{"title":"The evolutionary advantage of guilt: co-evolution of social and non-social guilt in structured populations.","authors":"Theodor Cimpeanu, Luis Moniz Pereira, The Anh Han","doi":"10.1098/rsif.2025.0164","DOIUrl":"10.1098/rsif.2025.0164","url":null,"abstract":"<p><p>Building ethical machines may involve bestowing upon them the emotional capacity to self-evaluate and repent for their actions. While apologies represent potential strategic interactions, the explicit evolution of guilt as a behavioural trait remains poorly understood. Our study delves into the co-evolution of two forms of emotional guilt: social guilt entails a cost, requiring agents to exert efforts to understand others' internal states and behaviours; and non-social guilt, which only involves awareness of one's own state, incurs no social cost. Resorting to methods from evolutionary game theory, we study analytically, and through extensive numerical and agent-based simulations, whether and how guilt can evolve and deploy, depending on the underlying structure of the systems of agents. Our findings reveal that in lattice and scale-free networks, strategies favouring emotional guilt dominate a broader range of guilt and social costs compared to non-structured well-mixed populations, leading to higher levels of cooperation. In structured populations, both social and non-social guilt can thrive through clustering with emotionally inclined strategies, thereby providing protection against exploiters, particularly for less costly non-social strategies. These insights shed light on the complex interplay of guilt and cooperation, enhancing our understanding of ethical artificial intelligence.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250164"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João M F Silva, María J Olmo-Uceda, Valerie J Morley, Paul E Turner, Santiago F Elena
{"title":"Taylor's Power Law rules the dynamics of allele frequencies during viral evolution in response to host changes.","authors":"João M F Silva, María J Olmo-Uceda, Valerie J Morley, Paul E Turner, Santiago F Elena","doi":"10.1098/rsif.2025.0146","DOIUrl":"10.1098/rsif.2025.0146","url":null,"abstract":"<p><p>Sudden and gradual changes from permissive to resistant hosts affect viral fitness, virulence and rates of molecular evolution. We analysed the roles of stochasticity and selection in evolving populations of Sindbis virus under different rates of host replacement. First, approximate Markov models within the Wright-Fisher diffusion framework revealed a reduction in effective population size by approximately half under sudden host changes. These scenarios were also associated with fewer weak beneficial mutations. Second, genetic distance between populations at consecutive time points indicated that populations undergoing gradual host changes evolved steadily until the original host disappeared. Distances to the ancestral sequence in these cases exhibited occasional leapfrog phenomena, where the rise of certain haplotypes is not predictable based on their relatedness to previously dominant ones. In contrast, populations exposed to sudden changes exhibited less-stable compositions and diverged from the ancestral sequence at a consistent rate. Third, we observed that the distribution of allele frequencies followed Taylor's Power Law. Both treatments exhibited high levels of allele aggregation and significant fluctuations, with neutral, beneficial and deleterious alleles distinguishable by their behaviour and position on Taylor's plot. Finally, we found evidence that the host replacement regime influences the temporal distribution of mutations across the genome.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250146"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam Knapp, Daniel A Cruz, Borna Mehrad, Reinhard C Laubenbacher
{"title":"Personalizing computational models to construct medical digital twins.","authors":"Adam Knapp, Daniel A Cruz, Borna Mehrad, Reinhard C Laubenbacher","doi":"10.1098/rsif.2025.0055","DOIUrl":"10.1098/rsif.2025.0055","url":null,"abstract":"<p><p>Digital twin technology, originally developed for engineering, is being adapted to biomedicine and healthcare. A key challenge in this process is dynamically calibrating computational models to individual patients using data collected over time. This calibration is vital for improving model-based predictions and enabling personalized medicine. Biomedical models are often complex, incorporating multiple scales of biology and both stochastic and spatially heterogeneous elements. Agent-based models, which simulate autonomous agents, such as cells, are commonly used to capture how local interactions affect system-level behaviour. However, no standard personalization methods exist for these models. The main challenge is bridging the gap between clinically measurable macrostates (e.g. blood pressure and heart rate) and the detailed microstate data (e.g. cellular processes) needed to run the model. In this article, we propose an algorithm that applies the ensemble Kalman filter, a classic data-assimilation technique, at the macrostate level. We then link the Kalman update at the macrostate to corresponding updates at the microstate level, ensuring that the resulting microstates are compatible with the desired macrostates and consistent with the model's dynamics. This approach improves the personalization of complex biomedical models and enhances model-based forecasts for individual patients.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250055"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Distinct evolutionary patterns of tumour-immune escape and elimination determined by extracellular matrix architectures.","authors":"Yijia Fan, Jason T George","doi":"10.1098/rsif.2025.0116","DOIUrl":"10.1098/rsif.2025.0116","url":null,"abstract":"<p><p>Cancer progression remains a significant clinical challenge. Phenotypic adaptation by tumour cells results in disease heterogeneity, which drives treatment resistance and immune escape. T-cell immunotherapy, while effective at treating some cancer subtypes, can also fail due to limits on tumour immunogenicity or T-cell recognition. For example, one potential contributor to immune escape involves the density and alignment of the extracellular matrix (ECM) surrounding tumours, also known as tumour-associated collagen signature (TACS). However, the specific mechanisms by which aligned fibres contribute to decreased patient survival rates have not yet been decoupled. Here, we developed EVO-ACT (EVOlutionary agent-based cancer T-cell interaction), a two-dimensional agent-based modelling framework designed to investigate how different TACS architectures impact tumour evolution and dynamic interactions with CD8[Formula: see text] T cells. Our results highlight that TACS-driven modulation of T-cell dynamics, combined with phenotypic adaptation, such as epithelial-to-mesenchymal transition, underlies differences in tumour immunogenicity and the application of our model can successfully recapitulate clinically observed breast cancer survival trends.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250116"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciatta Wobill, Samuel Steffen, Daniel Macken, Peter Fischer, Patrick Alberto Rühs
{"title":"<i>In situ</i> interfacial shear rheology of fungal films.","authors":"Ciatta Wobill, Samuel Steffen, Daniel Macken, Peter Fischer, Patrick Alberto Rühs","doi":"10.1098/rsif.2025.0058","DOIUrl":"10.1098/rsif.2025.0058","url":null,"abstract":"<p><p>Understanding the dynamic film formation of fungi is essential for designing and creating engineered living fungal materials. However, conventional growth measurements often neglect the three-dimensionality of fungal growth and thus only provide scarce information about the transient mechanical properties. In this study, we use interfacial shear rheology (ISR) to investigate the dynamic formation of fungal films. By using ISR we can identify the lag, exponential and stationary phases of fungal growth by measuring the film viscoelasticity. We observed an increase in storage modulus after 2 h before spore germination, most likely caused by the absorption of spores and metabolic by-products during swelling and germination. Modifying the sugar concentration in the liquid growth media allowed for delayed germination while enhancing the exponential propagation speed of fungi, as visible through colony diameter measurements, spectrophotometry and ISR. Furthermore, we were able to observe the film formation through an increase in interfacial moduli as a measure of biomass. In combination with spectrophotometry and colony diameter measurements, ISR provides a complete picture of the transient film formation over 3 days, shedding light on the germination, exponential growth and stationary phase by providing non-destructive, qualitative measures for biomass and quantitative measures for film strength.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250058"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Soft matter mechanics of immune cell aggregates.","authors":"Shohreh Askari, Guillem Saldo Rubio, Anagha Datar, Heidi Harjunpää, Susanna C Fagerholm, Matilda Backholm","doi":"10.1098/rsif.2025.0231","DOIUrl":"10.1098/rsif.2025.0231","url":null,"abstract":"<p><p>T-cells are a crucial subset of white blood cells that play a central role in the immune system. When T-cells bind antigens, it leads to cell activation and the induction of an immune response. If T-cells are activated by antigens <i>in vivo</i> or artificially <i>in vitro,</i> they form multicellular aggregates. The mechanical properties of such clusters provide valuable information on different T-cell activation pathways. Furthermore, the aggregate mechanics capture how T-cells are affected by mechanical forces and interact within larger conglomerates, such as lymph nodes and tumours. However, an understanding of collective T-cell adhesion and mechanics following cell activation is currently lacking. Probing the mechanics of fragile and microscopically small living samples is experimentally challenging. Here, the micropipette force sensor technique was used to stretch T-cell aggregates and directly measure their Young's modulus and ultimate tensile strength. A mechanistic model was developed to correlate how the stiffness of the mesoscale multicellular aggregate emerges from the mechanical response of the individual microscopic cells within the cluster. We show how the aggregate elasticity is affected by different activators and relate this to different activation pathways in the cells. Our soft matter mechanics study of multicellular T-cell aggregates contributes to our understanding of the biology behind immune cell activation.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250231"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ioana Bouros, Robin N Thompson, David J Gavaghan, Ben Lambert
{"title":"The time-dependent reproduction number for epidemics in heterogeneous populations.","authors":"Ioana Bouros, Robin N Thompson, David J Gavaghan, Ben Lambert","doi":"10.1098/rsif.2025.0095","DOIUrl":"10.1098/rsif.2025.0095","url":null,"abstract":"<p><p>The time-dependent reproduction number [Formula: see text] can be used to track pathogen transmission and to assess the efficacy of interventions. This quantity can be estimated by fitting renewal equation models to time series of infectious disease case counts. These models almost invariably assume a homogeneous population. Individuals are assumed not to differ systematically in the rates at which they come into contact with others. It is also assumed that the typical time that elapses between one case and those it causes (known as the generation-time distribution) does not differ across groups. But contact patterns are known to widely differ by age and according to other demographic groupings, and infection risk and transmission rates have been shown to vary across groups for a range of directly transmitted diseases. Here, we derive from first principles a renewal equation framework which accounts for these differences in transmission across groups. We use a generalization of the classic M'Kendrick-von Foerster equation to handle populations structured into interacting groups. This system of partial differential equations allows us to derive a simple analytical expression for [Formula: see text], which involves only group-level contact patterns and infection risks. We show that the same expression emerges from both deterministic and stochastic discrete-time versions of the model and demonstrate through simulations that our [Formula: see text] expression governs the long-run fate of epidemics. Our renewal equation model provides a basis from which to account for more realistic, diverse populations in epidemiological models and opens the door to inferential approaches which use known group characteristics to estimate [Formula: see text].</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250095"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: 'Optimization of periodic treatment strategies for bacterial biofilms using an agent-based <i>in silico</i> approach' (2024) by Blee <i>et al.</i>","authors":"Johanna Blee, Thomas Gorochowski, Sabine Hauert","doi":"10.1098/rsif.2025.0509","DOIUrl":"10.1098/rsif.2025.0509","url":null,"abstract":"","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250509"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering plasmid replication dynamics: a computational approach to predict ColE1-like plasmid copy number.","authors":"Rinat Saban, Ofri Tfilin, David Haggiag, Yam Tawachi, Matan Arbel, Tamir Tuller","doi":"10.1098/rsif.2024.0783","DOIUrl":"10.1098/rsif.2024.0783","url":null,"abstract":"<p><p>Plasmids constitute a key tool in synthetic biology, providing a versatile framework for various research and industrial ventures. An essential determinant of plasmid functionality is its copy number, impacting both protein production rates and host cell metabolic burden. However, currently there is no model that can computationally predict the plasmid copy number from the sequence of its origin of replication (ORI). We present a novel software solution tailored to simplify plasmid copy number design, poised to redefine plasmid engineering workflows. At the heart of our tool lies a comprehensive machine learning model, informed by numerous features extracted from the ORI. This computational model emphasizes the importance of promoter strength and the RNA folding dynamics of regulatory elements within the ORI. Additionally, we detail a robust protocol for the efficient manipulation of plasmid ORIs used to validate our model's predictive capabilities. This innovation represents a paradigm shift in plasmid-centric methodologies, offering unprecedented avenues for advancement in synthetic biology research and industrial applications. The software is available at: https://pcn-gradient.vercel.app/.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20240783"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advantages of using complement components in preventive and therapeutic vaccine strategies for infectious and non-infectious diseases.","authors":"Nur Hendri Wahyu Firdaus, Buddhadev Mallick, Kutty Selva Nandakumar, Akhilesh Kumar Shakya","doi":"10.1098/rsif.2025.0138","DOIUrl":"10.1098/rsif.2025.0138","url":null,"abstract":"<p><p>The complement system, a vital component of innate immunity, is indispensable to our immune defence mechanisms against microbial infections. Acting as a surveillance mechanism, it identifies and eliminates pathogens by activating several complement components and associated signalling pathways, which are also implicated in various diseases and disorders. Beyond its defensive role, the complement system has emerged as a promising target for vaccine development in therapeutic and preventive regimens, offering new vaccine strategies to combat non-infectious and infectious diseases. Activation of the complement pathways by various natural and synthetic adjuvants enhances protective immune responses, highlighting its utility in vaccine design. This approach could be useful for targeting autoimmune diseases, infectious diseases, cancer and neurological disorders.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250138"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}