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This undergraduate dissertation contributes to the existing scholarship about witches by exploring the intricate and myriad representations of the symbol over time, concretely, from its origin in the Early Modern Period to its revalorization in the present time. In addition, certain identities of the witch are analyzed: as a monster, as a girl, as a mother, as an old hag, as an herbalist-healer-midwife witch, queer and black. The focus of the research is Alix E. Harrow‘s postmodernist novel The Once and Future Witches. In it, the figure of the witch, affected by the shattered postmodern actuality, is reappropriated as a signifier of feminism. However, this study also reflects on the potential contradictions derived from its imitation of the shifting tendencies of the movement. The key findings demonstrate the advancement of the feminist agenda of the novel, although pointing simultaneously to regressive and patriarchal ideologies that are difficult to detach from the figure., Este trabajo de fin de grado contribuye a la bibliografía existente sobre brujas mediante la exploración de las complejas y múltiples representaciones del símbolo a lo largo del tiempo, en concreto, desde su origen en la Edad Moderna hasta su revalorización en la actualidad. A su vez, se analizan determinadas identidades de la bruja: como monstruo, como chica, como madre, como una anciana bruja, como una curandera o matrona, queer o negra. El enfoque de esta investigación es la novela postmodernista de Alix E. Harrow Las Brujas del Ayer y del Mañana. En ella, la figura de la bruja, siendo afectada por el mundo postmoderno fragmentado, es reapropiada como un significante del feminismo. Sin embargo, este estudio también refleja las posibles contradicciones derivadas de su imitación de las cambiantes corrientes del movimiento feminista. Los principales hallazgos demuestran el avance de la agenda feminista de la novela, aunque señalan simultanéamente las ideologías patriarcales y regresivas tan difíciles de separar de la figur, Departamento de Filología Inglesa, Grado en Estudios Ingleses

Gothic literature emerged in the eighteenth century, with the latter half of that century seeing its emergence on the American continent. While initially rejected due to American practicality, writers quickly adapted Gothic literary aspects to fit their cultural traits. Edgar Allan Poe, a well-known American Gothic writer of the twentieth century, exemplifies this trend in his work “The Fall of the House of Usher”. In 2023, Mike Flanagan created a contemporary adaptation of the work as a Netflix series, which is based on the original work, but also references both other works by Poe and his own life. The aim of this essay is to explore how the American Gothic has been modified in a twenty-first century TV series, while showing how one short story by Poe is used as framework for his whole life and works., La literatura gótica surgió en el siglo XVIII, siendo la segunda mitad de ese siglo testigo de su aparición en el continente americano. Aunque en un principio fue rechazada debido a la practicidad americana, los escritores no tardaron en adaptar los aspectos literarios góticos a sus rasgos culturales. E. A. Poe, conocido escritor gótico estadounidense del siglo XX, ejemplifica esta tendencia en su obra “La caída de la casa Usher”. En 2023, Mike Flanagan creó una adaptación contemporánea de la obra como serie de Netflix, basada en la obra original, pero también referencia a otras obras de Poe y a su propia vida. El objetivo de este ensayo es explorar cómo se ha modificado el gótico americano en una serie de televisión del siglo XXI, mostrando a su vez cómo un relato corto de Poe se utiliza como marco para toda su vida y obra., Departamento de Filología Inglesa, Grado en Estudios Ingleses

Telomeres are nucleoprotein structures at the end of chromosomes that maintain their integrity. Mutations in genes coding for proteins involved in telomere protection and elongation produce diseases such as dyskeratos is congenita oridiopathic pulmonary fibrosis known as telomeropathies. These diseases are characterized by premature telomere shortening, increased DNA damage and oxidative stress. Genetic diagnosis of telomeropathy patients has identified mutations in the genes TERT and TERC coding for telomerase components but the functional consequences of many of these mutations still have to be experimentally demonstrated. The activity of twelve TERT and five TERC mutants, five of them identified in Spanish patients, has been analyzed. TERT and TERC mutants were expressed in VA-13 human cells that express low telomerase levels and the activity induced was analyzed. The production of reactive oxygen species, DNA oxidation and TRF2 association at telomeres,DNA damage response and cell apoptosis were determined.Most mutations presented decreased telomerase activity,as compared to wild-type TERT and TERC.In addition,the expression of several TERT and TERC mutants induced oxidative stress, DNA oxidation, DNA damage, decreased recruitment of the shelterin component TRF2 to telomeres and increased apoptosis.These observations migh tindicate that the increase in DN Adamage and oxidative stress observed in cells from telomeropathy patients is dependent on their TERT or TERC mutations. Therefore, analysis of the effect of TERT and TERC mutations of unknown function on DNA damage and oxidative stress could be of great utility to determine the possible pathogenicity of these variants.

The purpose of this study is to prove the subversion of the figure of the Victorian woman in Sarah Waters’ neo-Victorian novel Fingersmith. Fingersmith follows the story of two women tangled in a web of lies and manipulations that will ultimately fall in love with each other in the process. Lesbian representation in literature is especially worthy of recovering and elevating, since it is lacking as opposed to the amount of literature that the gay community can claim from the Victorian period. Following the research from different critics in the background of the Victorian era, gender roles, feminism and lesbian fiction we will analyse how Sarah Waters female protagonists fit into their theories and if they, in fact, succeed in subverting the stereotype of the Victorian woman., El objetivo de este estudio consiste en probar la subvesión de la figura de la mujer victoriana en la novela neo-Victoriana Fingersmith o Falsa Identidad de Sarah Waters. Falsa Identidad es la historia de dos mujeres envueltas en una trama de mentiras y manipulaciones que se acabarán enamorando en el proceso. La representación lésbica en la literatura es digna de ser recuperada y elevada, ya que es escasa en comparación con la cantidad de literatura victoriana que puede ser revindicada por la comunidad gay. Continuando con la investigación de diferentes críticos especializados en la era victoriana, roles de género, feminismo y literatura lésbica analizaremos cómo los personajes femeninos de Sarah Waters encajan en sus teorías y si, en realidad, la autora consigue subvertir el estereotipo de la mujer victoriana con éxito., Departamento de Filología Inglesa, Grado en Estudios Ingleses

Even though innovation inside literary fiction has been widely studied, there is scarce information and research carried out about the new subgenres that appear as a product of the hybridization of traditional genres. This undergraduate dissertation tries to fill that empty space by analyzing a potential new subgenre, dystopian fantasy. This is achieved by constructing a framework consisting of the most relevant elements for both fantasy and dystopian fiction and using it to analyze Brandon Sanderson’s The Final Empire. The selection of this specific novel derives from its massive success and from the influence it has had in other media despite its contemporaneity. The analysis of this novel provides tangible examples, which in turn solidify the theoretical framework and make it more reliable. The consolidation of this framework promotes the further exploration and analysis of other comparable stories, as a means to relabel them as necessary., Aunque la innovación en la ficción literaria se ha estudiado de manera exhaustiva, hay escasa información y estudios sobre los nuevos subgéneros que han surgido de la hibridación de los géneros tradicionales. Este trabajo de fin de grado intenta llenar ese vacío con el análisis de un posible nuevo subgénero, la fantasía distópica. Para ello, se ha construído un marco teórico formado por los elementos más relevantes de la ficción fantástica y de la distópica, que se utilizan para analizar El Imperio Final, de Brandon Sanderson. La elección de esta novela deriva de su éxito masivo y de su influencia en otros medios a pesar de su contemporaneidad. El análisis de esta novela proporciona ejemplos tangibles, que a su vez solidifican el marco teórico y lo hacen más fiable. La consolidación de este marco promueve la exploración y análisis de otras historias similares, como método para reetiquetarlas según sea necesario., Departamento de Filología Inglesa, Grado en Estudios Ingleses

The early modern period experienced a more well-rounded creation of one of the most popular scapegoats at the time: the witch. As a result, thousands of women and men (to a lesser extent) were victims of the witch hunts in Europe, which also translated to New England. The following dissertation aims to discover and compare in which ways the stereotype of the early modern period is represented in the films The Witch and Akelarre. Following a thorough analysis of the characteristics of the witches in both films, light will be shed on how accurate the stereotype of the witch is represented in these, as well as how culture represents traditional imagery of witchcraft in contemporary society., La edad moderna fue testigo de la creación de una visión más compleja de uno de los chivos expiatorios más comunes de la época: la bruja. Como resultado, miles de mujeres y hombres (en menor medida) fueron víctimas de las cazas de brujas europeas, las cuales también se trasladaron a Nueva Inglaterra. El siguiente Trabajo de Fin de Grado tiene como objetivo descubrir y comparar de qué forma se representa el estereotipo de la bruja de este periodo en las películas La bruja y Akelarre. Tras un análisis completo de las características de las brujas en ambas películas, podremos concluir la fidelidad con que se representa el estereotipo de la bruja, además de cómo la cultura representa imágenes tradicionales como la brujería en la sociedad de hoy en día., Departamento de Filología Inglesa, Grado en Estudios Ingleses

Kv4 channels generate rapidly activating and inactivating outward currents responsible for the repolarization of both cardiac and neuronal action potentials through ITO (transient outward current) and IA (A-type Kþ current), respectively. Kv4 dysfunctions have been identified in both cardiac and neuronal diseases (Brugada syndrome, atrial fibrillation, epilepsy or Alzheimer’s disease). However, Kv4 channels need to assemble with regulatory subunits to fully reproduce ITO and IA currents. Among them, we will focus on KChIPs (potassium channel interacting proteins), being KChIP3 predominant in the brain and KChIP2 in both brain and heart. The assembly of these regulatory subunits not only modulates the biophysical properties of the channel, but also its pharmacology. For this reason, we have analysed the electrophysiological effects of IQM-22110 (a novel KChIP3 ligand) on the currents generated by Kv4.3, Kv4.3/KChIP3 and Kv4.3/KChIP2 channels. CHO cells were transiently transfected, and the potassium currents were recorded using the whole-cell patchclamp technique. Our results indicate that IQM-22110 exerts differential effects on these currents, being the concentration-dependence of inhibition modified, exhibiting a biphasic curve when KChIP3 is present, thus suggesting two binding sites for IQM-22110 in this complex. With molecular dynamics and site-directed mutagenesis, we have identified the binding pocket corresponding to the high affinity site. Also, we have demonstrated that IQM-22110 binds to the closed-active state of the channel. In this study: i) IQM-22110 has proven to be a selective inhibitor of Kv4.3/KChIP3 at low concentrations, and ii) a new binding pocket for selective KChIP3/Kv4.3 ligands has been identified.

SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.

Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics. Here, we evaluated the mechanical antinociceptive effect of IQM-PC332, a novel ligand of the multifunctional protein downstream regulatory element antagonist modulator (DREAM) in rats subjected to chronic constriction injury of the sciatic nerve as a model of neuropathic pain. IQM-PC332 administered by intraplantar (0.01–10 µg) or intraperitoneal (0.02–1 µg/kg) injection reduced mechanical sensitivity by ≈100% of the maximum possible effect, with ED50 of 0.27 ± 0.05 µg and 0.09 ± 0.01 µg/kg, respectively. Perforated-patch whole-cell recordings in isolated dorsal root ganglion (DRG) neurons showed that IQM-PC332 (1 and 10 µM) reduced ionic currents through voltage-gated K+ channels responsible for A-type potassium currents, low, T-type, and high voltage-activated Ca2+ channels, and transient receptor potential vanilloid-1 (TRPV1) channels. Furthermore, IQM-PC332 (1 µM) reduced electrically evoked action potentials in DRG neurons from neuropathic animals. It is suggested that by modulating multiple DREAM–ion channel signaling complexes, IQM-PC332 may serve a lead compound of novel multimodal analgesics., Ministerio de Ciencia e Innovación (MICINN)/FEDER, Instituto de Salud Carlos III (ISCIII), Universidad Complutense, Consejo Superior de Investigaciones Científicas (CSIC), Sección Deptal. de Farmacología y Toxicología (Veterinaria), Fac. de Veterinaria, TRUE, pub

Postmodernism in literature seeks to create new forms since it considers that everything has already been invented. For this reason, retellings arose, which are reinterpretations of previous works. This project will explain what masculinities consist of and what their objective is, in addition to showing what gender roles and stereotypes are attributed to men in fairy tales. Therefore, after an comparison between the male characters of four fairy tales in their original version and their respective postmodern versions, we will proceed to conclude if the theories that seek to blur rigid gender roles have achieved their goal in postmodern retellings or, on the contrary, the princes continue to maintain them in their physical appearance and behavior., El Postmodernismo en la literatura pretende crear nuevas formas ya que considera que ya está todo inventado. Por ello, surgieron los “retellings”, los cuales son reinterpretaciones de obras previas. En este proyecto se explicarán en qué consisten las masculinidades y cuál es su objetivo, además de mostrar cuales son los roles de género y los estereotipos que se atribuyen a los hombres en los cuentos de hadas. Por lo tanto, tras una comparación entre los personajes masculinos de cuatro cuentos de hadas en su versión original y sus respectivas versiones postmodernas, se procederá a concluir si las teorías que pretenden difuminar los rígidos roles de género han logrado su objetivo en los “retellings” postmodernistas o, por el contrario, los príncipes siguen manteniéndolos en su apariencia física y su comportamiento., Departamento de Filología Inglesa, Grado en Estudios Ingleses

The present invention relates to new derivatives of 2-phenyl-quinoline-4-carboxylic acid or pharmaceutically acceptable salt thereof and to combination of said compounds with other active ingredients, for use in the treatment and/or prevention of viral infections by virus from the family Coronaviridae, to the use of said compound or its combinations in the manufacture of a medicament for the treatment or prevention of said diseases and to a method of treating and/or preventing said diseases by administration of said compound or its combinations.

The present invention relates to new derivatives of 5-(2-(1H-indol-3-yl)ethyl-2-piperazin-2-one or pharmaceutically acceptable salts thereof and to combinations of said compounds with other active ingredients, for use in the treatment and/or prevention of viral infections by viruses from the family Coronaviridae, to the use of said compound or its combinations in the manufacture of a medicament for the treatment or prevention of said diseases and to a method of treating and/or preventing said diseases by administration of said compound or its combinations.

Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Within the heart, KV4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when KV4.3 assembles with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF), the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. Novel KChIP2 ligands could be a useful pharmacological tool to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this communication, we will describe a multidisciplinary approach that, starting with a structure-based virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.

Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.

The outward potassium current IKur is the main responsible of the atrial repolarization process and it is generated by the activation of KV1.5 channels, widely expressed in human atria. It is known that mutations in KCNA5 gene, which induce both gain- and loss-of-function in KV1.5 channel, enhance atrial fibrillation susceptibility. Thus, these channels represent a pharmacological target for the development of antiarrhythmic drugs useful in the treatment of supraventricular arrhythmias. KV1.5 channels assembly with several regulatory subunits such as KVß. It has been described that KVß2.1 interacts with KV1.5. Our research group has demonstrated that the molecule IQM-110 produces electrophysiological effects on the KV1.5. The aim of the present study is to analyze the electrophysiological effects of IQM-110 on KV1.5 channels when it was expressed together with the regulatory subunit KVß2.1. In order to achieve this objective, Ltk- cell line constitutively expressing KVß2.1 and with an induced expression of KV1.5 were used. Currents were recorded using the whole-cell configuration of the patch-clamp technique. The effects of IQM-110 on KV1.5/Kvß2.1 current were concentration-dependent with an IC50 of 166¿M (n=64). This compound at 100¿M produced a time-dependent block, inducing a: 1) faster activation (¿=2.8±0.3 vs. 4.1±0.3 ms, n=10, p<0.01), 2) faster inactivation reducing the slow time constant, (¿slow=3172.6±113.8 vs. 629.1±43.8ms, n=5, p<0.001), and 3) slower deactivation kinetics, (¿slow=73.5±3.5 vs. 115.2±12.1ms and ¿fast=19.5±1.3 vs. 27.9±1.9ms, n=10, p<0.01 and p<0.5 respectively). These results are consistent with an open channel block mechanism. Finally, IQM-110 (100 ¿M) enhanced the degree of use-dependent block of the current (1.7±0.4 vs. 47.7±2.4%, n=5, p<0.001). This phenomenon was explained by a slowing of the recovery process in the presence of IQM-110 (¿r=462.6±94.9 vs. 3545.0±254.1ms, n=5, p<0.001). In summary, IQM-110 modulates KV1.5/KVß2.1 channel

Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions, such as smooth muscle contraction or secretion of hormones. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3 and its role in atrial fibrillation (AF). KV4.3 channel is expressed in smooth muscle, heart and brain. Its activation generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current). KV4.3 plays a key role in AF, the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] To reproduce the ITO currents, KV4.3 channels need to assemble with other subunits, forming channelosome. KChIPs (Potassium Channel Interacting Proteins), which belong to the calcium binding protein superfamily, forms the KV4.3 channelosome, along with other proteins.[3] To study the complex interaction of KV4.3 channelosome and the development of modulators, the interplay of different techniques is central to advance knowledge. In this regard, the development of novel KChIPs modulators and fluorescent biosensors constitutes invaluable pharmacological tools to unravel the KV4 channelosome and its role in AF.[3] In this communication, we will describe preliminary results towards the identification of new pharmacological tools to study the KChIPs/KV4 interaction.

The transient outward potassium current (Itof) is generated by the activation of KV4 chan- nels assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 channels. CHO cells were transiently transfected with cDNAs codifying for different proteins (KV4.3/KChIP2, KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using the whole-cell patch-clamp technique. IQM-266 decreased the maximum peak of KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 currents, slowing their time course of inactivation in a concentration-, voltage-, time- and use-dependent manner. IQM-266 produced an increase in the charge in KV4.3/KChIP2 channels that was intensified when DPP6 was present and abolished in the presence of KCNE2. IQM-266 induced an activation unblocking effect during the applica- tion of trains of pulses to cells expressing KV4.3/KChIP2 and KV4.3/KChIP2/KCNE2, but not in KV4.3/KChIP2/DPP6 channels. Overall, all these results are consistent with a preferential IQM-266 binding to an active closed state of Kv4.3/KChIP2 and Kv4.3/KChIP2/KCNE2 channels, whereas in the presence of DPP6, IQM-266 binds preferentially to an inactivated state. In conclusion, DPP6 and KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266.

Since Freud's first publications on psychoanalysis, society has reacted with amazement to his theories. Taking people's childhood as a starting point and a critical phase of development, Freud analyses people's unconscious to understand the human personality. In addition to considering Freudian psychoanalysis as an important point for this undergraduate dissertation, gender identity will also be studied through the characters and the society in which they live. This is because gender identity has always been a taboo concept in many cultures and its study is important to understand the injustices and obstacles that certain communities have suffered. Hence, this paper aims to analyse the connection between childhood trauma and gender identity in the characters of The Silence of the Lambs (1988) by Thomas Harris to establish that the trauma that occurred in their past is directly connected to discrimination and gender characterization in their current lives., Desde las primeras publicaciones de Freud sobre el psicoanálisis, la sociedad ha reaccionado con asombro ante sus teorías. Tomando la infancia de las personas como punto de partida y fase crítica del desarrollo, Freud analiza el subconsciente de las personas para comprender la personalidad humana. Además de considerar el psicoanálisis freudiano como punto importante para este Trabajo de fin de Grado, también se estudiará la identidad de género a través de los personajes y la sociedad en la que viven. Esto se debe a que la identidad de género siempre ha sido un concepto tabú en muchas culturas y su estudio es importante para entender las injusticias y obstáculos que han sufrido ciertas comunidades. Por tanto, este trabajo pretende analizar la conexión entre el trauma de la infancia y la identidad de género en los personajes de El Silencio de los Corderos (1988), por Thomas Harris, para establecer que el trauma ocurrido en su pasado está directamente conectado con la discriminación y la personificación de género en sus vidas actuales., Departamento de Filología Inglesa, Grado en Estudios Ingleses

La presente invención se refiere al diseño y síntesis de nuevos fluoróforos con aplicación en el desarrollo de biosensores de fluorescencia, y particularmente, a derivados de 8- metoxi-2-oxo-1,2-dihidrociclopenta[de]quinolina y su aplicación como reactivos de marcaje de la luminiscencia de lantánidos. [ES], The present invention relates to the design and synthesis of new fluorophores that can be used to develop fluorescence biosensors, and particularly, to 8-methoxy-2-oxo-1,2-dihydrocyclopenta[de]quinoline derivatives and the use thereof as reagents for labelling lanthanide luminescence. [EN]

La irrupción del coronavirus SARS-CoV-2 y de la pandemia de covid-19 ha planteado un enorme desafío a la ciencia. Buscar soluciones a un virus que ha causado, hasta el momento, 130 millones de infectados y ha provocado casi 3 millones de muertes. Para desentrañar las claves de esta nueva amenaza global, el Consejo Superior de Investigaciones Científicas, el CSIC, puso en marcha en marzo de 2020 la Plataforma Temática Interdisciplinar Salud Global. Su objetivo es coordinar a cientos de equipos de diversas disciplinas en busca de soluciones a la pandemia, creando nuevas redes de colaboración con organismos públicos de investigación, universidades, la clínica y el sector empresarial. La plataforma ha reunido a expertos de la investigación en biomedicina (virólogos, inmunólogos, genetistas y biotecnólogos), junto a químicos y físicos, además de sociólogos y demógrafos. Su trabajo es determinar las características del virus y de la covid-19, y diseñar estrategias que permitan hacer frente a esta y futuras pandemias. Tras un año de investigación, la Plataforma Salud Global ha obtenido conocimientos fundamentales en todos los aspectos de la pandemia: prevención, contención, diagnóstico, terapia y vacunas, e impacto social.

Ion channels are macromolecular complexes present in the plasma membrane and intracellular organelles of cells. Dysfunction of ion channels results in a group of disorders named channelopathies, which represent an extraordinary challenge for study and treatment. In this review, we will focus on voltage-gated potassium channels (KV), specifically on the KV4-family. The activation of these channels generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current) and from the somata of hippocampal neurons (ISA). In the heart, KV4 dysfunctions are related to Brugada syndrome, atrial fibrillation, hypertrophy, and heart failure. In hippocampus, KV4.x channelopathies are linked to schizophrenia, epilepsy, and Alzheimer’s disease. KV4.x channels need to assemble with other accessory subunits () to fully reproduce the ITO and ISA currents. Subunits affect channel gating and/or the traffic to the plasma membrane, and their dysfunctions may influence channel pharmacology. Among KV4 regulatory subunits, this review aims to analyze the KV4/KChIPs interaction and the effect of small molecule KChIP ligands in the A-type currents generated by the modulation of the KV4/KChIP channel complex. Knowledge gained from structural and functional studies using activators or inhibitors of the potassium current mediated by KV4/KChIPs will better help understand the underlying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments.

La presente invención se refiere a un grupo de compuestos con un núcleo estructural derivado de fenilacetamida con la siguiente fórmula (I): que presentan capacidad de modulación del sensor neuronal de calcio DREAM, por lo que la presente invención también se refiere al uso de estos compuestos para el tratamiento o prevención de trastornos o enfermedades donde los niveles de DREAM están por encima o por debajo de los niveles considerados fisiológicamente normales. [ES], The present invention relates to a group of compounds with a structural nucleus derived from phenylacetamide, having the following formula (I): that can modulate the DREAM neuronal calcium sensor. Consequently, the present invention also relates to the use of these compounds for the treatment or prevention of disorders or diseases in which DREAM levels are above or below physiologically normal levels. [EN]

The present invention relates to a family of compounds which are capable of modulating KChIP proteins and are therefore useful for the treatment of heart diseases in which the expression levels of this protein are abnormal. These compounds have the following general formula: (I).