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Cardiovascular diseases are, as of now, the main cause of death in the developed world. Aging is amain risk factor determining their development. In most of the cases, pharmacological treatments donot directly asses the problem and have only palliative effects, which decreases quality life of thepatient and increase dependence on the treatment to follow a normal lifestyle. Therefore, looking fornovel effective therapies to treat the cause of the disease will be crucial in the near future.microRNAs (miRNA) have been proved to be master regulators of many biological processes that takeplaces in the cell, since they are capable of regulating gene expression. Studies in vitro and in vivo haveassociated dysregulation of the miRNAs expression with pathology in cardiovascular disease and aging,thus postulating them as possible therapeutic targets.As result, miRNAs-mimics and anti-miRs have emerged as a new promising therapeutic approach tocorrect gene expression alterations regulated by miRNAs that have been seen in disease. Here, adetailed revision of the application of miRNA-based therapies to treat CVD is made. Although, currentlythere are only 2 studies that have reached clinical trials, many preclinical studies have publishedencouraging results.Continuing previous work of the group BSICoS, a second aim of this master’s thesis is to develop toolsfor the study of the interaction of age-related miRNAs (BIO-AGEmiRNA) with their target genes inrelation to cardiac function using human iPSC-derived cardiomyocytes. A inducible expression vectorwas created to be expressed mature miRNAs, specifically miR-4435, downstream of a fluorescentreporter gene. The vector was tested in vitro in HEK293 cells and proper expression of the reporterwas observed. However, expression of the mature miR-4435, and therefore proper processing of thepre-miRNA, could not be confirmed due to technical issues. Future work will continue to validate theremaining BIO-AGE-miRNAs in vitro, first in HEk393 and then in iPSC-derived cardiomyocytes were themolecular mechanism and functionality of the BIO-AGEmiRNAs will be investigated. The developedvector will be most certainly a useful tool to complete this future work.

Cardiovascular diseases (CVD) are one of the main causes of death that affect worldwide. Thereare several risk factors for the development of CVD, among them, aging is important, whichimplies the anatomical and functional deterioration of the heart. CVD constitute a great burdenin advanced societies. There is a need for the development of therapies and non-invasiveprognostic and diagnostic biomarkers to effectively tackle them. microRNAs (miRNAs) are smallRNAs known to regulate main biological process. For this reason, miRNAs have been proposedas a powerful therapeutic targets or biomarkers.Here the role of miRNAs in the development of CVD and cardiac aging has been reviewed. Inaddition, the translation level of results in animal models to human has been investigated. Asresult, a complete compilation of miRNAs that contribute to CVD and cardiac aging is offered.This literature compilation points out that the great majority of the described miRNAs remainunstudied in human. Based in the high degree of miRNA sequence conservation between speciesand their target sequences, similar functions could be expected in human. Yet, otherphysiological differences in comparison with animal models could suggest the contrary. Toassess the contribution of miRNA in cardiac related pathophysiology, cardiomyocytes derivedfrom human induced pluripotent stem cells (iPSC-CMs) emerge as a model for their studyavoiding this translation difficulties.In addition, the BSICoS group has built a bioinformatic regulatory network controlled by miRNAsassociated with biological age (BIO-AGEmiRNAs) of the human myocardium. Experimentalvalidation of the interactions within this network is required. A new cost-effective validation toolhas been built using fluorescence. Last, luciferase reporter assays (DualGlo assay) are used tostudy interaction of cardiac-related genes with miR-3916. As a result, positive interaction trendshave been observed for CASQ2, ACTN2 and DSP with miR-3916. This fact highlights the potentialof miRNAs in the regulation of genes associated with human cardiac aging and CVD and theirpowerful value as therapeutic targets.

[EN] The invention relates to peptides of general formula S, wherein the carboxyl terminus (D-alanine, D-Ala) is replaced by an analogous amino alcohol. The invention also relates to the method for synthesising same and the use of the aforementioned peptides to treat inflammatory diseases. Formula (I), [ES] La invención se refiere a péptidos de fórmula general S, donde el extremo carboxilo terminal (D-Alanina, D-Aia) es reemplazado por un amlnoalcohol análogo. La invención también se refiere a su procedimiento de síntesis y al uso de los péptidos mencionados para el tratamiento de enfermedades inflamatorias. Formula (I), [FR] L'invention concerne des peptides de formule générale S, où l'extrémité carboxyle terminale (D-alanine, D-ala) est remplacée par un amino-alcool analogue. L'invention concerne également son procédé de synthèse et l'utilisation des peptides mentionnés pour le traitement de maladies inflammatoires. Formule (I), Consejo Superior de Investigaciones Científicas (España), Universidad Autónoma de Madrid, A1 Solicitud de patente con informe sobre el estado de la técnica

Uno de los criterios de evaluación contemplados en el currículum del tercer curso de la ESO en la asignatura de Biología y Geología es explicar la misión integradora del sistema nervioso ante diferentes estímulos y describir su funcionamiento. La actividad presentada tiene como objetivo el aprendizaje del funcionamiento de parte del sistema nervioso a nivel celular. Se usan modelos de órganos y neuronas en dos dimensiones para que los alumnos construyan un modelo de circuito neuronal que ocurre en distintas situaciones cotidianas tanto de actos voluntarios como de actos reflejos. La explicación del modelo se graba en vídeo. Para la evaluación de la actividad se dispone de instrumentos variados incluyendo rúbricas para la auto- y coevaluación.