Alberto Sols Biomedical Research Institute
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Más allá de la obesidad: señalización de p38 y comunicación entre órganos en la fisiopatología del tejido adiposo y cardiaco
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 14-09-2023Esta tesis tiene embargado el acceso al texto completo hasta el 14-09-2028Obesity and cardiovascular disease (CVD) remain one of the most significant global public health
challenges of our time, and their incidence is also expected to grow in the coming decades. CVDs
continue to be the leading cause of death globally, regardless of continuous efforts to prevent and curb
them. Obesity is the most common metabolic disorder worldwide and its prevalence has reached
pandemic proportions. Both diseases are closely related, with obesity contributing directly to the
development of CVDs. Adipose tissue dysfunction during obesity directly affects CVD development,
including heart failure, in part due to altered secretion of several adipokines and lipidic metabolites that
affect cardiac function. Stress-activated p38 kinases have been involved in both, metabolic and cardiac
disease, making them a potential target for novel therapeutic strategies. There are four p38 family
members (p38α, p38β, p38γ, and p38δ) that are activated by the upstream kinases MKK3 and MKK6.
To further elucidate the role of the p38 pathway in cardiac physiology, this work explored the impact
of MKK6 deficiency on cardiac hypertrophy and arrhythmia, particularly ventricular fibrillation. The
results obtained indicate that MKK6 deficiency induces hyperactivation of the MKK3-p38γ/δ pathway,
leading to cardiac hypertrophy through the activation of mTOR. Additionally, p38γ/δ activation
promoted susceptibility to stress-induced malignant ventricular arrhythmias by increased
phosphorylation of RyR2 and delocalization of the Kv4.3 channel. This was concomitant with
sarcoplasmic reticulum Ca2+ leak, action potential duration prolongation, and stress-triggered
arrhythmias.
The existing evidence regarding the role of the p38 pathway in adipose tissue physiology indicates
that this pathway is differently regulated in each adipose tissue depot, with each protein kinase of the
pathway having specific functions. Our results show that, upon high-fat diet feeding, global deficiency
of MKK6 in adipose tissue promoted increased body weight gain, together with increased food intake
and plasma and white adipose tissue levels of agouti-related peptide (AgRP). In contrast, deletion of
MKK6 restricted to brown adipocytes led to an opposite phenotype with reduced body weight gain due
to increased energy expenditure and brown adipose tissue temperature. Single-nucleus transcriptomic
analysis corroborated that MKK6 deletion promoted an increased expression of AgRP in adipocyte
progenitor cells within the white adipose tissue, while it caused changes in the populations of brown
adipocytes and an upregulation of genes involved in alternative thermogenic mechanisms in brown
adipose tissue.
Finally, our results show that obesity is associated with a reduced expression of peroxisomeproliferator-
activated receptor-γ coactivator-1α (PGC1α) in adipose tissue from mice and humans and
that depletion of PGC1α in adipose tissue promotes mitochondrial dysfunction, a hallmark of adipose
tissue dysfunction during obesity. Adipose tissue mitochondrial dysfunction due to lack of PGC1α did
not lead to obesity or obesity-related comorbidities, but promoted dilated cardiomyopathy, with
alteration of several plasma proteins potentially mediating a deleterious adipose tissue–heart
communication.
The results of this dissertation provide new insights into the role of the poorly investigated p38γ/δ
kinases in cardiac pathology and further evince a differential role of the p38 pathway in adipose tissue
physiology and obesity susceptibility. Furthermore, they also present a previously unrecognized role of
adipose tissue mitochondrial dysfunction in the promotion of obesity-related cardiomyopathy, including
the alteration of several obesity-associated plasma proteins and metabolite
Neutralidad y Jefatura del Estado
No full textHace dos siglos, Benjamín Constant buscó dar sentido a la Jefatura del Estado y elaboró, a tal efecto, la doctrina del poder neutro o preservador. Un siglo después de Constant, Carl Schmitt se sirvió de la imagen del poder neutro de Constant para construir la figura del Jefe del Estado como guardián de la Constitución, en relación dialéctica con Kelsen. El autor se pregunta si es viable y útil la figura del Jefe del Estado como poder neutral en las modernas democracias parlamentarias y, en particular,en nuestra monarquía parlamentaria. La respuesta a la pregunta la encontrará el lector en el libro que tiene en sus manosTrabajo realizado dentro del Proyecto de investigación financiado por el Plan Nacional de I+D+I: “La neutralidad Institucional en el Estado Constitucional” (PID2019-106043GB-100)
El aristotelismo después de Sila. ¿La (des)legitimación de un corpus?
No full textA partir de un análisis de fuentes procedentes fundamentalmente de Estrabón, Plutarco y Posidonio,
este artículo se propone abordar la transmisión de los textos de Aristóteles después de 84 a.C., fecha en la que
Sila los traslada de Atenas a Roma. Los manuscritos de Aristóteles y de Teofrasto permanecen como propiedad
particular de la familia de Neleo en Escepsis hasta la segunda mitad del II a.C., momento en que afloran de
nuevo. Apelicón consigue obtener los originales y, una vez de regreso a Atenas, se produce su diseminación. En
Roma Andronico adquiere y transmite los textos, ordenados y preparados por Tiranión a partir de los originales
de la biblioteca de Apelicón, pero en su trabajo crítico de edición y catalogación incorpora elementos de la
tradición alejandrina, que permiten la «legitimación» del corpus. Cincuenta años separan el floruit de Apelicón
del de Andronico. Cómo se estableció en este período el corpus aristotélico es, pues, el tema principal discutido
en este artículoAristotelianism after Sulla: the (de)legitimation of a corpus? · Based on an analysis of sources
mainly from Strabo, Plutarch and Posidonius, this article aims to address the transmission of Aristotle's texts
after 84 BC, when Sulla transferred them from Athens to Rome. The manuscripts of Aristotle and Theophrastus
remained the private property of the family of Neleus in Scepsis until the second half of the 2nd century BC,
when they reappeared. Apellicon managed to get hold of the originals and, once back in Athens, they were
disseminated. In Rome, Andronicus acquired and transferred the texts, arranged and prepared by Tyrannio from
the originals in Apellicon's library, whereas in his critical work of editing and cataloguing he incorporated
elements of the Alexandrian tradition, which allowed the corpus to be «legitimized». Fifty years separate
Apellicon's floruit from that of Andronicus. How in this period the Aristotelian corpus was established is thus
the main, much discussed topic of this articl
Crecimiento y caracterización de electrocatalizadores basados en borocarbonitruros y sulfuros metálicos para la producción de hidrógeno a partir de agua
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de Lectura: 20-07-2023Esta tesis tiene embargado el acceso al texto completo hasta el 20-07-2028The current climate situation is alarming due to the increase in global temperature, mainly caused by the emission of greenhouse gases from fossil fuel-based energy sources. In order to slow down this process, the energy transition to renewable sources has been proposed. However, one of the main problems of these clean sources is their intermittency, as their generation depends on factors such as the availability of the sun or wind. In this situation, hydrogen has become a promising option as an energy vector, as it can store renewable energy and permits its transport. Moreover, its production from water does not emit greenhouse gases if renewable energies are used.
There are several ways of obtaining clean hydrogen, including electrolysis and photoelectrolysis of water. Today, commercial electrolysers use electrodes based on elements that are relatively expensive and scarce, which could create new environmental and economic problems. Therefore, it is important to ensure that the materials used in their production are abundant, non-toxic, sustainable, efficient, and cheap.
This is the context of the present PhD thesis, in which materials based on elements abundant on Earth, such as nitrogen, carbon, oxygen, sulfur and titanium (among others), have been synthesised. Subsequently, an exhaustive characterization of these materials has been carried out using different morphological, structural, compositional, and optical characterization techniques. Finally, their properties for the water splitting reaction using electricity (electrolysis) or electricity and light (photoelectrolysis) have been investigated.
Different materials have been investigated in this thesis work, aiming at their use in different reactions related to the water splitting. First, ultrathin borocarbonitride (BCNs) layers have been grown on different photoanodes (flat Ti disks with a TiOx surface layer and TiO2 nanoribbons), to be used as electrocatalysts for the oxygen evolution reaction. Second, titanium trisulfide photoanodes (TiS3) have been protected against corrosion in alkaline aqueous media by growing a thin titanium dioxide layer (TiO2). Different electrocatalysts have been grown on these TiS3/TiO2 heterostructures in order to improve their photoelectrochemical performance. Next, nanostructured molybdenum disulfide ultrathin films (MoS2) have been grown to be used as (photo)-cathodes for the hydrogen evolution reaction in acidic solutions. It has been proved that the synthesis method plays a fundamental role in increasing the electrocatalytic properties of these materials. Lastly, the properties of strontium titanium trisulfide (SrTiS3) for the photo-production of hydrogen have been investigated for the first timeLa situación climática actual es cada vez más preocupante debido al aumento de la temperatura del planeta, provocado principalmente por la emisión de gases de efecto invernadero debido al uso de fuentes de energía basadas en combustibles fósiles. Para frenar este proceso, se ha propuesto realizar una transición energética hacia fuentes renovables. Sin embargo, uno de los principales problemas de estas fuentes limpias es su intermitencia, ya que su generación depende de factores como la disponibilidad del sol o el viento. Ante esta situación, el hidrógeno se ha convertido en una opción prometedora como vector energético, ya que permite almacenar energía renovable y transportarla. Además, su producción a partir de agua no emite gases de efecto invernadero si se utiliza energía renovable en el proceso.
Existen varias formas de obtener hidrógeno a partir de agua, entre las que destacan la electrólisis y fotoelectrólisis del agua. Hoy en día, los electrolizadores comerciales emplean electrodos basados en elementos poco abundantes en la Tierra, lo cual podría generar nuevos problemas medioambientales y económicos. No obstante, es importante asegurar que los materiales utilizados en su producción sean abundantes, sostenibles, no tóxicos, eficientes y de bajo coste.
En este contexto se enmarca la presente tesis doctoral, en la que se han sintetizado materiales basados en elementos abundantes en la Tierra, como el nitrógeno, carbono, oxígeno, azufre y titanio (entre otros). Posteriormente, se ha realizado una caracterización exhaustiva de los mismos empleando diferentes técnicas de caracterización morfológica, estructural, composicional y óptica. Finalmente, han sido investigadas sus propiedades para la disociación de la molécula del agua empleando electricidad (electrólisis) o electricidad y luz (fotoelectrólisis).
En esta tesis doctoral se han investigado diferentes materiales, con el objetivo de utilizarlos en distintas reacciones para la división del agua. En primer lugar, se han sintetizado capas ultrafinas de borocarbonitruro (BCNs) sobre diferentes fotoánodos (discos planos de Ti con una capa superficial de TiOx y nanocintas de TiO2), para ser utilizados como electrocatalizadores en la reacción de evolución de oxígeno. A continuación, se han protegido fotoánodos de trisulfuro de titanio (TiS3) contra la corrosión en medios acuosos alcalinos mediante el crecimiento de una fina capa de dióxido de titanio (TiO2). Sobre estas heteroestructuras TiS3/TiO2 se han crecido diferentes electrocatalizadores para mejorar su rendimiento fotoelectroquímico. Por otro lado, se han sintetizado películas ultrafinas nanoestructuradas de disulfuro de molibdeno (MoS2) para utilizarlas como (foto)-cátodos para la reacción de evolución de hidrógeno en soluciones ácidas. Se podido comprobar que el método de síntesis juega un papel fundamental en el aumento de las propiedades electrocatalíticas de estos materiales. Por último, se han investigado por primera vez las propiedades del trisulfuro de estroncio y titanio (SrTiS3) para la foto-producción de hidrógen
Neutralidad y Constitución económica
No full textTrabajo realizado dentro del Proyecto de investigación financiado por el Plan Nacional de I+D+I: “La neutralidad Institucional en el Estado Constitucional” (PID2019-106043GB-100)
Afficher un pouvoir négocié. L’héraldique nobiliaire dans une cité du domaine royal. Le cas des Velasco à Burgos au milieu du XVe siècle
No full textLes Velasco furent une des familles nobles les plus puissantes de Castille au bas Moyen-Âge.
Leur seigneurie s’étendait dans le nord du royaume, zone au sein de laquelle se détache la ville de
Burgos, cité marchande de premier ordre. Au milieu du XVe siècle, Pedro Fernández de Velasco et son
épouse, Mencía de Mendoza, y construisent un palais et une chapelle funéraire, de nouveaux édifices
sur lesquels ils déploient leurs armoiries. L’historiographie traditionnelle ne voyait dans l’héraldique
de ces édifices qu’une initiative familiale, moyen d’exalter le lignage, ignorant le fait qu’en réalité
l’exposition de ces décors résultait d’autres processus plus complexes et plus subtils, tels que les négociations
de pouvoir entre le groupe nobiliaire et les échevins. À travers cet article nous proposons d’analyser
les constructions réalisées par les Velasco à Burgos, en examinant dans un premier temps ce qu’elles
impliquèrent en termes de négociations avec les pouvoirs publics. Nous examinerons ensuite les armes
qui apparaissent – ou qui n’apparaissent pas – sur ces ouvrages. Jusqu’à quel point les armoiries sontelles
l’expression d’une volonté d’exaltation familiale? Quels rôles ont joué les devises dans ces discours?
Que nous apprend la confrontation des sources historiques urbaines et familiales avec les
sources artistiques sur le processus de négociation entre cité et lignage? Comment cette négociation
devient-elle visible dans la topographie urbaine et quel fut, en cela, le rôle de l’héraldique?"Más allá de la palabra. Comunicación y discursos políticos en la Castilla Trastámara (1367–1504)" (PID2021–125571NB100), financé par
MICIN/AEI/FEDER, UE "A way of making Europe
Environmental corporate reputation: evidence from capital markets
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias Económicas y Empresariales, Departamento de Contabilidad. Fecha de Lectura: 17-07-2023Esta Tesis tiene embargado el acceso al texto completo hasta el 04-01-2026Esta Tesis tiene concedido un nuevo periodo de embargo hasta el 02-09-2028The motivation for this study is based on the rising awareness of environmental issues and the growing expectation for corporations to take part in environmental initiatives. This dissertation seeks to broaden knowledge about how capital markets value environmental damage. We address each of these issues in two ways: (1) Exploring the disciplinary role of shareholders on corporate environmental (mis)conduct, i.e., rewarding and punishing firms through stock market forces; and (2) evaluating the effectiveness of environmental disclosures (e.g., ESG disclosure) as a communication instrument about the firm's engagement as well as a source of reputation. In accordance with our approach to these issues, we conduct three event studies. The empirical analyses examine capital markets and environmental events, including legal actions, industrial accidents, and political events worldwide. These events have a high-level impact on the media, exposing firms and potentially damaging their corporate reputations. Using a short-term event study analysis, we apply both the market model and the three-factor model. We find markets react by rewarding positive environmental conduct and punishing negative misconduct regarding ecological disasters. Investors are more inclined to reward good environmental behaviour than to punish negative behaviour. Finally, voluntary disclosures are perceived as relevant and are rewarded by investors in the context of potential reputational damage. The contribution of this thesis is multidisciplinary; it contributes by broadening knowledge in the fields of finance, business ethics, and corporate social responsibility (CSR). The main findings are of great value for companies, financial analysts, and academic
An operator model in the annulus
No full textFor an invertible linear operator T on a Hilbert space H, put
α (T*, T) := -T*2 T2 + (1 + r2)T*T – r2I,
where I stands for the identity operator on H and r Є (0, 1); this expression comes from applying Agler’s hereditary functional calculus to the polynomial α(t) = (1−t)(t−r2). We give a concrete unitarily equivalent functional model for operators satisfying α (T*, T) ≥ 0. In particular, we prove that the closed annulus r ≤ |z| ≤ 1 is a complete K-spectral set for T . We explain the relation of the model with the Sz.-Nagy–Foias one and with the observability gramian and discuss the relationship of this class with other operator classes related to the annulusThe first author was supported by National Science Centre, Poland grant UMO-2016/21/B/ST1/00241. The second author acknowledges partial support by Spanish Ministry of Science, Innovation and Universities (grant no. PGC2018-099124-B-I00) and the ICMAT Severo Ochoa project SEV-2015-0554 of the Spanish Ministry of Economy and Competitiveness of Spain and the European Regional Development Fund, through the “Severo Ochoa Programme for Centres of Excellence in R&D”. The second author also acknowledges financial support from the Spanish Ministry of Science and Innovation, through the “Severo Ochoa Programme for Centres of Excellence in R&D” (SEV-2015-0554) and from the Spanish National Research Council, through the “Ayuda extraordinaria a Centros de Excelencia Severo Ochoa” (20205CEX001