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Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation
No full textInhibitory killer cell immunoglobulin-like receptors (iKIRs) are randomly expressed by natural killer (NK) cell subsets and recognize motifs shared by HLA class-I (HLA-I) allotypes. Such interactions prevent NK cell autoreactivity while enhancing their response against cells lacking those HLA-I molecules (missing self), a situation defined in transplantation as iKIR-HLA-I mismatch (iKIR-MM), whose genotypic prediction has been associated with microvascular inflammation (MVI). Herein, we compared iKIR-MM in kidney transplant recipients with MVI ≥2 (n = 19) and controls with MVI ≤1 (n = 36). In parallel to genetic analysis of iKIR-MM, which was more frequent in MVI ≥2 patients, putative alloreactive iKIR-MM NK cells were defined by flow cytometry as NKG2A(-) cells bearing self-specific but lacking donor-specific iKIR. Although iKIR-MM NK cells were detected in both groups, their pretransplant numbers were higher in MVI ≥2 patients (median = 11.02, interquartile range = 0-58.31 vs median = 0, interquartile range = 0-9.46), especially in the presence of donor-specific antibodies or C4d, and correlated with MVI grade. Pretransplant, a subset of MVI ≥2 patients showed high proportions and numbers of oligoclonal iKIR-MM NK cells, which displayed an NKG2C(+) adaptive phenotype associated with cytomegalovirus infection. This pilot study provides a novel perspective on the contribution of iKIR-MM NK cells to MVI, with potential practical implications.J.F.V. had support from a grant awarded by the Catalan Transplantation Foundation. This study was supported by grants: “PI20/00090” and “PI23/00061”, funded by Instituto de Salud Carlos III (ISCIII) FIS and co-funded by the European Union (EU-FEDER); “PID2019-110609RB-C21” and “PID2019-110609RB-C22” (funded by Agencia Estatal de Investigación and cofunded by EU-FEDER; “P105/U/2018” (Fundació la Marató de TV3); “RD21/0005/0022” (National Network for Kidney Research RICORS2024, co-funded by Spanish Ministry of Health-ISCIIII and European Union-NextGenerationEU), Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS 2040-Renal (RD24/0004/0003) funded by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR), and a 2023 Nephrology Research grant (Spanish Society of Nephrology S.E.N)
Unravelling the molecular pathways of auditory and vestibular function: the roles of sall1a and the fgf13 genes in the zebrafish inner ear development
No full textL’oïda interna és un òrgan sensorial complex essencial per a les funcions auditiva i vestibular, que depèn de les cèl·lules ciliades per a la mecanotransducció i de les neurones sensorials per a transmetre senyals al sistema nerviós central. Mutacions en gens crítics per al desenvolupament de les cèl·lules ciliades i neurones sensorials poden provocar trastorns de l’audició i l’equilibri. No obstant això, el paper de molts gens implicats en desenvolupament i malaltia de l’oïda interna encara roman àmpliament inexplorat. Aquest és el cas dels gens sall1 i fgf13, ambdós expressats a les cèl·lules i neurones sensorials de l’oïda interna i associats a malalties humanes. Mitjançant la tecnologia CRISPR, vam generar línies transgèniques knockout en peix zebra per a aquests gens per tal d’avaluar els efectes de la seva pèrdua de funció a nivell molecular, cel·lular i conductual des de les 24 hores post-fertilització fins els 6 dies post-fertilització. Vam trobar que els mutants per a sall1a exhibien un nombre reduït de cèl·lules madures, una manca d’equilibri estacionari i una regulació a la baixa de tres gens associats a la pèrdua d’audició, entre altres gens importants per al desenvolupament de les cèl·lules ciliades. D’altra banda, els crispants de fgf13a/b presentaven desfasciculació dels axons i una forma ganglionar anormal. Sorprenentment, els mutants homozigots knockout per a fgf13a/b de la línia estable presentaven una morfologia normal del gangli estatoacústic, suggerint un possible mecanisme compensatori. En conclusió, aquest estudi suggereix que sall1a juga un paper crític en la maduració de les cèl·lules ciliades en el peix zebra, la qual cosa pot proporcionar informació respecte de la patogènesi de la pèrdua d’audició en malalties com ara la síndrome de Townes-Brocks. En relació als paralogs de fgf13, el paper d’aquests gens en el desenvolupament del gangli estatoacústic podria trobar-se esmorteït degut a mecanismes compensatoris potencials mediats per ARNm, tot i que les dades suggereixen que un dels seus papers podria estar relacionat al correcte establiment de projeccions d’axons.The inner ear is a complex sensory organ essential for auditory and vestibular functions, relying on hair cells for mechanotransduction and sensory neurons to transmit signals to the central nervous system. Mutations in genes critical for the development of hair cells and sensory neurons can lead to hearing and balance disorders. Nevertheless, the roles of many genes in inner ear development and disease remain largely unexplored. This is the case for the sall1 and fgf13 genes, both expressed in hair cells and sensory neurons of the inner ear and associated with human conditions. Using CRISPR technology, we generated zebrafish transgenic knockout lines for these genes to assess the effects of their loss-of-function at the molecular, cellular and behavioural level from 24 hours post-fertilization to 6 days post-fertilization. We found that sall1a mutants exhibited a reduced number of mature hair cells, a lack of stationary balance, and downregulation of three hearing loss-associated genes, among other genes important for hair cell development. On a different note, fgf13a/b crispants presented axonal defasciculation and an abnormal ganglionic shape. Surprisingly, homozygous mutants from the fgf13a/b stable knockout line displayed normal morphology of the statoacoustic ganglion, suggesting a possible compensatory mechanism. In conclusion, this study suggests that sall1a plays a critical role in the maturation of hair cells in zebrafish, which may provide insight into the pathogenesis of hearing loss in conditions like Townes-Brocks syndrome. Regarding fgf13 paralogues, potential mRNA-mediated compensatory mechanisms might be concealing the role of these genes in statoacoustic ganglion development, though data suggest that one of its roles could be related to the establishment of proper axonal projections.Programa de Doctorat en Biomedicin
Characterization of allosteric communication networks in GPCRs
No full textG protein-coupled receptors (GPCRs) are central to cellular signaling and pivotal in drug development. This thesis investigates allosteric communication in GPCRs, crucial for their effective modulation in pharmacotherapy. It introduces two distinct methodologies for characterizing allosteric communication networks. The first, a machine learning pipeline, predicts experimental variables from simulations, with a primary focus on modeling the stabilities of inter-residue contacts - a critical aspect of GPCR functionality. The second methodology, in contrast, applies machine learning and statistical tools descriptively, integrating deep biological system knowledge. This approach requires less data, offering a complementary perspective to the predictive nature of the first method. The first methodology has accurately predicted the pharmacology of various Class A GPCR ligands. Meanwhile, the second has been crucial in elucidating the mechanism for biased signaling in the type 2 cannabinoid receptor. Together, these approaches not only deepen our understanding of GPCR-mediated signal transduction but also mark a significant advancement in drug development, paving the way for more targeted and effective therapeutic strategies.Los receptores acoplados a proteína G (GPCRs) son clave en la señalización celular y fundamentales en el desarrollo de fármacos. Esta tesis investiga la comunicación alostérica en GPCRs, esencial para su modulación mediante farmacoterapia. Aquí se presentan dos metodologías distintas para caracterizar redes de comunicación alostérica. La primera, una infraestructura de aprendizaje automático, predice variables experimentales a partir de simulaciones. Esta está centrada en modelar la estabilidad de contactos inter-residuales, aspecto crítico de la funcionalidad de los GPCRs. La segunda metodología aplica herramientas de aprendizaje automático y estadística de manera descriptiva, integrando conocimientos profundos del sistema biológico. Esta aproximación requiere menos datos, ofreciendo una perspectiva complementaria a la naturaleza predictiva de la primera. La primera metodología ha predicho con precisión la farmacología de ligandos de varios GPCRs de clase A. Por otro lado, la segunda ha sido crucial en dilucidar un mecanismo para la señalización sesgada en el receptor de cannabinoides tipo 2. Juntas, estas metodologías no sólo profundizan nuestro entendimiento de la transducción de señales mediada por GPCRs, sino también marcan un avance significativo en el desarrollo de fármacos, abriendo camino para estrategias terapéuticas más dirigidas y efectivas.Programa de Doctorat en Biomedicin
China's pivot to Latin America?: revisiting the institutional impact on Sino-Latin American economic relations
No full textSince China’s presence in Latin America, there have been ongoing debates on what drives Chinese commercial activities in the region. Yet, there is little consensus on the institutional impact on Chinese economic engagement with Latin America. Using panel data for Sino-Latin American bilateral trade and Chinese outward FDI in the region, this empirical study applies the extended gravity model to test whether institutions and institutional distances, measured by the Worldwide Governance Indicators, the Index of Economic Freedom and Hofstede's national culture dimensions, foster or hinder economic activities. The findings show that institutions matter but they impact bilateral trade and Chinese FDI in different ways. I also challenge the conventional wisdom that like-minded countries in politico-economic systems and culture will have more business activities. A better understanding of this topic will shed more light on Chinese strategic considerations behind its ever-expanding economic influence on the Global South and the world.Desde la presencia de China en América Latina, se ha venido discutiendo sobre qué impulsa las actividades comerciales chinas en la región. Sin embargo, hay poco consenso sobre el impacto institucional en las relaciones económicas chinas con América Latina. Utilizando datos de panel del comercio bilateral entre China y América Latina y la IED china en la región, este estudio empírico aplica el modelo de gravedad ampliado para comprobar si las instituciones y las distancias institucionales, medidas por el Índice de Gobernanza Mundial, el Índice de Libertad Económica y las dimensiones de cultura nacional de Hofstede, fomentan o dificultan las actividades económicas. Los resultados muestran que las instituciones son importantes, pero que influyen en el comercio bilateral y en la IED china de forma diferente. También cuestiono la idea convencional de que los países afines en cuanto a la cultura y sistemas político-económicos tendrán más actividades de negocio. Una mejor comprensión de este tema arrojará luz sobre las consideraciones estratégicas chinas detrás de su influencia económica en el Sur Global y en el mundo.Programa de doctorat en Dre
Paisatges mediàtics: escenaris de futur per al periodisme i les empreses de mitjans
No full text“Paisatges mediàtics: Escenaris de futur per al periodisme i les empreses de mitjans” és un estudi realitzat en el marc de la Càtedra Futurs de la Comunicació que explora tres possibles escenaris futurs per al periodisme i la premsa. S’ha portat a terme durant l’any 2024 i principis del 2025. L’informe segueix l’estructura habitual dels estudis de prospectiva, partint de la definició de vectors clau, junt amb les variables tradicionals, i l’anàlisi de les seves variacions per dibuixar diferents panorames potencials
Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium
No full textIntroduction: We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition. Methods: Genetic data from five AMYPAD parent cohorts were harmonized, and PRS were computed for Alzheimer's disease (AD) susceptibility, cerebrospinal fluid (CSF) amyloid beta (Aβ)42, and CSF phosphorylated tau181. Cross-sectional amyloid (Centiloid [CL]) burden was available for all participants, and regression models determined if PRS were associated with CL burden. Results: After harmonization, data for 867 participants showed that high CL burden was most strongly predicted by CSF Aβ42 PRS compared to traditional AD susceptibility PRS. Discussion: This work emphasizes the importance of data harmonization and pooling of cohorts for large-powered studies. Findings suggest a genetic predisposition to amyloid pathology that may predispose individuals early in the AD continuum. This validates the potential use of PRS in clinical (trial) settings as a non-invasive tool to assess AD risk. Highlights: We developed a robust harmonization pipeline for multi-cohort genotype array data. Cerebrospinal fluid amyloid beta (Aβ)-specific polygenic risk scores (PRS) more strongly predicted global Aβ positron emission tomography burden than other PRS. Results suggest a strong genetic predisposition to early Aβ pathology. This work highlights the need for robust data harmonization and data pooling. This work also validates the potential use of PRS as a non-invasive tool to assess Alzheimer's disease risk.Introduction: We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition. Methods: Genetic data from five AMYPAD parent cohorts were harmonized, and PRS were computed for Alzheimer's disease (AD) susceptibility, cerebrospinal fluid (CSF) amyloid beta (Aβ)42, and CSF phosphorylated tau181. Cross-sectional amyloid (Centiloid [CL]) burden was available for all participants, and regression models determined if PRS were associated with CL burden. Results: After harmonization, data for 867 participants showed that high CL burden was most strongly predicted by CSF Aβ42 PRS compared to traditional AD susceptibility PRS. Discussion: This work emphasizes the importance of data harmonization and pooling of cohorts for large-powered studies. Findings suggest a genetic predisposition to amyloid pathology that may predispose individuals early in the AD continuum. This validates the potential use of PRS in clinical (trial) settings as a non-invasive tool to assess AD risk. Highlights: We developed a robust harmonization pipeline for multi-cohort genotype array data. Cerebrospinal fluid amyloid beta (Aβ)-specific polygenic risk scores (PRS) more strongly predicted global Aβ positron emission tomography burden than other PRS. Results suggest a strong genetic predisposition to early Aβ pathology. This work highlights the need for robust data harmonization and data pooling. This work also validates the potential use of PRS as a non-invasive tool to assess Alzheimer's disease risk.Introduction: We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition. Methods: Genetic data from five AMYPAD parent cohorts were harmonized, and PRS were computed for Alzheimer's disease (AD) susceptibility, cerebrospinal fluid (CSF) amyloid beta (Aβ)42, and CSF phosphorylated tau181. Cross-sectional amyloid (Centiloid [CL]) burden was available for all participants, and regression models determined if PRS were associated with CL burden. Results: After harmonization, data for 867 participants showed that high CL burden was most strongly predicted by CSF Aβ42 PRS compared to traditional AD susceptibility PRS. Discussion: This work emphasizes the importance of data harmonization and pooling of cohorts for large-powered studies. Findings suggest a genetic predisposition to amyloid pathology that may predispose individuals early in the AD continuum. This validates the potential use of PRS in clinical (trial) settings as a non-invasive tool to assess AD risk. Highlights: We developed a robust harmonization pipeline for multi-cohort genotype array data. Cerebrospinal fluid amyloid beta (Aβ)-specific polygenic risk scores (PRS) more strongly predicted global Aβ positron emission tomography burden than other PRS. Results suggest a strong genetic predisposition to early Aβ pathology. This work highlights the need for robust data harmonization and data pooling. This work also validates the potential use of PRS as a non-invasive tool to assess Alzheimer's disease risk.This work used data from AMYPAD PNHS that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking received support from the European Union's Horizon 2020 research and innovation programme and EFPIA. F.B. and E.S.L. have received support for data curation and storage from the Alzheimer's Disease Data Initiative (ADDI; paid to institution). L.E.C. has acquired research support from GE Healthcare and Springer Healthcare (paid by Eli Lilly), both paid to institution. L.E.C. is supported by the MSCA Postdoctoral fellowship (#101108819) and Alzheimer Association Research Fellowship (#23AARF-1029663) grants. N.V-T. receives funding from the Spanish Research Agency MICIU/AEI/10.13039/501100011033 (grant RYC2022-038136-I co-funded by the European Union FSE+, and grant PID2022-143106OA-I00 co-funded by the European Union FEDER). Additionally, N.V-T. is supported by the William H. Gates Sr. Fellowship from the Alzheimer's Disease Data Initiative, and grant 23S06083-001 funded by “la Caixa” Foundation and Barcelona City council. The F-PACK study was funded by the Stichting Alzheimer Onderzoek, Internal Funds KU Leuven, and Flemish Research Foundation (G0G1519N, G094418N), VLAIO (HBC.2019.2523, for R.V., Y.A., and I.C.). F.B. is supported by the NIHR biomedical research centre at UCLH
English TikTok videos: 'short lessons' or just waffle? An analysis of the 'comments' section
No full textData de publicació electrònica: 29-09-2025The number of people using social networks to learn languages is constantly increasing. Although TikTok is one of the most popular social networks, little research has been conducted on its use for language learning. Our study examines a corpus of English pronunciation videos to explore the relationship between this platform and language learning. Specifically, we aim to determine whether interactions in the comment section are focused on learning or primarily social in nature. We analyzed 750 comments using an adaptation of the Interaction Analysis Model (IAM) developed by Gunawardena et al. (1997). Our results indicate that users discuss pronunciation and other aspects of English linguistic competence, with the most frequent phases involving information sharing and socialization
Engaging with Chinese rural women influencers on Douyin: female viewers’ perspectives on gender norms
No full textIn recent years, the popularity of short videos has provided rural women in China with an unprecedented opportunity for self‐presentation and engagement with the outside world, enabling them to articulate their own narratives with authenticity. On Douyin, a leading short video platform, content produced by rural women has gained significant attention, resonating particularly with female audiences. This study, based on 21 semi‐structured interviews conducted with Chinese women viewers, investigates the factors driving the popularity of rural female influencers’ content, the gratifications that female viewers obtain, and their perceptions of these rural influencers’ authenticity. The findings reveal that female audiences gain insights into the structural challenges and vulnerabilities faced by rural women in China, as well as how these influencers challenge traditional gender norms. Ultimately, this study underscores the transformative potential of short videos to provide female audiences with a window into the lives of rural women, stimulating critical reflection on deeply embedded cultural constructs and advancing social inclusion. Promoting gender equality and social development may provide various opportunities for the autonomy of rural women in the future
Mapping enablers for SDG implementation in the private sector: a systematic literature review and research agenda
No full textAcademics and practitioners alike recognize the important role of businesses in achieving the UN's Sustainable Development Goals (SDGs). However, research is still needed to understand strategies that can aid the private sector in this regard. The objective of the current paper is twofold. First, it provides an interdisciplinary systematic literature review of 96 papers published between 2015 and 2022 to analyse the state-of-the-art of the academic literature on the enablers that can facilitate SDG implementation in businesses. The analysis provides evidence that enablers can be categorized depending on whether they are external to the company (industry, tools, and education), internal to the company (company characteristics, governance, and adoption of innovation and technology), or a combination of both (Public-Private Partnerships). Second, it provides a specific research agenda on each enabler, offering relevant recommendations for academics, practitioners and policy makers to work simultaneously to achieve the UN's 2030 Agenda
Essays on behavioral economics
No full textThis thesis consists of three independent essays on decision theory,
behavioral economics, and experimental economics. The first article
(Chapter 2) studies variety-seeking behavior, an empirically
well-documented driver of individual decision-making that is poorly
understood theoretically. Standard intertemporal discrete choice
models cannot account for such behavior. I fill this gap in the
literature by proposing and axiomatically characterizing a new intertemporal
choice model consistent with variety-seeking behavior.
The second article (Chapter 3) studies multiproduct monopolists’
optimal dynamic pricing strategies when facing variety-seeking
consumers with different degrees of foresight. Interestingly, the
monopolist’s optimal pricing strategy induces myopic agents to
act like forward-looking agents, as this allows the firm to extract
full surplus from both types of agents. The last article (Chapter
4) reports the results of the first randomized-controlled field experiment
studying the short-term effects of air pollution on economic
preferences.Aquesta tesi consta de tres articles independents sobre teoria de
la decisió, economia del comportament i economia experimental.
El primer article (Capítol 2) estudia el comportament de
recerca de varietats, un motor ben documentat empíricament
de la presa de decisions individuals però poc entès teòricament.
Els models estàndard d’elecció discreta intertemporal no poden
acomodar aquest comportament. Omplo aquest buit en la literatura
proposant i caracteritzant axiomàticament un nou model
d’elecció intertemporal consistent amb el comportament de recerca
de varietats. El segon article (Capítol 3) estudia les estratègies
de preus dinàmiques òptimes dels monopolistes multiproductes
quan s’enfronten a consumidors que busquen varietat i exhibeixen
diferents graus de previsió. Curiosament, l’estratègia de preusptima del monopolista indueix els agents miops a actuar com a
agents amb plena visió de futur, ja que això permet a l’empresa
extreure l’excedent total dels dos tipus d’agents. L’últim article
(Capítol 4) descriu els resultats del primer experiment de camp
controlat i aleatoritzat que estudia els efectes a curt termini de la
contaminació de l’aire sobre les preferències econòmiques.Esta tesis consta de tres artículos independientes sobre teoría
de la decisión, economía del comportamiento y economía experimental.
El primer artículo (Capítulo 2) estudia el comportamiento
de búsqueda de variedades, un motor bien documentado
empíricamente de la toma de decisiones individuales pero
poco entendido teóricamente. Los modelos estándar de elección
discreta intertemporal no pueden acomodar tal comportamiento.
Lleno este vacío en la literatura proponiendo y caracterizando
axiomáticamente un nuevo modelo de elección intertemporal consistente
con el comportamiento de búsqueda de variedades. El
segundo artículo (Capítulo 3) estudia las estrategias de precios
dinámicas óptimas de los monopolistas multiproductos cuando se
enfrentan a consumidores que buscan variedad y exhiben distintos
grados de previsión. Curiosamente, la estrategia de precios óptima
del monopolista induce a los agentes miopes a actuar como agentes
con plena visión de futuro, ya que esto permite a la empresa extraer
el excedente total de ambos tipos de agentes. El último
artículo (Capítulo 4) describe los resultados del primer experimento
de campo controlado y aleatorizado que analiza los efectos
a corto plazo de la contaminación del aire sobre las preferencias
económicas.Programa de doctorat en Economia, Finances i Empres