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Progenitor cell origin and birthdate govern glutamatergic and GABAergic neuronal differentiation in the hindbrain
No full textSymptomatic networks in suicide attempt and reattempt: relevance of psychiatric comorbidity
No full textBackground: One of the most relevant risk factors for suicide is the presence of previous attempts. The symptomatic profile of people who reattempt suicide deserves attention. Network analysis is a promising tool to study this field. Objective: To analyze the symptomatic network of patients who have attempted suicide recently and compare networks of people with several attempts and people with just one at baseline. Methods: 1043 adult participants from the Spanish cohort "SURVIVE" were part of this study. Participants were classified into two groups: single attempt group (n = 390) and reattempt group (n = 653). Different network analyses were carried out to study the relationships between suicidal ideation, behavior, psychiatric symptoms, diagnoses, childhood trauma, and impulsivity. A general network and one for each subgroup were estimated. Results: People with several suicide attempts at baseline scored significantly higher across all clinical scales. The symptomatic networks were equivalent in both groups of patients (p > .05). Although there were no overall differences between the networks, some nodes were more relevant according to group belonging. Conclusions: People with a history of previous attempts have greater psychiatric symptom severity but the relationships between risk factors show the same structure when compared with the single attempt group. All risk factors deserve attention regardless of the number of attempts, but assessments can be adjusted to better monitor the occurrence of reattempts
La Traducción español-chino para subtitulado de elementos de suspense
No full textEste estudio analiza las soluciones de los subtítulos español-chino para los ELSU (elementos de suspense) en películas del género thriller, fundamentándose en la teoría de la traducción audiovisual y estudios previos sobre el suspense. Se centra en cinco películas de thriller: Cien años de perdón (2016), Contratiempo (2017), El bar (2017), Durante la tormenta (2018), y Al final del túnel (2019). Utilizando una metodología descriptiva de la traducción audiovisual, se evidencia la expresión verbal, no verbal y paraverbal del suspense, así como las técnicas de suspense empleadas en estas películas. Posteriormente, se describen las soluciones subtituladas aplicadas para estos ELSU y técnicas de suspense mediante árboles binarios, para analizar las relaciones entre la creación del suspense en el texto de partida y su recreación mediante la traducción audiovisual en el texto de llegada. Este estudio aporta un avance en la comprensión de la subtitulación interlingüística español-chino acerca de los ELSU, dilucidando cuestiones asociadas con el suspense y desarrollando una metodología de análisis multimodal para abordar problemas en la traducción audiovisual.This thesis investigates Spanish-Chinese subtitle solutions for elements of suspense (ELSU) in thriller films, grounding its analysis in audiovisual translation theory and previous studies on suspense. Using a descriptive approach to audiovisual translation, this study delves into five thriller films: Cien años de perdón (2016), Contratiempo (2017), El bar (2017), Durante la tormenta (2018), y Al final del túnel (2019). It identifies and analyzes verbal, non-verbal, and paraverbal expressions of suspense, along with the suspense techniques employed in these films. The research further describes and outlines the subtitled solutions applied to these suspense elements and techniques, using binary trees to explore the relationships between the creation of suspense in the source text and its recreation through audiovisual translation in the target text. This study advances the understanding of Spanish-Chinese interlingual subtitling with respect to ELSUs, elucidates the associated challenges with suspense, and develops a multimodal analysis methodology to tackle issues in audiovisual translation.Aquest estudi analitza les solucions de subtitulació espanyol-xinès per als ELSU (elements de suspens) en pel·lícules del gènere thriller, basant-se en la teoria de la traducció audiovisual i estudis previs sobre el suspens. Es centra en cinc pel·lícules de thriller: Cien años de perdón (2016), Contratiempo (2017), El bar (2017), Durante la tormenta (2018) i Al final del túnel (2019). Mitjançant una metodologia descriptiva de la traducció audiovisual, es mostra l'expressió verbal, no verbal i paraverbal del suspens, així com les tècniques de suspens emprades en aquestes pel·lícules. Posteriorment, es descriuen les solucions de subtitulació aplicades a aquests ELSU i tècniques de suspens mitjançant arbres binaris, per analitzar les relacions entre la creació del suspens en el text de partida i la seva recreació mitjançant la traducció audiovisual en el text d'arribada. Aquest estudi aporta un avenç en la comprensió de la subtitulació interlingüística espanyol-xinès sobre els ELSU, ja que permet aclarir els problemes associats amb el suspens i desenvolupa una metodologia d'anàlisi multimodal per abordar problemes en la traducció audiovisual.Programa de Doctorat en Traducció i Ciències del Llenguatg
Normalizing flows for neuroimaging research
No full textPsychotic disorders are characterized by poorly understood pathophysiological mechanisms, with a remarkable heterogeneity among patients, both cross-sectionally and longitudinally. This results in a lack of definitive biomarkers, whose outcome could greatly benefit from early diagnosis and intervention. In this thesis, we propose to address these challenges in two directions: from a neuroanatomical, and neurochemical standpoints. Although intrinsically different problems, these can be approached from a common perspective: distribution modeling. To achieve this, in both cases we propose tools sustained on the use of Normalizing Flows (NF), a relatively new family of generative-based artificial intelligence methods, characterized by their explicitness, expressiveness, and intrinsic bijectivity, with the ability to work with large-dimensional and/or complex data. These properties are analyzed in this thesis and later adapted for the two objectives. In the first case, we propose a tool to generate highly personalized normative neuroanatomical models. In this context, we need tools able to accurately align observed entities with those of a reference distribution, a process contextualized within a temporal framework. We address the issue by introducing an adaptation of the classic NF models, using Optimal Transport (OT) concepts, to enable the approximation of a source distribution to any target distribution accessible through samples. The bidirectional parametric nature of NF is proposed to be used to 1) enable the dynamic alignment of distributions, while 2) constraining the transformation paths, enforcing them to be smooth. The intrinsic bijectivity of NF is exploited to enable image-to-image translation across different time points, without the need for paired samples, enabling the prediction of individual brain trajectories through the years. In the second case, we propose to target the disentanglement of factors underlying functional alterations already observed at the onset of the disease, as suggested by our experiments. We propose achieving this using available whole-brain mathematical models (WBM), which may help overcome experimental limitations, while further opening the possibility to address causality methodologically. However, their usefulness is sustained by their well-posedness. Thus, we propose to take advantage of the explicitness and expressiveness of NF, considering their limitations in the context of the complex network behavior of the brain, to closely approximate the posterior of the inferred parameters, in an efficient and amortized manner, potentially easing the WBM’s translation to its clinical use. While further work is required, by leveraging the strengths of NF, this thesis aims to pave the way for the development of more precise diagnostic tools for psychotic disorders, extensible to its application to other neurological conditions.Els trastorns psicòtics es caracteritzen per mecanismes fisiopatològics poc entesos, amb una notable heterogeneïtat entre els pacients, tant transversalment com longitudinal. Això dona lloc a una manca de biomarcadors definitius, l’existència dels quals podria beneficiar enormement el diagnòstic precoç i la intervenció de la malaltia. En aquesta tesi, proposem abordar aquestes dificultats en dues direccions: des d'un punt de vista neuroanatòmic i neuroquímic. Tot i ser problemes intrínsecament diferents, aquests podrien abordar-se des d'una perspectiva comuna: la modelització de distribucions. Per aconseguir-ho, en ambdós casos proposem eines basades en l'ús de Fluxos Normalitzadors (NF), una família relativament nova de mètodes generatius d'intel·ligència artificial, caracteritzats per la seva explicitat, expressivitat i bijectivitat intrínseca, amb la capacitat de treballar amb dades complexes i/o d'alta dimensionalitat. Dites propietats s'analitzen en aquesta tesi i s'adapten amb la finalitat d'assolir els objectius esmentats. En el primer cas, proposem una eina per generar models neuroanatòmics normatius personalitzats. En aquest context, necessitem eines capaces d'ajustar amb precisió les entitats observades amb les d'una distribució de referència, un procés contextualitzat dins d'un marc temporal. Abordem aquesta qüestió introduint una adaptació dels models NF clàssics, utilitzant conceptes de Transport Òptim (OT), per permetre l'aproximació d'una distribució font a qualsevol distribució de destinació accessible a través de mostres. Es proposa utilitzar la naturalesa paramètrica bidireccional dels NF per 1) possibilitar l'ajust dinàmic de les distribucions, mentre 2) restringim els camins de transformació, obligant-los a ser progressius. Així mateix, s'aprofita la bijectivitat intrínseca dels NF per permetre la traducció d'imatge a imatge a través de diferents punts temporals, sense necessitat de disposar de mostres aparellades, permetent la predicció de les trajectòries cerebrals individuals al llarg dels anys. En el segon cas, proposem desentrellar el paper dels factors subjacents a les alteracions funcionals ja observades en el començament de la malaltia, com suggereixen els nostres experiments. Proposem aconseguir-ho utilitzant models matemàtics capaços de generar simulacions a nivell de xarxa cerebral completa, els quals poden ajudar a superar les limitacions experimentals, i a més, obren la possibilitat d'abordar metodològicament la causalitat. No obstant això, la seva utilitat es basa en la seva bona formulació. Així, proposem aprofitar l’explicitat i expressivitat dels NF, considerant les seves limitacions en el context de la complexa xarxa cerebral, per aproximar la distribució posterior dels paràmetres inferits, de manera eficient i amortitzada, amb l'objectiu final de facilitar la translació dels models WBN al seu ús clínic. Tot i que es requereix més treball, aprofitant els punts forts dels NF, aquesta tesi té com a objectiu obrir el camí per al desenvolupament d'eines de diagnòstic més precises per a trastorns psicòtics, extensibles a la seva aplicació a altres condicions neurològiques.Programa de Doctorat en Tecnologies de la Informació i les Comunicacion
Synthetic biology for microbiome-based genetic domestication of the skin and the sea
No full textMicroorganisms exhibit remarkable adaptability and represent a vast genetic resource. Synthetic biology aims to leverage this diversity for sustainability and medicine. However, many microbes remain unexplored due to limited genetic tools. This research developed genetic engineering tools for Dinoroseobacter shibae and Cutibacterium acnes, abundant in the ocean and on the skin, respectively. For C. acnes, we investigated phage defenses and developed a genetic toolkit including expression tools, CRISPRi, biosensors, recombinases, and auxotrophic genes, facilitating its use in skin engineering. We created auxotrophic strains and an antioxidant strain reducing oxidative stress in UV-treated keratinocytes. For D. shibae, we engineered fimbrils to enhance biofilm adhesion and designed biosensors for temperature and oxygen, demonstrating its potential for marine applications. Additionally, we found that using preprints and inquiry-based lessons in teaching synthetic biology improved students' technical and soft skills, proving effective for interdisciplinary educationLos microorganismos poseen una gran adaptabilidad y representan un amplio recurso genético. La biología sintética busca aprovechar esta diversidad para la sostenibilidad y la medicina. Sin embargo, muchos microbios siguen sin explorarse debido la falta de herramientas genéticas. En este estudio, desarrollamos herramientas de ingeniería genética para Dinoroseobacter shibae y Cutibacterium acnes, abundantes en el océano y en la piel, respectivamente. Para C. acnes, investigamos las defensas contra fagos y desarrollamos un kit de herramientas genéticas que incluye herramientas de expresión, CRISPRi, biosensores, recombinasas y genes auxótrofos, facilitando su uso en la ingeniería del microbioma de la piel. Creamos cepas auxótrofas y una cepa antioxidante que reduce el estrés oxidativo en queratinocitos tratados con luz UV. Para D. shibae, diseñamos fimbrias para mejorar la adhesión de los biofilms y biosensores para temperatura y oxígeno, demostrando su potencial para aplicaciones marinas. Además, encontramos que el uso de preprints y lecciones basadas en la investigación mejoraron las habilidades técnicas y blandas de los estudiantes, demostrando ser efectivo para la educación interdisciplinarPrograma de Doctorat en Biomedicin
Neuromuscular junction dynamics in muscle growth and atrophy
No full textSkeletal muscle exhibits remarkable adaptability in response to physiological and pathological stimuli. This study explores the plasticity of the neuromuscular junction (NMJ), a neural–muscle interface that is crucial for synapse formation and force transmission, with a focus on terminal (tSCs), post-synaptic myonuclei (Syn-myo), and muscle stem cells (MuSCs). We have implemented a three-dimensional visualization technique that maintains the spatial tissue context to delineate the communication changes between NMJ and MuSCs at the morphologic and molecular levels in muscle atrophy or hypertrophy. Our findings reveal that a subset of MuSCs is in intimate contact with the NMJ domain, potentially contributing to the local accretion of new Syn-myo. Additionally, tSC proliferation dynamics vary in response to neural- and muscular-derived cues. Using single-cell and single-nucleus RNA-sequencing as well as spatial transcriptomics, we have now characterized the transcriptional adaptations of MuSCs, SCs, and Syn-myo to distinct conditions. This work enhances our understanding of NMJ modulation and its critical role in muscle degeneration or growth.El músculo esquelético muestra una notable adaptabilidad en respuesta a estímulos fisiológicos y patológicos. Este estudio explora la plasticidad de la unión neuromuscular (NMJ), la interfaz neurona-músculo crucial para la formación de la sinapsis y transmisión de fuerza, centrándose en las células de Schwann terminales (tSCs), los mionúcleos postsinápticos (Syn-myo), y las células madre musculares (MuSC). Hemos implementado una técnica de visualización tridimensional que mantiene el contexto del tejido para delinear cambios en la comunicación entre las NMJs y MuSCs en la atrofia e hipertrofia muscular. Nuestros hallazgos revelan que un subconjunto de MuSCs está en contacto íntimo con el dominio de NMJs, contribuyendo potencialmente a la incorporación local de nuevos Syn-myo. Asimismo, la dinámica de proliferación de tSCs varía en respuesta a señales neurales y musculares. Los avances en secuenciación de ARN de células y núcleos individuales, así como la transcriptómica espacial, han caracterizado las adaptaciones transcripcionales en MuSCs, SCs y Syn-myo, mejorando nuestra comprensión sobre la modulación de la NMJ y su papel crítico en la degeneración o crecimiento muscular.Programa de Doctorat en Biomedicin
Metabolomics in COPD
No full textThe clinical presentation of chronic obstructive pulmonary disease (COPD) is highly heterogeneous. Attempts have been made to define subpopulations of patients who share clinical characteristics (phenotypes and treatable traits) and/or biological characteristics (endotypes), in order to offer more personalized care. Assigning a patient to any of these groups requires the identification of both clinical and biological markers. Ideally, biological markers should be easily obtained from blood or urine, but these may lack specificity. Biomarkers can be identified initially using conventional or more sophisticated techniques. However, the more sophisticated techniques should be simplified in the future if they are to have clinical utility. The -omics approach offers a methodology that can assist in the investigation and identification of useful markers in both targeted and blind searches. Specifically, metabolomics is the science that studies biological processes involving metabolites, which can be intermediate or final products. The metabolites associated with COPD and their specific phenotypic and endotypic features have been studied using various techniques. Several compounds of particular interest have emerged, namely, several types of lipids and derivatives (mainly phospholipids, but also ceramides, fatty acids and eicosanoids), amino acids, coagulation factors, and nucleic acid components, likely to be involved in their function, protein catabolism, energy production, oxidative stress, immune-inflammatory response and coagulation disorders. However, clear metabolomic profiles of the disease and its various manifestations that may already be applicable in clinical practice still need to be defined
Bailar la muerte hacia una historiografía audiovisual del framenco en el franquismo
No full textEsta tesis trata de estudiar la representación visual del flamenco en el cine español durante el franquismo. El flamenco, tan presente en el imaginario con que lo español se presenta y se constituye, ha sido sin embargo, retratado de muchas formas distintas, mostrando una variedad de sentidos, muchas veces contradictorios. Para tal análisis, se parte de la premisa de que el cine español ha de estudiarse incluyendo en el corpus de películas españolas algunas obras realizadas por cineastas españoles en el exilio, que a pesar de su distinta nacionalidad económica, comparten sin embargo la misma tradición cultural. Se ha decidido para ello una investigación aplicada que pudiese acercarse de un modo más empírico a la noción de pervivencia que Aby Warburg acuñó para su Atlas Mnemosyne, esta vez aplicada a los modos y las formas de una parte del cine español mal conocida. Por ello, pervivencia, transnacionalidad y hauntología son las tres bases teóricas sobre las que se sustenta esta investigación. El resultado final de la investigación se propone dividido en dos, por una parte un ensayo fílmico de ochenta minutos, realizado con imágenes de archivo de películas, en las que se muestra las analogías y las divergencias de la representación del flamenco a un lado y otro del exilio, y una investigación teórica (indisolublemente unida al ensayo fílmico) donde se muestran las reflexiones teóricas e historiográficas que me llevaron a decidir la forma y la temática del ensayo fílmico. Esta doble propuesta, que se retroalimenta, me ha permitido no sólo analizar el alcance del flamenco como sintagma identitario, tan instrumentalizado política y artísticamente, sino también investigar sobre nuevos formatos y modelos de investigación sobre la historia del cine.This thesis attempts to study the visual representation of flamenco in Spanish cinema during the Franco regime. Flamenco, so present in the imaginary with which the Spanishness is presented and constituted, has nevertheless been portrayed in many different ways, showing a variety of meanings, often contradictory. For this analysis, we start from the premise that Spanish cinema has to be studied by including in the corpus of Spanish films some works made by Spanish filmmakers in exile, who despite their different economic nationality, nevertheless share the same cultural tradition. For this purpose, we have decided to carry out an applied research that could approach in a more empirical way the notion of survival that Aby Warburg coined for his Atlas Mnemosyne, this time applied to the modes and forms of a poorly known part of Spanish cinema. Therefore, survival, transnationality and hauntology are the three theoretical bases on which this research is based. The final result of the research is proposed divided in two, on the one hand a film essay of eighty minutes, made with archival images of films, which shows the analogies and divergences in the representation of flamenco on both sides of the exile, and a theoretical research (inextricably linked to the film essay) where the theoretical and historiographical reflections that led me to decide the form and theme of the film essay are shown. This double proposal, which feeds back on each other, has allowed me not only to analyze the scope of flamenco as an identity syntagma, so instrumentalized politically and artistically, but also to investigate new formats and models of research on the history of cinema.Programa de Doctorat en Comunicaci
The evolution of facultative symbiosis in stony corals
No full textData de publicació electrònica: 15-10-2025Most stony corals are obligate symbionts that are dependent on nutrients provided by the photosynthetic activity of dinoflagellates residing within specialized cells1. Disruption of this symbiotic consortium leads to coral bleaching and, ultimately, mortality2. However, a few coral species exhibit facultative symbiosis, allowing them to survive extended periods of bleaching3,4. Despite this resilience, the underlying biological mechanisms remain poorly understood. Here we investigate the genomic and cellular basis of facultative symbiosis in Oculina patagonica, a thermotolerant Mediterranean coral5,6. We sequenced and annotated a chromosome-scale genome of O. patagonica and built cell atlases for this species and two obligate symbiotic corals. Comparative genomic analysis revealed karyotypic and syntenic conservation across all scleractinians, with species-specific gene expansions primarily driven by tandem duplications. Single-cell transcriptomic profiling of symbiotic and naturally aposymbiotic wild specimens identified an increase in phagocytic immune cells and a metabolic shift in gastrodermal gene expression from growth-related functions to quiescent, epithelial-like states. Cross-species comparison of host cells uncovered Oculina-specific metabolic and signalling adaptations indicative of an opportunistic, dual-feeding strategy that decouples survival from symbiotic state
Supply chain disruption and reorganization: theory and evidence from Ukraine's war
No full textData de publicació electrònica: 11-09-2025How do localized conflicts disrupt supply chains and prompt firms to reorganize them? How do these forces affect firm-level and aggregate economic activity? Using firm-to-firm Ukrainian railway-shipment data before and during the 2014 Russia-Ukraine conflict, we document that firms with prior supplier and buyer exposure to the conflict areas substantially decreased their output. Simultaneously, firms reorganized their production linkages away from partners directly or indirectly exposed to the conflict shock. We build a general-equilibrium production-network model with endogenous link formation, and we show that our model's sufficient statistics accurately explain the observed relative decline in firm output once we account for network reorganization. Calibrating our model to the Ukrainian economy, we find that the localized conflict decreased aggregate output in nonconflict areas by 5.5%. This effect increases to 8.4% if we abstract from endogenous link formation, suggesting that production network reorganization partially mitigates the detrimental, far-reaching aggregate economic costs of conflicts.This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 870245