Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidoni...

Autores
Comba, Andrea; Almada, Luciana Victoria; Tolosa, Ezequiel J.; Iguchi, Eriko; Marks, David L.; Vara Messler, Marianela; Silva, Renata Alejandra; Fernandez-Barrena, Maite G.; Enriquez-Hesles, Elisa; Vrabel, Anne L.; Botta, Bruno; Di Marcotulio, Lucia; Ellenrieder, Volker; Eynard, Aldo Renato; Pasqualini, María Eugenia; Fernandez Zapico, Martin Ernesto
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells.Wedemonstrated that down-regulation of the transcription factor gliomaassociated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed thatAArepresses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AAinduced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.
Fil: Comba, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Almada, Luciana Victoria. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Tolosa, Ezequiel J.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Iguchi, Eriko. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Marks, David L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Vara Messler, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Silva, Renata Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Fernandez-Barrena, Maite G.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Enriquez-Hesles, Elisa. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Vrabel, Anne L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Botta, Bruno. Sapienza University; Italia
Fil: Di Marcotulio, Lucia. Sapienza University; Italia
Fil: Ellenrieder, Volker. University Medical Center Göttingen; Alemania
Fil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Pasqualini, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Materia
GLI1
ARACHIDONIC ACID
CANCER
APOPTOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/130675

id CONICETDig_a4096fdb79f3bcf11b066a8cc04f9cb1
oai_identifier_str oai:ri.conicet.gov.ar:11336/130675
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acidComba, AndreaAlmada, Luciana VictoriaTolosa, Ezequiel J.Iguchi, ErikoMarks, David L.Vara Messler, MarianelaSilva, Renata AlejandraFernandez-Barrena, Maite G.Enriquez-Hesles, ElisaVrabel, Anne L.Botta, BrunoDi Marcotulio, LuciaEllenrieder, VolkerEynard, Aldo RenatoPasqualini, María EugeniaFernandez Zapico, Martin ErnestoGLI1ARACHIDONIC ACIDCANCERAPOPTOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells.Wedemonstrated that down-regulation of the transcription factor gliomaassociated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed thatAArepresses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AAinduced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.Fil: Comba, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Almada, Luciana Victoria. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Tolosa, Ezequiel J.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Iguchi, Eriko. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Marks, David L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Vara Messler, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Silva, Renata Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Fernandez-Barrena, Maite G.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Enriquez-Hesles, Elisa. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Vrabel, Anne L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosFil: Botta, Bruno. Sapienza University; ItaliaFil: Di Marcotulio, Lucia. Sapienza University; ItaliaFil: Ellenrieder, Volker. University Medical Center Göttingen; AlemaniaFil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Pasqualini, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Fernandez Zapico, Martin Ernesto. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2016-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130675Comba, Andrea; Almada, Luciana Victoria; Tolosa, Ezequiel J.; Iguchi, Eriko; Marks, David L.; et al.; Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 291; 4; 1-2016; 1933-19470021-92581083-351XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/early/2015/11/24/jbc.M115.691972.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M115.691972info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:16:47Zoai:ri.conicet.gov.ar:11336/130675instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:16:47.819CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
title Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
spellingShingle Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
Comba, Andrea
GLI1
ARACHIDONIC ACID
CANCER
APOPTOSIS
title_short Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
title_full Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
title_fullStr Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
title_full_unstemmed Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
title_sort Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid
dc.creator.none.fl_str_mv Comba, Andrea
Almada, Luciana Victoria
Tolosa, Ezequiel J.
Iguchi, Eriko
Marks, David L.
Vara Messler, Marianela
Silva, Renata Alejandra
Fernandez-Barrena, Maite G.
Enriquez-Hesles, Elisa
Vrabel, Anne L.
Botta, Bruno
Di Marcotulio, Lucia
Ellenrieder, Volker
Eynard, Aldo Renato
Pasqualini, María Eugenia
Fernandez Zapico, Martin Ernesto
author Comba, Andrea
author_facet Comba, Andrea
Almada, Luciana Victoria
Tolosa, Ezequiel J.
Iguchi, Eriko
Marks, David L.
Vara Messler, Marianela
Silva, Renata Alejandra
Fernandez-Barrena, Maite G.
Enriquez-Hesles, Elisa
Vrabel, Anne L.
Botta, Bruno
Di Marcotulio, Lucia
Ellenrieder, Volker
Eynard, Aldo Renato
Pasqualini, María Eugenia
Fernandez Zapico, Martin Ernesto
author_role author
author2 Almada, Luciana Victoria
Tolosa, Ezequiel J.
Iguchi, Eriko
Marks, David L.
Vara Messler, Marianela
Silva, Renata Alejandra
Fernandez-Barrena, Maite G.
Enriquez-Hesles, Elisa
Vrabel, Anne L.
Botta, Bruno
Di Marcotulio, Lucia
Ellenrieder, Volker
Eynard, Aldo Renato
Pasqualini, María Eugenia
Fernandez Zapico, Martin Ernesto
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GLI1
ARACHIDONIC ACID
CANCER
APOPTOSIS
topic GLI1
ARACHIDONIC ACID
CANCER
APOPTOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells.Wedemonstrated that down-regulation of the transcription factor gliomaassociated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed thatAArepresses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AAinduced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.
Fil: Comba, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Almada, Luciana Victoria. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Tolosa, Ezequiel J.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Iguchi, Eriko. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Marks, David L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Vara Messler, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Silva, Renata Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Fernandez-Barrena, Maite G.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Enriquez-Hesles, Elisa. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Vrabel, Anne L.. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
Fil: Botta, Bruno. Sapienza University; Italia
Fil: Di Marcotulio, Lucia. Sapienza University; Italia
Fil: Ellenrieder, Volker. University Medical Center Göttingen; Alemania
Fil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Pasqualini, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic - Schuze Center Of Novel Therapeutic; Estados Unidos
description Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells.Wedemonstrated that down-regulation of the transcription factor gliomaassociated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed thatAArepresses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AAinduced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.
publishDate 2016
dc.date.none.fl_str_mv 2016-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/130675
Comba, Andrea; Almada, Luciana Victoria; Tolosa, Ezequiel J.; Iguchi, Eriko; Marks, David L.; et al.; Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 291; 4; 1-2016; 1933-1947
0021-9258
1083-351X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130675
identifier_str_mv Comba, Andrea; Almada, Luciana Victoria; Tolosa, Ezequiel J.; Iguchi, Eriko; Marks, David L.; et al.; Nuclear factor of activated T cells-dependent downregulation of the transcription factor glioma-associated protein 1 (GLI1) underlies the growth inhibitory properties of arachidonic acid; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 291; 4; 1-2016; 1933-1947
0021-9258
1083-351X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/early/2015/11/24/jbc.M115.691972.long
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M115.691972
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614115454091264
score 13.070432