Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene

BACKGROUND: Phosphodiesterases are an important protein family that catalyse the hydrolysis of cyclic nucleotide monophosphates (cAMP and cGMP), second intracellular messengers responsible for transducing a variety of extra-cellular signals. A number of different splice variants have been observed for the human phosphodiesterase 9A gene, a cGMP-specific high-affinity PDE. These mRNAs differ in the use of specific combinations of exons located at the 5' end of the gene while the 3' half, that codes for the catalytic domain of the protein, always has the same combination of exons. It was observed that to deduce the protein sequence with the catalytic domain from all the variants, at least two ATG start codons have to be used. Alternatively some variants code for shorter non-functional polypeptides. RESULTS: In the present study, we expressed different splice variants of PDE9A in HeLa and Cos-1 cells with EGFP fluorescent protein in phase with the catalytic domain sequence in order to test the different start codon usage in each splice variant. It was found that at least two ATG start codons may be used and that the open reading frame that includes the catalytic domain may be translated. In addition the proteins produced from some of the splice variants are targeted to membrane ruffles and cellular vesicles while other variants appear to be cytoplasmic. A hypothesis about the functional meaning of these results is discussed. CONCLUSION: Our data suggest the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants

Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene

Background: Phosphodiesterases are an important protein family that catalyse the hydrolysis of cyclic nucleotide monophosphates (cAMP and cGMP), second intracellular messengers responsible for transducing a variety of extra-cellular signals. A number of different splice variants have been observed for the human phosphodiesterase 9A gene, a cGMP-specific high-affinity PDE. These mRNAs differ in the use of specific combinations of exons located at the 5' end of the gene while the 3' half, that codes for the catalytic domain of the protein, always has the same combination of exons. It was observed that to deduce the protein sequence with the catalytic domain from all the variants, at least two ATG start codons have to be used. Alternatively some variants code for shorter non-functional polypeptides. Results: In the present study, we expressed different splice variants of PDE9A in HeLa and Cos- 1 cells with EGFP fluorescent protein in phase with the catalytic domain sequence in order to test the different start codon usage in each splice variant. It was found that at least two ATG start codons may be used and that the open reading frame that includes the catalytic domain may be translated. In addition the proteins produced from some of the splice variants are targeted to membrane ruffles and cellular vesicles while other variants appear to be cytoplasmic. A hypothesis about the functional meaning of these results is discussed. Conclusion: Our data suggest the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants

Bioactive Compounds Contained in Mediterranean Diet and Their Effects on Neurodegenerative Diseases

Neuroinflammatory processes in the brain are believed to play a crucial role in the development of neurodegenerative diseases, especially due to increased production of reactive oxygen species. The brain is susceptible to oxidative stress more than other organs due to the low activity of antioxidant defense systems. In agreement with these observations, increased oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer disease, Parkinson disease, ischemic diseases and aging. The Mediterranean diet is inspired by the traditional dietary pattern of some countries of the Mediterranean basin. From ancient times, these populations were characterized by simple food habits as high intake of whole cereals (pasta, bread, rice), fruits and vegetables (up to 400 g day−1 in Greece), legumes and fish, olive oil as the common source of fats, poor intake of meat and dairy products and a moderate, regular wine drinking. In the present chapter, there are going to be presented some bioactive substances present in the Mediterranean diet related to the prevention of neurodegenerative diseases. These substances are able to exert important antioxidant activity (through mechanisms such as sequestration of free radicals, inhibition of the production of hydrogen peroxide, activation of endogenous defense mechanisms

Probióticos

Los llamados alimentos funcionales son aquellos que, además de aportar los nutrientes recomendados, ejercen efectos beneficiosos sobre una o más funciones del organismo, fomentando la salud y reduciendo el riesgo de enfermedad. Los probióticos constituyen un subgrupo importante dentro de los alimentos funcionales con un gran atractivo comercial, por lo que es importante definir con claridad cuáles son los efectos beneficiosos que pueden ejercer sobre la salud. Ciertas bacterias colónicas producen ácidos grasos de cadena corta y ácido láctico como productos de la fermentación de carbohidratos, que disminuyen el pH del medio creando un microambiente donde las bacterias potencialmente patógenas no pueden crecer. Además, producen bacteriocinas, que actúan como antibióticos e inhiben el crecimiento de bacterias patógenas. Actualmente, los probióticos han demostrado ser útiles y beneficiosos en el tratamiento de diarrea aguda infecciosa en niños y adultos, en la prevención de la diarrea asociada a antibióticos, en enfermedades inflamatorias intestinales, en la mejora de los síntomas debidos a la mala digestión de la lactosa y de algunos síntomas del síndrome del colon irritable y en la prevención de la enterocolitis necrotizante en recién nacidos pre-término. También hay otras propiedades asociadas a este tipo de alimentos que necesitan más estudios que avalen su eficacia. Por tanto, los probióticos constituyen una importante fuente de salud, al garantizar un equilibrio a nivel de nuestra microflora endógena, fortaleciéndonos el sistema inmune y mejorando las funciones anatomofisiológicas del organismo. Además, tenemos que tener en cuenta que la investigación probiótica en la intersección de la gastroenterología con la inmunología y la microbiología es muy dinámica en los últimos años, tanto en la investigación básica como clínica y que el conocimiento de los mecanismos moleculares que conducen a la eficacia de los probióticos, estimulará la creación de nuevos alimentos con propiedades beneficiosas para la salud

Analysis of the influence of the líbero in different phases of game in volleyball

El objetivo del estudio fue analizar la participación y la influencia del jugador líbero en la fase de ataque y en la fase de defensa en voleibol masculino de alto nivel. La muestra de estudio estuvo compuesta por 1101 acciones de juego de recepción y defensa, de los cuatro equipos masculinos mejor clasificados en los JJOO de Pekin 2008. Las variables consideradas en el estudio fueron: clasificación del equipo, jugador receptor/defensa, zona de recepción/defensa, eficacia de recepción/defensa, eficacia de la colocación, zona de ataque/contraataque, tiempo de ataque/contraataque, eficacia de ataque/contraataque. La medida de dichas variables se realizó mediante la observación sistemática, indirecta y externa. Se recurrió a la estadística descriptiva y, posteriormente, se utilizaron técnicas de estadística inferencial, basada en tablas de contingencia, valores de Chi-cuadrado y V de Cramer. Los resultados mostraron que, en la fase de defensa, hubo asociaciones significativas entre: el jugador que defiende y la zona de defensa, predominando la defensa del líbero en zona 5; el jugador que defiende y la eficacia de la defensa, siendo mejorada por parte del líbero; el jugador que defiende y la zona de contraataque, incrementándose los ataques por zona 6 cuando defiende el líberoThe aim of the study was to analyse the libero’s participation and their influence in the attack and defence phases in men's elite volleyball. The sample of this study was composed by 1101 pass and defence game actions of the four highest-placed teams in the 2008 Beijing Olympic Games. The study’s variables include team classification, receiving/defending player, pass/defence zone, pass/defence effectiveness, setting effectiveness, attack/counterattack zone, attack/counterattack time, and attack/counterattack effectiveness. These variables were measured by both indirect and external systematic observation. A descriptive statistical study was used, followed by inferential statistical techniques based on contingency tables, Chi-square tests, and Cramer's V values. The results revealed that there were significant associations during the defensive stage of the game between the defending player and the defensive phase, the libero’s defence predominating in zone 5; the defending player and defence efficiency, which is improved by the libero; the defending player and counterattack, as attacks increased in zone 6 when the libero was defendin

Improving Bicyclic Peptide Phage Display and Development of Sortase A Inhibitors

Bicyclic peptide ligands are promising molecules for the development of new therapeutics. They combine advantages from large protein therapeutics and small molecule drugs. Large combinatorial libraries of bicyclic peptides can be generated and screened by phage display using a recently developed strategy. Potent and selective bicyclic peptide inhibitors against several therapeutic targets have already been developed and their therapeutic potential is currently being evaluated in animal models. One aim of my thesis was the exploration of ring size diversity in bicyclic peptides. I generated a set of libraries of the format Cys-(Xaa)m-Cys-(Xaa)n-Cys, where 'm' and 'n' = 3, 4, 5 or 6, and performed affinity selections against the serine protease urokinase-type plasminogen activator. Bicyclic peptide inhibitors from virtually all ring size combinations were isolated, suggesting that many peptide formats can be accommodated in the active site of this enzyme. Moreover, they showed a large variety of consensus sequences and several of the identified consensus sequences were exclusively found in bicyclic peptides having specific ring size combinations. Having available multiple leads isolated from such bicyclic peptide libraries with variable ring sizes could be a great asset for the generation of high affinity binders. Additionally, other targets may have preferences for specific peptide constraints and the availability of these libraries increases the chances to isolate high affinity binders to any desired target. A second goal of my thesis was to apply high throughput sequencing technologies to phage display selections of bicyclic peptides, in order to identify a larger number of specific target-binding sequences and motifs. I developed a procedure to efficiently compare the sequences of large numbers of phage-selected peptides to identify target-binding peptide motifs based on abundance and sequence similarity. Applying this approach to phage isolated in selections against five different protein targets, I was able to identify rare target-binding peptide motifs and could more precisely define groups and sub-groups of consensus sequences. This information is valuable to choose peptide leads for drug development and facilitates the identification of epitopes. Moreover, binding motifs could be identified after a single round of phage panning. The final aim of my thesis was to discover bicyclic peptides that could be used as new antibiotics. Towards this end, I combined the newly generated variable ring size libraries and high-throughput sequencing procedures. I focused on the development of inhibitors of Staphylococcus aureus sortase A, an antivirulence target for which no potent and specific inhibitors have been reported. For the isolation of bicyclic peptide inhibitors to this target, the ring size diversity of the libraries turned out to be key. Inhibitors all shared the same motif in a loop of 5 residues. Further characterization of their effects on S. aureus showed that they could inhibit sortase-mediated incorporation of external substrates on the staphylococcal cell wall. However, they were not sufficiently potent to compete with the native substrates of the enzyme. More potent inhibitors are needed to effectively inhibit sortase A on S. aureus cells, and the bicyclic peptide inhibitors isolated constitute promising leads for the development of future antisortase therapeutics

Study of carbons as matrices for lithium batteries

Tres de los grandes desafíos a los que se enfrenta la sociedad son el cambio climático, la creciente demanda de energía y la búsqueda del desarrollo sostenible. La Asamblea General de las Naciones Unidas estableció los Objetivos de Desarrollo Sostenible (ODS) en la Agenda 2030 para marcar el camino hacia la transición ecológica que deben seguir los países firmantes. Este proceso inevitablemente incluye la reducción del consumo de combustibles fósiles y su reemplazo por energías renovables. Sin embargo, este tipo de energías presentan la desventaja de una producción discontinua al depender de fenómenos atmosféricos (luz solar, viento, mareas, etc.). Para permitir un abastecimiento continuo de energía empleando fuentes renovables es necesario contar con sistemas de almacenamiento energético avanzados. Las baterías son sistemas de almacenamiento electroquímicos donde la electricidad producida se utiliza para llevar a cabo una reacción química no espontánea, y cuando se requiera electricidad se producirá la reacción espontánea transformando la energía química en eléctrica. Estos dispositivos constan fundamentalmente de tres componentes: cátodo, ánodo y electrolito. El desarrollo de estos componentes para cualquier tecnología de baterías es fundamental a la hora de avanzar en sistemas de almacenamiento que apoyen la consecución de los retos marcados en los ODS. La presente Tesis Doctoral pretende colaborar en los objetivos 7, 12 y 13 de los ODS mediante la síntesis de nuevos carbones que puedan emplearse como cátodos y ánodos en baterías de litio y que además presenten prestaciones superiores a los actualmente comercializados. Así mismo, se ha propuesto la síntesis de carbones a partir de biomasa residual, lo que supone una revalorización de subproductos de la industria agroalimentaria, aumentando la sostenibilidad de este tipo de dispositivos y potenciando la economía circular asociada al sector energético. La presente Tesis Doctoral titulada “Estudio de carbones como matrices para baterías de litio”, dirigida por los doctores D. Álvaro Caballero Amores y Dña. Almudena Benítez de la Torre, se encuadra en la línea de investigación “Materiales Avanzados para Baterías Recargables” del grupo FQM-175 “Química Inorgánica”, desarrollada en el Departamento de Química Inorgánica e Ingeniería Química de la Universidad de Córdoba. Fundamentalmente, esta memoria se ha elaborado gracias a la ayuda predoctoral para la formación de profesorado universitario (FPU) con referencia FPU16/03718 concedida por el Ministerio de Universidades (Gobierno de España). Así mismo, los trabajos de investigación se han llevado a cabo gracias a la financiación de los Proyectos Nacionales de I+D+i (i) MAT2014-55907-R “Grafeno como base de baterías avanzadas Li/S y Na/S para almacenamiento de energías renovables en redes eléctricas inteligentes” y (ii) MAT2017-87541-R “Avances en la tecnología de baterías litio-azufre: rendimiento, seguridad y sostenibilidad”. Los materiales sintetizados en esta Tesis Doctoral se han evaluado en dos tipos de tecnologías, las baterías de litio-ion (LIB) y litio-azufre (Li- S). Una exposición más detalla de la situación actual, así como del funcionamiento de las baterías basadas en litio se recoge en el capítulo 1. En resumen, el plan de trabajo seguido en todas las investigaciones ha sido: (i) análisis del estado del arte, para conocer los últimos avances en la temática y la tendencia seguida en otros grupos de investigación, (ii) síntesis de carbones, procurando un equilibrio entre las propiedades adquiridas por el material y la sostenibilidad del proceso de preparación, (iii) síntesis de la mezcla o composite carbón-azufre, sólo en caso de emplear ese material como cátodo en baterías Li-S, (iv) caracterización integral de los materiales, incluyendo un análisis estructural, morfológico, textural, composicional y de estabilidad térmica, (v) preparación de electrodos y ensamblaje de las celdas electroquímicas (baterías de litioion o litio-azufre), y finalmente, (vi) caracterización electroquímica, mediante la realización de medidas galvanostásticas de carga y descarga, voltamperometrías cíclicas (CV) y espectroscopía de impedancia electroquímica (EIS). A colación de lo anterior, una descripción pormenorizada de los materiales y métodos de síntesis empleados, así como de las técnicas de caracterización utilizadas se detalla en el capítulo 3. Por su parte, el capítulo 4 recoge los resultados y la discusión de los mismo obtenidos en los distintos trabajos de investigación desarrollados durante esta Tesis Doctoral. En este sentido, este capítulo se divide en cinco secciones en función del material sintetizado y la tecnología empleada. Inicialmente se recogen los trabajos sobre carbones obtenidos a partir de reactivos comerciales mediante diferentes métodos de preparación: (i) carbones grafénicos utilizados como ánodos en baterías Li-ión y (ii) carbón derivado de MOF utilizado como cátodo en una batería semi-líquida Li-S. Los siguientes apartados han sido dedicados a la optimización y revalorización de un carbón derivado de biomasa: (iii) en primer lugar, dos carbones obtenidos a partir de hueso de cereza preparados con distintos agentes activantes (KOH y H3PO4) han sido testeados como ánodos en baterías Li-ion, posteriormente (iv) se probaron estos carbones en baterías Li-S; y, por último, (v) seleccionando el mejor de estos carbones, se optimizó la configuración de la celda y la proporción de azufre incorporada en el composite con el propósito de aumentar la seguridad de la batería Li-S y lograr mejores prestaciones en esta tecnología.Three of the great challenges society faces are climate change, the growing demand for energy and the search for sustainable development. The United Nations General Assembly established the Sustainable Development Goals (SDG) in the 2030 Agenda to mark the path towards the ecological transition that the signatory countries must follow. This process inevitably includes reducing the consumption of fossil fuels and replacing them with renewable energy. However, this type of energy has the disadvantage of discontinuous production as it depends on atmospheric phenomena (sunlight, wind, tides, etc.). To allow a continuous supply of energy using renewable sources, it is necessary to have advanced energy storage systems. Batteries are electrochemical storage systems where the electricity produced is used to carry out a non-spontaneous chemical reaction, and when electricity is required, the spontaneous reaction will occur, transforming chemical energy into electricity. These devices basically consist of three components: cathode, anode and electrolyte. The development of these components for any battery technology is essential when advancing in storage systems that support the achievement of the challenges set out in the SDGs. This Doctoral Thesis aims to collaborate in goals 7, 12 and 13 of the SDGs through the synthesis of new carbons that can be used as cathodes and anodes in lithium batteries and that also present superior performance to those currently marketed. Likewise, the synthesis of carbons from residual biomass has been proposed, which implies a revaluation of by-products of the agri-food industry, increasing the sustainability of this type of device and promoting the circular economy associated with the energy sector. This Doctoral Thesis titled "Study of carbons as matrices for lithium batteries", directed by doctors D. Álvaro Caballero Amores and Ms. Almudena Benítez de la Torre, falls within the line of research "Advanced Materials for Rechargeable Batteries" of the group FQM-175 "Inorganic Chemistry", developed in the Department of Inorganic Chemistry and Chemical Engineering of the University of Córdoba. Fundamentally, this report has been prepared thanks to the predoctoral grant for university teacher training (FPU) with reference FPU16/03718 granted by the Ministry of Universities (Government of Spain). Likewise, the research work has been carried out thanks to the financing of the National R+D+i Projects (i) MAT2014-55907-R “Graphene as a base for advanced Li/S and Na/S batteries for storage of renewable energies in smart electrical networks” and (ii) MAT2017-87541-R “Advances in lithium-sulfur battery technology: performance, safety and sustainability”. The materials synthesized in this Doctoral Thesis have been evaluated in two types of technologies, lithium-ion batteries (LIB) and lithium-sulfur (Li-S). A more detailed exposition of the current situation, as well as the operation of lithium-based batteries, is included in chapter 1. In summary, the work plan followed in all the investigations has been: (i) analysis of the state of the art, to find out about the latest advances in the subject and the trend followed in other research groups, (ii) synthesis of carbons, seeking a balance between the properties acquired by the material and the sustainability of the preparation process, (iii) synthesis of the mixture or carbon-sulfur composite, only if this material is used as a cathode in Li-S batteries, (iv) comprehensive characterization of the materials, including a structural, morphological, textural, compositional, and thermal stability analysis, (v) preparation of electrodes and assembly of electrochemical cells (lithium-ion or lithium-sulfur batteries), and finally, (vi) electrochemical characterization, by performing galvanostatic charge measurement and discharge, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In light of the above, a detailed description of the materials and synthesis methods used, as well as the characterization techniques used, is detailed in chapter 3. On the other hand, chapter 4 collects the results and the discussion of the results obtained in the different research works developed during this Doctoral Thesis. In this sense, this chapter is divided into five sections depending on the synthesized material and the technology used. Initially, the works on carbons obtained from commercial reagents by different preparation methods are collected: (i) graphenic carbons used as anodes in Li-ion batteries and (ii) carbon derived from MOF used as cathode in a semi-liquid Li-ion battery -S. The following sections have been dedicated to the optimization and revaluation of a carbon derived from biomass: (iii) firstly, two carbons obtained from cherry pits prepared with different activating agents (KOH and H3PO4) have been tested as anodes in Li-ion batteries, later (iv) these carbons were tested in Li-S batteries; and, finally, (v) by selecting the best of these carbons, the cell configuration and the proportion of sulfur incorporated into the composite were optimized with the purpose of increasing the safety of the Li-S battery and achieving better performance in this technology

Clasificación de niveles de estrés utilizando señales fisiológicas

Historically, the term stress has been used to describe the different reactions that the human body presents under pressure. These unconcious responses occur in order to presserve the individuals integrity and could appear in human signals such as heart activity, sweating or pupil dilatation. The main goal of this Bachellor Thesis is to provide a system that classifies different levels of stress using physiological signals. For this purpose, an experiment that causes stress has been designed. The experiment consists in four incongruents tests of increasing difficulty performed by 24 participants. Their reaction time and correct answers will be used to approach the performance of the participants to the Yerkes-Dodson curves. The more stress the participant is suffering, the worse is the performance. Two physiological signals have been acquired aiming to classify different stress levels: Electrocardiogram (ECG) and Galvanic Skin Response (GSR). The sensors used to capture these signals were SHIMMER3 ECG UNIT and Q sensor respectively. Heart activity is extracted form ECG signal and electrodermal activity is extracted from GSR signal. The features that characterize the heart activity are related to the heart rate, while the features extracted from the GSR signal are related to the sweating. The classification has been developed applying Logistic Regression (LR) and KNN using leave-one-out cross validation (LOOCV). Two classifications will be proposed: relax and test stress levels and relax, concentration and anxiety levels. After obtaining the results, the stress levels have been succesfully classified using a KNN model with K = 3. The accuracy of the system is 75.38% for two stress levels and 63.08% for three stress levels, achieving the main goals of the thesis. According to the LR model, it can also be concluded that the features that provide more information about stress are heart rate variability and the area under the curve of the GSR signal.Ingeniería de Sistemas Audiovisuale

Identificación de factores genéticos asociados con el desarrollo de la microalbuminuria en la hipertensión esencial

IDENTIFICACIÓN DE FACTORES GENÉTICOS ASOCIADOS CON EL DESARROLLO DE LA MICROALBUMINURIA EN LA HIPERTENSIÓN ESENCIAL La excreción urinaria de albúmina es uno de los marcadores de riesgo más utilizados en el estudio del desarrollo de la enfermedad cardiovascular. El incremento de los valores de EUA está provocado por el aumento de la filtración glomerular a nivel del túbulo proximal, la cual puede estar producida por un aumento sistemático de la presión arterial. Tradicionalmente se ha venido estudiando la presencia de microalbuminuria en relación a otros factores de riesgo cardiovascular como son la diabetes mellitus y la hipertensión, debido la relevacia de estas patologías en el desarrollo de daño orgánico. Existen múltiples estudios que buscan establecer una base genética en el incremento de los valores de excreción urinaria de albúmina asociado a la hipertensión esencial. Hipotesis y Objetivos: Existe una base genética de rasgos complejos en el incremento de los niveles de excreción urinaria de albúmina asociados en la hipertensión. Nuestro grupo ha realizado un GWAS en población hipertensa con el objetivo de identificar una serie de marcadores involucrados en el incremento de la excreción urinaria de albúmina. Nuestro objetivo actual es verificar las asociaciones encontradas, así como otras asociaciones descritas para otras poblaciones. Materiales y Métodos: Se llevó a cabo el genotipado de 1.536 SNPS, procedentes del GWAS realizado previamente por nuestro grupo, en una nueva población hipertensa de 910 individuos utilizando la tecnología Infinium GoldenGate Genotyping Assay de Illumina, a partir de los resultados obtenidos, se validaron mediante secuenciación NGS en la población del Estudio [email protected] (n = 4.785) los 20 SNPs más significativos en su asociación con las variables relacionadas con la excreción urinaria de albúmina. Para el estudio de secuenciación se utilizó la tecnología paired-end 150x2 de Illumina. Resultados: Los análisis realizados dieron como resultado la asociación de varios loci con las variables relacionadas con la excreción urinaria de albúmina en la población general: rs6972824 (p.valor 0.015) y rs2820950 (p.valor 0.016). También se obtuvieron resultados para la asociación con la enfermedad renal crónica de los polimorfismos rs13232567 (p.valor 1.03e-3) y rs12322500 (p.valor 0.037). Así mismo se realizaron los análisis en la población hipertensa en la cual se asoció con los valores de excreción urinaria de albúmina, cuantitativa o cualitativamente los polimorfismos rs3114316 (p.valor 7.35e-3), rs3114316 (p.valor 0.031), rs6972824 (p.valor 0.014) y rs9950398 (p.valor 0.030), asociándose también con los valores de presión arterial. Conclusiones: Según nuestros estudios, diferentes marcadores genéticos se asocian con los valores de excreción urinaria de albúmina, además algunos de ellos se han asociado a su vez con los valores de presión arterial. Estos resultados ponen de manifiesto la relación genética entre los valores de excreción urinaria de albúmina y presión arterial.IDENTIFICATION OF GENETIC FACTORS ASSOCIATED WITH THE DEVELOPMENT OF MICROALBUMINURIA IN ESSENTIAL HYPERTENSION Urinary albumin excretion is one of the most commonly used risk markers in the development of cardiovascular disease. High urinary albumin excretion values are caused by an increase of the glomerular filtration at the proximal tubule, which may be caused by a systematic increase in blood pressure. The presence of microalbuminuria has traditionally been studied in relation to other cardiovascular risk factors such as diabetes mellitus and hypertension, due to the relevance of these pathologies in the development of organic damage. There are multiple studies that seek to establish a genetic basis in the increase of urinary albumin excretion values associated with hypertension. Hypothesis and Objectives: There is a genetic basis of complex traits in increasing urinary albumin excretion levels associated with hypertension. Our group has performed a GWAS in a hypertensive population with the goal of identifying different markers involved in the increase of the urinary albumin excretion. Our current objective is to verify the associations found previously, as well as other associations described for other populations. Materials and Methods: Genotyping of 1,536 SNPS from the GWAS previously performed by our group was carried out in a hypertensive population of 910 individuals using the Infinium GoldenGate Genotyping Assay technology from Illumina. From the results obtained, we validated by NGS sequencing in the population of the [email protected] Study (n = 4,785) the 20 most significant SNPs in their association with urinary albumin excretion-related variables. For the sequencing study, the technology was NGS paired-end 150x2 from Illumina. Results: The analysis performed resulted in the association of several loci with urinary albumin excretion -related variables in the general population: rs6972824 (p.value 0.015) and rs2820950 (p.value 0.016). Results were also obtained for the association between chronic kidney disease and rs13232567 (p.value 1.03e-3) and rs12322500 (p.value 0.037) polymorphisms. We also performed analysis in the hypertensive population of [email protected] Study in which we observed association between the urinary albumin excretion levels, as a quantitative or qualitative trait, and the polymorphisms rs3114316 (p.value 7.35e-3), rs3114316 (p.value 0.031), rs6972824 (p.value) 0.014) and rs9950398 (p.value 0.030). These SNPs were also associated with blood pressure values. Conclusions: According to our studies, different genetic markers are associated with urinary albumin excretion values, in addition, some of them have been associated with blood pressure values. These results highlight the genetic basis of the relationship between urinary albumin excretion and blood pressure levels

Prórroga en contratación pública. Conceptos reclamables y vías de reclamación en los supuestos en los que se sigue realizando la prestación de un contrato público tras su finalización

El presente trabajo tratará de abordar las disfuncionalidades que se pueden detectar en la adecuada delimitación de la duración de los contratos públicos, la correcta aplicación de su régimen de prórrogas y el cumplimiento de los deberes de planificar y programar la actividad contractual, centrando su análisis en las prórrogas de los contratos una vez transcurrido el plazo máximo previsto en el pliego y las consecuencias que ello entraña para el contratista. En concreto, se trata de analizar los distintos conceptos reclamables y las diferentes vías de reclamación.Depto. de Derecho AdministrativoFac. de DerechoTRUEsubmitte