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2. Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes

Author

Vicencio, Jeremy, Sánchez-Bolaños, Carlos, Moreno-Sánchez, Ismael, Brena, David, Vejnar, Charles E., Kukhtar, Dmytro, Ruiz-López, Miguel, Cots-Ponjoan, Mariona, Rubio, Alejandro, Melero, Natalia Rodrigo, Crespo-Cuadrado, Jesús, Carolis, Carlo, Pérez-Pulido, Antonio J., Giráldez, Antonio J., Kleinstiver, Benjamin P., Cerón, Julián, and Moreno-Mateos, Miguel A.

Published
2022
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7. Supplementary fig 2 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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8. Suplementary fig 3 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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9. Supplementary fig 5 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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10. Supplementary figure 1 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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11. Supplementary data from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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12. Supplementary fig 4 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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14. Relación entre el nivel de actividad física y el rendimiento académico en estudiantes de una institución universitaria: Estudio multicéntrico

Author

Cerón, Julián D., Gonzalez Marmolejo, Wilson, Mora Rojas, Diana Liceth, Fernandez Barona, Esther Julia, Cerón, Julián D., Gonzalez Marmolejo, Wilson, Mora Rojas, Diana Liceth, and Fernandez Barona, Esther Julia

Abstract

Physical activity (PA) may influence the academic performance of university students. Scientific studies have identified that university students practice little physical activity and exhibit sedentary habits that affect the acquisition of healthy behaviors and influence their academic performance. Main objective: To determine the relationship between the level of physical activity and academic performance in students of a university institution. Methodology: 486 students from a university institution with campuses in four Colombian cities participated. The research approach was quantitative, cross-sectional and descriptive. The International Physical Activity Questionnaire (IPAQ), a sociodemographic characterization questionnaire and grade point average as an indicator of academic performance were used. Results: Women perform more physical activity of mild intensity while men perform more physical activity of moderate intensity; students belonging to low socioeconomic strata have a mild level of physical activity, while students belonging to the middle or high strata tend to have mostly a moderate level of physical activity. It was found that having a moderate or vigorous level of physical activity increases twice the possibility of a student obtaining a GPA higher than 3.7 (on a scale of 0 - 5). Conclusion: There is a positive relationship between the level of physical activity and academic performance, reflecting the need to sensitize students to the importance of physical activity., La actividad física (AF) puede influir en el rendimiento académico de estudiantes universitarios. Estudios científicos han identificado que los estudiantes universitarios practican poca actividad física y presentan hábitos sedentarios que afectan la adquisición de comportamientos saludables e influyen en sus logros académicos. Objetivo principal: Determinar la relación entre el nivel de actividad física y el rendimiento académico en estudiantes de una institución universitaria. Metodología: Participaron 486 estudiantes de una institución universitaria, con sedes en cuatro ciudades de Colombia, Enfoque de investigación cuantitativo, de corte transversal y de tipo descriptivo. Se utilizó el cuestionario internacional de actividad física (IPAQ), un cuestionario de caracterización sociodemográfico y el promedio de calificaciones como indicador del rendimiento académico. Resultado: Las mujeres realizan más actividad física de intensidad leve mientras que los hombres realizan más actividad física de intensidad moderada; los estudiantes pertenecientes a estratos socioeconómicos bajos tienen un nivel de actividad física leve, mientras que estudiantes pertenecientes a los estratos medios o altos suelen tener en su mayoría un nivel de actividad física moderada. Se encontró que tener un nivel de actividad física moderada o vigorosa aumenta dos veces la posibilidad de que un estudiante obtenga un promedio académico superior a 3.7 (en una escala de 0 - 5).Conclusión: Existe una relación positiva entre el nivel de actividad física y el rendimiento académico, reflejando la necesidad de sensibilizar a los estudiantes sobre la importancia de realizar actividad física.

Published
2023

15. Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, ALBA Synchrotron, Universidad Autónoma de Barcelona, Consejo Superior de Investigaciones Científicas (España), Srinivasan, Sumithra Y., Alvarez-Illera, Pilar, Kukhtar, Dmytro, Benseny-Cases, Núria, Cerón, Julián, Álvarez. Javier, Fonteriz, Rosalba I., Montero, Mayte, Laromaine, Anna, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, ALBA Synchrotron, Universidad Autónoma de Barcelona, Consejo Superior de Investigaciones Científicas (España), Srinivasan, Sumithra Y., Alvarez-Illera, Pilar, Kukhtar, Dmytro, Benseny-Cases, Núria, Cerón, Julián, Álvarez. Javier, Fonteriz, Rosalba I., Montero, Mayte, and Laromaine, Anna

Abstract

Experimental studies and clinical trials of nanoparticles for treating diseases are increasing continuously. However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans (C. elegans) can bridge the gap between in vitro and vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes’ pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs and polypyrrole nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs’ biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegans in two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegans offers a simple system to test drugs and nanoparticles, as elucidated through Ppy NPs.

Published
2023

16. Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles [Dataset]

Author

Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72], Srinivasan, Sumithra Y., Alvarez-Illera, Pilar, Kukhtar, Dmytro, Benseny-Cases, Núria, Cerón, Julián, Álvarez. Javier, Fonteriz, Rosalba I., Montero, Mayte, Laromaine, Anna, Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72], Srinivasan, Sumithra Y., Alvarez-Illera, Pilar, Kukhtar, Dmytro, Benseny-Cases, Núria, Cerón, Julián, Álvarez. Javier, Fonteriz, Rosalba I., Montero, Mayte, and Laromaine, Anna

Abstract

Experimental studies and clinical trials of nanoparticles for treating diseases are increasing continuously. However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans (C. elegans) can bridge the gap between in vitro and vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes’ pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs and polypyrrole nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs’ biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegans in two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegans offers a simple system to test drugs and nanoparticles, as elucidated through Ppy NPs.

Published
2023

20. Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes

Author

Generalitat de Catalunya, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Universidad Pablo de Olavide, Ministerio de Asuntos Económicos y Transformación Digital (España), Junta de Andalucía, Consejo Superior de Investigaciones Científicas (España), Fundación la Caixa, European Commission, Consejo Nacional de Ciencia y Tecnología (México), National Institutes of Health (US), Vicencio, Jeremy, Sánchez-Bolaños, Carlos, Moreno-Sánchez, Ismael, Brena, David, Vejnar, Charles E., Kukhtar, Dmytro, Ruiz-López, Miguel, Cots-Ponjoan, Mariona, Rubio, Alejandro, Rodrigo Melero, Natalia, Crespo-Cuadrado, Jesús, Carolis, Carlo, Pérez-Pulido, Antonio J., Giraldez, Antonio J., Kleinstiver, Benjamin P., Cerón, Julián, Moreno-Mateos, Miguel A., Generalitat de Catalunya, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Universidad Pablo de Olavide, Ministerio de Asuntos Económicos y Transformación Digital (España), Junta de Andalucía, Consejo Superior de Investigaciones Científicas (España), Fundación la Caixa, European Commission, Consejo Nacional de Ciencia y Tecnología (México), National Institutes of Health (US), Vicencio, Jeremy, Sánchez-Bolaños, Carlos, Moreno-Sánchez, Ismael, Brena, David, Vejnar, Charles E., Kukhtar, Dmytro, Ruiz-López, Miguel, Cots-Ponjoan, Mariona, Rubio, Alejandro, Rodrigo Melero, Natalia, Crespo-Cuadrado, Jesús, Carolis, Carlo, Pérez-Pulido, Antonio J., Giraldez, Antonio J., Kleinstiver, Benjamin P., Cerón, Julián, and Moreno-Mateos, Miguel A.

Abstract

The requirement for Cas nucleases to recognize a specific PAM is a major restriction for genome editing. SpCas9 variants SpG and SpRY, recognizing NGN and NRN PAMs, respectively, have contributed to increase the number of editable genomic sites in cell cultures and plants. However, their use has not been demonstrated in animals. Here we study the nuclease activity of SpG and SpRY by targeting 40 sites in zebrafish and C. elegans. Delivered as mRNA-gRNA or ribonucleoprotein (RNP) complexes, SpG and SpRY were able to induce mutations in vivo, albeit at a lower rate than SpCas9 in equivalent formulations. This lower activity was overcome by optimizing mRNA-gRNA or RNP concentration, leading to mutagenesis at regions inaccessible to SpCas9. We also found that the CRISPRscan algorithm could help to predict SpG and SpRY targets with high activity in vivo. Finally, we applied SpG and SpRY to generate knock-ins by homology-directed repair. Altogether, our results expand the CRISPR-Cas targeting genomic landscape in animals.

Published
2022

21. BAP1 Malignant Pleural Mesothelioma Mutations in Caenorhabditis elegans Reveal Synthetic Lethality between ubh-4 / BAP1 and the Proteasome Subunit rpn-9 / PSMD13.

Author

Martínez-Fernández, Carmen, Jha, Sweta, Aliagas, Elisabet, Holmberg, Carina I., Nadal, Ernest, and Cerón, Julián

Subjects
CAENORHABDITIS elegans, MISSENSE mutation, GENETIC testing, TUMOR suppressor genes, MESOTHELIOMA, CRISPRS, GENETIC mutation
Abstract

The deubiquitinase BAP1 (BRCA1-associated protein 1) is associated with BAP1 tumor predisposition syndrome (TPDS). BAP1 is a tumor suppressor gene whose alterations in cancer are commonly caused by gene mutations leading to protein loss of function. By CRISPR-Cas, we have generated mutations in ubh-4, the BAP1 ortholog in Caenorhabditis elegans, to model the functional impact of BAP1 mutations. We have found that a mimicked BAP1 cancer missense mutation (UBH-4 A87D; BAP1 A95D) resembles the phenotypes of ubh-4 deletion mutants. Despite ubh-4 being ubiquitously expressed, the gene is not essential for viability and its deletion causes only mild phenotypes without affecting 20S proteasome levels. Such viability facilitated an RNAi screen for ubh-4 genetic interactors that identified rpn-9, the ortholog of human PSMD13, a gene encoding subunit of the regulatory particle of the 26S proteasome. ubh-4[A87D], similarly to ubh-4 deletion, cause a synthetic genetic interaction with rpn-9 inactivation affecting body size, lifespan, and the development of germ cells. Finally, we show how ubh-4 inactivation sensitizes animals to the chemotherapeutic agent Bortezomib, which is a proteasome inhibitor. Thus, we have established a model to study BAP1 cancer-related mutations in C. elegans, and our data points toward vulnerabilities that should be studied to explore therapeutic opportunities within the complexity of BAP1 tumors. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes

Author

Vicencio, Jeremy, primary, Sánchez-Bolaños, Carlos, additional, Moreno-Sánchez, Ismael, additional, Brena, David, additional, Kukhtar, Dmytro, additional, Ruiz-López, Miguel, additional, Cots-Ponjoan, Mariona, additional, Vejnar, Charles E., additional, Rubio, Alejandro, additional, Melero, Natalia Rodrigo, additional, Carolis, Carlo, additional, Pérez-Pulido, Antonio J., additional, Giráldez, Antonio J., additional, Kleinstiver, Benjamin P., additional, Cerón, Julián, additional, and Moreno-Mateos, Miguel A., additional

Published
2021
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25. Fluorizoline-induced apoptosis requires prohibitins in nematodes and human cells

Author

Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), European Research Council, Junta de Andalucía, Instituto de Salud Carlos III, European Commission, Universidad de Barcelona, Generalitat de Catalunya, Saura-Esteller, José, Sánchez-Vera, Ismael, Núñez-Vázquez, Sonia, Jabalquinto-Carrasco, Judith, Cosialls, Ana M., Mendive-Tapia, Lorena, Kukhtar, Dmytro, Martínez-Bueno, Manuel, Lavilla, Rodolfo, Cerón, Julián, Artal-Sanz, Marta, Pons, Gabriel, Iglesias-Serret, Daniel, Gil, Joan, Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), European Research Council, Junta de Andalucía, Instituto de Salud Carlos III, European Commission, Universidad de Barcelona, Generalitat de Catalunya, Saura-Esteller, José, Sánchez-Vera, Ismael, Núñez-Vázquez, Sonia, Jabalquinto-Carrasco, Judith, Cosialls, Ana M., Mendive-Tapia, Lorena, Kukhtar, Dmytro, Martínez-Bueno, Manuel, Lavilla, Rodolfo, Cerón, Julián, Artal-Sanz, Marta, Pons, Gabriel, Iglesias-Serret, Daniel, and Gil, Joan

Abstract

We previously showed that fluorizoline, a fluorinated thiazoline compound, binds to both subunits of the mitochondrial prohibitin (PHB) complex, PHB1 and PHB2, being the expression of these proteins required for fluorizoline-induced apoptosis in mouse embryonic fibroblasts. To investigate the conservation of this apoptotic mechanism, we studied the effect of PHB downregulation on fluorizoline activity on two human cell lines, HEK293T and U2OS. Then, we asked whether PHBs mediate the effect of fluorizoline in a multicellular organism. Interestingly, reduced levels of PHBs in the human cells impaired the induction of apoptosis by fluorizoline. We observed that fluorizoline has a detrimental dose-dependent effect on the development and survival of the nematode model Caenorhabditis elegans. Besides, such effects of fluorizoline treatment in living nematodes were absent in PHB mutants. Finally, we further explored the apoptotic pathway triggered by fluorizoline in human cell lines. We found that the BH3-only proteins NOXA, BIM and PUMA participate in fluorizoline-induced apoptosis and that the induction of NOXA and PUMA is dependent on PHB expression.

Published
2021

26. Additional file 8 of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Abstract

Additional file 8: Co-AP assays involving MRG15 and MRGX. Supplementary Figure 4 containing results of co-AP assays involving MRG15 and MRGX. (PDF 1 MB)

Published
2020
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27. Additional file 7 of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Subjects
ComputingMethodologies_PATTERNRECOGNITION, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Hardware_INTEGRATEDCIRCUITS, Hardware_REGISTER-TRANSFER-LEVELIMPLEMENTATION
Abstract

Additional file 7: Co-AP and co-IP assays. Supplementary Figure 3 containing results of the co-AP and co-IP assays. (PDF 3 MB)

Published
2020
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28. Additional file 16 of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Subjects
Data_FILES
Abstract

Authors’ original file for figure 2

Published
2020
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29. Additional file 5 of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Subjects
fungi
Abstract

Additional file 5: Gene co-expression. Supplementary Figure 1 containing results of the gene co-expression analysis. (PDF 638 KB)

Published
2020
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30. Additional file 9 of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, nutritional and metabolic diseases
Abstract

Additional file 9: siRNA-mediated depletion of MRG15 and FANCD2 monoubiquitinylation. Supplementary Figure 5 containing results of siRNA-mediated depletion of MRG15 and FANCD2 monoubiquitinylation. (PDF 1 MB)

Published
2020
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31. Additional file of Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Subjects
skin and connective tissue diseases
Abstract

Additional file of Exploring the link between MORF4L1 and risk of breast cancer

Published
2020
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33. Ancestral function of Inhibitors-of-kappaB regulatesCaenorhabditis elegansdevelopment

Author

Brena, David, primary, Bertran, Joan, additional, Porta-de-la-Riva, Montserrat, additional, Guillén, Yolanda, additional, Cornes, Eric, additional, Kukhtar, Dmytro, additional, Campos-Vicens, Lluís, additional, Fernández, Lierni, additional, Pecharroman, Irene, additional, Garcia-López, Albert, additional, Islam, Khademul, additional, Marruecos, Laura, additional, Bigas, Anna, additional, Cerón, Julián, additional, and Espinosa, Lluís, additional

Published
2020
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36. Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-de-la-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Lázaro, Conxi, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, Evans, D Gareth, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Ong, Kai-Ren, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Chen, Xiaoqing, Beesley, Jonathan, Rookus, Matti A, Verhoef, Senno, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, van Os, Theo A, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Wang, Xianshu, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Janavicius, Ramunas, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, de Pauw, Antoine, Bignon, Yves-Jean, Uhrhammer, Nancy, Peyrat, Jean-Philippe, Vennin, Philippe, Ferrer, Sandra Fert, Collonge-Rame, Marie-Agnès, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel

Published
2011
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37. Genetic and cellular sensitivity of to the chemotherapeutic agent cisplatin

Author

García-Rodríguez, Francisco Javier, Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda-Vizuete, Antonio, Villanueva, Alberto, Cerón, Julián, Sub Developmental Biology, and Developmental Biology

Subjects
RNA-seq, Cisplatin, Caenorhabditis elegans
Abstract

Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties, namely the onset of resistance to the drug and the cytotoxic effect in patients. Here, we used Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause of cisplatin-induced infertility. RNA sequencing data indicate that cisplatin triggers a systemic stress response, in which DAF-16/FOXO and SKN-1/NRF2, two conserved transcription factors, are key regulators. We determined that inhibition of the DNA damage-induced apoptotic pathway does not confer cisplatin protection to the animal. However, mutants for the pro-apoptotic BH3-only gene ced-13 are sensitive to cisplatin, suggesting a protective role of the intrinsic apoptotic pathway. Finally, we demonstrated that our system can also be used to identify mutations providing resistance to cisplatin and therefore potential biomarkers of innate cisplatin-refractory patients. We show that mutants for the redox regulator trxr-1, ortholog of the mammalian thioredoxin reductase 1 TRXR1, display cisplatin resistance. By CRISPR/Cas9, we determined that such resistance relies on the presence of the single selenocysteine residue in TRXR-1.This article has an associated First Person interview with the first author of the paper.

Published
2018

38. 'Identificacion, modelado y control del proceso planta piloto de destilacion para produccion de alcohol carburante'

Author

González, Jesús Alberto, Machuca, Fiderman, Franco Mejía, Edinson, Acevedo, Jairo Andrés, Franco, Diego Fernando, Espítia Serrato, Erick Salomón, and Cruz Cerón, Julián Ramiro de la

Subjects
Destilación, Alcohol carburante, Proceso de producción, Automatización, Planta piloto, Modelado
Abstract

El proceso de producción de alcohol carburante de la región demanda grandes retos desde el punto de vista de la automatización; las exigencias de altos consumos de energía requieren el estudio de estrategias de control avanzadas que a pesar de existir información de investigaciones para columnas de destilación, no se encuentran implementadas en las plantas de producción de alcohol carburante de la región. Para obtener estrategias de control es necesario disponer de buenos modelos que reflejen todos los modos dinámicos, para tal efecto en este proyecto se procede a estudiar y diseñar los experimentos para realizar la identificación de la planta a partir de datos experimentales. Simultáneamente se estudian las estrategias de control las cuales son verificadas mediante corridas de simulación. La investigación se desarrolla alrededor de una planta de destilación binaria (PDB) de etanol y agua existente en el Laboratorio de Procesos Químicos de la Facultad de Ingeniería; aquí, la separación de la mezcla etanol-agua se realiza en una columna de platos perforados, la cual es un cilindro vertical en el que se lleva a cabo la ebullición de los componentes de la mezcla. La investigación se orientó al modelado, identificación y simulación, aplicado a la PDB, se analizó el comportamiento estático y dinámico de diferentes variables físico-químicas que intervienen en el proceso, se analizaron las estrategias o configuraciones para el control de las columnas de destilación binaria, se realizó un análisis de sensibilidad, se diseñaron controladores por desacople para las tres configuraciones más relevantes, se analizó el consumo energético para cada uno de los escenarios, se diseñaron las señales de prueba para la identificación fuera de línea, se mejoró el sensado, transmisión y actuación de la planta, se instaló el software de mando y control, un Controlador Lógico Programable y el sistema Scada. Por falta de presupuesto no fue posible la Automatización al 100%, lo que imposibilitó la implementación de muchas de las investigaciones desarrolladas en este proyecto. Sin embargo, los resultados alcanzados permitieron establecer estrategias para ser consideradas en las plantas de destilación de la región. Con la divulgación de los resultados obtenidos al sector productivo se espera fortalecer el acercamiento entre la universidad y los ingenios productores de alcohol, para establecer lazos de cooperación técnica y científica.

Published
2018

42. Genetic and cellular sensitivity of Caenorhabditis elegans to the chemotherapeutic agent cisplatin

Author

Instituto de Biomedicina de Sevilla (IBIS), García-Rodríguez, Francisco Javier, Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda Vizuete, Antonio, Villanueva, Alberto, Cerón, Julián, Instituto de Biomedicina de Sevilla (IBIS), García-Rodríguez, Francisco Javier, Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda Vizuete, Antonio, Villanueva, Alberto, and Cerón, Julián

Abstract

Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties, namely the onset of resistance to the drug and the cytotoxic effect in patients. Here, we used Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause of cisplatin-induced infertility. RNA sequencing data indicate that cisplatin triggers a systemic stress response, in which DAF-16/FOXO and SKN-1/NRF2, two conserved transcription factors, are key regulators. We determined that inhibition of the DNA damage-induced apoptotic pathway does not confer cisplatin protection to the animal. However, mutants for the pro-apoptotic BH3-only gene ced-13 are sensitive to cisplatin, suggesting a protective role of the intrinsic apoptotic pathway. Finally, we demonstrated that our system can also be used to identify mutations providing resistance to cisplatin and therefore potential biomarkers of innate cisplatin-refractory patients. We show that mutants for the redox regulator trxr-1, ortholog of the mammalian thioredoxin reductase 1 TRXR1, display cisplatin resistance. By CRISPR/Cas9, we determined that such resistance relies on the presence of the single selenocysteine residue in TRXR-1.

Published
2018

43. Genetic and cellular sensitivity of to the chemotherapeutic agent cisplatin

Author

Sub Developmental Biology, Developmental Biology, García-Rodríguez, Francisco Javier, Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda-Vizuete, Antonio, Villanueva, Alberto, Cerón, Julián, Sub Developmental Biology, Developmental Biology, García-Rodríguez, Francisco Javier, Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda-Vizuete, Antonio, Villanueva, Alberto, and Cerón, Julián

Published
2018

44. Genetic and cellular sensitivity of Caenorhabditis elegans to the chemotherapeutic agent cisplatin

Author

Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Netherlands Organization for Scientific Research, Sociedad Española de Oncología Médica, Consejo Nacional de Ciencia y Tecnología (México), García-Rodríguez, Francisco J., Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda-Vizuete, Antonio, Villanueva, Alberto, Cerón, Julián, Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Netherlands Organization for Scientific Research, Sociedad Española de Oncología Médica, Consejo Nacional de Ciencia y Tecnología (México), García-Rodríguez, Francisco J., Martínez-Fernández, Carmen, Brena, David, Kukhtar, Dmytro, Serrat, Xènia, Nadal, Ernest, Boxem, Mike, Honnen, Sebastian, Miranda-Vizuete, Antonio, Villanueva, Alberto, and Cerón, Julián

Abstract

Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties, namely the onset of resistance to the drug and the cytotoxic effect in patients. Here, we used Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause of cisplatin-induced infertility. RNA sequencing data indicate that cisplatin triggers a systemic stress response, in which DAF-16/FOXO and SKN-1/NRF2, two conserved transcription factors, are key regulators. We determined that inhibition of the DNA damage-induced apoptotic pathway does not confer cisplatin protection to the animal. However, mutants for the pro-apoptotic BH3-only gene ced-13 are sensitive to cisplatin, suggesting a protective role of the intrinsic apoptotic pathway. Finally, we demonstrated that our system can also be used to identify mutations providing resistance to cisplatin and therefore potential biomarkers of innate cisplatin-refractory patients. We show that mutants for the redox regulator trxr-1, ortholog of the mammalian thioredoxin reductase 1 TRXR1, display cisplatin resistance. By CRISPR/Cas9, we determined that such resistance relies on the presence of the single selenocysteine residue in TRXR-1.

Published
2018

45. Orthoxenografts of testicular germ cell tumors demonstrate genomic changes associated with cisplatin resistance and identify PDMP as a resensitizing agent

Author

Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundació La Marató de TV3, Generalitat de Catalunya, European Commission, Piulats, Josep Maria, Vidal, August, García-Rodríguez, Francisco J., Muñoz, Clara, Nadal, Marga, Moutinho, Catia, Martínez-Iniesta, María, Mora, Josefina, Figueras, Agnès, Guinó, Elisabet, Padullés, Laura, Aytes, Álvaro, Molleví, David G., Puertas, Sara, Martínez-Fernández, Carmen, Castillo, Wilmar, Juliachs, Merce, Moreno, Víctor, Muñoz, Purificación, Stefanovic, Milica, Pujana, Miguel Ángel, Condom, Enric, Esteller, Manel, Germà, Josep R., Capella, Gabriel, Farré, Lourdes, Morales, Albert, Viñals, Francesc, García-del-Muro, Xavier, Cerón, Julián, Villanueva, Alberto, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundació La Marató de TV3, Generalitat de Catalunya, European Commission, Piulats, Josep Maria, Vidal, August, García-Rodríguez, Francisco J., Muñoz, Clara, Nadal, Marga, Moutinho, Catia, Martínez-Iniesta, María, Mora, Josefina, Figueras, Agnès, Guinó, Elisabet, Padullés, Laura, Aytes, Álvaro, Molleví, David G., Puertas, Sara, Martínez-Fernández, Carmen, Castillo, Wilmar, Juliachs, Merce, Moreno, Víctor, Muñoz, Purificación, Stefanovic, Milica, Pujana, Miguel Ángel, Condom, Enric, Esteller, Manel, Germà, Josep R., Capella, Gabriel, Farré, Lourdes, Morales, Albert, Viñals, Francesc, García-del-Muro, Xavier, Cerón, Julián, and Villanueva, Alberto

Abstract

[Purpose] To investigate the genetic basis of cisplatin resistance as efficacy of cisplatin-based chemotherapy in the treatment of distinct malignancies is often hampered by intrinsic or acquired drug resistance of tumor cells., [Experimental Design] We produced 14 orthoxenograft transplanting human nonseminomatous testicular germ cell tumors (TGCT) in mice, keeping the primary tumor features in terms of genotype, phenotype, and sensitivity to cisplatin. Chromosomal and genetic alterations were evaluated in matched cisplatin-sensitive and their counterpart orthoxenografts that developed resistance to cisplatin in nude mice., [Results] Comparative genomic hybridization analyses of four matched orthoxenografts identified recurrent chromosomal rearrangements across cisplatin-resistant tumors in three of them, showing gains at 9q32-q33.1 region. We found a clinical correlation between the presence of 9q32-q33.1 gains in cisplatin-refractory patients and poorer overall survival (OS) in metastatic germ cell tumors. We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain. Moreover, other four genes (GCS, ZNF883, CTR1, and FLJ31713) were deregulated in all five resistant tumors independently of the 9q32-q33.1 amplification. RT-PCRs in tumors and functional analyses in Caenorhabditis elegans (C. elegans) indicate that the influence of 9q32-q33.1 genes in cisplatin resistance can be driven by either up- or downregulation. We focused on glucosylceramide synthase (GCS) to demonstrate that the GCS inhibitor DL-threo-PDMP resensitizes cisplatin-resistant germline-derived orthoxenografts to cisplatin, [Conclusions] Orthoxenografts can be used preclinically not only to test the efficiency of drugs but also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance.

Published
2018

47. Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, additional, García-Rodríguez, Francisco J., additional, Muñoz, Clara, additional, Nadal, Marga, additional, Moutinho, Catia, additional, Martínez-Iniesta, María, additional, Mora, Josefina, additional, Figueras, Agnés, additional, Guinó, Elisabet, additional, Padullés, Laura, additional, Aytés, Àlvaro, additional, Molleví, David G., additional, Puertas, Sara, additional, Martínez-Fernández, Carmen, additional, Castillo, Wilmar, additional, Juliachs, Merce, additional, Moreno, Victor, additional, Muñoz, Purificación, additional, Stefanovic, Milica, additional, Pujana, Miguel A., additional, Condom, Enric, additional, Esteller, Manel, additional, Germà, Josep R., additional, Capella, Gabriel, additional, Farré, Lourdes, additional, Morales, Albert, additional, Viñals, Francesc, additional, García-del-Muro, Xavier, additional, Cerón, Julián, additional, and Villanueva, Alberto, additional

Published
2018
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48. Genetic and cellular sensitivity of Caenorhabditis elegans to the chemotherapeutic agent cisplatin

Author

García-Rodríguez, Francisco Javier, primary, Martínez-Fernández, Carmen, additional, Brena, David, additional, Kukhtar, Dmytro, additional, Serrat, Xènia, additional, Nadal, Ernest, additional, Boxem, Mike, additional, Honnen, Sebastian, additional, Miranda–Vizuete, Antonio, additional, Villanueva, Alberto, additional, and Cerón, Julián, additional

Published
2018
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49. Effect of the diet type and temperature on theC. eleganstranscriptome

Author

Gómez-Orte, Eva, primary, Cornes, Eric, additional, Zheleva, Angelina, additional, Sáenz-Narciso, Beatriz, additional, de Toro, María, additional, Iñiguez, María, additional, López, Rosario, additional, San-Juan, Juan-Félix, additional, Ezcurra, Begoña, additional, Sacristán, Begoña, additional, Sánchez-Blanco, Adolfo, additional, Cerón, Julián, additional, and Cabello, Juan, additional

Published
2017
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