3MgZGVyZWNob3MgcGF0cmltb25pYWxlcyBkZSBhdXRvciwgYXN1bWlyw6FuIHRvZGEgbGEgcmVzcG9uc2FiaWxpZGFkIGNpdmlsLCBhZG1pbmlzdHJhdGl2YSB5L28gcGVuYWwgcXVlIHB1ZWRhIGRlcml2YXJzZSBkZSBsYSBwdWJsaWNhY2nDs24gZGUgbGEgb2JyYS4gIAoKZikJQXV0b3JpemFuIGEgbGEgVW5pdmVyc2lkYWQgTmFjaW9uYWwgZGUgQ29sb21iaWEgaW5jbHVpciBsYSBvYnJhIGVuIGxvcyBhZ3JlZ2Fkb3JlcyBkZSBjb250ZW5pZG9zLCBidXNjYWRvcmVzIGFjYWTDqW1pY29zLCBtZXRhYnVzY2Fkb3Jlcywgw61uZGljZXMgeSBkZW3DoXMgbWVkaW9zIHF1ZSBzZSBlc3RpbWVuIG5lY2VzYXJpb3MgcGFyYSBwcm9tb3ZlciBlbCBhY2Nlc28geSBjb25zdWx0YSBkZSBsYSBtaXNtYS4gCgpnKQlFbiBlbCBjYXNvIGRlIGxhcyB0ZXNpcyBjcmVhZGFzIHBhcmEgb3B0YXIgZG9ibGUgdGl0dWxhY2nDs24sIGxvcyBmaXJtYW50ZXMgc2Vyw6FuIGxvcyByZXNwb25zYWJsZXMgZGUgY29tdW5pY2FyIGEgbGFzIGluc3RpdHVjaW9uZXMgbmFjaW9uYWxlcyBvIGV4dHJhbmplcmFzIGVuIGNvbnZlbmlvLCBsYXMgbGljZW5jaWFzIGRlIGFjY2VzbyBhYmllcnRvIENyZWF0aXZlIENvbW1vbnMgeSBhdXRvcml6YWNpb25lcyBhc2lnbmFkYXMgYSBzdSBvYnJhIHBhcmEgbGEgcHVibGljYWNpw7NuIGVuIGVsIFJlcG9zaXRvcmlvIEluc3RpdHVjaW9uYWwgVU5BTCBkZSBhY3VlcmRvIGNvbiBsYXMgZGlyZWN0cmljZXMgZGUgbGEgUG9sw610aWNhIEdlbmVyYWwgZGUgbGEgQmlibGlvdGVjYSBEaWdpdGFsLgoKCmgpCVNlIGF1dG9yaXphIGEgbGEgVW5pdmVyc2lkYWQgTmFjaW9uYWwgZGUgQ29sb21iaWEgY29tbyByZXNwb25zYWJsZSBkZWwgdHJhdGFtaWVudG8gZGUgZGF0b3MgcGVyc29uYWxlcywgZGUgYWN1ZXJkbyBjb24gbGEgbGV5IDE1ODEgZGUgMjAxMiBlbnRlbmRpZW5kbyBxdWUgc2UgZW5jdWVudHJhbiBiYWpvIG1lZGlkYXMgcXVlIGdhcmFudGl6YW4gbGEgc2VndXJpZGFkLCBjb25maWRlbmNpYWxpZGFkIGUgaW50ZWdyaWRhZCwgeSBzdSB0cmF0YW1pZW50byB0aWVuZSB1bmEgZmluYWxpZGFkIGhpc3TDs3JpY2EsIGVzdGFkw61zdGljYSBvIGNpZW50w61maWNhIHNlZ8O6biBsbyBkaXNwdWVzdG8gZW4gbGEgUG9sw610aWNhIGRlIFRyYXRhbWllbnRvIGRlIERhdG9zIFBlcnNvbmFsZXMuCgoKClBBUlRFIDIuIEFVVE9SSVpBQ0nDk04gUEFSQSBQVUJMSUNBUiBZIFBFUk1JVElSIExBIENPTlNVTFRBIFkgVVNPIERFIE9CUkFTIEVOIEVMIFJFUE9TSVRPUklPIElOU1RJVFVDSU9OQUwgVU5BTC4KClNlIGF1dG9yaXphIGxhIHB1YmxpY2FjacOzbiBlbGVjdHLDs25pY2EsIGNvbnN1bHRhIHkgdXNvIGRlIGxhIG9icmEgcG9yIHBhcnRlIGRlIGxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhIHkgZGUgc3VzIHVzdWFyaW9zIGRlIGxhIHNpZ3VpZW50ZSBtYW5lcmE6CgphLglDb25jZWRvIGxpY2VuY2lhIGVuIGxvcyB0w6lybWlub3Mgc2XDsWFsYWRvcyBlbiBsYSBwYXJ0ZSAxIGRlbCBwcmVzZW50ZSBkb2N1bWVudG8sIGNvbiBlbCBvYmpldGl2byBkZSBxdWUgbGEgb2JyYSBlbnRyZWdhZGEgc2VhIHB1YmxpY2FkYSBlbiBlbCBSZXBvc2l0b3JpbyBJbnN0aXR1Y2lvbmFsIGRlIGxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhIHkgcHVlc3RhIGEgZGlzcG9zaWNpw7NuIGVuIGFjY2VzbyBhYmllcnRvIHBhcmEgc3UgY29uc3VsdGEgcG9yIGxvcyB1c3VhcmlvcyBkZSBsYSBVbml2ZXJzaWRhZCBOYWNpb25hbCBkZSBDb2xvbWJpYSAgYSB0cmF2w6lzIGRlIGludGVybmV0LgoKCgpQQVJURSAzIEFVVE9SSVpBQ0nDk04gREUgVFJBVEFNSUVOVE8gREUgREFUT1MgUEVSU09OQUxFUy4KCkxhIFVuaXZlcnNpZGFkIE5hY2lvbmFsIGRlIENvbG9tYmlhLCBjb21vIHJlc3BvbnNhYmxlIGRlbCBUcmF0YW1pZW50byBkZSBEYXRvcyBQZXJzb25hbGVzLCBpbmZvcm1hIHF1ZSBsb3MgZGF0b3MgZGUgY2Fyw6FjdGVyIHBlcnNvbmFsIHJlY29sZWN0YWRvcyBtZWRpYW50ZSBlc3RlIGZvcm11bGFyaW8sIHNlIGVuY3VlbnRyYW4gYmFqbyBtZWRpZGFzIHF1ZSBnYXJhbnRpemFuIGxhIHNlZ3VyaWRhZCwgY29uZmlkZW5jaWFsaWRhZCBlIGludGVncmlkYWQgeSBzdSB0cmF0YW1pZW50byBzZSByZWFsaXphIGRlIGFjdWVyZG8gYWwgY3VtcGxpbWllbnRvIG5vcm1hdGl2byBkZSBsYSBMZXkgMTU4MSBkZSAyMDEyIHkgZGUgbGEgUG9sw610aWNhIGRlIFRyYXRhbWllbnRvIGRlIERhdG9zIFBlcnNvbmFsZXMgZGUgbGEgVW5pdmVyc2lkYWQgTmFjaW9uYWwgZGUgQ29sb21iaWEuIFB1ZWRlIGVqZXJjZXIgc3VzIGRlcmVjaG9zIGNvbW8gdGl0dWxhciBhIGNvbm9jZXIsIGFjdHVhbGl6YXIsIHJlY3RpZmljYXIgeSByZXZvY2FyIGxhcyBhdXRvcml6YWNpb25lcyBkYWRhcyBhIGxhcyBmaW5hbGlkYWRlcyBhcGxpY2FibGVzIGEgdHJhdsOpcyBkZSBsb3MgY2FuYWxlcyBkaXNwdWVzdG9zIHkgZGlzcG9uaWJsZXMgZW4gd3d3LnVuYWwuZWR1LmNvIG8gZS1tYWlsOiBwcm90ZWNkYXRvc19uYUB1bmFsLmVkdS5jbyIKClRlbmllbmRvIGVuIGN1ZW50YSBsbyBhbnRlcmlvciwgYXV0b3Jpem8gZGUgbWFuZXJhIHZvbHVudGFyaWEsIHByZXZpYSwgZXhwbMOtY2l0YSwgaW5mb3JtYWRhIGUgaW5lcXXDrXZvY2EgYSBsYSBVbml2ZXJzaWRhZCBOYWNpb25hbCBkZSBDb2xvbWJpYSBhIHRyYXRhciBsb3MgZGF0b3MgcGVyc29uYWxlcyBkZSBhY3VlcmRvIGNvbiBsYXMgZmluYWxpZGFkZXMgZXNwZWPDrWZpY2FzIHBhcmEgZWwgZGVzYXJyb2xsbyB5IGVqZXJjaWNpbyBkZSBsYXMgZnVuY2lvbmVzIG1pc2lvbmFsZXMgZGUgZG9jZW5jaWEsIGludmVzdGlnYWNpw7NuIHkgZXh0ZW5zacOzbiwgYXPDrSBjb21vIGxhcyByZWxhY2lvbmVzIGFjYWTDqW1pY2FzLCBsYWJvcmFsZXMsIGNvbnRyYWN0dWFsZXMgeSB0b2RhcyBsYXMgZGVtw6FzIHJlbGFjaW9uYWRhcyBjb24gZWwgb2JqZXRvIHNvY2lhbCBkZSBsYSBVbml2ZXJzaWRhZC4gCgo= |