Atomic Force Microscopy characterization of DNA-binding proteins involved in the repair and organisation of DNA

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de la Materia Condensada. Fecha de lectura: 28-11-2019Esta tesis tiene embargado el acceso al texto completo hasta el 28-05-2021The invention of the Atomic Force Microscope played a fundamental role in the characterization of nanometric molecular complexes. The Atomic Force Microscope is a suitable research technique for the study of biomolecules one by one with the advantage to be an effective technique inside and outside a liquid medium. However, its use in biology has been limited by the availability of faster visualization techniques which do not need to deposit a sample on top of a flat surface. In this thesis I present the result obtained in the study of three biological processes from a biophysical point of view with Atomic Force Microscopes. In the first project, three centromere-binding proteins are studied in the context of their plasmid partition systems. Plasmid partition systems consist of a group of proteins and DNA-sequences employed for the transmission and stabilization of plasmid molecules during cellular division. The three organisms, B. subtilis, C. crescentus and C. botulinum, have developed their partition systems differently. Regardless, these systems consist of a centromeric sequence near the origin of replication, a centromeric-binding protein and a NTPase motor protein. The formation of a segrosome complex, Centromeric-Binding protein bound to DNA, is showed by Atomic Force Microscopy images revealing a very different structure for the three biological organisms. In the second project, two protein of the Homologous Recombination mechanism are studied. The first, CtIP, is a tetrameric protein with some studies pointing to a short-resection of DNA-ends activity. The second, Dna2, is a helicase/nuclease protein with a defined role in the long-resection of DNA-ends in Homologous Recombination. However, the binding-mode of these proteins to DNA molecules is not completely understood. Here, I present the data obtained on CtIP and Dna2 DNA-binding properties. Surprisingly, CtIP reliably binds to non-canonical DNAends and was found to join DNA molecules. In the third project, the activity of the DNA mismatch repair mechanism in natural competent bacteria is studied. These organisms can introduce and incorporate exogenous DNA into its own DNA material. However, the DNA mismatch repair mechanism regulates and repairs the divergent regions between the two DNA strands. The deactivation of this mechanism increases mutation rate in bacteria. In this work, the role of mismatch repair proteins of competent B. subtilis bacteria is shown for the strand-exchange proces

Introducing the concept of infinite series: Preliminary analyses of curriculum content and pedagogical practice

Introducing the concept of infinite series: preliminary analyses of curriculum content and pedagogical practice

Covariation between variables in a modelling process: The ACODESA (collaborative learning, scientific debate and self-reflection) method

Semiotic representations have been an important topic of study in mathematics education. Previous research implicitly placed more importance on the development of institutional representations of mathematical concepts in students rather than other types of representations. In the context of an extensive research project, in progress since 2005, related to modelling mathematical situations in Québec secondary schools (grades 8 and 9), we have addressed the problem of constructing a specific mathematical concept: covariation between variables as a prerequisite for the concept of function and its graphical representation. However, our research differs from previous studies as we attempt to take into consideration, in a cultural semiotic perspective, the spontaneous non-institutional representations that students produce when solving a problem situation in mathematics. We report our results with a group of students in grade 9, discussing the evolution of the representations the students produced to solve a problem situation, and the key role that the concept of covariation seems to play in helping students grasp the graphical representation of functions. We also discuss the different stages of the teaching method used, based upon collaborative learning, scientific debate and self-reflection (the ACODESA method of teaching) which aims to help the students acquire a cultural semiotic system.Conseil de Recherche en Sciences Humaines du Canada (No. 410-2008-1836, CID 130 252)

Influence of magnification on extraction efficiency in laser resonators with non-overlapping beams

The magnification and the Fresnel number determine the mode profile and losses in a bare unstable resonator. Upon inclusion of gain, both the beam pattern and the reflectivity are changed, more than in a stable cavity, because the counter-propagation intensities differ spatially and saturate the amplifier in a way that alters the mode profile, the reflectivity and the conditions of optimal operation. In this paper we present a numerical study of two types of cavities and compute the mode profile and losses in presence of an amplifier that saturates homogeneously. We compare these results with experimental data obtained on a TEA CO2 laser.Fil: González, Martín Germán. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; ArgentinaFil: Peuriot, Alejandro Luis. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; ArgentinaFil: Garea, María Teresa. Universidad de Buenos Aires. Facultad de Ingeniería; ArgentinaFil: Santiago, G.D.. Universidad de Buenos Aires. Facultad de Ingeniería; Argentin

El gasto social de los ayuntamientos en la isla de Tenerife. Años 2015-2017

This work is aimed at the study of social spending on the island of Tenerife for a period between 2015 and 2017. For this purpose, the term budget is introduced, as well as a broad description of it, ranging from basic principles to settlement of it at the end of each exercise. In addition, various graphs and tables are shown in which important data about the social expenditure approved and executed by local authorities can be observed, both at an aggregate level and at a particular level. Also, an analysis of ratios such as budget execution and expenditure per capita is carried out, for which the political factor is taken into account. Finally, reference is made to other concepts related to society, especially the term poverty, and also to others such as unemployment or pensions. All of them are studied at the autonomous level.Este trabajo tiene como objeto el estudio del gasto social en la isla de Tenerife para un periodo comprendido entre los años 2015 y 2017. Para ello se introduce el término presupuesto, así como una amplia descripción del mismo, abarcando desde los principios básicos hasta la liquidación al final de cada ejercicio. Además, se muestran diversos gráficos y tablas en las que se pueden observar datos importantes acerca del gasto social aprobado y ejecutado por los entes locales, tanto a nivel agregado como a nivel particular. También, se lleva a cabo un análisis de ratios como el de ejecución presupuestaria y el de gasto por habitante, para los que se tiene en cuenta el factor político. Finalmente, se hace referencia a otros conceptos relacionados con la sociedad, especialmente al término pobreza, y también a otros como el desempleo o las pensiones. Todos ellos se estudian a nivel autonómico

Sobre la comprensión en estudiantes de matemáticas del concepto de integral impropia : algunas dificultades, obstáculos y errores

En el presente trabajo mostramos algunas de las dificultades, obstáculos y errores que los alumnos universitarios encuentran al aprender los conceptos relativos a la integración impropia; algunos de ellos parecen inherentes al propio concepto de integral impropia y otros vienen relacionados con ausencia de significado o con otros conceptos del cálculo. Con el objetivo de analizar estas dificultades, obstáculos y errores construimos un marco teórico basado, principalmente, en la teoría de Duval sobre los registros semióticos de representación y construimos un modelo de competencia para evaluar la comprensión de nuestros alumnos.In this paper we present some difficulties, obstacles and errors university students face when learning the concepts relative to improper integration. Some of them seem to be inherent to the improper integral concept itself and some others are related to lack of meaning or to other concepts of calculus. With the aim of analysing these difficulties, obstacles and errors we built up a theoretical framework based, fundamentally, on Duval's theory of semiotic registers of representation and we designed a competence model to assess our students' comprehension

Standardization Framework for Sustainability from Circular Economy 4.0

The circular economy (CE) is widely known as a way to implement and achieve sustainability, mainly due to its contribution towards the separation of biological and technical nutrients under cyclic industrial metabolism. The incorporation of the principles of the CE in the links of the value chain of the various sectors of the economy strives to ensure circularity, safety, and efficiency. The framework proposed is aligned with the goals of the 2030 Agenda for Sustainable Development regarding the orientation towards the mitigation and regeneration of the metabolic rift by considering a double perspective. Firstly, it strives to conceptualize the CE as a paradigm of sustainability. Its principles are established, and its techniques and tools are organized into two frameworks oriented towards causes (cradle to cradle) and effects (life cycle assessment), and these are structured under the three pillars of sustainability, for their projection within the proposed framework. Secondly, a framework is established to facilitate the implementation of the CE with the use of standards, which constitute the requirements, tools, and indicators to control each life cycle phase, and of key enabling technologies (KETs) that add circular value 4.0 to the socio-ecological transition

Estrategia de implantación de infraestructura ciclista en la ciudad de Valencia

[ES] La bicicleta es un fenómeno contemporáneo para el que las ciudades no están adaptadas. A través de este trabajo de investigación, se busca desarrollar las estrategias de inserción de la bicicleta como medio de transporte en la ciudad de Valencia para así entender mejor como está evolucionando una metrópoli en la que predomina el tráfico motorizado. Tras estudiar el desarrollo histórico reciente de la infraestructura ciclista, es importante situar la bicicleta en la sociedad actual. Conceptos como Sostenibilidad, Ecología y Salud están indiscutiblemente ligados a este medio de transporte. Estos ideales son relativamente recientes y las ciudades tratan de satisfacerlos por diferentes medios. Es relevante no perder de vista las ciudades que ya incorporan una estructura ciclista asentada, ya que nos revelan los pasos a seguir para llegar a ese nivel. El objetivo principal de esta investigación es desarrollar la estrategia actual fomentada localmente, además de proponer una nueva aproximación basada en las propuestas de otras ciudades del ámbito nacional. Es importante catalogar el plan de actuación que se está llevando a cabo y comprobar si el punto de vista es el óptimo para el usuario, tanto ciclista como peatón. Por otra parte, en muchas ciudades del panorama nacional como San Sebastián o Sevilla se han realizado importantes modificaciones a sus tejidos urbanos buscando adoptar una creciente demanda de infraestructura ciclista. Comparándolas con el planteamiento local, podremos determinar las medidas más prometedoras para adaptar la ciudad y así elaborar un criterio de actuación. Finalmente, la conclusión elaborará una valoración crítica tanto de la estrategia actual como de la propuesta, reuniendo los aspectos positivos de ambas buscando reconciliarlas. Se trata de buscar un conjunto de acciones que faciliten una ciudad más peatonal y ciclista que vaya alejando al coche de su núcleo, para crear una nueva identidad urbana.[EN] The bicycle is a contemporary phenomenon to which the cities are not adapted. The purpose of this investigation report is to develop the strategies of inserting the bicycle as a mean of transport in the city of Valencia, in order to understand how a metropolis dominated by motorized traffic is evolving. After studying the recent historical development of the cycling infrastructure, it is relevant to place the bicycle in the actual society. Concepts like Sustainability, Ecology and Health are undoubtedly related to this vehicle. These ideals are relatively recent and cities struggle to satisfy them through different paths. It is vital not to lose sight of the urban areas that already have a settled bicycle network, because they will reveal the steps to reach their level. The main objective of this investigation is to insight into the strategy fomented locally, besides proposing a new approximation based in the schemes of other cities of the national panorama. It is important to categorize the plan that is being implemented and to check if the point of view adopted benefits the user, both cyclist and pedestrian. Furthermore, many other metropolis of the national sphere, such as San Sebastian and Seville, have made important modifications to their urban fabric aiming to satisfy the growing demand for bicycle infrastructure. Comparing those models with the local one, we can determine the most promising initiatives to adapt the city and thereby create action criteria. Finally, the conclusion will elaborate a critical evaluation of the actual and proposed strategies, gathering the positive aspects of both of them pursuing their reconciliation. The purpose is to collect a set of actions that will provide a more pedestrian and cyclist city, which simultaneously will gradually expulse the car out of its nucleus, creating a new urban identity.González Martín, A. (2017). Estrategia de implantación de infraestructura ciclista en la ciudad de Valencia. http://hdl.handle.net/10251/102042TFG

Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.Junta de Andalucía PI-0272-2017Ministerio de Ciencia, Innovación y Universdad CD16/00118, CP19/00046, PI16/00259, BFU2017-83588-P, CP14/00105, PI18/01590, PI17/02104, PIC18/0010, IC19/0052Juvenile Diabetes Research Foundation (USA) 2-SRA-2019-837-S-BFundación Española para la Ciencia y la Tecnología 2018-00023