PNAS nexus最新文献_第3页

Perfluorinated compounds exposure and atherogenic risk characteristics in a high-fat diet condition: In vitro/in vivo models and population panel study. 高脂肪饮食条件下全氟化合物暴露和动脉粥样硬化风险特征：体外/体内模型和人群小组研究

IF 2.2

PNAS nexus Pub Date : 2025-05-09 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf153

Ziyuan Li, Ze Zhang, Biao Zhang, Chengying Zhou, Hongyan Yu, Liting Xu, Zhicong He, Pu Chen, Wei Peng, Mingliang Ye, Guangbo Qu, Xiaomin Zhang, Yang Song, Xiaoting Jin, Yuxin Zheng

{"title":"Perfluorinated compounds exposure and atherogenic risk characteristics in a high-fat diet condition: In vitro/in vivo models and population panel study.","authors":"Ziyuan Li, Ze Zhang, Biao Zhang, Chengying Zhou, Hongyan Yu, Liting Xu, Zhicong He, Pu Chen, Wei Peng, Mingliang Ye, Guangbo Qu, Xiaomin Zhang, Yang Song, Xiaoting Jin, Yuxin Zheng","doi":"10.1093/pnasnexus/pgaf153","DOIUrl":"10.1093/pnasnexus/pgaf153","url":null,"abstract":"Perfluorinated compounds (PFCs) are a well-recognized environmental risk factor for atherosclerosis. However, corresponding atherogenic risk in susceptible populations consuming high-fat diets (HFDs) remains unclear. Here, we found that perfluorooctane sulfonic acid (PFOS), a canonical PFCs, elevated the atherogenic risk in mice fed with HFD, which was characterized by an increased number of pro-inflammatory phenotype macrophages. We also found that macrophages exhibited a metabolic reprogramming to glycolysis, which was attributed to increased intracellular Fe2+ level. Mechanistic investigation revealed that PFOS directly bound to the iron-storage site on the ferritin heavy chain, subsequently weakening the iron-storage function. Notably, PFCs with acidic substituents and short chains had a higher atherogenic risk, as evidenced in the crucial indicators and observed in a population with a high triglyceride level. These findings highlight the potential atherogenic risk posed by PFCs exposure in susceptible populations consuming HFD and provide a potential intervention target.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf153"},"PeriodicalIF":2.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096109","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}

引用次数: 0

Reputation-based reciprocity in human-bot and human-human networks. 人-机器人和人-人网络中基于声誉的互惠。

IF 2.2

PNAS nexus Pub Date : 2025-05-09 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf150

Ashley Harrell, Margaret L Traeger

{"title":"Reputation-based reciprocity in human-bot and human-human networks.","authors":"Ashley Harrell, Margaret L Traeger","doi":"10.1093/pnasnexus/pgaf150","DOIUrl":"10.1093/pnasnexus/pgaf150","url":null,"abstract":"People help those with a reputation for helping others; as a result, they are more likely to behave generously when reputational concerns are present. Because people are increasingly making helping decisions in the presence of both humans and AI in \"hybrid systems,\" here we ask whether and how reputation-based reciprocity (RBR) promotes generosity in human-bot networks, compared with human-only ones. In two experiments-one where interactants were embedded in a patterned indirect reciprocity network and either knew or did not know that bots were present and another entailing one-shot interactions between humans and bots-we demonstrate that RBR is significantly less effective at fostering generosity in hybrid systems. At the network level, people are less generous when they know bots are present. In line with prior work, our findings suggest that this is driven by altered norms about helping in (known) hybrid networks governed by RBR: people do not believe bots deserve help like humans do, reducing overall generosity. In one-shot dyadic interactions, we likewise demonstrate that people are less willing to help bots even when they can receive reputational rewards for helping and even toward bots that have reputations for helping humans (or bots). People are also less likely to help people who help bots (compared with people who help people) and punish people who fail to help bots (compared with people who fail to help people). Adding bots to RBR networks affects not only humans' prosocial behavior, but also their evaluations of generosity toward human and bot alters.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf150"},"PeriodicalIF":2.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096112","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}

引用次数: 0

Conformational modulation of intrinsically disordered transactivation domains for cancer therapy. 癌症治疗中内在无序转激活结构域的构象调节。

IF 2.2

PNAS nexus Pub Date : 2025-05-09 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf152

Thibault Vosselman, Cagla Sahin, David P Lane, Marie Arsenian Henriksson, Michael Landreh, Dilraj Lama

{"title":"Conformational modulation of intrinsically disordered transactivation domains for cancer therapy.","authors":"Thibault Vosselman, Cagla Sahin, David P Lane, Marie Arsenian Henriksson, Michael Landreh, Dilraj Lama","doi":"10.1093/pnasnexus/pgaf152","DOIUrl":"10.1093/pnasnexus/pgaf152","url":null,"abstract":"Intrinsically disordered proteins are implicated in many diseases, but their overrepresentation among transcription factors, whose deregulation can cause disproportionate expression of oncogenes, suggests an important role in cancer. Targeting disordered transcription factors for therapy is considered challenging, as they undergo dynamic transitions and exist as an ensemble of interconverting states. This enables them to interact with multiple downstream partners, often through their transactivation domains (TADs) by the mechanisms of conformational selection, folding-upon-binding, or formation of \"fuzzy\" complexes. The TAD interfaces, despite falling outside of what is considered \"classical\" binding pockets, can be conformationally modulated to interfere with their target recruitment and hence represent potentially druggable sites. Here, we discuss the structure-activity relationship of TADs from p53, c-MYC, and the androgen receptor, and the progresses made in modulating their interactions with small molecules. These recent advances highlight the potential of targeting these so far \"undruggable\" proteins for cancer therapy.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf152"},"PeriodicalIF":2.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129801","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}

引用次数: 0

Interferon-dependent R-loop induction by Zika virus contributes to growth attenuation. 寨卡病毒诱导干扰素依赖的r环有助于生长衰减。

IF 2.2

PNAS nexus Pub Date : 2025-05-07 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf147

Yijing Zhao, Anna D Metzler, Yangping Li, Paola Urlich, Yilin Wang, David M Gilbert, Bing Yao, Hengli Tang

引用次数: 0

Astrocyte Fabp7 modulates nocturnal seizure threshold and activity-dependent gene expression in mouse brain. 星形胶质细胞Fabp7调节小鼠大脑夜间癫痫阈值和活动依赖基因表达。

IF 2.2

PNAS nexus Pub Date : 2025-05-07 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf146

Micah Lefton, Carlos C Flores, Yuji Owada, Christopher J Davis, Thomas N Ferraro, Yool Lee, Wheaton L Schroeder, Jason R Gerstner

{"title":"Astrocyte Fabp7 modulates nocturnal seizure threshold and activity-dependent gene expression in mouse brain.","authors":"Micah Lefton, Carlos C Flores, Yuji Owada, Christopher J Davis, Thomas N Ferraro, Yool Lee, Wheaton L Schroeder, Jason R Gerstner","doi":"10.1093/pnasnexus/pgaf146","DOIUrl":"10.1093/pnasnexus/pgaf146","url":null,"abstract":"Epileptic seizures often track with time of day and/or changes in vigilance state; however, specific molecular and cellular mechanisms driving the ictal and temporal associations are lacking. Astrocytes are a type of glial cell known to modulate neuronal excitability and circadian rhythms. These cells also abundantly express fatty acid-binding protein 7 (Fabp7), a clock-driven molecule necessary for normal sleep regulation, lipid signaling, and gene transcription. To determine whether Fabp7 influences time-of-day-dependent seizure susceptibility, we tested male C57/BL6N wild-type (WT) and Fabp7 knockout (KO) mice using electroshock seizure threshold. Compared with WT mice, Fabp7 KO mice exhibited markedly higher general- and maximal-electroshock seizure thresholds (GESTs and MESTs, respectively) during the dark phase, but not the light phase. We used RNA-seq to determine the role of Fabp7 in activity-dependent gene expression in nocturnal seizures and compared genome-wide mRNA expression in cortical/hippocampal tissue collected from WT-MEST and Fabp7 KO-MEST mice with WT-SHAM and Fabp7 KO-SHAM mice during the dark period. Whereas significant differential expression of immediate early genes was observed in WT-MEST compared with WT-SHAM, this effect was blocked in the Fabp7 KO-MEST versus Fabp7 KO-SHAM. Gene ontology and pathway analysis of all groups revealed significant overlap between WT-MEST:WT-SHAM and Fabp7 KO-SHAM:WT-SHAM comparisons, suggesting basal mRNA levels of core molecular and cellular mechanisms in the brain of Fabp7 KO approximate postictal WT brain. Together, these data suggest that Fabp7 regulates time-of-day-dependent neural excitability and that neural activity likely interacts with astrocyte Fabp7-mediated signaling cascades to influence activity-dependent gene expression.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf146"},"PeriodicalIF":2.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096122","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}

引用次数: 0

Resilience of science after austerity. 紧缩后科学的恢复力。

IF 2.2

PNAS nexus Pub Date : 2025-05-07 eCollection Date: 2025-06-01 DOI: 10.1093/pnasnexus/pgaf122

Ye Sun, Athen Ma, Georg von Graevenitz, Vito Latora

{"title":"Resilience of science after austerity.","authors":"Ye Sun, Athen Ma, Georg von Graevenitz, Vito Latora","doi":"10.1093/pnasnexus/pgaf122","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf122","url":null,"abstract":"In 2009, many governments implemented austerity measures. This often resulted in restrictions on science funding, increasing competition for funds. Here, we study the allocation of funding across universities by using a competitiveness measure from complexity science based on the bipartite network of universities and scientific subjects. Drawing on a comprehensive data set of 43,430 UK-funded grants between 2006 and 2020, a period covering the onset and relaxation of austerity, we provide two main results. First, we find that the effect of austerity on university grant income depended on research competitiveness: highly competitive universities increased grant income under austerity, while low-ranked universities lost income. Then, we study the resilience of science to austerity exploiting the natural experiment arising from the 2015 UK general election, when austerity was relaxed unexpectedly. We discover that the resilience of researchers at less competitive universities was surprisingly high. The number and size of grant applications grew more after 2015 at less competitive universities, increasing their grant income. Overall, results show that our network-based measure is a better proxy for research competitiveness than aggregate grant income across scientific subjects.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 6","pages":"pgaf122"},"PeriodicalIF":2.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210445","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}

引用次数: 0

Experimental infection of shrews (Crocidura russula) with Borna disease virus 1: Insights into viral spread and shedding. 鼩鼱（Crocidura russula）与博纳病病毒1的实验感染：对病毒传播和脱落的见解。

IF 2.2

PNAS nexus Pub Date : 2025-05-06 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf144

Daniel Nobach, Leif Raeder, Jana Müller, Sibylle Herzog, Markus Eickmann, Christiane Herden

{"title":"Experimental infection of shrews (Crocidura russula) with Borna disease virus 1: Insights into viral spread and shedding.","authors":"Daniel Nobach, Leif Raeder, Jana Müller, Sibylle Herzog, Markus Eickmann, Christiane Herden","doi":"10.1093/pnasnexus/pgaf144","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf144","url":null,"abstract":"Numbers of human encephalitis cases caused by infection with Borna disease virus 1 (BoDV1) increase continuously in endemic areas. The reservoir host of BoDV1 is the bicolored white-toothed shrew, albeit few naturally infected individuals of other shrew species have been detected. To establish a reliable experimental reservoir model, 15 greater white-toothed shrews were infected with a shrew-derived BoDV1 isolate by different inoculation routes (intracerebral, intranasal, oral, subcutaneous, and intraperitoneal) and monitored up to 41 days. Except for the oral route, all other animals (12/15) were successfully infected, and the majority of them displayed temporarily reduced feed intake and loss of body weight but no inflammatory lesions. Infectious virus was isolated from 11/12 infected animals. Viral RNA was demonstrated by qRT-PCR in the central nervous system (CNS) and the majority of organs. Immunohistochemistry demonstrated BoDV1 antigen in neurons and astrocytes in the CNS and peripheral nerves. High viral loads in the CNS and the spinal cord points towards spread from periphery to the CNS to enhance viral replication and subsequent centrifugal spread to organs capable of secretion and excretions. In general, successful experimental BoDV1 infection of shrews proves their usefulness as animal model, enabling further studies on maintenance, transmission, pathogenesis, and risk assessment for human spillover infections.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf144"},"PeriodicalIF":2.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082613","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}

引用次数: 0

Learning the complexity of urban mobility with deep generative network. 基于深度生成网络的城市交通复杂性研究。

IF 2.2

PNAS nexus Pub Date : 2025-05-06 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf081

Yuan Yuan, Jingtao Ding, Depeng Jin, Yong Li

{"title":"Learning the complexity of urban mobility with deep generative network.","authors":"Yuan Yuan, Jingtao Ding, Depeng Jin, Yong Li","doi":"10.1093/pnasnexus/pgaf081","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf081","url":null,"abstract":"City-scale individual movements, population flows, and urban morphology are intricately intertwined, collectively contributing to the complexity of urban mobility and impacting critical aspects of a city, from socioeconomic exchanges to epidemic transmission. Existing models, derived from fundamental laws of human mobility, often capture only partial facets of this complexity. This article introduces DeepMobility, a powerful deep generative collaboration network designed to encapsulate the multifaceted nature of complex urban mobility within one unified model, bridging the gap between the heterogeneous behaviors of individuals and the collective behaviors emerging from the entire population. As the first generative deep learning model to integrate micro- and macrolevel dynamics through bidirectional collaboration, DeepMobility generates high-fidelity synthetic mobility data, overcoming key limitations of prior approaches. Our experiments, conducted on mobility trajectories and flows in cities of China and Senegal, reveal that unlike state-of-the-art deep learning models that tend to \"memorize\" observed data, DeepMobility excels in learning the intricate data distribution and successfully reproduces the existing universal scaling laws that characterize human mobility behaviors at both individual and population levels. DeepMobility also exhibits robust generalization capabilities, enabling it to generate realistic trajectories and flows for cities lacking corresponding training data. Our approach underscores the feasibility of employing generative deep learning to model the underlying mechanism of human mobility and establishes a versatile framework for mobility data generation that supports sustainable and livable cities.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf081"},"PeriodicalIF":2.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055743","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}

引用次数: 0

The role of polygenic indices in inequality of opportunity. 多基因指数在机会不平等中的作用。

IF 2.2

PNAS nexus Pub Date : 2025-05-05 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf140

Michael Grätz, Sonia Petrini

{"title":"The role of polygenic indices in inequality of opportunity.","authors":"Michael Grätz, Sonia Petrini","doi":"10.1093/pnasnexus/pgaf140","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf140","url":null,"abstract":"Equality of opportunity is a principle of social justice, although there are different conceptions of it. We distinguish between liberal and radical (in)equality of opportunity. Both conceptions consider unfair inequalities in life outcomes that result from ascribed characteristics such as social origin, migration background, and sex. However, they differ in that liberal inequality of opportunity considers it fair when natural talents affect life outcomes. Conversely, radical inequality of opportunity places natural talents in the category of morally arbitrary factors that do not provide a fair basis for inequalities in life outcomes. We use polygenic indices (PGIs) to better disentangle the role of natural talents from the roles of ascribed characteristics and individual choices. We compare using PGIs to using measures of skills observed later in life. We apply this approach to two survey datasets, (i) the Wisconsin Longitudinal Study and (ii) the German Socio-Economic Panel Study. According to our results, radical inequality of opportunity is considerably larger than liberal inequality of opportunity, especially for education. Measuring natural talents using PGIs leads to very similar conclusions as using skills measured later in life. However, the differences between liberal and radical inequality of opportunity are smaller using PGIs than using measures of observed skills.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf140"},"PeriodicalIF":2.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082619","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}

引用次数: 0

Immunotherapy of endometrial cancer via CD47 blockade-mediated macrophage phagocytosis. CD47阻断介导巨噬细胞吞噬的子宫内膜癌免疫治疗。

IF 2.2

PNAS nexus Pub Date : 2025-05-05 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf143

Kerem Yucebas, Sooah Ko, Jinyu Zhou, Elizabeth M Hamel, Mia G Hackworth, Edgar Andres Diaz Miranda, Haley S Carpenter, Mark I Hunter, Omair M Khan, Irving L Weissman, Shiying Jin

引用次数: 0