Inflammation, glucose, and vascular cell damage: The role of the pentose phosphate pathway

Background: Hyperglycemia is acknowledged as a pro-inflammatory condition and a major cause of vascular damage. Nevertheless, we have previously described that high glucose only promotes inflammation in human vascular cells previously primed with pro-inflammatory stimuli, such as the cytokine interleukin (IL)1β. Here, we aimed to identify the cellular mechanisms by which high glucose exacerbates the vascular inflammation induced by IL1β. Methods: Cultured human aortic smooth muscle cells (HASMC) and isolated rat mesenteric microvessels were treated with IL1β in medium containing 5.5-22 mmol/L glucose. Glucose uptake and consumption, lactate production, GLUT1 levels, NADPH oxidase activity and inflammatory signalling (nuclear factor-ΚB activation and inducible nitric oxide synthase expression) were measured in HASMC, while endothelium-dependent relaxations to acetylcholine were determined in rat microvessels. Pharmacological inhibition of IL1 receptors, NADPH oxidase and glucose-6-phosphate dehydrogenase (G6PD), as well as silencing of G6PD, were also performed. Moreover, the pentose phosphate pathway (PPP) activity and the levels of reduced glutathione were determined. Results: We found that excess glucose uptake in HASMC cultured in 22 mM glucose only occurred following activation with IL1β. However, the simple entry of glucose was not enough to be deleterious since over-expression of the glucose transporter GLUT1 or increased glucose uptake following inhibition of mitochondrial respiration by sodium azide was not sufficient to trigger inflammatory mechanisms. In fact, besides allowing glucose entry, IL1β activated the PPP, thus permitting some of the excess glucose to be metabolized via this route. This in turn led to an over-activation NADPH oxidase, resulting in increased generation of free radicals and the subsequent downstream pro-inflammatory signalling. Moreover, in rat mesenteric microvessels high glucose incubation enhanced the endothelial dysfunction induced by IL1β by a mechanism which was abrogated by the inhibition of the PPP. Conclusions: A pro-inflammatory stimulus like IL1β transforms excess glucose into a vascular deleterious agent by causing an increase in glucose uptake and its subsequent diversion into the PPP, promoting the pro-oxidant conditions required for the exacerbation of pro-oxidant and pro-inflammatory pathways. We propose that over-activation of the PPP is a crucial mechanism for the vascular damage associated to hyperglycemia.This study was supported with grants from Plan Nacional de I+ D (SAF2014-52762-R), Sociedad Española de Farmacología-Almirall, Fundación Eugenio Rodríguez Pascual, and ISCIII (RETICEF-R12/0043/0021) and Junta de Castilla y León (SA003U13). LV was supported by a fellowship from CONACYT (Mexico). TR is the recipient of a Marie Curie Intra-European Fellowship (2012-IEF-328793 ADDIO

Competition in the industry of asset management - analysis on different settings

Este estudo analisa o comportamento de competição/estratégico entre fundos de investimento mobiliário de vários países da União Europeia (UE). Para o efeito é utilizada a metodologia de Brown, Harlow e Starks (1996) aplicada em diferentes cenários. Assim, é analisado o comportamento de competição/estratégico em subperíodos de igual duração e em subperíodos que correspondem a diferentes ciclos de mercado, são consideradas as características dos fundos (a dimensão das suas carteiras e o seu período de atividade), assim como o possível efeito do survivorship bias. Os resultados obtidos evidenciam a existência de comportamento estratégico entre os fundos de investimento mobiliário na UE, sendo o mesmo mais intenso entre os fundos da Bélgica, Espanha e Reino Unido. Este comportamento, com exceção do Reino Unido, mostra-se mais intenso entre os fundos com menor período de atividade e no período mais recente. Desta forma, parece que, por um lado, a maior interação estratégica entre os fundos com menor período de atividade pode advir da sua maior audácia, por contraposição aos fundos mais experientes que tendem a revelar maior cautela. Por outro, o crescimento dos mercados da UE em termos do número de fundos parece contribuir para o aumento do comportamento estratégico

Primordial black holes as dark matter: Interferometric tests of phase transition origin

We show that primordial black holes - in the observationally allowed mass window with $f_{\rm pbh}=1$ - formed from late nucleating patches in a first order phase transition imply upcoming gravitational wave interferometers will see a large stochastic background arising from the bubble collisions. As an example, we use a classically scale invariant $B-L$ model, in which the right handed neutrinos explain the neutrino masses and leptogenesis, and the dark matter consists of primordial black holes. The conclusion regarding the gravitational waves is, however, expected to hold model independently for black holes coming from such late nucleating patches.Comment: 33 page

Magnetogenesis with gravitational waves and primordial black hole dark matter

Strongly supercooled first order phase transitions (FOPTs) can produce primordial black hole (PBH) dark matter (DM) along with observable gravitational waves (GWs) from bubble collisions. Such FOPTs may also produce coherent magnetic fields generated by bubble collisions and by turbulence in the primordial plasma. Here we find that the requirement for PBH DM can produce large primordial magnetic fields which subsequently yield intergalactic magnetic fields in the present universe (with magnitude $\lesssim 20$ pG across coherence length scales of $\simeq 0.001$-$0.01$ Mpc, assuming maximally helical magnetic fields) that easily exceed lower bounds from blazar observations. We follow a largely model independent approach and highlight the possibility of producing DM and observable multi-messenger magnetic fields and GW signals visible in next generation experiments.Comment: 8 pages, 3 figure

Si hay sangre, hay noticia

Esta investigación tiene como propósito mostrar cómo las noticias relacionadas con muertes, catástrofes y otras calamidades, generan mucha más audiencia que cualquier otro tipo de noticia, por muy relevante que sea. Y el cine, por su enorme capacidad comunicativa, es el medio perfecto para demostrarlo. El principal objetivo que se quiere alcanzar al realizar este estudio, es mostrar el poder que tiene la crónica roja para captar la atención del receptor e incidir en sus emociones, analizando el largometraje: Nightcrawler (Dan Gilroy, 2014). Se estudiarán tres secuencias de la película donde expondremos el tema principal relacionado con el periodismo que expresa cada una, su descripción (personajes, escenarios, iluminación, sonido, etc.), para concluir con un breve comentario sobre cada secuencia en referencia a la ética del periodismo. Por último, expondremos los resultados del análisis y unas conclusiones en las que trataremos de reflejar cómo la película ejemplifica la frase que da título a este trabajo fin de Grado: ``si hay sangre, hay noticia´´.This research aims to suggest how news related to deaths, catastrophes and other calamities are of more interest to citizens and generate much more audience than any other type of news, however relevant it may be. And the cinema, due to its enormous communicative capacity, is the perfect medium to demonstrate it. The main objective of this study is to show the power of the crime report to capture the attention of the receiver and influence their emotions, by analyzing the feature film Nightcrawler (Dan Gilroy, 2014). We will study three sequences of the film where we will expose the main theme related to journalism that each one expresses, its description (characters, settings, lighting, sound, etc.), to conclude with a brief commentary on each sequence in reference to the ethics of journalism. Finally, we will present the results of the analysis and some conclusions in which we will try to reflect how the film exemplifies the phrase that gives the title to this thesis: ``if there is blood, there is news''.Grado en Periodism

Tsuki mo mite: veinte poetas japonesas desde el siglo XVII hasta la actualidad

El objetivo principal del presente Trabajo de Fin de Grado es la reivindicación del papel e importancia de las mujeres en la literatura y, particularmente, en el haiku, a través de la traducción, hasta ahora inédita en español, de diversas composiciones poéticas de veinte poetas, realizando, asimismo, un recorrido diacrónico desde los haiku clásicos del siglo XVII hasta las formas más modernas que adoptan en el siglo XX. Por otra parte, se ofrece una somera reflexión sobre los diversos temas que han tratado estas autoras a lo largo de estos cuatro siglos y que conforman el universo de la mujer en Japón, para que así el lector interesado pueda sacar sus propias conclusiones acerca de las diferencias y similitudes que puedan tener con sus compañeros masculinos y entre ellas mismas.The main goal of this End-of-Degree Project is the recognition of women’s role and importance in literature and, particularly, in haiku poetry, since the translation, so far unpublished in Spanish, of several poetic compositions written by twenty poets through a diachronic journey from classical haiku from the 17th century to the most modern forms that it adopts in the 20th century. Moreover, it is offered a brief reflection on the various themes treated by these authors throughout these four centuries and that make up the universe of women in Japan, so that the interested reader will be able to draw his or her own conclusions about the differences or similarities that they may have with their male counterparts and with each other

Hacer de la pintura una feria: el folklore en la práctica artística

[EN] We think of painting as an open space, a habitable and comfortable place where we can meet others. In this work we present the cloud of influences that have conditioned this conception: the culture of cante jondo, by its expression of intimate feeling through a party, of the putting in community, where the artistic practice acts as a catalyst of sorrows for joys. What will take us to take Andalusia as the inevitable landscape of our painting and reflect on the artistic object as an object of consolation, a shaper of the everyday that softens reality and helps us to feel comfortable in it. Thus, our pictorial approach to different means of creation (the painting itself, ceramics and artist's book) will try to achieve this closeness through the search for common territories; understanding these ¿territories¿ as the images that make up the common imaginary (popular culture), because images are our occupation. We will try to create a comforting, fun or tender artistic object: to make painting a feria[ES] Pensamos la pintura como un espacio abierto, un lugar habitable y cómodo donde propiciar un encuentro con los demás. En este trabajo hemos querido presentar la nube de influencias que han condicionado esta concepción: la cultura del cante jondo, por su expresión del sentimiento íntimo a través de una fiesta, de la puesta en comunidad, donde la práctica artística actúa como catalizador de las penas por alegrías. Esto nos llevará a tomar Andalucía como el paisaje inevitable de nuestra pintura y reflexionar sobre el objeto artístico como un objeto de consuelo, un moldeador de lo cotidiano que reblandece la realidad y nos ayuda a sentirnos cómodos en ella. Así, nuestro acercamiento pictórico a distintos medios de creación (la propia pintura, la cerámica y el libro de artista) tratará de lograr esta cercanía a través de la búsqueda de territorios comunes; entendiendo por estos ¿territorios¿ las imágenes que conforman el imaginario común (la cultura popular), pues es a las imágenes a lo que nos dedicamos. Trataremos de conformar un objeto artístico reconfortante, divertido o tierno: hacer de la pintura una feriaSánchez Romacho, Á. (2018). Hacer de la pintura una feria: el folklore en la práctica artística. http://hdl.handle.net/10251/109128TFG