PNAS nexus最新文献_第5页

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

The dual edges of AI: Advancing knowledge while reducing diversity. 人工智能的双重优势：提升知识的同时减少多样性。

IF 2.2

PNAS nexus Pub Date : 2025-05-03 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf138

Sukwoong Choi, Hyo Kang, Namil Kim, Junsik Kim

引用次数: 0

Dirac-equation signal processing: Physics boosts topological machine learning. 狄拉克方程信号处理：物理促进拓扑机器学习。

IF 2.2

PNAS nexus Pub Date : 2025-05-02 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf139

Runyue Wang, Yu Tian, Pietro Liò, Ginestra Bianconi

{"title":"Dirac-equation signal processing: Physics boosts topological machine learning.","authors":"Runyue Wang, Yu Tian, Pietro Liò, Ginestra Bianconi","doi":"10.1093/pnasnexus/pgaf139","DOIUrl":"10.1093/pnasnexus/pgaf139","url":null,"abstract":"Topological signals are variables or features associated with both nodes and edges of a network. Recently, in the context of topological machine learning, great attention has been devoted to signal processing of such topological signals. Most of the previous topological signal processing algorithms treat node and edge signals separately and work under the hypothesis that the true signal is smooth and/or well approximated by a harmonic eigenvector of the higher-order Laplacian, which may be violated in practice. Here, we propose Dirac-equation signal processing, a framework for efficiently reconstructing true signals on nodes and edges, also if they are not smooth or harmonic, by processing them jointly. The proposed physics-inspired algorithm is based on the spectral properties of the topological Dirac operator. It leverages the mathematical structure of the topological Dirac equation to boost the performance of the signal processing algorithm. We discuss how the relativistic dispersion relation obeyed by the topological Dirac equation can be used to assess the quality of the signal reconstruction. Finally, we demonstrate the improved performance of the algorithm with respect to previous algorithms. Specifically, we show that Dirac-equation signal processing can also be used efficiently if the true signal is a nontrivial linear combination of more than one eigenstate of the Dirac equation, as it generally occurs for real signals.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf139"},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082677","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

AI system for diagnosing mucosa-associated lymphoid tissue lymphoma and diffuse large B cell lymphoma using ImageNet and hematoxylin and eosin-stained specimens. 使用ImageNet和苏木精、伊红染色标本诊断粘膜相关淋巴组织淋巴瘤和弥漫性大B细胞淋巴瘤的AI系统。

IF 2.2

PNAS nexus Pub Date : 2025-04-30 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf137

Shuto Yamaguchi, Teijiro Isokawa, Nobuyuki Matsui, Naotake Kamiura, Tatsuaki Tsuruyama

{"title":"AI system for diagnosing mucosa-associated lymphoid tissue lymphoma and diffuse large B cell lymphoma using ImageNet and hematoxylin and eosin-stained specimens.","authors":"Shuto Yamaguchi, Teijiro Isokawa, Nobuyuki Matsui, Naotake Kamiura, Tatsuaki Tsuruyama","doi":"10.1093/pnasnexus/pgaf137","DOIUrl":"10.1093/pnasnexus/pgaf137","url":null,"abstract":"AI-assisted morphological analysis using whole-slide images (WSIs) shows promise in supporting complex pathological diagnosis. However, the implementation in clinical settings is costly and demands extensive data storage. This study aimed to develop a compact, practical classification model using patch images selected by pathologists from representative disease areas under a microscope. To evaluate the limits of classification performance, we applied multiple pretraining strategies and convolutional neural networks (CNNs) specifically for the diagnosis of particularly challenging malignant lymphomas and their subtypes. The EfficientNet CNN, pretrained with ImageNet, exhibited the highest classification performance among the tested models. Our model achieved notable accuracy in a four-class classification (normal lymph node and three B cell lymphoma subtypes) using only hematoxylin and eosin-stained specimens (AUC = 0.87), comparable to results from immunohistochemical and genetic analyses. This finding suggests that the proposed model enables pathologists to independently prepare image data and easily access the algorithm and enhances diagnostic reliability while significantly reducing costs and time for additional tests, offering a practical and efficient diagnostic support tool for general medical facilities.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf137"},"PeriodicalIF":2.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051817","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

Dopaminergic encoding of future defensive actions in the mouse nucleus accumbens. 小鼠伏隔核未来防御行为的多巴胺能编码。

IF 2.2

PNAS nexus Pub Date : 2025-04-29 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf128

Austen A Fisher, L Sofia Gonzalez, Zoe R Cappel, Kassidy E Grover, Ronald R Waclaw, J Elliott Robinson

引用次数: 0

Coexistence of balance and hierarchies: An ego perspective to explain empirical networks. 平衡与等级的共存：从自我的角度解释经验网络。

IF 2.2

PNAS nexus Pub Date : 2025-04-29 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf130

Piotr J Górski, Adam Sulik, Georges Andres, Giacomo Vaccario, Janusz A Hołyst

{"title":"Coexistence of balance and hierarchies: An ego perspective to explain empirical networks.","authors":"Piotr J Górski, Adam Sulik, Georges Andres, Giacomo Vaccario, Janusz A Hołyst","doi":"10.1093/pnasnexus/pgaf130","DOIUrl":"10.1093/pnasnexus/pgaf130","url":null,"abstract":"The formation of positive and negative relations between individuals in social networks can be described by different approaches. Two prominent mechanisms are structural balance and status hierarchies. Balance motivates stability among friends and enemies in triads (e.g. an enemy of my friend is my enemy). Status considers respect and disregard originating from social hierarchy (e.g. positive relations towards those we respect). We demonstrate that integrating the two mechanisms through the concept of ego dynamics is key to understanding observable patterns in many social groups. We propose an agent-based model where dynamical changes result from agents aiming to resolve inconsistencies with structural balance and status. In contrast to previous models, our approach employs the ego perspective. Agents have limited, local knowledge and can only change their own relations. By fitting the model to real-world networks, we successfully replicated the observed over- and under-representations of certain triads in 36 empirical signed networks. This close matching to empirical data is achievable only by taking the ego perspective and not assuming global knowledge. Additionally, the model reveals that, when the status mechanism dominates, people in real networks tend to strive for the top of the hierarchy. Finally, our numerical simulations and analytic solutions demonstrate that a previously thought as continuous phase transition towards the paradise state (all links positive) can become discontinuous when the status mechanism is involved. This discontinuity indicates that desirable social configurations may, in fact, be quite fragile.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf130"},"PeriodicalIF":2.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082673","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

Unraveling the causal influences of drought and crop production on groundwater levels across the contiguous United States. 揭示干旱和作物生产对美国相邻地区地下水水位的因果影响。

IF 2.2

PNAS nexus Pub Date : 2025-04-28 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf129

Nitin K Singh, Sheila M Saia, Ruchi Bhattacharya, Hoori Ajami, David M Borrok

{"title":"Unraveling the causal influences of drought and crop production on groundwater levels across the contiguous United States.","authors":"Nitin K Singh, Sheila M Saia, Ruchi Bhattacharya, Hoori Ajami, David M Borrok","doi":"10.1093/pnasnexus/pgaf129","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf129","url":null,"abstract":"Groundwater depletion in agricultural-dominated regions is attributed to climate and irrigation withdrawals that support crop production. However, despite decades of effort, knowledge gaps remain in understanding the relative influence of drought and crop production on groundwater levels at the continental scale. Here, utilizing empirical observations, we simultaneously track how long-term trajectories of groundwater levels, crop production of seven crops, and drought have evolved over time, and then integrate these observations with a causality-based attribution framework to unravel the relative impact of drought and crop production on groundwater levels across the contiguous United States (CONUS). We find a dominant pattern of decreases in groundwater levels with increases (25-61%) or no change (1-15%) in crop production across the CONUS. We estimate a significant (P < 0.1) causal influence of crop production and drought on groundwater levels in ∼32% (n = 101) and ∼20% (n = 62) of counties, respectively. Further, the extent of impact of crop production on groundwater varies with region and is most pronounced for cotton (42%, n = 18) and wheat (17%, n = 39). The memory effects of crop production (median: 7 years) and drought (median: 3 years) on groundwater levels imply that their impact could last much longer than the annual crop production cycle or the drought exposure period. Further, these findings allude to circular causality between groundwater and crop production, where both entities depend on each other at different time scales. Our work builds on past work and contributes to the growing understanding of food security and groundwater availability to manage these commodities to meet future demands.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf129"},"PeriodicalIF":2.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058005","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 priming phosphorylation of KaiC is activated by the release of its autokinase autoinhibition. KaiC的启动磷酸化是通过释放其自激酶自抑制而激活的。

IF 2.2

PNAS nexus Pub Date : 2025-04-28 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf136

Yoshihiko Furuike, Yasuhiro Onoue, Shinji Saito, Toshifumi Mori, Shuji Akiyama

{"title":"The priming phosphorylation of KaiC is activated by the release of its autokinase autoinhibition.","authors":"Yoshihiko Furuike, Yasuhiro Onoue, Shinji Saito, Toshifumi Mori, Shuji Akiyama","doi":"10.1093/pnasnexus/pgaf136","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf136","url":null,"abstract":"KaiC, a cyanobacterial circadian clock protein with autokinase activity, catalyzes the dual phosphorylation of its own S431 and T432 residues in a circadian manner in the presence of KaiA and KaiB. Priming phosphorylation at T432 is a key step that promotes secondary phosphorylation at S431. Although KaiA binding is considered essential for KaiC phosphorylation, the mechanisms underlying the activation and inactivation of priming phosphorylation remain elusive. We found that although the priming phosphorylation is autoinhibited within KaiC, it actually proceeds at a rate constant of 0.019 h-1 even in the absence of KaiA. The autoinhibition of KaiC and the mechanism underlying the release from autoinhibition by KaiA were examined by KaiC structural analysis and by classical molecular dynamics and quantum mechanics/molecular mechanics simulations. We found that the side chain of T432 adopts two rotamers in dephosphorylated KaiC, one of which places T432 in a position suitable for a nucleophilic attack on the terminal phosphate of adenosine triphosphate. However, the nucleophilicity of T432 was insufficient to overcome an energy barrier of ∼21 kcal mol-1 because the catalytic function of a nearby base, E318, was self-suppressed by hydrogen bonding to positively charged R385. Biochemical assays of KaiC mutants showed that the autoinhibition of KaiC autokinase activity is attenuated by conferring T432 high nucleophilicity through the KaiA-assisted release of R385 from E318 to E352. During the circadian cycle, R385 switches interacting partners to inactivate/activate the autokinase function and to ensure the unidirectionality of the KaiC phosphorylation cycle.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf136"},"PeriodicalIF":2.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051819","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

An inverse relationship between fitness and secretion efficiency in a gram-positive bacterium. 革兰氏阳性细菌的适应性和分泌效率之间的反比关系。

IF 2.2

PNAS nexus Pub Date : 2025-04-28 eCollection Date: 2025-05-01 DOI: 10.1093/pnasnexus/pgaf131

Kamilla Wiull, Morten Kjos, Vincent G H Eijsink, Geir Mathiesen

{"title":"An inverse relationship between fitness and secretion efficiency in a gram-positive bacterium.","authors":"Kamilla Wiull, Morten Kjos, Vincent G H Eijsink, Geir Mathiesen","doi":"10.1093/pnasnexus/pgaf131","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf131","url":null,"abstract":"Lactiplantibacillus plantarum and other lactic acid bacteria are emerging as promising candidates for mucosal delivery of surface-displayed antigens. However, producing secreted heterologous proteins and anchoring these using LPxTG anchors can significantly reduce bacterial fitness. To understand the underlying mechanisms and limiting factors, we analyzed 11 recombinant L. plantarum strains expressing the HaloTag reporter protein with the same LPxTG anchor but varying signal peptides. By labeling the reporter protein with fluorescent ligands, this approach allowed simultaneous detection of correctly folded intracellular and extracellular protein, revealing signal peptide-dependent variation in the relative amounts of intra- and extracellularly folded HaloTag. Furthermore, this analysis uncovered an unexpected correlation between secretion efficiency and bacterial fitness. Strains with better growth showed more premature intracellular folding and reduced protein translocation and surface display. Conversely, strains with a higher fraction of surface-displayed protein, i.e. strains with greater secretion efficiency, exhibited impaired growth, likely due to increased interactions between the signal peptide and the secretion machinery, leading to secretion overload. Correlation analyses and confirmation of observed correlations by mutational studies of the signal peptides showed that signal peptide hydrophobicity is positively correlated with higher secretion efficiency but is accompanied by a trade-off in fitness. These findings underscore the critical role of signal peptides in balancing protein secretion and bacterial viability, offering valuable insights for optimizing protein secretion and anchoring in gram-positive bacteria.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf131"},"PeriodicalIF":2.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030698","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