PNAS nexusPub Date : 2025-07-25eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf232
Ildefonso M De la Fuente, Jose Carrasco-Pujante, Maria Fedetz, Carlos Bringas, Alberto Pérez-Samartín, Gorka Pérez-Yarza, Luis Martínez, José I López, Jesus M Cortes, Iker Malaina
{"title":"Migratory responses in enucleated cells: The forces driving the locomotion movement of unicellular organisms.","authors":"Ildefonso M De la Fuente, Jose Carrasco-Pujante, Maria Fedetz, Carlos Bringas, Alberto Pérez-Samartín, Gorka Pérez-Yarza, Luis Martínez, José I López, Jesus M Cortes, Iker Malaina","doi":"10.1093/pnasnexus/pgaf232","DOIUrl":"10.1093/pnasnexus/pgaf232","url":null,"abstract":"<p><p>Locomotion movements are a fundamental characteristic of a variety of species, including prokaryotic and eukaryotic, that has a high impact on essential physiological and pathological processes. For decades, many different authors have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. Recently, we have shown that locomotion movements are regulated by integrative self-organized molecular processes operating at the systemic level. Here, to verify that said systemic behavior also exists in extreme critical physiological conditions such as those corresponding to enucleated cells, we carried out an extensive study with 200 enucleated cells (cytoplasts) belonging to the <i>Amoeba proteus</i> species. The migratory movements of both enucleated and nonenucleated cells (400 in total) have been individually studied in four different scenarios: in the absence of stimuli, under a galvanotactic field, in a chemotactic gradient, and under complex conditions such as simultaneous galvanotactic and chemotactic stimuli. All the experimental trajectories were analyzed using nonlinear quantitative metrics for individual cell trajectories. The results show that both nonenucleated amoebas and cytoplasts display the same type of dynamic migratory patterns. The locomotion displacements of enucleated cells are a consequence of complex self-organized molecular dynamics, modulated at a systemic-cytoplasmic level. We have also quantitatively detected that enucleation clearly affects the correlation times and the intensity of the migratory responses of cytoplasts. The fact that cytoplasts preserved the dynamic properties of their migratory trajectories when compared with nonenucleated cells suggests that nuclear activity has a minor role in regulating the locomotion displacements of cells.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf232"},"PeriodicalIF":3.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-25eCollection Date: 2025-07-01DOI: 10.1093/pnasnexus/pgaf224
{"title":"Correction to: The influence of improved wheat and maize varieties on infant mortality in China.","authors":"","doi":"10.1093/pnasnexus/pgaf224","DOIUrl":"10.1093/pnasnexus/pgaf224","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pnasnexus/pgaf048.].</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf224"},"PeriodicalIF":3.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-23eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf226
Lei Xiang, Rouyan Chen, Joanne Tsui Ming Tan, Victoria Nankivell, Christina A Bursill, Robert A McLaughlin, Jiawen Li
{"title":"Identification and removal of system-induced autofluorescence in miniaturized fiber-optic fluorescence endoscopes.","authors":"Lei Xiang, Rouyan Chen, Joanne Tsui Ming Tan, Victoria Nankivell, Christina A Bursill, Robert A McLaughlin, Jiawen Li","doi":"10.1093/pnasnexus/pgaf226","DOIUrl":"10.1093/pnasnexus/pgaf226","url":null,"abstract":"<p><p>Miniaturized fiber-optic fluorescence endoscopes play a crucial role in medical diagnostics and research, but system-induced autofluorescence remains a significant challenge, particularly in single-fiber setups. While recent advances, such as double-clad fiber (DCF) and DCF couplers, have reduced background noise, complete elimination remains challenging. Research on the various sources of system-induced autofluorescence and the methods to remove them is scarce. This study seeks to fulfill this need by proposing practical approaches to the removal of system-induced autofluorescence. This study presents the methods to suppress static background noise and proposes an algorithm based on least-squares linear spectral unmixing to remove variable system-induced autofluorescence artifacts. The algorithm was evaluated on a single-fiber DCF intravascular imaging system, with phantom and rodent in vivo experiments confirming its effectiveness. Results showed accurate differentiation between true sample fluorescence and system-induced autofluorescence artifacts through the validation with optical coherence tomography images and histology results, further verified by statistical analysis. Unlike simple background subtraction, the method addresses both background noise and incidental artifacts, providing robust performance under varying conditions. Our method may be adapted to various fiber-based endoscopy setups and be compatible with different fluorescent agents and autofluorescence imaging, broadening its applicability in biomedical imaging.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf226"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-23eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf228
Claus Kadelka, Kishore Hari
{"title":"Critical assessment of the ability of Boolean threshold models to describe gene regulatory network dynamics.","authors":"Claus Kadelka, Kishore Hari","doi":"10.1093/pnasnexus/pgaf228","DOIUrl":"10.1093/pnasnexus/pgaf228","url":null,"abstract":"<p><p>The inference of gene regulatory networks (GRNs) from high-throughput data constitutes a fundamental and challenging task in systems biology. Boolean networks are a popular modeling framework to understand the dynamic nature of GRNs. In the absence of reliable methods to infer the regulatory logic of Boolean GRN models, researchers frequently assume threshold logic as a default. Using the largest repository of published expert-curated Boolean GRN models as best proxy of reality, we systematically compare the ability of two popular threshold formalisms, the Ising and the 01 formalism, to truthfully recover biological functions and biological system dynamics. While Ising rules match fewer biological functions exactly than 01 rules, they yield a better average agreement. In general, more complex regulatory logic proves harder to be represented by either threshold formalism. Informed by these results and a meta-analysis of regulatory logic, we propose modified versions for both formalisms, which provide a better function-level and dynamic agreement with biological GRN models than the usual threshold formalisms. For small biological GRN models with low connectivity, corresponding threshold networks exhibit similar dynamics. However, they generally fail to recover the dynamics of large networks or highly connected networks. In conclusion, this study provides new insights into an important question in computational systems biology: how truthfully do Boolean threshold networks capture the dynamics of GRNs?</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf228"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-23eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf230
Lei Zhu, Zhuang Liang, Zhihao Yan, Xi Ming, Hongbo Duan, Bin Su, Shouyang Wang
{"title":"Air-conditioning replacement to enhance the reliability of renewable power systems under extreme weather risks.","authors":"Lei Zhu, Zhuang Liang, Zhihao Yan, Xi Ming, Hongbo Duan, Bin Su, Shouyang Wang","doi":"10.1093/pnasnexus/pgaf230","DOIUrl":"10.1093/pnasnexus/pgaf230","url":null,"abstract":"<p><p>The increasing demand for residential heating and cooling significantly affects power systems, especially during extreme weather events. The replacement of outdated room air-conditioning (RAC) with a high-efficiency model demonstrated considerable potential in alleviating this effect. In this study, the impacts of extreme warm, cold, and drought events on power demand and supply are explored. By simulating residential heating and cooling loads in southern Chinese cities and integrating these loads into a provincial power dispatch model, we confirm the positive role of RAC replacement in carbon mitigation and power system cost reductions. It also enhances the power system reliability, especially facing extreme weathers. Specifically, RAC replacement may reduce peak power demand by up to 12.2% for advanced high-efficiency units. Compared with the battery storage system, RAC replacement has better cost and emission reductions, given the same budget. This research highlights the pivotal role of improving residential energy efficiency in the transition toward a green power system in China, especially the pronounced benefits of RAC replacement in enhancing energy resilience when facing extreme weather risks.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf230"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-22eCollection Date: 2025-07-01DOI: 10.1093/pnasnexus/pgaf209
Adam Skinner, Isabel Li, Mathew Varidel, Frank Iorfino, Jo-An Occhipinti, Yun Ju Christine Song, Min K Chong, Ian B Hickie
{"title":"Dynamic Bayesian network analysis of the social determinants of mental health.","authors":"Adam Skinner, Isabel Li, Mathew Varidel, Frank Iorfino, Jo-An Occhipinti, Yun Ju Christine Song, Min K Chong, Ian B Hickie","doi":"10.1093/pnasnexus/pgaf209","DOIUrl":"10.1093/pnasnexus/pgaf209","url":null,"abstract":"<p><p>Mental disorders contribute substantially to the global burden of disease, accounting for up to 16.5% of all years of healthy life lost due to disability and premature mortality. Epidemiological evidence indicates that mental health problems are associated with a diverse range of demographic, social, and economic factors, referred to collectively as social determinants; however, the causal mechanisms underlying these associations are widely recognized to be complex and are only incompletely understood. Here, we use recently developed structure learning methods for Bayesian networks and high-quality panel data from Australia to construct a provisional dynamic network model of the causal dependencies connecting a broad selection of social determinants and mental health. This provisional causal model identifies a heterogeneous set of proximate risk-modifying factors (direct causes), including subjective financial well-being, community connectedness, loneliness, and general health, that mediate the individual-level mental health effects of all remaining variables included in our analyses. Simulation analyses indicate that ideal preventive interventions targeting people's sense of financial security, local community engagement, and loneliness have the greatest capacity to improve population mental health outcomes, while significant reductions in the prevalence of mental health problems may also be achieved by promoting physical well-being and participation in volunteer or charity work and paid employment. We conclude that policies such as a Job Guarantee that are capable of simultaneously altering multiple adverse (or protective) social and economic exposures are likely to be critical in effectively addressing the substantial personal and societal costs of mental health-related disability.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf209"},"PeriodicalIF":2.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-22eCollection Date: 2025-07-01DOI: 10.1093/pnasnexus/pgaf207
Saloni Dash, Yiwei Xu, Madeline Jalbert, Emma S Spiro
{"title":"The persuasive potential of AI-paraphrased information at scale.","authors":"Saloni Dash, Yiwei Xu, Madeline Jalbert, Emma S Spiro","doi":"10.1093/pnasnexus/pgaf207","DOIUrl":"10.1093/pnasnexus/pgaf207","url":null,"abstract":"<p><p>In this article, we study how AI-paraphrased messages have the potential to amplify the persuasive impact and scale of information campaigns. Building from social and cognitive theories on repetition and information processing, we model how <i>CopyPasta</i>-a common repetition tactic leveraged by information campaigns-can be enhanced using large language models. We first extract CopyPasta from two prominent disinformation campaigns in the United States and use ChatGPT to paraphrase the original message to generate <i>AIPasta</i>. We then validate that AIPasta is lexically diverse in comparison to CopyPasta while retaining the semantics of the original message using natural language processing metrics. In a preregistered experiment comparing the persuasive potential of CopyPasta and AIPasta (<i>N</i> = 1,200), we find that AIPasta (but not CopyPasta) is effective at increasing perceptions of consensus in the broad false narrative of the campaign while maintaining similar levels of sharing intent with respect to Control (CopyPasta reduces such intent). Additionally, AIPasta (vs. Control) increases belief in the exact false claim of the campaign, depending on political orientation. However, across most outcomes, we find little evidence of significant persuasive differences between AIPasta and CopyPasta. Nonetheless, current state-of-the-art AI-text detectors fail to detect AIPasta, opening the door for these operations to scale successfully. As AI-enabled information operations become more prominent, we anticipate a shift from traditional CopyPasta to AIPasta, which presents significant challenges for detection and mitigation.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf207"},"PeriodicalIF":2.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-21eCollection Date: 2025-07-01DOI: 10.1093/pnasnexus/pgaf217
{"title":"Correction to: Confidence and second-order errors in cortical circuits.","authors":"","doi":"10.1093/pnasnexus/pgaf217","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf217","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pnasnexus/pgae404.].</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf217"},"PeriodicalIF":2.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-21eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf223
Andrew J MacDonald, Dan Sousa, Amy Quandt, Samantha Sambado, Terrell J Sipin, Zoe Rennie, Ashley E Larsen
{"title":"Extreme climate whiplash events drive divergent responses of mosquito-borne disease.","authors":"Andrew J MacDonald, Dan Sousa, Amy Quandt, Samantha Sambado, Terrell J Sipin, Zoe Rennie, Ashley E Larsen","doi":"10.1093/pnasnexus/pgaf223","DOIUrl":"10.1093/pnasnexus/pgaf223","url":null,"abstract":"<p><p>There is mounting concern surrounding climate change effects on human health. Vector-borne diseases-transmitted by ectotherms like mosquitos-are sensitive to abiotic conditions, and there is a significant interest in modeling their response to future climate change. However, changing climate also contributes to increasing variability and frequency of extreme weather, including \"climate whiplash\" events, when weather conditions abruptly shift between extremes. These events may have more immediate effects on vector-borne diseases, though they have received less attention. Here, we use the series of extreme atmospheric rivers of 2022/2023 in California, following years of extreme drought, as a natural experiment to assess the effect of climate whiplash on vector-borne disease risk. Using high spatiotemporal resolution standing water remote sensing, mosquito and viral surveillance, and community science observations of key reservoir hosts, we estimate mosquito species- and virus-specific responses to flooding following atmospheric rivers using panel regression models. We find significant positive effects of flooding on abundance of the rural West Nile virus (WNV) vector in California's Central Valley, with the largest effects at landscape scales. We find no significant effects for the urban WNV vector, or globally invasive yellow fever mosquito. Finally, we find similarly divergent effects on WNV and Saint Louis Encephalitis virus (SLEV) infection: WNV rates decline significantly in the urban vector and SLEV increases significantly in the rural vector. These results reveal species-specific responses to climate whiplash that are predictable by mosquito ecology, relevant to globally important mosquito vectors and diseases, and inform public health response to future extreme events.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf223"},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PNAS nexusPub Date : 2025-07-18eCollection Date: 2025-08-01DOI: 10.1093/pnasnexus/pgaf221
Priyanka Mehra, Arend Hintze
{"title":"From valleys to peaks: The role of evolvability in fitness landscape navigation.","authors":"Priyanka Mehra, Arend Hintze","doi":"10.1093/pnasnexus/pgaf221","DOIUrl":"10.1093/pnasnexus/pgaf221","url":null,"abstract":"<p><p>Understanding the balance between evolvability and mutational robustness is crucial for exploring adaptation in complex fitness landscapes. This study examines how heterogeneous populations adapt under varying mutation rates (<i>μ</i>) and fitness landscape ruggedness (<i>K</i>), emphasizing their distinct starting conditions in valleys, slopes (low prominence), or peaks (high prominence). Using an extended NK model, we simulate populations capable of initiating anywhere in the landscape. Our findings reveal that starting positions strongly influence whether robustness or evolvability is advantageous. Populations beginning in low-prominence regions (valleys and slopes) exhibited high levels of epistasis ( <math><mi>ϵ</mi></math> ) and pleiotropy (<i>π</i>), enhancing evolvability and enabling exploration of the fitness landscape. In contrast, populations starting in high-prominence regions (peaks) reduced <math><mi>ϵ</mi></math> and <i>π</i>, prioritizing robustness to maintain stability against mutations. This study highlights the role of starting conditions in shaping evolutionary trajectories, offering insights into the interplay between evolvability and robustness.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf221"},"PeriodicalIF":3.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}