Sensibilización hacia la inclusión. Experiencia en Binéfar.

Este Trabajo de Fin de Grado se basa en una reflexión sobre una experiencia, vivida en la localidad de Binéfar (Huesca), de prácticas de sensibilización hacia la inclusión. Considero que es un tema fundamental tanto para la comunidad educativa como para el resto de la sociedad. Se ha logrado avanzar en el camino hacia la inclusión, pero se tiene que seguir incidiendo para que se consigan mayores metas

Revisión del régimen fiscal de las reestructuraciones: propuestas de modificación

The object of this article is to highlight various aspects of our tax regulations that are related to restructurings which, in our opinion, should be amended in order to conform to the recent commercial regulations concerning restructurings or to EU law, or simply for technical tax reasons. The proposals for modification that we comment on do not only apply to the legal texts, but also to the criteria for interpretation maintained by the Tax Administration, being the Spanish Directorate of Taxes (Dirección General de Tributos) or the Economic Administrative Courts (Tribunales Económico-Administrativos), used in the application of the regulations which govern restructurings. We believe that the amendments that we propose are necessary, as well as desirable, since the aim of such amendments is to help businesses restructure without the tax regime curbing or obstructing its achievement, as well as to achieve legal certainty.El presente artículo tiene por objeto poner de manifiesto aquellos aspectos de nuestra normativa fiscal relativos a las operaciones de reestructuración que, a nuestro juicio, sería conveniente que fueran objeto de modificación, ya sea para su adecuación a la reciente normativa mercantil en materia de reestructuraciones, para su adaptación al Derecho de la Unión Europea, o bien por meras razones de técnica tributaria. Las propuestas de modificación que comentamos se refieren no únicamente a los textos legales, sino también a los criterios interpretativos mantenidos por la Administración tributaria, ya sea la Dirección General de Tributos o los Tribunales Económico-Administrativos, en aplicación de las normas que regulan las operaciones de reestructuración. Entendemos que estas modificaciones que proponemos son necesarias, al tiempo que convenientes, dado que la finalidad que se persigue con las mismas es facilitar que las empresas puedan llevar a cabo operaciones de reestructuración sin que la fiscalidad suponga un freno o un obstáculo para la consecución de las mismas, así como ganar en seguridad jurídica

Reversible and Noisy Progression towards a Commitment Point Enables Adaptable and Reliable Cellular Decision-Making

Cells must make reliable decisions under fluctuating extracellular conditions, but also be flexible enough to adapt to such changes. How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood. To study this issue we quantitatively measured gene expression and protein localization in single cells of the model organism Bacillus subtilis during the progression to spore formation. We found that sporulation proceeded through noisy and reversible steps towards an irreversible, all-or-none commitment point. Specifically, we observed cell-autonomous and spontaneous bursts of gene expression and transient protein localization events during sporulation. Based on these measurements we developed mathematical population models to investigate how the degree of reversibility affects cellular decision-making. In particular, we evaluated the effect of reversibility on the 1) reliability in the progression to sporulation, and 2) adaptability under changing extracellular stress conditions. Results show that reversible progression allows cells to remain responsive to long-term environmental fluctuations. In contrast, the irreversible commitment point supports reliable execution of cell fate choice that is robust against short-term reductions in stress. This combination of opposite dynamic behaviors (reversible and irreversible) thus maximizes both adaptable and reliable decision-making over a broad range of changes in environmental conditions. These results suggest that decision-making systems might employ a general hybrid strategy to cope with unpredictably fluctuating environmental conditions

Dinámica de circuitos de regulación genética en bacterias

El objetivo de esta Tesis es el estudio de diferentes comportamientos celulares dinámicos en Escherichia coli y Bacillus subtilis. Es interesante comprender cómo estos organismos sencillos poseen mecanismos complejos para responder al entorno en el que se encuentran. Dicha respuesta está regulada por complicadas redes de regulación formadas por genes y proteínas, donde al igual que los instrumentistas de una orquesta, cada elemento de las redes genéticas debe tomar parte en armonía, en el momento justo y la cantidad adecuada para dar lugar a la respuesta celular apropiada. La Parte I introduce aspectos básicos de la metodología utilizada y conceptos fundamentales para la comprensión de los resultados. El Capítulo 1 es una breve introducción a los circuitos de regulación genética y el uso de proteínas fluorescentes para el estudio in vivo y en células individuales de la dinámica de dichos circuitos. El Capítulo 2 describe los materiales y técnicas utilizadas, desde el cultivo y obtención de cepas bacterianas, los métodos para filmar dichas cepas con microscopía de fluorescencia temporalizada, al análisis de las imágenes. El Capítulo 3 describe las características básicas de los procesos biológicos de estudio. El Capítulo 4 describe ciertos aspectos de la dinámica celular como el comportamiento oscilatorio o excitable de algunos sistemas biológicos, y las herramientas matemáticas usadas para contrastar los datos experimentales. La Parte II corresponde a los resultados. El Capítulo 5 describe los resultados del estudio del control del inicio de la replicación cromosómica en E. coli. Mediante una serie de perturbaciones en las proteínas que regulan este proceso, y mediante el análisis de las imágenes obtenidas por microscopía, se cuantificó el efecto ejercido sobre el inicio de replicación, comparando los resultados con una cepa control. El Capítulo 6 describe los resultados del estudio de la forma en que el circuito genético que regula la competencia en B. subtilis integra múltiples señales simultáneas. Se caracterizó experimentalmente y con un análisis de bifurcación del modelo matemático del circuito, la respuesta en células individuales e in vivo a señales químicas de diferente intensidad que controlan la expresión constitutiva de los genes que forman el circuito, y a la variación del número de copias de uno de estos genes. El Capítulo 7 describe los resultados del estudio del proceso de toma de decisión celular en B. subtilis, basado en la decisión de estas bacterias por optar entre los programas de diferenciación en competencia genética y esporulación, los cuales compiten entre sí en el tiempo. El análisis simultáneo y en células individuales de ambos programas permitió descubrir por qué las bacterias optan por uno u otro mediante un mecanismo de carrera molecular entre estos dos programas en competición. El Capítulo 8 describe los resultados del estudio de la adaptación celular al estrés mediante esporulación y la toma de decisión de una forma robusta en B. subtilis. Se analizó de forma cuantitativa la expresión de los genes implicados en la progresión hacia la formación de esporas y se desarrolló un modelo matemático poblacional para estudiar el efecto de la reversibilidad en el proceso de adaptación celular a cambios en los niveles de estrés. La Parte III corresponde a las Conclusiones y la perspectiva futura para los resultados descritos en la Parte II. Los resultados obtenidos contribuyen a la comprensión de determinados comportamientos en E. coli y B. subtilis. Estas bacterias, sencillas si se comparan con organismos superiores, ofrecen la posibilidad de estudiar mecanismos utilizados por sistemas más complejos, pero que para su estudio se requieren técnicas complicadas. El estudio en células individuales de la dinámica de redes de regulación mediante las técnicas utilizadas nos permite el análisis in vivo y en tiempo real de lo que sucede con dichas redes en el interior de las células respecto al exterior celular.The aim of this Thesis is the study of different dynamic cellular behaviors in Escherichia coli and Bacillus subtilis. It is interesting to understand how these simple organisms have not so simple mechanisms to respond to their environment. This response is regulated by complex regulatory networks consisting of genes and proteins, where as instrumentalists in an orchestra, each element of the network should operates in harmony, at the right time and the right amount to give an appropriate cellular response. Part I introduces basic aspects of the methodology and concepts for the understanding of the results presented in this Thesis. Chapter 1 provides a brief introduction to genetic regulatory circuits and the fluorescent proteins used for the study of the dynamics of such circuits in vivo and in individual cells. Chapter 2 describes the materials and techniques used, from growing and obtaining bacterial strains, to the methodology used for filming these strains by temporalized fluorescence microscopy, and to the analysis of the obtained images. Chapter 3 describes the main features of the dynamical biological processes studied in E. coli and B. subtilis. Chapter 4 refers to certain aspects of cellular dynamics such as oscillatory or excitable behavior of some biological systems, as well as the mathematical tools used to compare the data obtained experimentally. Part II corresponds to the results. Chapter 5 describes the results of the study of the control of chromosome replication initiation in E. coli. We implemented a set of perturbations in the main proteins that regulate this process, and their effect on the initiation of replication, quantified by analyzing the images obtained by fluorescence microscopy, comparing the results with a control strain. Chapter 6 describes the results obtained from the study of how a genetic circuit in B. subtilis, namely the one regulating competence, integrates multiple simultaneous inputs. We characterized experimentally the response of individual cells in vivo to different chemical signals that control the strength of the constitutive expression of genes forming the circuit, in addition to the copy number variation of one of these genes. The results were compared with a bifurcation analysis of the mathematical model of the circuit. Chapter 7 describes the results obtained in a study of the decision making process of microorganism B. subtilis. Specifically, we studied the decision of these bacteria between two differentiation programs such as genetic competence and sporulation, which compete with each other in time. The simultaneous analysis in individual cells of both programs allowed us to uncover the way in which bacteria choose between these two competing programs, showing that the competition occurs through a molecular race. Finally, Chapter 8 describes the results obtained in the study of reversible progression towards an all-or-none switch in the sporulation of B. subtilis. We quantitatively analyzed the expression of genes involved in the progression towards spore formation and a population model was developed to study the effect of reversibility in the process of cellular adaptation to changes in stress levels. Part III details the conclusions and a description of the possible future perspectives for each of the results described in Part II. The results obtained contribute to the understanding of certain dynamic behaviors in the microorganisms E. coli and B. subtilis. These bacteria, although simple when compared with higher organisms, offer the possibility of studying mechanisms that are frequently utilized by more complex systems, which require more sophisticated analysis techniques. The study at the single cell level of network dynamics of gene regulation by the techniques used in this Thesis, allows the analysis in vivo and in real time of the underlying dynamic of such networks inside cells in response to the cell environment

Promoter architecture determines cotranslational regulation of mRNA

Information that regulates gene expression is encoded throughout each gene but if different regulatory regions can be understood in isolation, or if they interact, is unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible or constitutive promoter. We find that the strength of cotranslational regulation on mRNA levels is determined by promoter architecture. By using a novel computational genetic screen of 6402 RNA-seq experiments, we identify the RNA helicase Dbp2 as the mechanism by which cotranslational regulation is reduced specifically for inducible promoters. Finally, we find that for constitutive genes, but not inducible genes, most of the information encoding regulation of mRNA levels in response to changes in growth rate is encoded in the ORF and not in the promoter. Thus, the ORF sequence is a major regulator of gene expression, and a nonlinear interaction between promoters and ORFs determines mRNA levels.L.B.C. was supported by Ministerio de Economía y Competitividad (MINECO) (BFU2015-68351-P), AGAUR (2014SGR0974), and the Unidad de Excelencia María de Maeztu, funded by the MINECO (MDM-2014-0370)

Reversible and noisy progression towards a commitment point enables adaptable and reliable cellular decision-making

Cells must make reliable decisions under fluctuating extracellular conditions, but also be flexible enough to adapt to such changes. How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood. To study this issue we quantitatively measured gene expression and protein localization in single cells of the model organism Bacillus subtilis during the progression to spore formation. We found that sporulation proceeded through noisy and reversible steps towards an irreversible, all-or-none commitment point. Specifically, we observed cell-autonomous and spontaneous bursts of gene expression and transient protein localization events during sporulation. Based on these measurements we developed mathematical population models to investigate how the degree of reversibility affects cellular decision-making. In particular, we evaluated the effect of reversibility on the 1) reliability in the progression to sporulation, and 2) adaptability under changing extracellular stress conditions. Results show that reversible progression allows cells to remain responsive to long-term environmental fluctuations. In contrast, the irreversible commitment point supports reliable execution of cell fate choice that is robust against short-term reductions in stress. This combination of opposite dynamic behaviors (reversible and irreversible) thus maximizes both adaptable and reliable decision-making over a broad range of changes in environmental conditions. These results suggest that decision-making systems might employ a general hybrid strategy to cope with unpredictably fluctuating environmental conditions.GMS acknowledges support by NIH Grant No. NIGMS RO1 GM088428, Welch Foundation (Grant No. I-1674), and James S. McDonnell Foundation (Grant No. 220020141). JGO acknowledges financial support from the Ministerio de Ciencia e Innovación (Spain, Project No. FIS2009-13360) and the ICREA/nAcademia programme

Promoter architecture determines cotranslational regulation of mRNA

Information that regulates gene expression is encoded throughout each gene but if different regulatory regions can be understood in isolation, or if they interact, is unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible or constitutive promoter. We find that the strength of cotranslational regulation on mRNA levels is determined by promoter architecture. By using a novel computational genetic screen of 6402 RNA-seq experiments, we identify the RNA helicase Dbp2 as the mechanism by which cotranslational regulation is reduced specifically for inducible promoters. Finally, we find that for constitutive genes, but not inducible genes, most of the information encoding regulation of mRNA levels in response to changes in growth rate is encoded in the ORF and not in the promoter. Thus, the ORF sequence is a major regulator of gene expression, and a nonlinear interaction between promoters and ORFs determines mRNA levels.L.B.C. was supported by Ministerio de Economía y Competitividad (MINECO) (BFU2015-68351-P), AGAUR (2014SGR0974), and the Unidad de Excelencia María de Maeztu, funded by the MINECO (MDM-2014-0370)

Strand asymmetry influences mismatch resolution during a single-strand annealing

Background: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage. Results: Here, we develop a genome-wide assay whereby the same DNA lesion is repaired in different genomic contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated if the break is repaired through single-strand annealing. The resolution of the mismatch showed a 60-80% bias in favor of the strand with the longest 3' flap. The location of the lesion in the genome and the type of mismatch had little influence on the bias. Instead, we observe a complete reversal of the bias when the longest 3' flap is moved to the opposite strand by changing the position of the double-strand break in the reporter. Conclusions: These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during a single-strand annealing.We acknowledge the financial support of the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN-2020-06377), the Spanish Ministry of Economy, Industry and Competitiveness (“Centro de Excelencia Severo Ochoa 2013-2017”, Plan Estatal PGC2018-099807-B-I00), of the CERCA Programme/Generalitat de Catalunya, and of the European Research Council (Synergy Grant 609989). VOP was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie programme (665385). We also acknowledge the support of the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnershi

Revista de educación

Resumen basado en el de la publicación. Monográfico con el título: 'La transición a la vida activa'Se estudia la valoración que dos amplias muestras de graduados del sistema universitario catalán hacen del nivel de desarrollo de las mismas en su etapa formativa, así como de los déficits competenciales en relación a su desempeño profesional. Se trata de un análisis secundario y diferencial de las bases de datos institucionales provenientes de los estudios de inserción de las cohortes de 2002 y 2004 realizadas por AQU Catalunya. Los resultados ponen de manifiesto las diferencias valorativas de satisfacción con el nivel formativo tanto entre áreas disciplinares como entre graduados con desempeño o no de funciones universitarias. Así mismo, aparece un claro diferencial entre el nivel de formación y su utilidad en la tarea profesional. Finalmente, se identifican los ámbitos y estrategias de acción formativa en los que la enseñanza universitaria puede favorecer la empleabilidad de sus graduados bien sea a través de la auditoría de empleabilidad, el diseño de los programas formativos o las actuaciones dentro de los planes de orientación y tutoría.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]