Mechanisms of transcriptional regulation mediated by "IXR1" in yeast

[Resumen] Ixrl es una proteína de Saccharomyces cerevisiae previamente relacionada con la respuesta a hipoxia y a estrés oxidativo, así como en la resistencia a cisplatino. El trabajo presentado en esta Tesis permite ampliar el conocimiento de los mecanismos de regulación mediante los cuales Ixr1 participa en estos procesos. Se realizaron experimentos de transcriptómica y localización de los sitios de unión de Ixr1 a lo largo del genoma y sus características. Los resultados mostraron que Ixr1 participa en la regulación de la asimilación de azufre y en el metabolismo de compuestos que contienen azufre, de aminoácidos de cadena larga y en diversas etapas de la biogénesis de ribosomas. La implicación de Ixr1 en el control energético de la célula es un factor indispensable para explicar la adaptación de la célula a los niveles de oxígeno o al daño producido por cisplatino. La caracterización bioquímica de Ixr1, acompañada de análisis funcionales de distintos motivos de la proteína, mostró que su unión al ADN se produce mediante los HMG-box en tándem, según un modelo secuencial con cooperatividad positiva. Además, las regiones que flanquean a los dominos de unión a ADN presentan un alto grado de desorden estructural V con tendencia a la agregación en forma de fibras amiloides, lo que sugiere la posibilidad de que Ixr1 pueda actuar como prion.[Resumo] Ixrl é unha proteína de Saccharomyces cerevisiae anteriormente relacionada coa resposta á hipoxia e frente ó estrés oxidativo, así como na resistencia a cisplatino. O traballo presentado nesta Tese permite ampliar o naso eoilecemento dos mecanismos de regulación polos cales Ixrl participa nestes procesos. Experimentos de transcriptomica e localización dos sitios de unión de Ilxr1 ao langa do xenoma e as súas características foron realizados. Os resultados mostraron que Ixrl participa na regulación da asimilación de xofre e do metabolismo de compostos que conteñen xofre, aminoácidos de cadea langa e en varios estadios da bioxénese dos ribosomas. A implicación de Ixrl no control da enerxética da célula é indispensable para explicar a adaptación da célula os niveis de osrxeno ou os danos por cisplatino. A caracterización bioquímica de Ixrl, acompañada polo análise funcional de varios motivos proteicos, mostrou que a súa unión ao AON acorre a través dos seus dominios HMG-box, seguindo un modelo secuencial con cooperatividade positiva. Ademais, as rexi6ns que flanquean os dominas de unión ao AON teñen un elevado grao de desorde estrutural e tendencia a agregar en forma de amiloides, suxerindo a posibilidade de que Ixrl poida actuar coma un prion.[Abstract] Ixrl is a protein from Saccharomyces cerevisiae that was previouslV involved in the response to hypoxia and oxidative stress, as well as in cisplatin resistance. The work presented here allows expanding the knowledge regarding the regulatory mechanisms by which Ixrl participates in these processes. Transcriptome analyses and experiments to identify the position and charaeteristics of Ixrl binding sites along the genome were pertormed. They showed that Ixrl participates in the regulation of sulphur assimilation, the metabolism of sulphur compounds, long chain amino acids and in diverse steps of ribosome biogenesis. The implication of Ixrl on the control of cellular energetics is a crucial faetor for explaining cellular adaptation to oxygen levels or cellular damage produced bV cisplatin. Biochemical characterization of Ixrl, accompanied by funetional analvsis of different domains in the protein, also revealed that the binding to DNA is produced through its tandem HMG-box domains in a sequential model with positive cooperativity. Moreover, regions flanking the DNA binding domains show high structural disorder and thev are prone to aggregate in amyloid fibrils, raising the possibility that Ixrl could act as a prion

Fact-checking platforms in Spanish. Features, organisation and method

Fact-checking has become one of the most relevant activities of recent years, as a result of the increase in the flow of fake news and of the ease to spread news through platforms such as social media. The goal of the research is to assess the task of fact-checking developed by initiatives that use Spanish as a vehicle for comparing inaccurate and false information. We carried out a case study of 19 international projects that use Spanish as the main language to materialise their fact-checking actions and the analysis of contents published aims at understanding where these companies develop their activities, how are them internally organized and which methods they use to translate the data obtained to the audience. Results show that most of fact-checking projects in Spanish –launched most of them in the period 2014-2016– remain active. In South America, these organizations have more weight. Most of them have a journalistic nature, although there is a large number of civic and independent projects. Among strategies for verification, text is the preferred formula, although some innovative methods to present the degree of accuracy of assessed contents have been found.La verificación de la información o fact-checking se ha convertido en una de las actividades periodísticas que más relevancia ha adquirido a lo largo de los últimos años. Como consecuencia del incremento de la circulación de las noticias falsas y de la facilidad para difundir las mismas a través de plataformas como las redes sociales. El objetivo de este artículo es analizar la tarea de verificación llevada a cabo por las iniciativas que emplean el español como vehículo para el contraste de las informaciones dudosas o falsas. A través del estudio de caso de los diecinueve proyectos internacionales que hacen uso del español como lengua principal para materializar sus acciones de fact-checking y el análisis de los contenidos publicados se busca comprender dónde desempeñan su actividad estas organizaciones, cuál es su organización interna y los métodos empleados para trasladar al público las comprobaciones realizadas. Los resultados muestran que la mayor parte de los proyectos de verificación de la información en español –iniciados en su mayor parte en el período 2014-2016– permanecen activos hoy en día y se han mantenido en el tiempo. Proporcionalmente, es en América del Sur es donde cuentan con más peso. Son en su mayoría iniciativas vinculadas a organizaciones periodísticas, aunque existe un alto número de proyectos cívicos o independientes. Entre las estrategias para la verificación, el texto es la fórmula preferida por este tipo de medios, si bien se han encontrado algunos métodos innovadores para la presentación del grado de veracidad de los contenidos analizados

Plataformas de fact-checking en español. Características, organización y método

Fact-checking has become one of the most relevant activities of recent years, as a result of the increase in the flow of fake news and of the ease to spread news through platforms such as social media. The goal of the research is to assess the task of fact-checking developed by initiatives that use Spanish as a vehicle for comparing inaccurate and false information. We carried out a case study of 19 international projects that use Spanish as the main language to materialise their fact- checking actions and the analysis of contents published aims at understanding where these companies develop their activities, how are them internally organized and which methods they use to translate the data obtained to the audience. Results show that most of fact-checking projects in Spanish –launched most of them in the period 2014-2016– remain active. In South America, these organizations have more weight. Most of them have a journalistic nature, although there is a large number of civic and independent projects. Among strategies for verification, text is the preferred formula, although some innovative methods to present the degree of accuracy of assessed contents have been foundLa verificación de la información o fact-checking se ha convertido en una de las actividades periodísticas que más relevancia ha adquirido a lo largo de los últimos años. Como consecuencia del incremento de la circulación de las noticias falsas y de la facilidad para difundir las mismas a través de plataformas como las redes sociales. El objetivo de este artículo es analizar la tarea de verificación llevada a cabo por las iniciativas que emplean el español como vehículo para el contraste de las informaciones dudosas o falsas. A través del estudio de caso de los diecinueve proyectos internacionales que hacen uso del español como lengua principal para materializar sus acciones de fact-checking y el análisis de los contenidos publicados se busca comprender dónde desempeñan su actividad estas organizaciones, cuál es su organización interna y los métodos empleados para trasladar al público las comprobaciones realizadas. Los resultados muestran que la mayor parte de los proyectos de verificación de la información en español –iniciados en su mayor parte en el período 2014-2016– permanecen activos hoy en día y se han mantenido en el tiempo. Proporcionalmente, es en América del Sur es donde cuentan con más peso. Son en su mayoría iniciativas vinculadas a organizaciones periodísticas, aunque existe un alto número de proyectos cívicos o independientes. Entre las estrategias para la verificación, el texto es la fórmula preferida por este tipo de medios, si bien se han encontrado algunos métodos innovadores para la presentación del grado de veracidad de los contenidos analizadosThe text is prepared within the framework of the project “Uses and informative preferences in the new media map in Spain: journalism models for mobile devices” (Reference: CSO2015-64662-C4-4-R), funded by the Ministry of Economy and Competitiveness (Government of Spain) and co-funded by the European Regional Development Fund (ERDF). It also belongs to the activities promoted by the International Research Network of Communication Management — XESCOM (Reference: ED341D R2016/019), supported by the Regional Ministry of Culture, Education and University Organization from the Xunta de Galicia. Ángel Vizoso and Jorge Vázquez-Herrero benefit from the Education’s University Faculty Training Programme (FPU), financed by the Ministry of Science, Innovation and Universities (Government of Spain)S

The Challenges and Opportunities of lncRNAs in Ovarian Cancer Research and Clinical Use

[Abstract] Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs’ regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.This work was funded by Plan Estatal I + D + I by the Instituto de Salud Carlos III (ISCIII, Spain) under grant agreement AES number PI18/01714, cofounded by Fondo Europeo de Desarrollo Regional-FEDER (The European Regional Development Fund-ERDF) “A way of Making Europe,” and by Xunta de Galicia (Consolidación Grupos Referencia Competitiva contract number ED431C 2016-012). M.S.M. was funded by a predoctoral fellowship from FPU-2018 (Spain)Xunta de Galicia; ED431C 2016-01

Thanksgiving to Yeast, the HMGB Proteins History from Yeast to Cancer [Review]

This article belongs to the Special Issue Yeasts Biochemistry and Biotechnology[Abstract] Yeasts have been a part of human life since ancient times in the fermentation of many natural products used for food. In addition, in the 20th century, they became powerful tools to elucidate the functions of eukaryotic cells as soon as the techniques of molecular biology developed. Our molecular understandings of metabolism, cellular transport, DNA repair, gene expression and regulation, and the cell division cycle have all been obtained through biochemistry and genetic analysis using different yeasts. In this review, we summarize the role that yeasts have had in biological discoveries, the use of yeasts as biological tools, as well as past and on-going research projects on HMGB proteins along the way from yeast to cancer.This research was funded by Plan Estatal I+D+i, Instituto de Salud Carlos III (ISCIII, Spain) (grant nos. PI14/01031 and PI18/01417) and Ministerio de Ciencia e Innovación (grant no. PID2021-124564OB-I00), and cofunded by the Fondo Europeo de Desarrollo Regional-FEDER (The European Regional Development Fund-ERDF) “A way of Making Europe” and by Xunta de Galicia (Consolidación Grupos Referencia Competitiva grant no. ED431C 2020-08)Xunta de Galicia; ED431C 2020-0

Technological and communicative innovation to fight misinformation: 135 experiences for a change of direction

El impacto social de la desinformación en la sociedad red, alimentado por el efecto de las denominadas fake news, ha encendido numerosas luces de alarma en la segunda década del tercer milenio. La gran cantidad de mensajes que circula por las infraestructuras tecnológicas y las estrategias aplicadas para que alcancen el mayor impacto en los comporta- mientos sociales han incrementado la complejidad del escenario de la ubicuidad comunicativa. Esta situación ha sido interpretada desde el periodismo como una amenaza para la credibilidad y como un desafío para buscar antídotos que, mediante el cultivo del periodismo de calidad, ofrezcan respuestas a los ciudadanos interesados en la información veraz. En este trabajo se analizan 135 iniciativas de fact-checking de todo el mundo y se profundiza en la caracterización de seis casos seleccionados. Los resultados identifican modelos diferenciados en la organización, el contenido y las fórmulas de verificación para un cambio de rumboThe social impact of misinformation in the network society, fueled by the effect of the so-called fake news, has awaken numerous warning lights in the second decade of the third millennium. The large number of messages that circulate through technological infrastructures and the strategies applied for them to achieve the greatest impact on social beha- vior have increased the complexity of the communicative ubiquity context. This situation has been interpreted by jour- nalism as a threat to credibility and as a challenge to seek antidotes that offer answers to citizens interested in truthful information, through the cultivation of quality journalism. This article analyzes 135 fact-checking initiatives around the world and delves into the characterization of six selected cases. The results identify different models in the organization, the content and the verification formulae for a change of directionEste texto está elaborado en el marco del proyecto Cibermedios nativos digitales en España: formatos narrativos y estrategia móvil (RTI2018-093346-B-C33), del Ministerio de Ciencia, Innovación y Universidades”. Este proyecto está cofinanciado por el fondo es- tructural Feder. Forma parte también de las actividades promovidas a través de la Red Internacional de Gestión de la Comunicación – Xescom (Referencia: ED341D R2016/019), apoyada por la Consellería de Cultura, Educación e Ordenación Universitaria de la Xunta de Galicia. Los autores Ángel Vizoso y Jorge Vázquez-Herrero son beneficiarios del Programa de Formación del Profesorado Universitario finan- ciado por el Ministerio de Ciencia, Innovación y Universidades (Gobierno de España)S

Adaptación de la docencia práctica de materias de Bioquímica en tiempos de la pandemia por el Covid-19

[Resumen] En este trabajo se comentan los retos que nos vimos obligados a afrontar y las soluciones tomadas por el profesorado a fin de adaptar la docencia de prácticas de laboratorio a la situación de pandemia causada por el SARS-CoV2 (Covid-19). Esta situación, además de ser nueva, fue variando con el tiempo principalmente a causa de confinamientos y variaciones en las restricciones de movilidad. Por tanto, pasamos de momentos con docencia completamente virtual a situaciones con docencia híbrida y también con clases presenciales. Presentamos nuestra experiencia adaptando el sistema tradicional de docencia práctica con grupos de 16-18 alumnos en un laboratorio manejando instrumental y compartiendo espacios a una situación de docencia con oscilaciones entre presencial, virtual e híbrida.[Abstract] This paper discusses the challenges that we were forced to face and the solutions taken by the teaching staff in order to adapt the teaching of laboratory practices to the pandemic situation caused by SARS-CoV2 (Covid-19). This situation, in addition to being new, varied over time mainly due to confinements and variations in mobility restrictions. Therefore, we went from moments with completely virtual teaching to situations with hybrid teaching and also with face-to-face classes. We present our experience adapting the traditional system of practical teaching with groups of 16-18 students in a laboratory, handling instruments and sharing space to a teaching situation with oscillations between face-to-face, virtual and hybrid.http://hdl.handle.net/2183/2879

The HMGB Protein KlIxr1, a DNA Binding Regulator of Kluyveromyces lactis Gene Expression Involved in Oxidative Metabolism, Growth, and dNTP Synthesis

[Abstract] In the traditional fermentative model yeast Saccharomyces cerevisiae, ScIxr1 is an HMGB (High Mobility Group box B) protein that has been considered as an important regulator of gene transcription in response to external changes like oxygen, carbon source, or nutrient availability. Kluyveromyces lactis is also a useful eukaryotic model, more similar to many human cells due to its respiratory metabolism. We cloned and functionally characterized by different methodologies KlIXR1, which encodes a protein with only 34.4% amino acid sequence similarity to ScIxr1. Our data indicate that both proteins share common functions, including their involvement in the response to hypoxia or oxidative stress induced by hydrogen peroxide or metal treatments, as well as in the control of key regulators for maintenance of the dNTP (deoxyribonucleotide triphosphate) pool and ribosome synthesis. KlIxr1 is able to bind specific regulatory DNA sequences in the promoter of its target genes, which are well conserved between S. cerevisiae and K. lactis. Oppositely, we found important differences between ScIrx1 and KlIxr1 affecting cellular responses to cisplatin or cycloheximide in these yeasts, which could be dependent on specific and non-conserved domains present in these two proteins.This work has been funded by the contract ED431C 2020–08 from Xunta de Galicia (Consolidación Grupos Referencia Competitiva). A.R.-D. was funded by a research fellowship from Diputacion da Coruña-2017 (Spain)Xunta de Galicia; ED431C 2020–0

The HMGB1-2 Ovarian Cancer Interactome: the Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response

[Abstract] High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.This work has been funded by the Projects Nº PI14/01031 and PI18/01714, integrated in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 of the ISCIII- General Subdirection of Assesment and Promotion of the Research – European Regional Development Fund (FEDER) “A way of making Europe”. Funding is also acknowledged from Xunta de Galicia (Consolidación Grupos Referencia Competitiva Contract no. ED431C 2016–012). Aida Barreiro-Alonso was funded by a predoctoral fellowship from Xunta de Galicia-2013 (Spain) cofinanced by FEDERXunta de Galicia; ED431C 2016–01