Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro
The increasing of the temperature is one of the principal consequences of the climate change, which affect human populations due of the emergence and re-emergency of infection diseases. The Leishmaniases are diseases cause by protozoans’ parasites of the genus Leishmania; these diseases are composed...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2019
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- spa
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/19055
- Acceso en línea:
- https://doi.org/10.48713/10336_19055
http://repository.urosario.edu.co/handle/10336/19055
- Palabra clave:
- Transcriptomic
Heat stress
Response to external stimulus
Growth curves
Enfermedades
Leishmaniasis
Infecciones por protozoarios
- Rights
- License
- Atribución-NoComercial-SinDerivadas 2.5 Colombia
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repository_id_str |
|
dc.title.spa.fl_str_mv |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
dc.title.alternative.spa.fl_str_mv |
Temperature shifts impacts on Leishmania braziliensis |
title |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
spellingShingle |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro Transcriptomic Heat stress Response to external stimulus Growth curves Enfermedades Leishmaniasis Infecciones por protozoarios |
title_short |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
title_full |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
title_fullStr |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
title_full_unstemmed |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
title_sort |
Transcriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitro |
dc.contributor.advisor.none.fl_str_mv |
Ramírez, Juan David |
dc.contributor.none.fl_str_mv |
Vásquez, Nubia Marcela Patiño, Luz H. Cruz-Saavedra, Lissa |
dc.subject.spa.fl_str_mv |
Transcriptomic Heat stress Response to external stimulus Growth curves |
topic |
Transcriptomic Heat stress Response to external stimulus Growth curves Enfermedades Leishmaniasis Infecciones por protozoarios |
dc.subject.ddc.spa.fl_str_mv |
Enfermedades |
dc.subject.lemb.spa.fl_str_mv |
Leishmaniasis Infecciones por protozoarios |
description |
The increasing of the temperature is one of the principal consequences of the climate change, which affect human populations due of the emergence and re-emergency of infection diseases. The Leishmaniases are diseases cause by protozoans’ parasites of the genus Leishmania; these diseases are composed by different clinical manifestations, one of the most important in the New World is Cutaneous Leishmaniasis for which the most common causative species is Leishmania braziliensis. This species as the other members of the Trypanosomatidae family present a genomic plasticity and a particular gene expression regulation that allow to the parasites to adapt and response to several stimulus, for that reason the aim of this study is evaluate the transcriptome profiles of L. braziliensis promastigotes subjected to temperature shifts. To reach this aim the authors performed an RNA-Seq that permitted to find several genes associated with a direct response to the treatments; also, through the growth curves done the authors evidenced a decrease in the cell proliferation in all the temperatures tested, where the most affected was 30°C. The results obtained in this study demonstrated a fast response of L. braziliensis promastigotes to temperature shifts. |
publishDate |
2019 |
dc.date.accessioned.none.fl_str_mv |
2019-02-13T12:53:11Z |
dc.date.available.none.fl_str_mv |
2019-02-13T12:53:11Z |
dc.date.created.none.fl_str_mv |
2019-02-05 |
dc.date.issued.none.fl_str_mv |
2019 |
dc.type.eng.fl_str_mv |
bachelorThesis |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
dc.type.document.spa.fl_str_mv |
Análisis de caso |
dc.type.spa.spa.fl_str_mv |
Trabajo de grado |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.48713/10336_19055 |
dc.identifier.uri.none.fl_str_mv |
http://repository.urosario.edu.co/handle/10336/19055 |
url |
https://doi.org/10.48713/10336_19055 http://repository.urosario.edu.co/handle/10336/19055 |
dc.language.iso.none.fl_str_mv |
spa |
language |
spa |
dc.rights.spa.fl_str_mv |
Atribución-NoComercial-SinDerivadas 2.5 Colombia Atribución-NoComercial-SinDerivadas 2.5 Colombia |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
dc.rights.uri.none.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/2.5/co/ |
rights_invalid_str_mv |
Atribución-NoComercial-SinDerivadas 2.5 Colombia Abierto (Texto Completo) http://creativecommons.org/licenses/by-nc-nd/2.5/co/ http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf image/jpeg |
dc.publisher.spa.fl_str_mv |
Universidad del Rosario |
dc.publisher.department.spa.fl_str_mv |
Facultad de Ciencias Naturales y Matemáticas |
dc.publisher.program.spa.fl_str_mv |
Biología |
institution |
Universidad del Rosario |
dc.source.bibliographicCitation.spa.fl_str_mv |
Barria, C., Malecki, M., & Arraiano, C. M. (2013). Bacterial adaptation to cold. Microbiology, 159(Pt_12), 2437–2443. Bifeld, E., Lorenzen, S., Bartsch, K., Vasquez, J.-J., Siegel, T. N., & Clos, J. (2018). Ribosome Profiling Reveals HSP90 Inhibitor Effects on Stage-Specific Protein Synthesis in Leishmania donovani. MSystems, 3(6), 1–18. Bussotti, G., Gouzelou, E., Côrtes Boité, M., Kherachi, I., Harrat, Z., Eddaikra, N., Späth, G. F. (2018). Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification. MBio, 9(6), e01399-18. Dumetz, F., Imamura, H., Sanders, M., Seblova, V., Myskova, J., & Pescher, P. (2017). Modulation of Aneuploidy in Leishmania In Vitro and In Vivo Environments and Its impact on gene expression. mBio, 8(3), 1–14. Cardenas, R., Sandoval, C., & Rodriguez-Morales, a. (2007). P530 Impact of climate variability in the occurrence of leishmaniasis in Southern departments of Colombia. International Journal of Antimicrobial Agents, 29(2), S117–S118. Cardoso de Paiva, R. M., Grazielle-silva, V., Cardoso, M. S., Canavaci, C., Melo, N. S., & Martinelli, P. M. (2015). Amastin Knockdown in Leishmania braziliensis Affects Parasite- Macrophage Interaction and Results in Impaired Viability of Intracellular Amastigotes. PLoS Pathogens, 11(12), 1–24. Clayton, C. E. (2002). Life without transcriptional control? From fly to man and back again. EMBO, 21(8), 1881–1888. Clayton, C., & Shapira, M. (2007). Post-transcriptional regulation of gene expression in trypanosomes and leishmanias. Molecular & Biochemical Parasitology, 156, 93–101. Coughlan, S., Taylor, A. S., Feane, E., Sanders, M., Schonian, G., Cotton, J. A., & Downing, T. (2018). Leishmania naiffi and Leishmania guyanensis reference genomes highlight genome structure and gene evolution in the Viannia subgenus. Royal Society Open Science, 5(4). Downing, T., Imamura, H., & Decuypere, S. (2011). Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome, 21, 2143–2156. Dujardin, J. C., Mannaert, A., Durrant, C., & Cotton, J. A. (2014). Mosaic aneuploidy in Leishmania: The perspective of whole genome sequencing. Trends in Parasitology, 30(12), 554–555. Dumetz, F., Imamura, H., Sanders, M., Seblova, V., Myskova, J., & Pescher, P. (2017). Modulation of aneuploidy in Leishmania in vitro and in vivo environments and its impact on gene expression. MBio, 8(3), 1–14. Folgueira, C., Quijada, L., Soto, M., Abanades, D. R., Alonso, C., & Requena, J. M. (2005). The translational efficiencies of the two Leishmania infantum HSP70 mRNAs, differing in their 3′-untranslated regions, are affected by shifts in the temperature of growth through different mechanisms. Journal of Biological Chemistry, 280(42), 35172–35183. González, C., Wang, O., Strutz, S. E., González-Salazar, C., Sánchez-Cordero, V., & Sarkar, S. (2010). Climate change and risk of leishmaniasis in North America: Predictions from ecological niche models of vector and reservoir species. PLoS Neglected Tropical Diseases, 4(1). Hanke, T., Ramiro, M. J., Trigueros, S., Roca, J., & Larraga, V. (2003). Cloning, functional analysis and post-transcriptional regulation of a type II DNA topoisomerase from Leishmania infantum. A new potential target for anti-parasite drugs. Nucleic Acids Research, 31(June 2014), 4917–4928. Hlavacova, J., Votypka, J., & Volf, P. (2013). The Effect of Temperature on Leishmania (Kinetoplastida: Trypanosomatidae) Development in Sand Flies. Journal of Medical Entomology, 50(4), 1–4. Hombach, A., Ommen, G., Chrobak, M., & Clos, J. (2013). The Hsp90 – Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages. Cellular Microbiology, 15(November 2012), 585–600. Hombach, A., Ommen, G., Macdonald, A., & Clos, J. (2014). A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani. Cell Science, 127, 4762–4773. Iantorno SA, Durrant C, Khan A, S., MJ, Beverley SM, Warren WC, Berriman M, S., DL, Cotton JA, G. M. 2017. G. expression, By, in L. is regulated predominantly, Https://doi.org/, gene dosage. mBio 8: e01393-17., & 10.1128/mBio.01393-17. (2017). Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage, 8(5), 1–20. Imamura, H., Downing, T., Broeck, F. Van Den, Muylder, D., Dumetz, F., Rai, K., … Roy, S. (2016). Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. ELife, 5, 1–39. Jensen, B. C., Sivam, D., Kifer, C. T., Myler, P. J., & Parsons, M. (2009). Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei. BMC Genomics, 24. Koch, L. K., Kochmann, J., Klimpel, S., & Cunze, S. (2017). Modeling the climatic suitability of leishmaniasis vector species in Europe. Scientific Reports, 7(1), 1–10. Kramer, S. (2012). Developmental regulation of gene expression in the absence of transcriptional control: The case of kinetoplastids. Molecular & Biochemical Parasitology, 181(2), 61–72. Lafferty, K. D., & Mordecai, E. A. (2016). The rise and fall of infectious disease in a warmer world. F1000Research, 5(0), 2040. Lawrence, F., & Robertgero, M. (1985). Induction of heat shock and stress proteins promastigotes of three Leishmania species. Proc. Natl. Acad. Sci. USA, 82(July), 4414–4417. Lean, J. L., & Rind, D. H. (2009). How will Earth’s surface temperature change in future decades? Geophysical Research Letters, 36(15), 1–5. Leon, L. L., Soares, M. J., & Temporal, R. M. (1995). Effects of Temperature on Promastigotes of Several Species of Leishmania. J. Euk. Microbiol., 42(3), 219–223. Leprohon, P., Le, D., Girard, I., Papadopoulou, B., & Ouellette, M. (2006). Modulation of Leishmania ABC Protein Gene Expression through Life Stages and among Drug-Resistant Parasites. Eukaryotic Cell, 5(10), 1713–1725. Liang, L., & Gong, P. (2017). Climate change and human infectious diseases: A synthesis of research findings from global and spatio-temporal perspectives. Environment International, 103, 99–108. Mandal, G., Mandal, S., Sharma, M., & Charret, K. S. (2015). Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1. PLoS Neglected Tropical Diseases, 1–29. Marquis, N., Gourbal, B., Rosen, B. P., Mukhopadhyay, R., & Ouellette, M. (2005). Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. Molecular Microbiology, 57, 1690–1699. Mcnicoll, F., Drummelsmith, J., Müller, M., Madore, É., Boilard, N., Ouellette, M., & Papadopoulou, B. (2006). A combined proteomic and transcriptomic approach to the study of stage differentiation in Leishmania infantum. Proteomics, 6, 3567–3581. Mondelaers, A., Sanchez-Cañete, M. P., Hendrickx, S., Eberhardt, E., Garcia-Hernandez, R., Lachaud, L., Maes, L. (2016). Genomic and Molecular Characterization of Miltefosine Resistance in Leishmania infantum Strains with Either Natural or Acquired Resistance through Experimental Selection of Intracellular Amastigotes. PloS One, 11(4), e0154101. Nedwell, D. B. (1999). Effect of low temperature on microbial growth: Lowered affinity for substrates limits growth at low temperature. FEMS Microbiology Ecology, 30(2), 101–111. Ouellette, M., Danielle, L., Haimeur, A., Grondin, K., Brochu, C., & Papadopaulou, B. (1998). ABC transporters in Leishmania and their role in drug resistance. Drug Resistance Updates, 1, 43–48. Patino, L. H., Mendez, C., Rodriguez, O., Romero, Y., Velandia, D., Alvarado, M., Ramírez, J. D. (2017). Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army. PLoS Neglected Tropical Diseases, 11(8), 1–15. Patino, L. H., & Ramírez, J. D. (2017). RNA-seq in kinetoplastids: A powerful tool for the understanding of the biology and host-pathogen interactions. Infection, Genetics and Evolution, 49, 273–282. Pays, E., Coquelet, H., Pays, A., Tebabi, P., & Steinert, M. (1989). Trypanosoma brucei: Posttranscriptional Control of the Variable Surface Glycoprotein Gene Expression Site. Molecular and cellular biology, 9(9), 4018–4021. Prieto Barja, P., Pescher, P., Bussotti, G., Dumetz, F., Imamura, H., Kedra, D., Späth, G. F. (2017). Haplotype selection as an adaptive mechanism in the protozoan pathogen Leishmania donovani. Nature Ecology & Evolution, 1(12), 1961–1969. Queiroz, R., Benz, C., Fellenberg, K., Hoheisel, J. D., & Clayton, C. (2009). Transcriptome analysis of differentiating trypanosomes reveals the existence of multiple post-transcriptional regulons. BMC Genomics, 19, 1–19. Rajesh, K., & Sanjay, K. (2013). Change in global Climate and Prevalence of Visceral Leishmaniasis. International Journal of Scientific and Research Publications, 3(1), 1–2. Ramírez, J. D., Hernández, C., León, C. M., Ayala, M. S., Flórez, C., & González, C. (2016). Taxonomy, diversity, temporal and geographical distribution of Cutaneous Leishmaniasis in Colombia: A retrospective study. Scientific Reports, 6(March), 1–10. Rastrojo, A., García-Hernández, R., Vargas, P., Camacho, E., Corvo, L., Imamura, H., Requena, J. M. (2018). Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs. International Journal for Parasitology: Drugs and Drug Resistance, 8(2), 246–264. Rogers, M. B., Hilley, J. D., Dickens, N. J., Wilkes, J., Bates, P. A., Depledge, D. P., Mottram, J. C. (2011). Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Research, 21, 2129–2142. Seraphim, T. V, Alves, M. M., Silva, I. M., Gomes, F. E. R., & Silva, K. P. (2013). Low Resolution Structural Studies Indicate that the Activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis Has an Elongated Shape Which Allows Its Interaction with Both N- and MDomains of Hsp90. PLoS ONE, 8(6), 1–14. Shaw, C. D., Lonchamp, J., Downing, T., Imamura, H., Freeman, T. M., Cotton, J. A., Carter, K. C. (2016). In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: Genomic and metabolomic characterization. Molecular Microbiology, 99(6), 1134–1148. Späth, G. F., Drini, S., & Rachidi, N. (2015). A touch of Zen: post-translational regulation of the Leishmania stress response, 17(April), 632–638. Teixeira, D. E., Benchimol, M., Rodrigues, J. C. F., Crepaldi, P. H., Pimenta, P. F. P., & de Souza, W. (2013). The Cell Biology of Leishmania: How to Teach Using Animations. PLoS Pathogens, 9(10), 8–11. Teixeira, S. M. R., Kirchhoff, L. V, & Donelson, J. E. (1995). Post-transcriptional Elements Regulating Expression of mRNAs from the Amastin / Tuzin Gene Cluster of Trypanosoma cruzi. The Journal of Biological Chemistry, 270(38), 22586–22594. Torres, C., Marı, J., Paroditalice, A., Marı, J., Gamarro, F., & Castanys, S. (2003). The overexpression of a new ABC transporter in Leishmania is related to phospholipid trafficking and reduced infectivity. Biochemical et Biophysica Acta, 1612, 195–207. Toye, P., & Remold, H. (1989). The influence of temperature and serum deprivation on the synthesis of heat-shock proteins and alpha and beta tubulin in promastigotes of Leishmania major. Molecular & Biochemical Parasitology, 35, 1–10. Valdivia, H. O., Reis-Cunha, J. L., Rodrigues-Luiz, G. F., Baptista, R. P., Baldeviano, G. C., Gerbasi, R. V., Bartholomeu, D. C. (2015). Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. BMC Genomics, 16(1), 1–10. Vanaerschot, M., Decuypere, S., Downing, T., Imamura, H., Stark, O., De Doncker, S., Rijal, S. (2012). Genetic markers for SSG resistance in leishmania donovani and SSG treatment failure in visceral leishmaniasis patients of the Indian subcontinent. Journal of Infectious Diseases, 206(5), 752–755. Wu, X., Lu, Y., Zhou, S., Chen, L., & Xu, B. (2016). Impact of climate change on human infectious diseases: Empirical evidence and human adaptation. Environment International, 86, 14–23. Zilberstein, D., & Shapira, M. (1994). The role of pH and temperature in the development of Leishmania parasites. Annu. Rev. Microbiol., 48, 449–470. Zilka, A., Garlapati, S., Dahan, E., Yaolsky, V., & Shapira, M. (2001). Developmental Regulation of Heat Shock Protein 83 in Leishmania. The Journal of Biological Chemistry, 276(51), 47922–47929. |
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Vásquez, Nubia MarcelaPatiño, Luz H.Cruz-Saavedra, LissaRamírez, Juan David1011716118600Ballesteros Chitiva, NathaliaBiólogoFull timedb2f7350-66d6-436d-a738-ceb7a756cd776002019-02-13T12:53:11Z2019-02-13T12:53:11Z2019-02-052019The increasing of the temperature is one of the principal consequences of the climate change, which affect human populations due of the emergence and re-emergency of infection diseases. The Leishmaniases are diseases cause by protozoans’ parasites of the genus Leishmania; these diseases are composed by different clinical manifestations, one of the most important in the New World is Cutaneous Leishmaniasis for which the most common causative species is Leishmania braziliensis. This species as the other members of the Trypanosomatidae family present a genomic plasticity and a particular gene expression regulation that allow to the parasites to adapt and response to several stimulus, for that reason the aim of this study is evaluate the transcriptome profiles of L. braziliensis promastigotes subjected to temperature shifts. To reach this aim the authors performed an RNA-Seq that permitted to find several genes associated with a direct response to the treatments; also, through the growth curves done the authors evidenced a decrease in the cell proliferation in all the temperatures tested, where the most affected was 30°C. The results obtained in this study demonstrated a fast response of L. braziliensis promastigotes to temperature shifts.2021-02-14 01:01:01: Script de automatizacion de embargos. info:eu-repo/date/embargoEnd/2021-02-13Dirección de investigación e innovación de la Universidad del Rosarioapplication/pdfimage/jpeghttps://doi.org/10.48713/10336_19055 http://repository.urosario.edu.co/handle/10336/19055spaUniversidad del RosarioFacultad de Ciencias Naturales y MatemáticasBiologíaAtribución-NoComercial-SinDerivadas 2.5 ColombiaAtribución-NoComercial-SinDerivadas 2.5 ColombiaAbierto (Texto Completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma.http://creativecommons.org/licenses/by-nc-nd/2.5/co/http://purl.org/coar/access_right/c_abf2Barria, C., Malecki, M., & Arraiano, C. M. (2013). Bacterial adaptation to cold. 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The Journal of Biological Chemistry, 276(51), 47922–47929.instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURTranscriptomicHeat stressResponse to external stimulusGrowth curvesEnfermedades616600LeishmaniasisInfecciones por protozoariosTranscriptome profiles evaluation of Leishmania braziliensis promastigotes subjected to temperature shifts in vitroTemperature shifts impacts on Leishmania braziliensisbachelorThesisAnálisis de casoTrabajo de gradohttp://purl.org/coar/resource_type/c_7a1fORIGINALBallesterosChitiva-Nathalia-2019.pdfBallesterosChitiva-Nathalia-2019.pdfArtículo principalapplication/pdf273673https://repository.urosario.edu.co/bitstreams/8b68c7ab-4a6b-42cc-8f05-4ef7c44547dd/download28baafbabc328b8caad5b86ad02f1b15MD512Imagenes_Ballesteros_Chitiva_Nathalia.zipImagenes_Ballesteros_Chitiva_Nathalia.zip application/zip2728342https://repository.urosario.edu.co/bitstreams/fff057b0-a98e-468d-b677-fcb49001b661/downloadebe84c7b05f781f1d29322d67f8a8964MD523Table S1.pdfTable S1.pdfMaterial suplementario 1application/pdf419759https://repository.urosario.edu.co/bitstreams/4c97ab6e-476a-4fd9-b062-64f95c18e444/download98419aa034a56ce77bb7298567c4f4e4MD517Table S2.pdfTable S2.pdfMaterial suplementario 2application/pdf412734https://repository.urosario.edu.co/bitstreams/334f63f1-b7b3-48d6-a062-369608ccbd8b/download00efe7e6b6610a8ec40c64f84ef250edMD518Table S3.pdfTable S3.pdfMaterial suplementario 3application/pdf410258https://repository.urosario.edu.co/bitstreams/bc423394-bb78-4043-aa77-aa12da06f264/downloadce8df18a8eed8710a2e3c57943aaf2e6MD519Table S4.pdfTable S4.pdfMaterial suplementario 4application/pdf414346https://repository.urosario.edu.co/bitstreams/68b95ce8-f482-4efb-9872-7840ddb8c56d/downloadc8f7606dc9a83656ac4a75aacd869de2MD520LICENSElicense.txtlicense.txttext/plain1475https://repository.urosario.edu.co/bitstreams/5c06f1ae-5b2e-4aed-9824-c79c1bd01c32/downloadfab9d9ed61d64f6ac005dee3306ae77eMD521CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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