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Investigating protein functions of understudied genes, proteoforms and novel localisations
No full textThe eukaryotic protein landscape, although extensively studied, still harbors a vast array of uncharacterized functional proteoforms that limit our understanding of biological processes. This thesis explores three aspects: (1) the functional characterization of understudied proteins across the proteome using a next-generation covariation map; (2) a workflow for differentially identifying peptidoforms from bottom-up proteomics data, enabling the investigation of the proteoform landscape under various perturbations; and (3) the identification of a novel nuclear subcellular localization for Peroxiredoxin 1 (PRDX1) and its moonlighting role in chromatin during DNA damage recovery. This work puts the explored topics in the context of protein homeostasis, protein functions, modifications, and the challenges in investigating protein function.El panorama de las proteínas eucariotas, aunque ampliamente estudiado, todavía alberga una amplia gama de proteoformas funcionales no caracterizadas que limitan nuestra comprensión de los procesos biológicos. Esta tesis explora tres aspectos: (1) la caracterización funcional de proteínas poco estudiadas en todo el proteoma utilizando un mapa de covariación de próxima generación; (2) un flujo de trabajo para identificar diferencialmente peptidoformas a partir de datos proteómicos bottom-up, lo que permite la investigación del panorama de proteoformas bajo diversas perturbaciones; y (3) la identificación de una nueva localización subcelular nuclear para la peroxiredoxina 1 (PRDX1) y su papel de pluriempleo en la cromatina durante la recuperación del DNA-damage. Este trabajo sitúa los temas explorados en el contexto de la homeostasis de las proteínas, las funciones de las proteínas, las modificaciones y los desafíos en la investigación de la función de las proteínas.Programa de Doctorat en Biomedicin
A novel mismatch repair deficient lung adenocarcinoma model for immunotherapy research
No full textImmunotherapy has revolutionised cancer treatment, yet responses vary significantly based on tumour characteristics and microenvironment. Here, we developed and analysed subcutaneous and orthotopic immunocompetent mice models of mismatch repair-deficient (dMMR) lung adenocarcinoma (LUAD) by selectively ablating Mlh1. Subcutaneous tumours demonstrated partial sensitivity to anti-PD-1 therapy, whereas orthotopic tumours exhibited robust responses, with substantial reductions in tumour burden. Although both models displayed to some extent a robust immune microenvironment, they differed in immune cell infiltration patterns following anti-PD-1 treatment, underscoring the critical influence of anatomical site and tumour context in shaping immunotherapy outcomes. Furthermore, the use of clonal cell lines with enriched neoantigen frequency in the orthotopic model highlighted the role of clonal heterogeneity in modulating therapeutic efficacy. Together, our findings emphasise the relevance of orthotopic models for preclinical evaluation and suggest that they more accurately reflect clinical responses to immune checkpoint blockade in dMMR LUAD.We thank Dr A. Celià-Terrassa, and Dr. K. Sutherland for providing reagents; Dr. Yacine Kharraz and CRG/UPF Flow Cytometry Unit with sample preparation and analysis. This work was supported by grants from the Spanish Ministry of Science and Innovation Grant (PID2021-127710OB-I00, PID2021-128721OB-I00, PID2023-151556OB-I00, CNS2024-154742, CNS2023-144819), “La Caixa” foundation (51110009 and HR22-00402), Worldwide Cancer Research (20–0144), ESF+ (ERDF A way of making Europe), European Union NextGenerationEU/PRTR (ESF Investing in your future). A.J. was supported by Ramon y Cajal Research Fellowship (RYC2018-025244-I), I.Z. is funded by an AECC Postdoctoral Fellowship (POSTD234858ZADR). C.L.-R. is supported by the ICREA Acadèmia program of Generalitat de Catalunya. A.K. was supported by a predoctoral fellowship of the Spanish Ministry of Science and Innovation (PRE2019-088166). L.P. was founded by PID2023-151556OB-I00, CNS2024-154742, “ERDF A way of making Europe” and, as appropriate, by “ESF Investing in your future”, by “ESF+” or by “European Union NextGenerationEU/PRTR”. This work was made possible through the “Unidad de Excelencia María de Maeztu'' funded by the MCIN and AEI (CEX2018-000792-M)
Rural spaces/narratives in flux: an emerging literature?
No full textThis article aims to study the phenomenon of the appearance of a large number of rural-themed literary works in recent Catalan literature. This phenomenon will be approached from two perspectives. First, I critically review the notion of "emergence," a concept that can be applied to identify literary works that are not recognized from the point of view of a hegemonic conception of literature. Second, I relate the publication of these new forms of representation of rurality to the transformations introduced in a significant part of contemporary Catalan narrative, where nonfiction has gained recognition. The study focuses on Mercè Ibarz's Tríptic de la terra (2020), Francesc Serés's La pell de la frontera (2014) and Julià Guillamon's Les hores noves(2022), which are based on autobiography and information from the world of journalism
Radical care in displacement: Rohingya women’s activism amidst neoliberal humanitarianism and repression
No full textThis paper examines the activism and care work of Rohingya women in displacement settings, focusing on grassroots efforts in Cox’s Bazar refugee camps and transnational advocacy by diaspora activists. Drawing on 43 in-depth interviews and applying a feminist ethics of care framework, we argue that these women's activism constitutes a form of radical care that challenges both neoliberal humanitarian practices and repressive state policies. Rohingya women activists forge networks of solidarity and empowerment that extend beyond conventional humanitarian interventions, providing emotional support and shared experiences that contribute to the social ecology of care for refugee women. Their grassroots work contests the neoliberal emphasis on individual self-reliance, instead highlighting the vital role of relational care in fostering collective resilience. However, these activists face significant risks from multiple sources, including state repression, community backlash, and online harassment. They employ strategies such as ‘strategic invisibility’ and digital activism to navigate these dangers. Despite the transformative potential of their work, it remains systematically undervalued, leaving activists vulnerable to burnout and depletion. By centering the experiences and agency of Rohingya women, this study reveals a complex landscape of resistance, care, and empowerment, offering insights into how refugee women create change amidst intersecting forms of oppression
Recovering the history of Bergen Belsen using an interactive 3D reconstruction in a mixed reality space the role of pre-knowledge on memory recollection
No full textComunicació presentada a: 2015 Digital Heritage International Congress, celebrada del 28 de setembre al 2 d¡oactubre de 2015 a Granada, Espanya.The question addressed by our work is twofold: On the one hand we want to contribute to the preservation of the Holocaust cultural heritage using digital technology, on the other hand, we want to investigate the impact of pre-knowledge on context information when this information is acquired in a virtual environment. Specifically, we wanted to investigate the user experience after factual or emotional information prior exposure to a virtual environment showing historical information, in this case related to the Holocaust. We developed a 3D reconstruction of the delousing building of the Bergen Belsen concentration camp and deployed it in an interactive mixed reality space. Here the user was engaged in a guided tour of the delousing building and was exposed to factual information on the configuration of the building and its history through pictures and a narrating voice. The results of our study show that prior knowledge i.e "emotional vs factual" affects memory recollection and thus our ability to retain relevant information. The utcome of our study supports the usefulness of digital and interactive technologies as a tool to recover and preserve cultural heritage
The evolutionary history of Drosophila buzzatii. XXXV. Inversion polymorphism and nucleotide variability in different regions of the second chromosome
No full textInversions are portions of a chromosome where the gene order is reversed relative to a standard reference orientation. Because of reduced levels of recombination in heterokaryotypes, inversions have a potentially important effect on patterns of nucleotide variability in those genomic regions close to, or included in, the inverted fragments. Here we report sequence variation at three anonymous regions (STSs) located at different positions in relation to second-chromosome inversion breakpoints in 29 isochromosomal lines derived from an Argentinean population of Drosophila buzzatii. In agreement with previous findings in Drosophila, gene flux (crossing over and/or gene conversion) between arrangements seems to appreciably increase as we approach the middle sections of inversion 2j, and patterns of nucleotide variability within, as well as genetic differentiation between chromosome arrangements, are comparable to those observed at the molecular marker outside the inverted fragments. On the other hand, nucleotide diversity near the proximal breakpoint of inversion 2j is reduced when contrasted with that found at the other regions, particularly in the case of derived inverted chromosomes. Using the data from the breakpoint, we estimate that the inversion polymorphism is approximately 1.63 N generations old, where N is the effective population size. An excess of low-frequency segregating polymorphisms is detected; mostly in the ancestral 2st arrangement and probably indicating a population expansion that predates the coalescent time of inversion 2j. Heterogeneity in mutation rates between the markers linked to the inversions may be sufficient to explain the different levels of nucleotide diversity observed. When considered in the context of other studies on patterns of variation relative to physical distance to inversion breakpoints, our data appear to be consistent with the conclusion that inversions are unlikely to be "long-lived" balanced polymorphisms
Análisis y traducción de los convenios reguladores de divorcio en la combinación español-chino
No full textEl ámbito de la traducción jurídica en la combinación españolchino constituye una línea de investigación reciente que requiere de nuevos trabajos que impulsen su desarrollo. La mayoría de las publicaciones se centran en la traducción de leyes escritas, por lo que el estudio de otros géneros textuales jurídicos se hace más necesario aún. Así, este trabajo se ocupa de los convenios reguladores de divorcio, textos pertenecientes al derecho de familia, esenciales en los procesos de divorcio. El corpus se compone de un total de diez convenios reguladores de divorcio, cinco en español y cinco en chino. Mediante la aplicación de un análisis textual contrastivo, el objetivo del presente artículo es identificar las especificidades tanto textuales como estilísticas del género objeto de estudio para poder ofrecer soluciones discursivas adecuadas en una traducción. Para ello, se lleva a cabo el análisis a dos niveles principales: el macrotextual, que abarca la estructura textual y la disposición de la información; y el microtextual, centrado en los aspectos lingüístico-discursivos, como las formas oracionales, las formas verbales y las nominalizaciones. Tras el análisis contrastivo, se examina en qué medida las características macrotextuales y microtextuales identificadas pueden aplicarse para naturalizar el estilo jurídico de la lengua de llegada. En conjunto, el estudio demuestra la utilidad del análisis textual contrastivo como herramienta pretraslativa para mejorar la naturalidad y la precisión en la traducción jurídica entre el español y el chino
A natural history of FUT2 polymorphism in humans
No full textBecause pathogens are powerful selective agents, host-cell surface molecules used by pathogens as identification signals can reveal the signature of selection. Most of them are oligosaccharides, synthesized by glycosyltransferases. One known example is balancing selection shaping ABO evolution as a consequence of both, A and B antigens being recognized as receptors by some pathogens, and anti-A and/or anti-B natural antibodies produced by hosts conferring protection against the numerous infectious agents expressing A and B motifs. These antigens can also be found in tissues other than blood if there is activity of another enzyme, FUT2, a fucosyltransferase responsible for ABO biosynthesis in body fluids. Homozygotes for null variants at this locus present the nonsecretor phenotype (se), because they cannot express ABO antigens in secretions. Multiple independent mutations have been shown to be responsible for the nonsecretor phenotype, which is coexisting with the secretor phenotype in most populations. In this study, we have resequenced the coding region of FUT2 in 732 individuals from 39 worldwide human populations. We report a complex pattern of natural selection acting on the gene. Although frequencies of secretor and nonsecretor phenotypes are similar in different populations, the point mutations at the base of the phenotypes are different, with some variants showing a long history of balancing selection among Eurasian and African populations, and one recent variant showing a fast spread in East Asia, likely due to positive selection. Thus, a convergent phenotype composition has been achieved through different mutations with different evolutionary histories. © The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.This research was funded by grants BFU2005-00243 and SAF-2007-63171 awarded by Ministerio de Educación y Ciencia (Spain) and by the Direcció General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608). Funds were also from the Etablissement Français du Sang (EFS) Centre Atlantique, and from the Ministère Français de la Recherche (EA3034)
Evaluation of ChatGPT-4 for the detection of surgical site infections from electronic health records after colorectal surgery: a pilot diagnostic accuracy study
No full textBackground: Surveillance of surgical site infection (SSI) relies on manual methods that are time-consuming and prone to subjectivity. This study evaluates the diagnostic accuracy of ChatGPT for detecting SSI from electronic health records after colorectal surgery via comparison with the results of a nationwide surveillance programme. Methods: This pilot, retrospective, multicentre analysis included 122 patients who underwent colorectal surgery. Patient records were reviewed by both manual surveillance and ChatGPT, which was tasked with identifying SSI and categorizing them as superficial, deep, or organ-space infections. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Receiver operating characteristic (ROC) curve analysis determined the model's diagnostic performance. Results: ChatGPT achieved a sensitivity of 100 %, correctly identifying all SSIs detected by manual methods. The specificity was 54 %, indicating the presence of false positives. The PPV was 67 %, and the NPV was 100 %. The area under the ROC curve was 0.77, indicating good overall accuracy for distinguishing between SSI and non-SSI cases. Minor differences in outcomes were observed between colon and rectal surgeries, as well as between the hospitals participating in the study. Conclusions: ChatGPT shows high sensitivity and good overall accuracy for detecting SSI. It appears to be a useful tool for initial screenings and for reducing manual review workload. The moderate specificity suggests a need for further refinement to reduce the rate of false positives. The integration of ChatGPT alongside electronic medical records, antibiotic consumption and imaging data results for real-time analysis may further improve the surveillance of SSI. Clinicaltrials: gov Identifier: NCT06556017