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2. Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Author

Martina Sola, Azucena Rendon-Angel, Viviana Rojo Martinez, Jacopo Sgrignani, Claudia Magrin, Ester Piovesana, Andrea Cavalli, Paolo Paganetti, and Stéphanie Papin

Subjects
Medicine, Science
Abstract

Abstract Tau gene mutations cause a progressive dementia and neurotoxic Tau forms deposited in neurofibrillary tangles are hallmarks of neurodegenerative tauopathies. Loss of non-canonical Tau functions may contribute to disease. In fact, Tau depletion affects the cellular response to DNA damage and tauopathies exhibit the accumulation of DNA lesions. Moreover, Tau modulates P53 activity and cell fate. Considering that MDM2 is the main antagonist of P53, we investigated, using orthogonal assays, if Tau interacts with MDM2. We report the existence in cells and brain of a Tau-MDM2 complex that, in vitro, exhibits reduced P53 ubiquitination activity in a manner sensitive to a Tau mutation. The Tau-MDM2 interaction involves the microtubule-binding domain of Tau and the acidic domain of MDM2, reminiscent of the binding of Tau to negatively charged microtubules. Notably, MDM2 accumulates aberrantly in neurofibrillary tangles. Aging-associated insults may expose a novel loss-of-function of Tau in neurodegeneration and cancer.

Published
2023
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3. Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study

Author

Abraham, Philip, Acir Crippa Júnior, Mauro, Aguilar, Humberto, Ahmed, Tasneem, Altorjay, Istvan, Andersen, Vibeke, Arai, Ronen, Arnold, Hays, Ausk, Karlee, Axler, Jeffrey, Ayub, Kamran, Balekuduru, Avinash, Barbalaco Neto, Guerino, Bassan, Isaac, Behm, Brian, Bekal, Pradeep, Bhatia, Shobna, Bod, Barnabas, Brandão Mello, Carlos Eduardo, Brandeburova, Julia, Breedt, Johannes, Bressler, Brian, Chopey, Ivan, Connor, Michael, Corlin, Richard, Cortez Hernandez, Carlos Alejandro, De, Arijit, de Sá Rolim, Alexander, Di Felice Boratto, Sandra, Dixon, Tyler, Dourado Poli, Debora, Dresner, David, Du Vall, George Aaron, Ebert, Matthias, Ehehalt, Robert, Ertan, Atilla, Escarcega Valencia, Ruben, Etzel, Jason, Fallingborg, Jan, Feagan, Brian, Fedurco, Miroslav, Fernandez Castro, Enrique, Ferreira de Almeida Borges, Valéria, Finklestein, Mark, Fischer, Andreas, Fleisher, Mark, Flores Rendon, Angel Ricardo, Fogel, Ronald, Franceschi Junior, Osvaldo, Freedland, Curtis, Gatof, David, Gill, Kanwar, Glerup, Henning, Gokak, Vardaraj, Goldin, Eran, Gomez Jaramillo, Hector Alejandro, Gupta, Nitin, Gurzo, Zoltan, Gyrina, Olga, Habeeb, Mohammed Aejaz, Hanauer, Stephen, Hardi, Robert, Harlan, William, Hemaidan, Ammar, Heyman, Melvin, Hoffmann, Peter, Holderman, William, Holtkamp-Endemann, Frank, Horvat, Gyula, Isaacs, Kim, Israeli, Eran, Jankiel Miszputen, Sender, Jensen, Søren, Johnson, Kenneth, Jones, Jennifer, Junior, Osvaldo, Kadleckova, Barbora, Kalla, Mukesh, Kallo, Zsuzsanna, Karyotakis, Nicholas, Katz, Lior, Katz, Leo, Kaur, Nirmal, Khanna, Reena, Kohout, Pavel, Lakatos, Peter, Larriva de los Reyes, Emmanuel, Lee, Robert, Leman, Bernard, Levchenko, Olena, Levine, Henry, Libanez Bessa Campelo Braga, Lúcia, Loftus, Edward, Lohdanidi, Tetiana, Longman, Randy, Lozano, Josefina, Maaser, Christian, Madi-Szabo, Laszlo, Malluta, Everson Fernando, Marshall, John, Martinez Silva, Francisca, Maynard, Kenneth, Meder, Agnieszka, Mehta, Chetan, Minarik, Peter, Mueller, Joachim, Mukewar, Shrikant, Nagy, Bela, Neiko, Vasyl, Neurath, Markus, Nichol, Brian, Novick, James, Pai, Nitin, Pandak, William, Panigrahi, Sarat, Pape, Ulrich-Frank, Paraná, Raymundo, Parekh, Nimisha, Patel, Bhaktasharan, Pecsi, Gyula, Peralta, Sergio, Pesta, Martin, Peterfai, Eva, Petruzzellis, Carlo, Petryka, Robert, Pica, Roberta, Piniella, Carlos, Pratha, Vijayalakshmi, Prochazka, Vlastimil, Prokopchuk, Sergey, Prystupa, Ludmyla, Puri, Amarender, Rainis, Tova, Ramesh Kumar, Bhashyakarla, Ramos Júnior, Odery, Rishko, Iaroslava, Ritter, Timothy, Robbins, Bryan, Rock, Elizabeth, Rodrigues Borba, Marcelo, Rodriguez, Miguel, Rozciecha, Jerzy, Ruiz Flores, Azalia Yuriria, Rydzewska, Grazyna, Safadi, Rifaat, Saibeni, Simone, Schirbel, Anja, Schmiegel, Wolff, Schnabel, Róbert, Schneider, Herbert, Segui, Armando, Seidelin, Jakob, Seidler, Ursula, Sellin, Joseph, Shafran, Ira, Shah, Saumin, Sheikh, Aasim, Sherman, Alex, Shirin, Haim, Shukla, Akash, Siddiqui, Firdous, Sike, Robert, Sood, Ajit, Stallmach, Andreas, Stanislavchuk, Mykola, Staun, Michael, Stein, Daniel, Steinberg, Alon, Steinhart, Hillary, Stifft, Jonathas, Tandon, Rakesh, Tantry, Vishwanath, Thiwan, Syed, Treiber, Matthias, Ulbrych, Jan, Valentine, John, Vasudeva, Rajeev, Vaughn, Byron, Velasco, Brenda, Vincze, Aron, Volfova, Miroslava, Waterman, Mattitiahu, Weiss, L. Michael, Wiesner, Elise, Williams, Alonzo, Witthoeft, Thomas, Wohlman, Robert, Wright, John, Yamamoto Furusho, Jesus Kazuo, Younes, Ziad, Yousuf, Khurshid, Zborivskyy, Yaroslav, Zeuzem, Stefan, Zhdan, Vyacheslav, Vermeire, Severine, Lakatos, Peter L, Kadva, Alysha, Tyrrell, Helen, Oh, Young S, Tole, Swati, Chai, Akiko, Pulley, Jennifer, Eden, Christopher, Zhang, Wenhui, and Feagan, Brian G

Published
2022
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6. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Author

Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., Barile L., Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., and Barile L.

Abstract

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be consider

Published
2022

7. Doxorubicin-induced cardiotoxicity enhance SARS-CoV-2 infection susceptibility in human cardiomyocytes

Author

Lazzarini, Edoardo, primary, Rendon-Angel, Azucena, additional, Bassi, Jessica Marcandalli, additional, Lodrini, Alessandra Maria, additional, Biemmi, Vanessa, additional, Balbi, Carolina, additional, Altomare, Claudia, additional, Bolis, Sara, additional, Ameri, Pietro, additional, Bollini, Sveva, additional, Perez, Laurent, additional, Rocchetti, Marcella, additional, and Barile, Lucio, additional

Published
2022
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8. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Author

Edoardo Lazzarini, Alessandra Maria Lodrini, Martina Arici, Sara Bolis, Sara Vagni, Stefano Panella, Azucena Rendon-Angel, Melissa Saibene, Alessia Metallo, Tiziano Torre, Giuseppe Vassalli, Pietro Ameri, Claudia Altomare, Marcella Rocchetti, Lucio Barile, Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, and Barile, L

Subjects
senescence, aging, Induced Pluripotent Stem Cells, Medicine (miscellaneous), Action Potentials, heart, Mice, Sarcoplasmic Reticulum, Induced pluripotent stem cell-derived cardiomyocyte, Animals, Humans, Calcium, Myocytes, Cardiac, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Cellular Senescence, Aged
Abstract

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans.

Published
2022

9. Protective role of cardiac progenitor cell-derived-exosomes in a new human model of ageing-induced cardiac dysfunction

Author

E Lazzarini, AM Lodrini, S Bolis, M Arici, S Vagni, S Panella, A Rendon Angel, T Torre, G Vassalli, P Ameri, C Altomare, M Rocchetti, and L Barile

Subjects
Physiology, Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Velux Stiftung Background Ageing of cardiomyocytes (CM) involves structural and functional adverse remodelling that finally could result in heart failure (HF) insurgence, which incidence rise along with age (1). Current medical therapies for HF may not always be tolerated in elder patients(2). Having shown that cardiac progenitor cells (CPCs) secrete nanoparticles named exosomes (EXO) enriched of cardioprotective factors(3,4), we are exploring EXO’s capacity to ameliorate senescence-derived modification into CMs. However, human models of in vitro cardiac aging are currently missing(5). Aim This study exploits CMs derived from human induced pluripotent stem cells (hiPSCs) as an in vitro model for cardiac senescence, that will be used as platform to characterize mechanisms involved in cardiac ageing and to test protective effect of CPC-derived EXO. Methods Patient-derived CPCs were reprogrammed into hiPSCs and subsequently expanded and differentiated into cardiomyocytes (hiPSC-CMs). Senescence-like phenotype was induced by short exposure (3 hours) to doxorubicin (DOX) at sub-lethal concentration (0.2 µM), followed by washing and medium change. Following DOX exposure, cells were exposed to EXO, derived from the purification of conditioned culture media of CPCs using an ultracentrifugation-based isolation method and quantified and sized using a NTA counter. Senescence induction was highlighted by protein and gene expression analysis and senescence-associated b-galactosidase (SA-β-gal) assay.Electrical activity of hiPSC-CMs was evaluated recording extracellular field potentials through multi-microelectrode arrays (MEA) and by single cell patch clamp. Metabolic features were analysed with western blot, real time RT-PCR and specific biochemical assays. Results DOX treatment in hiPSC-CMs induced senescence, as confirmed by activation of p21 and p16 pathways and increasing of SA-β-gal staining as compared to untreated cells (CTR). Biochemical and gene expression analysis revealed an increased ROS production and a reduction in mitochondrial potential, which drives a strong decrease in the ATP/AMP ratios. Real Time PCR analysis reveal an increased transcription of molecules related to the senescence associated secretory phenotype in DOX-CMs. Moreover, DOX-CMs showed impaired Ca++ handling, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence in comparison to CTR. EXO treatment mitigated the senescent phenotype induced by DOX, as shown by a decreased ROS induction, higher mitochondrial potential which drives a restored ATP/AMP ratio. Furthermore, DOX-induced QTc prolongation was prevented by EXO treatment. Conclusion Our hiPSC-CMs based cellular model recapitulates the phenotype of aged CMs in terms of senescence markers, electrical and metabolic proprieties. CPC-derived EXOs limit age-related modifications, highlighting the cardioprotective role of small molecules released by EXO.

Published
2022

12. Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study

Author

Vermeire, Severine, primary, Lakatos, Peter L, additional, Ritter, Timothy, additional, Hanauer, Stephen, additional, Bressler, Brian, additional, Khanna, Reena, additional, Isaacs, Kim, additional, Shah, Saumin, additional, Kadva, Alysha, additional, Tyrrell, Helen, additional, Oh, Young S, additional, Tole, Swati, additional, Chai, Akiko, additional, Pulley, Jennifer, additional, Eden, Christopher, additional, Zhang, Wenhui, additional, Feagan, Brian G, additional, Abraham, Philip, additional, Acir Crippa Júnior, Mauro, additional, Aguilar, Humberto, additional, Ahmed, Tasneem, additional, Altorjay, Istvan, additional, Andersen, Vibeke, additional, Arai, Ronen, additional, Arnold, Hays, additional, Ausk, Karlee, additional, Axler, Jeffrey, additional, Ayub, Kamran, additional, Balekuduru, Avinash, additional, Barbalaco Neto, Guerino, additional, Bassan, Isaac, additional, Behm, Brian, additional, Bekal, Pradeep, additional, Bhatia, Shobna, additional, Bod, Barnabas, additional, Brandão Mello, Carlos Eduardo, additional, Brandeburova, Julia, additional, Breedt, Johannes, additional, Chopey, Ivan, additional, Connor, Michael, additional, Corlin, Richard, additional, Cortez Hernandez, Carlos Alejandro, additional, De, Arijit, additional, de Sá Rolim, Alexander, additional, Di Felice Boratto, Sandra, additional, Dixon, Tyler, additional, Dourado Poli, Debora, additional, Dresner, David, additional, Du Vall, George Aaron, additional, Ebert, Matthias, additional, Ehehalt, Robert, additional, Ertan, Atilla, additional, Escarcega Valencia, Ruben, additional, Etzel, Jason, additional, Fallingborg, Jan, additional, Feagan, Brian, additional, Fedurco, Miroslav, additional, Fernandez Castro, Enrique, additional, Ferreira de Almeida Borges, Valéria, additional, Finklestein, Mark, additional, Fischer, Andreas, additional, Fleisher, Mark, additional, Flores Rendon, Angel Ricardo, additional, Fogel, Ronald, additional, Franceschi Junior, Osvaldo, additional, Freedland, Curtis, additional, Gatof, David, additional, Gill, Kanwar, additional, Glerup, Henning, additional, Gokak, Vardaraj, additional, Goldin, Eran, additional, Gomez Jaramillo, Hector Alejandro, additional, Gupta, Nitin, additional, Gurzo, Zoltan, additional, Gyrina, Olga, additional, Habeeb, Mohammed Aejaz, additional, Hardi, Robert, additional, Harlan, William, additional, Hemaidan, Ammar, additional, Heyman, Melvin, additional, Hoffmann, Peter, additional, Holderman, William, additional, Holtkamp-Endemann, Frank, additional, Horvat, Gyula, additional, Israeli, Eran, additional, Jankiel Miszputen, Sender, additional, Jensen, Søren, additional, Johnson, Kenneth, additional, Jones, Jennifer, additional, Junior, Osvaldo, additional, Kadleckova, Barbora, additional, Kalla, Mukesh, additional, Kallo, Zsuzsanna, additional, Karyotakis, Nicholas, additional, Katz, Lior, additional, Katz, Leo, additional, Kaur, Nirmal, additional, Kohout, Pavel, additional, Lakatos, Peter, additional, Larriva de los Reyes, Emmanuel, additional, Lee, Robert, additional, Leman, Bernard, additional, Levchenko, Olena, additional, Levine, Henry, additional, Libanez Bessa Campelo Braga, Lúcia, additional, Loftus, Edward, additional, Lohdanidi, Tetiana, additional, Longman, Randy, additional, Lozano, Josefina, additional, Maaser, Christian, additional, Madi-Szabo, Laszlo, additional, Malluta, Everson Fernando, additional, Marshall, John, additional, Martinez Silva, Francisca, additional, Maynard, Kenneth, additional, Meder, Agnieszka, additional, Mehta, Chetan, additional, Minarik, Peter, additional, Mueller, Joachim, additional, Mukewar, Shrikant, additional, Nagy, Bela, additional, Neiko, Vasyl, additional, Neurath, Markus, additional, Nichol, Brian, additional, Novick, James, additional, Pai, Nitin, additional, Pandak, William, additional, Panigrahi, Sarat, additional, Pape, Ulrich-Frank, additional, Paraná, Raymundo, additional, Parekh, Nimisha, additional, Patel, Bhaktasharan, additional, Pecsi, Gyula, additional, Peralta, Sergio, additional, Pesta, Martin, additional, Peterfai, Eva, additional, Petruzzellis, Carlo, additional, Petryka, Robert, additional, Pica, Roberta, additional, Piniella, Carlos, additional, Pratha, Vijayalakshmi, additional, Prochazka, Vlastimil, additional, Prokopchuk, Sergey, additional, Prystupa, Ludmyla, additional, Puri, Amarender, additional, Rainis, Tova, additional, Ramesh Kumar, Bhashyakarla, additional, Ramos Júnior, Odery, additional, Rishko, Iaroslava, additional, Robbins, Bryan, additional, Rock, Elizabeth, additional, Rodrigues Borba, Marcelo, additional, Rodriguez, Miguel, additional, Rozciecha, Jerzy, additional, Ruiz Flores, Azalia Yuriria, additional, Rydzewska, Grazyna, additional, Safadi, Rifaat, additional, Saibeni, Simone, additional, Schirbel, Anja, additional, Schmiegel, Wolff, additional, Schnabel, Róbert, additional, Schneider, Herbert, additional, Segui, Armando, additional, Seidelin, Jakob, additional, Seidler, Ursula, additional, Sellin, Joseph, additional, Shafran, Ira, additional, Sheikh, Aasim, additional, Sherman, Alex, additional, Shirin, Haim, additional, Shukla, Akash, additional, Siddiqui, Firdous, additional, Sike, Robert, additional, Sood, Ajit, additional, Stallmach, Andreas, additional, Stanislavchuk, Mykola, additional, Staun, Michael, additional, Stein, Daniel, additional, Steinberg, Alon, additional, Steinhart, Hillary, additional, Stifft, Jonathas, additional, Tandon, Rakesh, additional, Tantry, Vishwanath, additional, Thiwan, Syed, additional, Treiber, Matthias, additional, Ulbrych, Jan, additional, Valentine, John, additional, Vasudeva, Rajeev, additional, Vaughn, Byron, additional, Velasco, Brenda, additional, Vincze, Aron, additional, Volfova, Miroslava, additional, Waterman, Mattitiahu, additional, Weiss, L. Michael, additional, Wiesner, Elise, additional, Williams, Alonzo, additional, Witthoeft, Thomas, additional, Wohlman, Robert, additional, Wright, John, additional, Yamamoto Furusho, Jesus Kazuo, additional, Younes, Ziad, additional, Yousuf, Khurshid, additional, Zborivskyy, Yaroslav, additional, Zeuzem, Stefan, additional, and Zhdan, Vyacheslav, additional

Published
2022
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13. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Author

Lazzarini, Edoardo, primary, Lodrini, Alessandra Maria, additional, Arici, Martina, additional, Bolis, Sara, additional, Vagni, Sara, additional, Panella, Stefano, additional, Rendon-Angel, Azucena, additional, Saibene, Melissa, additional, Metallo, Alessia, additional, Torre, Tiziano, additional, Vassalli, Giuseppe, additional, Ameri, Pietro, additional, Altomare, Claudia, additional, Rocchetti, Marcella, additional, and Barile, Lucio, additional

Published
2022
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15. Ironía, parrhesía, cinismo y posverdad como despliegues de la intención del discurso

Author

RENDON ANGEL, JUAN EDILBERTO, MORENO MOSQUERA, VICTOR JULIAN, and PALACIO MESA, RUBEN DARIO

Subjects
Parrhesía, Intención, Ironía, Posverdad, Cinismo, Identidad
Abstract

El artículo, empleando un método de interpretación apoyado por revisión documental, sostiene que, al tener en cuanta la intención, no es posible un discurso que sea simultáneamente político e irónico. Tiene cinco secciones: primera, un análisis de la postura que asume el empleo de la ironía en el discurso político; segunda, una semblanza del ironista y su presencia en política como problemática; tercera, la función o utilidad negativa y privada de la ironía y su impropiedad política; cuarta, tres modos 2 propios del discurso político que excluyen y reemplazan la ironía: la parrhesía, el cinismo y la posverdad; y concluye explicando la inadecuación política de la ironía. Tonos Digital

Published
2021

17. S1349 Impact of Chronic Nausea and Vomiting Syndrome on Work Productivity and Quality of Life: A Prospective Case-Control Study

Author

Felix Tellez, Francisco Alejandro, primary, Leon Martinez, Antonio A., additional, Picazo Mendoza, Denisse Alejandra, additional, Martínez, Melissa Encarnación, additional, Coeto Cano, Ana Maria, additional, Lugo Vences, Francisco Daniel, additional, Sandoval Colin, Daniel Eduardo, additional, Ramirez, Ricardo Santiago, additional, and Flores Rendon, Angel Ricardo, additional

Published
2020
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18. S0504 Impact of Chronic Constipation on Economic Status and Work Productivity: A Prospective Case-Control Study

Author

Felix Tellez, Francisco Alejandro, primary, Leon Martinez, Antonio A., additional, Picazo Mendoza, Denisse Alejandra, additional, Martínez, Melissa Encarnación, additional, Coeto Cano, Ana Maria, additional, Lugo Vences, Francisco Daniel, additional, Sandoval Colin, Daniel Eduardo, additional, Flores Rendon, Angel Ricardo, additional, and Ramirez, Ricardo Santiago, additional

Published
2020
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19. La metáfora: transformación y cambio de escenario a partir de su proceso redescriptivo (II). The metaphor: transformation and change of scenery from its re-descriptive process (II)

Author

rendon angel, juan edilberto

Subjects
metafora, hermeneutica, redescripcion, literatura, identidad personal
Abstract

Este artículo sigue la noción deubicuidad del lenguaje para proponer la metáfora como su mecanismo de renovación redescriptiva, comenzando con una crítica a su papel como simple figura literaria y llevando su influencia semántica hasta el punto de convertirla en la fuerza que permite laapertura hermenéutica entre las obras arte, particularmente las producidas por la literatura, y sus lectores, gracias a una relación peculiar que los involucra y hace posible que modifiquen el complejo tejido de palabras que los lectores son al vitalizar las obras ampliando su horizonte hermenéutico y dándoles la posibilidad de que también hagan una obra de arte de su identidad al lograr un estilo original. La metáfora es, entonces, el estímulo que permite toda renovación y cambio de perspectiva en todas las regiones del lenguaje, desde las certezas científicas más fuertes hasta los estados de ánimo poéticos más pasajeros. This article follows the notion of ubiquity of language to propose the metaphor like its mechanism of re-descriptive renovation, beginning with a critique of its role as a mere literary figure and leading its semantic influence to the point where it became the force that allows the opening of hermeneutics between art works, particularly those produced by literature and its readers, thanks to a special relationship that involves them and makes it possible to modify the complex web of words that readers are when they revitalize the works expanding their hermeneutic horizons and giving them the possibility also to make an art work of their identity to obtain an original style. The metaphor is, then, the stimulus that allows any renovation and change of perspective in all areas of language, from the strongest scientific certainty to the most fleeting poetic moods.

Published
2010

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