Structure-function relationship in viral RNA genomes: The case of hepatitis C virus

The acquisition of a storage information system beyond the nucleotide sequence has been a crucial issue for the propagation and dispersion of RNA viruses. This system is composed by highly conserved, complex structural units in the genomic RNA, termed functional RNA domains. These elements interact with other regions of the viral genome and/or proteins to direct viral translation, replication and encapsidation. The genomic RNA of the hepatitis C virus (HCV) is a good model for investigating about conserved structural units. It contains functional domains, defined by highly conserved structural RNA motifs, mostly located in the 5’-untranslatable regions (5’UTRs) and 3’UTR, but also occupying long stretches of the coding sequence. Viral translation initiation is mediated by an internal ribosome entry site located at the 5’ terminus of the viral genome and regulated by distal functional RNA domains placed at the 3’ end. Subsequent RNA replication strongly depends on the 3’UTR folding and is also influenced by the 5’ end of the HCV RNA. Further increase in the genome copy number unleashes the formation of homodimers by direct interaction of two genomic RNA molecules, which are finally packed and released to the extracellular medium. All these processes, as well as transitions between them, are controlled by structural RNA elements that establish a complex, direct and long-distance RNARNA interaction network. This review summarizes current knowledge about functional RNA domains within the HCV RNA genome and provides an overview of the control exerted by direct, long-range RNA-RNA contacts for the execution of the viral cycle.Spanish Ministry of Economy and Competitiveness, No. BFU2012-31213; Junta de Andalucía, No. CVI-7430; and FEDER funds from the EUPeer reviewe

The role of the RNA-RNA interactome in the hepatitis C virus life cycle

RNA virus genomes are multifunctional entities endowed with conserved structural elements that control translation, replication and encapsidation, among other processes. The preservation of these structural RNA elements constraints the genomic sequence variability. The hepatitis C virus (HCV) genome is a positive, single-stranded RNA molecule with numerous conserved structural elements that manage different steps during the infection cycle. Their function is ensured by the association of protein factors, but also by the establishment of complex, active, long-range RNA-RNA interaction networks-the so-called HCV RNA interactome. This review describes the RNA genome functions mediated via RNA-RNA contacts, and revisits some canonical ideas regarding the role of functional high-order structures during the HCV infective cycle. By outlining the roles of long-range RNA-RNA interactions from translation to virion budding, and the functional domains involved, this work provides an overview of the HCV genome as a dynamic device that manages the course of viral infection.This work was supported by the Spanish Ministerio de Economía y Competitividad (BFU2015-64359-P) grant to A.B.-H.; work at our laboratory is partially supported by FEDER funds from the E

La flexibilidad en la Arquitectura. Estrategias de Junya Ishigami

Este trabajo ofrece una investigación de nuevas formas de trabajar a través de la arquitectura experimental japonesa. El arquitecto estudiado es Junya Ishigami, un innovador en su campo. Se basa en conocer, y así clasificar los proyectos más significativos para mí respecto unos conceptos generales y básicos, como lo es la estructura, la materialidad, la luz, los recorridos y los espacios de estancias. Así, conocer los soportes que usa como esqueleto del edificio, los materiales empleados en sus proyectos, la manera de iluminarse ya sea natural o artificial y, por último, como se transitan las zonas generadas para ello.This work offers an investigation of new ways of working through the japanese experimental architecture. The architect studied is Junya Ishigami, an innovator in his field. It is based on knowing, and thus classifying the most significant projects for me with respect to general and basic concepts, such as structure, materiality, light, routes and living spaces. Thus, to know the supports that it uses as a skeleton of the building, the materials used in its projects, the way to illuminate itself, whether natural or artificial, and, finally, how the areas generated for it are transited.Universidad de Sevilla. Grado en Fundamentos de la Arquitectur

Turismo en ciudades patrimonio de la humanidad. Reflexiones desde el periodo post-covid en la zona de la Axerquía, Córdoba. El caso de San Francisco-Ribera

El turismo es el motor principal que mueve la economía mundial. Con este Trabajo de Fin de Grado, se pretende conocer los impactos producidos en las ciudades, concretamente en sus centros históricos, como consecuencia de un turismo descontrolado (turismo masivo). Dichos impactos tienen connotaciones positivas y negativas, siendo estas últimas el detonante de cambios y transformaciones para una pérdida de identidad de la ciudad. Las áreas metropolitanas pretenden competir a escala global como destinos turísticos. Para ello, se basan en unas políticas urbanas neoliberales donde prima el mercado. Estos territorios se transforman en parques temáticos con paisajes homogéneos. Renuevan zonas deterioradas ya sea bien para atraer a un sector determinado (gentrificación) o al turista (turistificación). En ambos casos, el sector perjudicado es la población residente, que llegan a no reconocer el lugar donde ha vivido la mayor parte de su vida. El aumento del precio del suelo, la renovación de viviendas y la pérdida del comercio local son algunas de estas consecuencias negativas. En Córdoba, una parte del centro histórico está totalmente turistificado y se está extendiendo por la zona de la Axerquía, región perteneciente al centro histórico donde ya se evidencian signos de que el distrito se está gentrificando. En este trabajo se estudiará uno de sus barrios para la investigación y corroboración de que este proceso está ocurriendo.Tourism is the main engine that drives the world economy. With this Endof-Degree Research Project, it is intended to know the impacts produced in cities, specifically in their old towns, as a consequence of uncontrolled tourism (mass tourism). These impacts have positive and negative connotations, the latter being the trigger for changes and transformations for a loss of identity of the city. Metropolitan areas seek to compete on a global scale as tourist destinations. To do this, they are based on neoliberal urban policies where the market prevails. These territories are transformed into theme parks with homogeneous landscapes. They renovate deteriorated areas either to attract a certain sector (gentrification) or tourists (touristification). In both cases, the affected sector is the resident population, who doesn’t recognize the place where they have lived most of their lives. The increase in the price of land, home renovation and loss of local trade are some of these negative consequences, In Córdoba, a part of the old town is fully touristic and it’s spreading through the Axerquía area, a region belonging to the old town where there are already signs that the district is gentrifying. In this research, one of its neighborhoods will be studied for the investigation and corroboration that this process is taking place.Universidad de Sevilla. Grado en Fundamentos de la Arquitectur

Análisis de la legislación que regula la Distribución de los Bienes Comunales a causa del Divorcio en Nicaragua

El divorcio es un tema muy polémico puesto que tras intentar disolver el vímatrimonial existente entre los cónyuges, acarrea consigo efectos jurídicos que afectan a terceros, por lo cual es importante realizar un estudio minucioso y exhaustivo de l os efectos que surge a raíz de este . Esta investigación tiene como finalidad realizar un análisis sobre los tipos de regímenes matrimoniales en la disolución del vínculo matrimonial, por lo que se utilizó el método cualitativo, análisis, recolección de datos teóricos y prácticos a través de textos, sitios web, trabajos monográficos, expedientes logrando desarrollar tres capítulos que tratan respectivamente sobre generalidades de la disolución del vínculo matrimonial, regímenes matrimoniales y legislación que regula esta materia. Siendo necesario analizar el tipo de régimen económico que los cónyuges deciden constituir, y poder encontrar de esta forma cual sería el beneficio que se obtendría de cada régimen para los esposos que decidan poner fin a su relación conyugal y por consiguiente darnos cuenta si ambos adquieren igualdad de derechos como resultado de la disolución del vínculo matrimonial. En conclusión se considera que Nicaragua debe recoger en un sola norma todo lo relacionado a los regímenes económicos matrimoniales enfocada a garantizar una efectiva y justa liquidación del régimen que los cónyuges hayan estipulado al celebrar capitulaciones matrimoniales antes o durante su matrimonio con la finalidad de que exista una igualdad de derechos ante la ley una vez que se decida romper con su lazo conyugal

Synthesis and study of biological activity of tetrahydro-1H-[3]-benzazepines

The 3-Benzazepines are an important class of compounds in drug discovery due to their biological activity such as analgesic, antihypertensive or anticancer properties as well as dopaminergic or antidopaminergic activity. In particular, the tetrahydro-1H-[3]- benzazepine is a common skeleton in a number of natural and pharmaceutical products. As consequence of the interesting biological properties, derivatives of the tetrahydro-1H-[3]-benzazepines, especially the 1-aryl substituted have been synthesized by different routes and evaluated their pharmacologic activity. [1,2] The stereoselective synthetic approaches of tetrahydro-1H-[3]-benzazepine have focused on ring enlargements, as the Stevens rearrangement (SR) which is a good regio- and diastereoselective synthetic methodology. In my research group, the reaction conditions to synthesize tetrahydro-1H-[3]-benzazepines 1,2-disubstituted by via SR from tetrahydroisoquinolinium salts conveniently functionalized have been optimized. [3,4] This methodology allowed us to obtain a wide variety of tetrahydro-1H-[3]- benzazepines 1,2-disubstituted with different substituents at A-ring (Cl, OMe) and the C-1 (-C6H4X, X = H, OMe, Cl, NO2, NMe2, NH2, SMe) and C-2 (Electron-withdrawing groups) positions. The demethylation of the synthesized tetrahydroisoquinolines and tetrahydro-1H-[3]-benzazepines 1,2-disubstituted, lead us to get catechol structure, an important requirement for their dopaminergic activity. We have studied the dopaminergic activity of the synthesized compounds by radioligand binding assays, establishing a structure-activity relationships. Literature: [1] A. Gini, Adv. Synth. Catal. 2016, 358, 4049. [2] H. Damsen, Eur. J. Org. Chem. 2015, 36, 7880. [3] M. Valpuesta, Eur. J. Org. Chem. 2010, 23, 4393. [4] M. Ariza, Eur. J. Org. Chem. 2011, 32, 6507.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of bioactive compounds. Studies of their attachment to nanoparticles

The 1-aryl tetrahydroisoquinolines have attracted great attention in medicinal chemistry due to their biological activity. These compounds present antitumor, anti-HIV and antibacterial activities. Several analogues of 1-aryl tetrahydroisoquinoline are used for the treatment of neurodegenerative diseases such as Parkinson´s and Alzheimer´s diseases since also act as dopaminergic antagonists and N-methyl-D-aspartate receptor antagonist. [1] The 1-substituted tetrahydro-3-benzazepines have also been studied for their affinity to the Phencylclidine binding site of the NMDA receptor as well as for their affinity to the dopaminergic receptors. [2] In the last years, various methods have been carried out to satisfy the demand of novel tetrahydroisoquinolines and tetrahydro-3-benzazepines. We have synthesized nor-1-aryl tetrahydroisoquinolines with different substituents in the aryl group of C-1 (H, NMe2, SMe, NO2, NH2). In addition to this, we have performed the synthesis of nor-tetrahydro-3-benzazepinas by different routes, obtaining the best results via opening of epoxides by arylphenethylamines and subsequent cyclization. The nor-tetrahydroisoquinolines and nor-tetrahydro-3-benzazepines have been derivatized to obtain appropiate adsorbates which can be attached to nanoparticles. This fact is crutial in drug delivery systems as well as in the improvement of the biocompatibility of these compounds. Literature: [1] Toshiaki Saitoh, Eur. J. Med. Chem. 2006, 41, 241. Mattias Ludwig, Eur. J. Med. 2006, 41, 1003. [2] Olaf Krull, Bioorg. Med. Chem. 2004, 12, 1439.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Inhibition of hepatitis C virus internal ribosome entry site-mediated translation by an RNA targeting the conserved IIIf domain

Hepatitis C virus (HCV) translation initiation depends on an internal ribosome entry site (IRES). We previously identified an RNA molecule (HH363–10) able to bind and cleave the HCV IRES region. This paper characterizes its capacity to interfere with IRES function. Inhibition assays showed that it blocks IRES activity both in vitro and in a human hepatoma cell line. Although nucleotides involved in binding and cleavage reside in separate regions of the inhibitor HH363–10, further analysis demonstrated the strongest effect to be an intrinsic feature of the entire molecule; the abolishment of either of the two activities resulted in a reduction in its function. Probing assays demonstrate that HH363–10 specifically interacts with the conserved IIIf domain of the pseudoknot structure in the IRES, leading to the inhibition of the formation of translationally competent 80S particles. The combination of two inhibitory activities targeting different sequences in a chimeric molecule may be a good strategy to avoid the emergence of resistant viral variants.This work was supported by grant BFU2006-02568 from the Spanish Ministerio de Educación y Ciencia and CTS-233 from the Junta de Andalucía to A. B-H C. R-L was funder by grant BMC2003-669. R. D-G was the recipient of a fellowship from the Spanish Ministerio de Educación y CienciaPeer reviewe

La Asociación de Flautistas de España como instrumento de formación, difusión e innovación

Sin resumenDepartamento de Didáctica de la Expresión Musical, Plástica y CorporalMáster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

Aptamers: Future Pharmaceutical Drugs

In vitro selection strategies are powerful tools for the identification of nucleic acids with unsuspected activities. Their successful application during last two decades has positioned these technologies among those most promising for the development of therapeutic and diagnostic agents. Aptamers are DNA or RNA molecules with special conformational features, able to efficiently bind to a target molecule. They are obtained by SELEX, a particular in vitro selection strategy, and have found utility during last years as a novel class of pharmaceuticals compounds. This review summarizes the progress made in the use of aptamers as therapeutic agents, paying special attention to those examples that have concluded in pharmacological formulations currently included in preclinical and clinical trials.The work in the group of A.B.-H. is funded by grant BFU2009-08137 from the Spanish Ministry of Science and Innovation; grant CTS-5077 from the Junta de Andalucía; and by FEDER funds from the EU.Peer Reviewe