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Navigating protein landscapes with a machine-learned transferable coarse-grained model
No full textThe most popular and universally predictive protein simulation models employ all-atom molecular dynamics, but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model with similar prediction performance has been a long-standing challenge. By combining recent deep-learning methods with a large and diverse training set of all-atom protein simulations, we here develop a bottom-up CG force field with chemical transferability, which can be used for extrapolative molecular dynamics on new sequences not used during model parameterization. We demonstrate that the model successfully predicts metastable states of folded, unfolded and intermediate structures, the fluctuations of intrinsically disordered proteins and relative folding free energies of protein mutants, while being several orders of magnitude faster than an all-atom model. This showcases the feasibility of a universal and computationally efficient machine-learned CG model for proteins.We thank all members of the Clementi and Noé groups for their help in different phases of this work. We gratefully acknowledge funding from the European Commission (grant no. ERC CoG 772230 ‘ScaleCell’), the International Max Planck Research School for Biology and Computation (IMPRS–BAC), the Bundesministerium für Bildung und Forschung BMBF (Berlin Institute for Learning and Data, BIFOLD, and project FAIME 01IS24076), the Berlin Mathematics Center MATH+ (AA1-6, EF1-2) and the Deutsche Forschungsgemeinschaft DFG (NO 825/2, NO 825/3, NO 825/4; SFB/TRR 186, Project A12; SFB 1114, Projects B03, B08 and A04; SFB 1078, Project C7; and RTG 2433, Projects Q05 and Q04), the National Science Foundation (CHE-1900374 and PHY-2019745) and the Einstein Foundation Berlin (Project 0420815101). We gratefully acknowledge the computing time provided on the supercomputer Lise at NHR@ZIB as part of the NHR infrastructure, and on the supercomputer JUWELS operated by the Jülich Supercomputing Centre. We thank volunteers at GPUGRID.net for contributing computational resources and Acellera for funding
The urban physical environment and leisure-time physical activity in early midlife: a FinnTwin12 study
No full textUnder the exposome framework, this study examined the relationship between the urban physical environment and leisure-time physical activity during early midlife based on 394 participants (mean age: 37, range 34-40) from the FinnTwin12 cohort, residing in five major Finnish cities in 2020. We curated 145 urban physical exposures based on residential addresses and measured three outcomes: total leisure-time physical activity (total LTPA) and two sub-domains: leisure-time physical activity without commuting activity (LTPA) and commuting activity. K-prototypes clustering identified three urban clusters: "original city center," "new city center," and "suburban," each with distinct environmental patterns. Regression models showed that participants in the "suburban" cluster had lower levels of total LTPA and LTPA compared to those in the "original city center" cluster, while we found null findings for commuting activity. Then, repeated regression models with a p-value threshold of 0.01 were used to initially select candidates. eXtreme Gradient Boosting models identified greenspaces and road characteristics as the top important factors influencing total LTPA, while pocket park and greenness were ranked as the top important factors influencing LTPA. The relationships were non-linear. There were thresholds for the count and size of pocket parks within 800 m walking distance and the modified soil adjusted vegetation index, determining whether they positively or negatively predict LTPA. Our findings suggested that the urban environment in Finnish cities was associated with leisure-time physical activity, which revealed new residential pattern and identified key exposures of road, pocket park, and greenness with non-linear effect, that can guide future policies.This research was partly funded by the European Union's Horizon 2020 research and innovation program under grant agreement No 874724 (Equal-Life). Equal-Life is part of the European Human Exposome Network. Data collection in FinnTwin12 has been supported by the National Institute on Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to Richard J. Rose, and AA015416 to Danielle Dick and Jessica Salvatore) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073, 336823, and 352792 to Jaakko Kaprio). Jaakko Kaprio acknowledges support by the Academy of Finland (grants 265240, 263278). ISGlobal acknowledges support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program
La narración audiovisual de mujeres jóvenes. Un relato de autoconocimiento
No full textEste artículo presenta parte de los resultados de la investigación Activismos en Femenino. El discurso feminista de mujeres jóvenes en grupos culturales y en su cotidianidad (ACTIFEM), financiada por la Agencia Catalana de Juventud de la Generalitat de Cataluña la convocatoria 2019-2020 y realizada en dos ciudades españolas, Barcelona y Lleida. El artículo tiene por objetivo evaluar cómo las participantes se definen en tanto que mujeres jóvenes a través del relato audiovisual, y si este ejercicio les ofrece herramientas o espacios de empoderamiento. Para ello se analizan cuatro cápsulas autobiográficas y su proceso de creación, complementado por observación no participante e historias de vida. Este estudio exploratorio permite detectar tópicos y estrategias recurrentes entre las mujeres jóvenes, altamente significativas para considerar la autonarración audiovisual como herramienta de empoderamiento
Associations between air pollution and surrounding greenness with internalizing and externalizing behaviors among schoolchildren
No full textBackground: Air pollution and greenness are emerging as modifiable risk and protective factors, respectively, in child psychopathology. However, research shows inconsistencies. Here, we examined associations between air pollution and surrounding greenness with internalizing and externalizing behaviors. In addition, the potential modifying role of the genetic susceptibility for these traits and socioeconomic status (SES) was explored. Methods: This population-based study included 4485 schoolchildren aged 5-18 years from Spain. Internalizing and externalizing behaviors were assessed using the Child Behavior Checklist (CBCL). Average air pollution (NO2, PM2.5, PM10, PMcoarse, and PM2.5 absorbance) and surrounding greenness (NDVI within 100-m, 300-m, and 500-m buffers) school exposure were estimated for 12 months before outcome assessment. Genetic liability was assessed by computing polygenic risk scores (PRS) and SES was calculated using the Hollingshead Four-Factor Index. Associations were analyzed using negative binomial mixed-effects models. Results: Although no associations survived multiple testing, we found that increases of 5.48 μg/m3 in PM10 and 2.93 μg/m3 in PMcoarse were associated with a 6% (Mean Ratio (MR) = 1.06; 95% CI: 1.01-1.12) and a 4% (MR = 1.04; 95% CI: 1.00-1.09) increase in internalizing behavior scores. A 0.1 increase in NDVI within a 100-m buffer was associated with a 6% decrease in externalizing behavior (MR = 0.94; 95% CI: 0.89-0.99). Neither differences by sex or age, or moderation effects by PRS or SES, were observed. Conclusions: We found preliminary evidence of detrimental effects of air pollution on internalizing behavior and protective effects of greenness on externalizing behavior, which were not modified by sex, age, SES, or genetic liability. If confirmed, these results reinforce the need for improving air quality, especially around schools, as part of preventive strategies focused on childhood psychopathology
Diversity and evolution of South Pacific Eumolpinae (Coleoptera: Chrysomelidae) and the role of New Caledonia in their diversification
No full textThe South Pacific is an intriguing region for studying evolutionary biology, presenting an exceptional diversity and complex geological and environmental characteristics. New Caledonia, in particular, hosts a rich and unique biodiversity with outstanding levels of endemism at different scales. The hyper-diverse Eumolpinae leaf-beetles are particularly rich and highly endemic in the region and are poorly known under many aspects. Integrating taxonomy, macroevolution, and biogeography, this thesis improves our understanding on the diversity and evolution of this group in South Pacific. Twenty new species of the genera Taophila and Tricholapita have been described from New Caledonia and the phylogenetic relationship among them has been assessed. This diversity is the result of allopatric speciation and a slow-down in diversification dynamics which may be associated with the current micro-endemic distribution pattern, influenced by geo-environmental changes. Finally, in a wider scale, New Caledonia can be considered a pump and hub of biodiversity for the Eumolpinae that colonised the South Pacific with repeated dispersal events during the Neogene.El Pacífico Sur es una área importante para el estudio de la evolución, por sus características y por la riqueza de su diversidad. Nueva Caledonia, en particular, alberga una biodiversidad única y exceptionalmente endémica. Un enfoque filogenético al estudio de la diversidad de esta región es fundamental para entender su origen, su diversificación y su distribución. Los crisomélidos Eumolpinae, están presentes en la región con numerosas especies, pero son muy poco conocidos. A través del estudio taxonómico, macroevolutivo y biogeográfico del grupo, esta tesis logra incrementar nuestro conocimiento sobre su diversidad y evolución en el Pacífico Sur. Veinte nuevas especies de Taophila y Tricholapita han sido descritas para Nueva Caledonia. La especiación alopátrica junta con factores ambientales resultan el mecanismo principal en la formación de la distribución micro-endémica de estos dos géneros. Finalmente, Nueva Caledonia representa un centro de diversificación para los Eumolpinos que han colonizado repetidamente el resto del Pacifico Sur en el Neogene.Programa de Doctorat en Biomedicin
Exploring situated stabilities of a rhythm generation system through variational cross-examination
No full textThis paper investigates GrooveTransformer, a real-time rhythm generation system, through the postphenomenological framework of Variational Cross-Examination (VCE). By reflecting on its deployment across three distinct artistic contexts, we identify three stabilities: an autonomous drum accompaniment generator, a rhythmic control voltage sequencer in Eurorack format, and a rhythm driver for a harmonic accompaniment system. The versatility of its applications was not an explicit goal from the outset of the project. Thus, we ask: how did this multistability emerge? Through VCE, we identify three key contributors to its emergence: the affordances of system invariants, the interdisciplinary collaboration, and the situated nature of its development. We conclude by reflecting on the viability of VCE as a descriptive and analytical method for Digital Musical Instrument (DMI) design, emphasizing its value in uncovering how technologies mediate, co-shape, and are co-shaped by users and contexts.This research was funded by (1) the Secretaría de Estado de Digitalización e Inteligencia Artificial, and the European Union-Next Generation EU, under the program Cátedras ENIA 2022. "IA y Música: Cátedra en Inteligencia Artificial y Música" (Reference: TSI-100929-2023-1), (2) the Maria de Maeztu Strategic Research Program (CEX2021-001195-M) and (3) the IMPA Project PID2023-152250OB-I00 funded by MCIU/AEI/10.13039/501100011033/FEDER, UE
Dysregulated microRNAs in blood correlate with central nervous system neuropathology of prion disease
No full textThe role of microRNAs (miRNAs) in neurodegenerative diseases has gained significant attention because of their involvement in gene regulation and potential as biomarkers. In prion diseases, including scrapie, miRNAs may modulate pathogenesis and disease progression. This study investigated circulating miRNA profiles in the blood of sheep naturally affected by scrapie at preclinical and clinical stages using small RNA sequencing and RT-qPCR validation. While only one novel miRNA was dysregulated in preclinical blood samples, 66 previously annotated miRNAs were significantly dysregulated in clinical sheep compared with healthy sheep. These miRNAs are associated with pathways commonly altered in neurodegenerative diseases, such as autophagy, ubiquitin-mediated proteolysis, and endoplasmic reticulum protein processing. Notably, miR-1271-5p, let-7f-5p, miR-186-5p, and miR-425-5p were consistently upregulated in the central nervous system of clinical animals, replicating the results observed in blood, with an increasing trend already in the preclinical stage and a strong correlation with neuropathological prion features. Additionally, predicted target genes such as UBQLN2, PGK1, KRAS, and CLTC were inversely expressed relative to these miRNAs, supporting their regulatory roles. These findings highlight the relevance of circulating miRNAs in prion neuropathology and support further research into the specific functional roles of these miRNAs and their predictive capacity for disease progression.This research was funded by the project PID2021-125398OB-I00, co-financed by the Spanish Agencia Estatal de Investigación and the European Union. These funding sources were not involved in the study design, collection and analysis of data, writing of the report or submission for publication
Measuring progress in equitable urban sustainability: six key questions from European cities
No full textThere is mounting evidence and concern that humanity is failing to equitably meet social needs while overshooting the Earth’s ecological boundaries. Efforts to monitor progress towards equitable urban sustainability have expanded significantly over the years; however, challenges remain in comprehensively assessing and comparing the progress made in different settings. To stimulate critical thinking and guide capacity-building efforts, we assessed the main dimensions and indicators used to monitor urban sustainability and equity in a selection of European cities. We analysed city reports to identify major recurring underlying themes, which we framed as guiding questions, and suggested areas for further development. The purpose was not to highlight the strengths and limitations of specific cities’ efforts. Our critical assessment identified several areas that require attention: the need for the more explicit use of theories or conceptual frameworks to select dimensions and indicators and to frame problems (and subsequently to guide intervention design); the standardisation of indicators; and improved data availability, reliability, and disaggregation to support data capturing, reporting, and comparability across settings. Despite meaningful progress, further efforts are needed to strengthen cities’ capacities to measure, monitor, and report on equitable urban sustainability. These efforts should be complemented with educational initiatives to foster the socio-cultural and behavioural changes necessary to achieve more equitable, sustainable, and healthy urban environments
A feminist economic approach to the Spanish and Italian economic press during the state of alarm for covid
No full textThe consequences of the pandemic have shone a spotlight on the current economic system, often formulated as a dichotomy between life and the economy. This article analyses opinion articles published in the Italian and Spanish economic press during the state of alarm in Spring 2020, applying a gender and a feminist economics approach. The research was organised in two phases. In the first phase, quantitative analysis was applied to a sample of 1,284 opinion articles from leading economic blogs and newspapers in the Italian and Spanish press. In the second phase, qualitative content analysis was performed to explore the incorporation of gender or feminist economics. The results indicate an over-representation of male authors in both countries and a low percentage of gender perspective indicators. Except for inclusive language, both countries follow similar patterns: a relative presence of indicators of gender economics and little incorporation of indicators characteristic of feminist economics.This paper is supported by the AEI-PID2021-128521OB-I00 grant of the Spanish Ministry of Science and Innovation
Negative symptoms and sex differences in first episode schizophrenia: What's their role in the functional outcome? A longitudinal study
No full textIntroduction: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. Material and methods: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. Results: Females showed fewer NS (p=0.031; Cohen's d=-0.312), especially those related to EXP (p=0.024; Cohen's d=-0.326) rather than MAP (p=0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R2=0.494; p<0.001), while only higher deficits in MAP predicted worse functioning in males (R2=0.088; p=0.012). Conclusions: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes.The study has been supported by a BITRECS project conceded to N. Verdolini. BITRECS project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754550 and from “La Caixa” Foundation