Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli
Toxoplasma gondii is an apicomplexan parasite responsible for Toxoplasmosis, a disease with a high prevalence in tropical and subtropical regions and also in Europe. GRAS proteins of Toxoplasma gondii including GRA3, GRA5, GRA7 and GRA8 have significant roles in the host-parasite interaction. They h...
- Autores:
-
García López, Laura Lorena
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2016
- Institución:
- Universidad del Quindío
- Repositorio:
- Repositorio Universidad del Quindío
- Idioma:
- eng
- OAI Identifier:
- oai:bdigital.uniquindio.edu.co:001/6792
- Acceso en línea:
- https://bdigital.uniquindio.edu.co/handle/001/6792
https://bdigital.uniquindio.edu.co
- Palabra clave:
- Toxoplasma gondii
structural modeling
recombinant protein
- Rights
- openAccess
- License
- Derechos reservados Universidad del Quindío
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Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| title |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| spellingShingle |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli Toxoplasma gondii structural modeling recombinant protein |
| title_short |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| title_full |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| title_fullStr |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| title_full_unstemmed |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| title_sort |
Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coli |
| dc.creator.fl_str_mv |
García López, Laura Lorena |
| dc.contributor.advisor.none.fl_str_mv |
Murillo león, Mateo |
| dc.contributor.author.none.fl_str_mv |
García López, Laura Lorena |
| dc.contributor.researchgroup.spa.fl_str_mv |
GEPAMOL (Grupo de estudio en Parasitología Molecular) |
| dc.subject.proposal.eng.fl_str_mv |
Toxoplasma gondii structural modeling recombinant protein |
| topic |
Toxoplasma gondii structural modeling recombinant protein |
| description |
Toxoplasma gondii is an apicomplexan parasite responsible for Toxoplasmosis, a disease with a high prevalence in tropical and subtropical regions and also in Europe. GRAS proteins of Toxoplasma gondii including GRA3, GRA5, GRA7 and GRA8 have significant roles in the host-parasite interaction. They have the capacity to alter and modulate the expression and activity of the host cell; facilitating the invasion and stabilization of parasite within the cells. Specifically, GRA3 protein is important for the virulence phenotype of the type II strains of Toxoplasma gondii. Like many dense granules, GRA3 has no homology to proteins with described structure. A 3D theoretical model of GRA3 was built by an ab initio approach and by searching of structural orthologs we found structural similarity with BCL-XL (PDB id 1Bxl). T. gondii GRA3 has two conserved transmembrane regions like BCL-2 family members and an elongated hydrophobic cleft. This cleft may represent the binding site for other members of the Bcl-2. In the molecular docking between GRA3 model and Bak as a ligand, the binding free energy was -5.2 kcal / mol. This was congruent with the control docking between BCL-XL and Bak with a binding free energy of -5.7 Kcal / mol. Finally, recombinant protein GST-TgGRA3 expressed in E. coli and it was purified by affinity chromatography with GST column in the AKTA system in native conditions. The purification of recombinant GST-TgGRA3 was confirmed by Western-blot. |
| publishDate |
2016 |
| dc.date.issued.none.fl_str_mv |
2016 |
| dc.date.accessioned.none.fl_str_mv |
2024-04-19T16:17:46Z |
| dc.date.available.none.fl_str_mv |
2024-04-19T16:17:46Z |
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Trabajo de grado - Pregrado |
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http://purl.org/coar/resource_type/c_7a1f |
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info:eu-repo/semantics/draft |
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Text |
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https://purl.org/redcol/resource_type/TP |
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Universidad del Quindio |
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Repositorio Institucional |
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https://bdigital.uniquindio.edu.co |
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eng |
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Achbarou, A., Mercereau-Puijalon, O., Sadak, A., Fortier, B., Leriche, M. A., Camus, D., & Dubremetz, J. F. (1991). Differential targeting of dense granule proteins in the parasitophorous vacuole of Toxoplasma gondii. Parasitology, 103 Pt 3, 321–329. http://doi.org/10.1017/S0031182000059837 Adjogble, Koku D Z, Corinne Mercier, Jean Francois Dubremetz, Christian Hucke, Colin R. MacKenzie, Marie France Cesbron-Delauw, and Walter Däubener. 2004. “GRA9, a New Toxoplasma Gondii Dense Granule Protein Associated with the Intravacuolar Network of Tubular Membranes.” International Journal for Parasitology 34 (11): 1255–64. doi:10.1016/j.ijpara.2004.07.011. Blackman, M. J., & Bannister, L. H. (2001). Apical organelles of Apicomplexa: biology and isolation by subcellular fractionation. Molecular and Biochemical Parasitology, 117(1), 11–25. http://doi.org/10.1016/S0166-6851(01)00328-0 Bornhorst JA, F. J. (2000). Purification of proteins using polyhistidine affinity tags. Methods Enzymol, 326:245–54. Bougdour A, Durandau E, Brenier-Pinchart MP, et al. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression. Cell Host Microbe. 2013;13(4):489-500. doi:10.1016/j.chom.2013.03.002. Carmen, John C., and Anthony P. Sinai. 2007. “Suicide Prevention: Disruption of Apoptotic Pathways by Protozoan Parasites.” Molecular Microbiology. doi:10.1111/j.1365-2958.2007.05714.x. Cesbron-D.delauw M.-F., M. F., Gendrin, C., Travier, L., Ruffiot, P., & Mercier, C. (2008). Apicomplexa in mammalian cells: Trafficking to the parasitophorous vacuole. Traffic. http://doi.org/10.1111/j.1600-0854.2008.00728.x Faherty, Christina S., and Anthony T. Maurelli. 2008. “Staying Alive: Bacterial Inhibition of Apoptosis during Infection.” Trends in Microbiology. doi:10.1016/j.tim.2008.02.001. Feng, Pinghui, Junsoo Park, Bok-Soo Lee, Sun-Hwa Lee, Richard J Bram, and Jae U Jung. 2002. “Kaposi’s Sarcoma-Associated Herpesvirus Mitochondrial K7 Protein Targets a Cellular Calcium-Modulating Cyclophilin Ligand to Modulate Intracellular Calcium Concentration and Inhibit Apoptosis.” Journal of Virology 76 (22): 11491–504. doi:10.1128/JVI.76.22.11491-11504.2002. Galluzzi, Lorenzo, Catherine Brenner, Eugenia Morselli, Zahia Touat, and Guido Kroemer. 2008. “Viral Control of Mitochondrial Apoptosis.” PLoS Pathogens. doi:10.1371/journal.ppat.1000018. Gene Runner for Windows, available on-line at www.generunner.com. Gómez, J. E, Byron Ruiz, Jorge Cortés, José Montoya, and Alejandro Agudelo. 2007. “Guía de Práctica Clínica Para Toxoplasmosis Durante El Embarazo Y Toxoplasmosis Congénita.” Infect. vol.11 no.3 Bogotá July/Sept. 2007, 1–13. H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne, The Protein Data Bank, Nucleic Acids Research 28 (2000) 235–242 Hanada, M., C. Aime-Sempe, T. Sato, and J. C. Reed. 1995. “Structure-Function Analysis of Bcl-2 Protein. Identification of Conserved Domains Important for Homodimerization with Bcl-2 and Heterodimerization with Bax.” Journal of Biological Chemistry. doi:10.1074/jbc.270.20.11962. Hasnain, Seyed E, Rasheeda Begum, K V a Ramaiah, Sudhir Sahdev, E M Shajil, Tarvinder K Taneja, Manjari Mohan, M Athar, Nand K Sah, and M Krishnaveni. 2003. “Host-Pathogen Interactions during Apoptosis.” Journal of Biosciences 28 (3): 349–58. doi:10.1007/BF02970153. Jessica C. Kissinger, Bindu Gajria,1 Li Li,1 Ian T. Paulsen,2 and David S. Roos1,* ToxoDB: accessing the Toxoplasma gondii genome. ToxoDB (http://ToxoDB.org). Nucleic Acids Res. 2003 Jan 1; 31(1): 234–236. Kemp LE, Yamamoto M, Soldati-Favre D. Subversion of host cellular functions by the apicomplexan parasites. FEMS Microbiol Rev. 2013;37(4):607-631. doi:10.1111/1574-6976.12013. Kim K, Weiss LM. Toxoplasma gondii: The model apicomplexan. Int J Parasitol. 2004;34(3):423-432. doi:10.1016/j.ijpara.2003.12.009. L. Slabinski, L. Jaroszewski, L. Rychlewski, I.A. Wilson, S.A. Lesley, A. Godzik, XtalPred: a web server for prediction of protein crystallizability, Bioinformatics 23 (24) (2007) 3403–3405. Labruyère, E., Lingnau, M., Mercier, C., and Sibley, L.D. (1999) Differential membrane targeting of the secretory proteins GRA4 and GRA6 within the parasitophorous vacuole formed by Toxoplasma gondii. Mol. Biochem. Parasitol. 102, 311-324 Ma, J. S., Sasai, M., Ohshima, J., Lee, Y., Bando, H., Takeda, K., & Yamamoto, M. (2014). Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. The Journal of Experimental Medicine, 211(10), 2013–32. http://doi.org/10.1084/jem.20131272 Matthiesen SH, Shenoy SM, Kim K, Singer RH, Satir BH. A parafusin-related Toxoplasma protein in Ca2 + -regulated secretory organelles. Eur. J. Cell. Biol. 2001; 80:775–783. [PubMed: 11831391] Nicolle C, M. L. (1908). Sur une infection a corps de Leishman (ou organisms voisons) du gondi. Sci, C. R. Acad, 147:763. Nilsson J., Stahl S., J. Lundeberg, Uhlen M., N. P. (1997). Affinity fusion strategies for detection, purification, and immobilization of recombinant proteins. Protein Expr Purif., 11 1-16 10. Oltvai, Zoltán N., and Stanley J. Korsmeyer. 1994. “Checkpoints of Dueling Dimers Foil Death Wishes.” Cell 79 (2): 189–92. doi:10.1016/0092-8674(94)90188-0. Petros, A M, D G Nettesheim, Y Wang, E T Olejniczak, R P Meadows, J Mack, K Swift, et al. 2000. “Rationale for Bcl-xL/Bad Peptide Complex Formation from Structure, Mutagenesis, and Biophysical Studies.” Protein Science : A Publication of the Protein Society 9 (12): 2528–34. doi:10.1110/ps.9.12.2528. Pope, B., & Kent, H. M. (1996). High efficiency 5 min transformation of Escherichia coli. Nucleic Acids Research, 24(3), 536–537. http://doi.org/10.1093/nar/24.3.536 Randall, L. M., & Hunter, C. A. (2011). Parasite dissemination and the pathogenesis of toxoplasmosis. European Journal of Microbiology and Immunology, 1(1), 3–9. Rath A, Glibowicka M, Nadeau VG, Chen G, Deber CM. Detergent binding explains anomalous SDS-PAGE migration of membrane proteins. Proc Natl Acad Sci U S A. 2009;106(6):1760-1765. doi:10.1073/pnas.0813167106. Santos T.R., Costa A.J., Toniollo G.H., Luvizotto M.C.R., Benetti A.H., Santos R.R., Matta D.H., Lopes W.D.Z., Oliveira J.A. & Oliveira G.P. 2009. Prevalence of anti-Toxoplasma gondii antibodies in dairy cattle, dogs and humans from the Jauru micro-region, Mato Grosso state, Brazil. Vet. Parasitol. 161:324-326. Sattler, M. 1997. “Structure of Bcl-xL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis.” Science 275 (5302): 983–86. doi:10.1126/science.275.5302.983. Terpe, K. (2003). Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems. Applied Microbiology and Biotechnology, 60(5), 523–533. http://doi.org/10.1007/s00253-002-1158-6 Weikert C, Sauer U, Bailey JE. An Escherichia coli host strain useful for efficient overproduction of secreted recombinant protein. Biotechnol Bioeng. 1998;59(3):386-391. doi:10.1002/(SICI)1097-0290(19980805)59:3<386::AID-BIT16>3.0.CO;2-C. X.-M. Yin, Z. N. Oltvai, S. J. Korsmeyer, “BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax”. Nature 369, 321 (1994). |
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Derechos reservados Universidad del Quindío |
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Murillo león, MateoGarcía López, Laura LorenaGEPAMOL (Grupo de estudio en Parasitología Molecular)2024-04-19T16:17:46Z2024-04-19T16:17:46Z2016https://bdigital.uniquindio.edu.co/handle/001/6792Universidad del QuindioRepositorio Institucionalhttps://bdigital.uniquindio.edu.coToxoplasma gondii is an apicomplexan parasite responsible for Toxoplasmosis, a disease with a high prevalence in tropical and subtropical regions and also in Europe. GRAS proteins of Toxoplasma gondii including GRA3, GRA5, GRA7 and GRA8 have significant roles in the host-parasite interaction. They have the capacity to alter and modulate the expression and activity of the host cell; facilitating the invasion and stabilization of parasite within the cells. Specifically, GRA3 protein is important for the virulence phenotype of the type II strains of Toxoplasma gondii. Like many dense granules, GRA3 has no homology to proteins with described structure. A 3D theoretical model of GRA3 was built by an ab initio approach and by searching of structural orthologs we found structural similarity with BCL-XL (PDB id 1Bxl). T. gondii GRA3 has two conserved transmembrane regions like BCL-2 family members and an elongated hydrophobic cleft. This cleft may represent the binding site for other members of the Bcl-2. In the molecular docking between GRA3 model and Bak as a ligand, the binding free energy was -5.2 kcal / mol. This was congruent with the control docking between BCL-XL and Bak with a binding free energy of -5.7 Kcal / mol. Finally, recombinant protein GST-TgGRA3 expressed in E. coli and it was purified by affinity chromatography with GST column in the AKTA system in native conditions. The purification of recombinant GST-TgGRA3 was confirmed by Western-blot.1.Introducción 1-- 2. Materiales y métodos 3-- 3. Resultados 7-- 4. Discusión 17--5. Conclusiones 19-- 6. Bibliografía --21PregradoBiólogo31 paginasapplication/pdfengUniversidad del QuindioFacultad de Ciencias Básicas y TecnologíasArmenia Quindio ColombiaCiencias Básicas y Tecnologías - BiologíaDerechos reservados Universidad del Quindíohttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)http://purl.org/coar/access_right/c_abf2Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coliTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/draftTexthttps://purl.org/redcol/resource_type/TPhttp://purl.org/coar/version/c_b1a7d7d4d402bcceToxoplasma gondiistructural modelingrecombinant proteinAchbarou, A., Mercereau-Puijalon, O., Sadak, A., Fortier, B., Leriche, M. A., Camus, D., & Dubremetz, J. F. (1991). Differential targeting of dense granule proteins in the parasitophorous vacuole of Toxoplasma gondii. Parasitology, 103 Pt 3, 321–329. http://doi.org/10.1017/S0031182000059837Adjogble, Koku D Z, Corinne Mercier, Jean Francois Dubremetz, Christian Hucke, Colin R. MacKenzie, Marie France Cesbron-Delauw, and Walter Däubener. 2004. “GRA9, a New Toxoplasma Gondii Dense Granule Protein Associated with the Intravacuolar Network of Tubular Membranes.” International Journal for Parasitology 34 (11): 1255–64. doi:10.1016/j.ijpara.2004.07.011.Blackman, M. J., & Bannister, L. H. (2001). Apical organelles of Apicomplexa: biology and isolation by subcellular fractionation. Molecular and Biochemical Parasitology, 117(1), 11–25. http://doi.org/10.1016/S0166-6851(01)00328-0Bornhorst JA, F. J. (2000). Purification of proteins using polyhistidine affinity tags. Methods Enzymol, 326:245–54.Bougdour A, Durandau E, Brenier-Pinchart MP, et al. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression. Cell Host Microbe. 2013;13(4):489-500. doi:10.1016/j.chom.2013.03.002.Carmen, John C., and Anthony P. Sinai. 2007. “Suicide Prevention: Disruption of Apoptotic Pathways by Protozoan Parasites.” Molecular Microbiology. doi:10.1111/j.1365-2958.2007.05714.x.Cesbron-D.delauw M.-F., M. F., Gendrin, C., Travier, L., Ruffiot, P., & Mercier, C. (2008). Apicomplexa in mammalian cells: Trafficking to the parasitophorous vacuole. Traffic. http://doi.org/10.1111/j.1600-0854.2008.00728.xFaherty, Christina S., and Anthony T. Maurelli. 2008. “Staying Alive: Bacterial Inhibition of Apoptosis during Infection.” Trends in Microbiology. doi:10.1016/j.tim.2008.02.001.Feng, Pinghui, Junsoo Park, Bok-Soo Lee, Sun-Hwa Lee, Richard J Bram, and Jae U Jung. 2002. “Kaposi’s Sarcoma-Associated Herpesvirus Mitochondrial K7 Protein Targets a Cellular Calcium-Modulating Cyclophilin Ligand to Modulate Intracellular Calcium Concentration and Inhibit Apoptosis.” Journal of Virology 76 (22): 11491–504. doi:10.1128/JVI.76.22.11491-11504.2002.Galluzzi, Lorenzo, Catherine Brenner, Eugenia Morselli, Zahia Touat, and Guido Kroemer. 2008. “Viral Control of Mitochondrial Apoptosis.” PLoS Pathogens. doi:10.1371/journal.ppat.1000018. Gene Runner for Windows, available on-line at www.generunner.com.Gómez, J. E, Byron Ruiz, Jorge Cortés, José Montoya, and Alejandro Agudelo. 2007. “Guía de Práctica Clínica Para Toxoplasmosis Durante El Embarazo Y Toxoplasmosis Congénita.” Infect. vol.11 no.3 Bogotá July/Sept. 2007, 1–13.H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne, The Protein Data Bank, Nucleic Acids Research 28 (2000) 235–242Hanada, M., C. Aime-Sempe, T. Sato, and J. C. Reed. 1995. “Structure-Function Analysis of Bcl-2 Protein. Identification of Conserved Domains Important for Homodimerization with Bcl-2 and Heterodimerization with Bax.” Journal of Biological Chemistry. doi:10.1074/jbc.270.20.11962.Hasnain, Seyed E, Rasheeda Begum, K V a Ramaiah, Sudhir Sahdev, E M Shajil, Tarvinder K Taneja, Manjari Mohan, M Athar, Nand K Sah, and M Krishnaveni. 2003. “Host-Pathogen Interactions during Apoptosis.” Journal of Biosciences 28 (3): 349–58. doi:10.1007/BF02970153.Jessica C. Kissinger, Bindu Gajria,1 Li Li,1 Ian T. Paulsen,2 and David S. Roos1,* ToxoDB: accessing the Toxoplasma gondii genome. ToxoDB (http://ToxoDB.org). Nucleic Acids Res. 2003 Jan 1; 31(1): 234–236.Kemp LE, Yamamoto M, Soldati-Favre D. Subversion of host cellular functions by the apicomplexan parasites. FEMS Microbiol Rev. 2013;37(4):607-631. doi:10.1111/1574-6976.12013.Kim K, Weiss LM. Toxoplasma gondii: The model apicomplexan. Int J Parasitol. 2004;34(3):423-432. doi:10.1016/j.ijpara.2003.12.009.L. Slabinski, L. Jaroszewski, L. Rychlewski, I.A. Wilson, S.A. Lesley, A. Godzik, XtalPred: a web server for prediction of protein crystallizability, Bioinformatics 23 (24) (2007) 3403–3405.Labruyère, E., Lingnau, M., Mercier, C., and Sibley, L.D. (1999) Differential membrane targeting of the secretory proteins GRA4 and GRA6 within the parasitophorous vacuole formed by Toxoplasma gondii. Mol. Biochem. Parasitol. 102, 311-324Ma, J. S., Sasai, M., Ohshima, J., Lee, Y., Bando, H., Takeda, K., & Yamamoto, M. (2014). Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. The Journal of Experimental Medicine, 211(10), 2013–32. http://doi.org/10.1084/jem.20131272Matthiesen SH, Shenoy SM, Kim K, Singer RH, Satir BH. A parafusin-related Toxoplasma protein in Ca2 + -regulated secretory organelles. Eur. J. Cell. Biol. 2001; 80:775–783. [PubMed: 11831391]Nicolle C, M. L. (1908). Sur une infection a corps de Leishman (ou organisms voisons) du gondi. Sci, C. R. Acad, 147:763.Nilsson J., Stahl S., J. Lundeberg, Uhlen M., N. P. (1997). Affinity fusion strategies for detection, purification, and immobilization of recombinant proteins. Protein Expr Purif., 11 1-16 10.Oltvai, Zoltán N., and Stanley J. 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Trabajos de grado Structural modeling, Cloning, Expression and Purification of Toxoplasma gondii dense granule protein 3 (GRA3) in E.coliapplication/pdf1506277https://bdigital.uniquindio.edu.co/bitstreams/4a7f0c3d-0a8b-4855-9ae7-afe4fd86fe63/download729795855c8bd5e3896d2facbd99bb82MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://bdigital.uniquindio.edu.co/bitstreams/aa8006f4-7dc5-4318-85b9-a23bae5aa205/download2f9959eaf5b71fae44bbf9ec84150c7aMD52TEXTFINAL.PAPER.pdf.txtFINAL.PAPER.pdf.txtExtracted texttext/plain56359https://bdigital.uniquindio.edu.co/bitstreams/935368ef-1479-409c-a295-29c8475b86e9/download13d638e2238d50299bedbb235549818eMD53THUMBNAILFINAL.PAPER.pdf.jpgFINAL.PAPER.pdf.jpgGenerated Thumbnailimage/jpeg13448https://bdigital.uniquindio.edu.co/bitstreams/d69c768b-8cd8-407f-a8dc-e0098cf77cec/downloada0aa48dc32cea31706b1ef754630c96aMD54001/6792oai:bdigital.uniquindio.edu.co:001/67922024-06-07 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