Proceedings of the National Academy of Sciences of the United States of America最新文献_第3页

Exploring the social life of urban spaces through AI. 通过人工智能探索城市空间的社会生活。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2424662122

Arianna Salazar-Miranda,Zhuangyuan Fan,Michael Baick,Keith N Hampton,Fabio Duarte,Becky P Y Loo,Edward Glaeser,Carlo Ratti

引用次数: 0

Optimal kinetics for catalytic cycles from a single path-sampling simulation. 从单路径采样模拟催化循环的最佳动力学。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2500934122

Peter G Bolhuis

{"title":"Optimal kinetics for catalytic cycles from a single path-sampling simulation.","authors":"Peter G Bolhuis","doi":"10.1073/pnas.2500934122","DOIUrl":"https://doi.org/10.1073/pnas.2500934122","url":null,"abstract":"A catalyst's efficiency for accelerating a reaction rate is determined by its molecular structure and interactions with the substrate. While one can predict kinetics for a particular molecular model, tuning the (potentially many) model parameters to reach a desired or optimal kinetics for a catalytic cycle is usually considered computationally prohibitively expensive, especially in solvated systems. Here, we show for a simple model representing a minimal catalytic cycle that such optimization is possible using only one single (path-sampling) simulation, by applying a maximum caliber based path reweighting method. We compute the path ensemble for a single parameter setting of the molecular interactions and then expand the kinetic landscape around these parameters. We find that optimal catalytic turnover or efficiency is orders of magnitude improved and is achieved by relevant parameters that induce strain in the system. Thus, path-reweighting based optimization is not only capable of finding important ingredients that lead to desired kinetic rates but can also identify the mechanistic origins of the rate optimization at a fraction of the costs of a direct evaluation. We demonstrate the versatility of the methodology on a minimal model for kinase signaling. The approach promises efficient computational design of (complex) catalysts using realistic models.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"17 1","pages":"e2500934122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction for Lin et al., BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. 纠正Lin等人的说法，BRIT1/MCPH1是一种DNA损伤反应蛋白，调节Brca1-Chk1通路，与小头畸形的检查点功能障碍有关。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2517068122

引用次数: 0

Cell type-specific purifying selection of synonymous mitochondrial DNA variation. 同义线粒体DNA变异的细胞类型特异性纯化选择。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2505704122

Caleb A Lareau,Patrick Maschmeyer,Yajie Yin,Jacob C Gutierrez,Ryan S Dhindsa,Anne-Sophie Gribling-Burrer,Sebastian Zielinski,Yu-Hsin Hsieh,Lena Nitsch,Veronika Dimitrova,Benan Nalbant,Frank A Buquicchio,Tsion Abay,Robert R Stickels,Jacob C Ulirsch,Patrick Yan,Fangyi Wang,Zhuang Miao,Katalin Sandor,Bence Daniel,Vincent Liu,Paul L Mendez,Petra Knaus,Manpreet Meyer,William J Greenleaf,Anshul Kundaje,Redmond P Smyth,Mathias Munschauer,Leif S Ludwig,Ansuman T Satpathy

{"title":"Cell type-specific purifying selection of synonymous mitochondrial DNA variation.","authors":"Caleb A Lareau,Patrick Maschmeyer,Yajie Yin,Jacob C Gutierrez,Ryan S Dhindsa,Anne-Sophie Gribling-Burrer,Sebastian Zielinski,Yu-Hsin Hsieh,Lena Nitsch,Veronika Dimitrova,Benan Nalbant,Frank A Buquicchio,Tsion Abay,Robert R Stickels,Jacob C Ulirsch,Patrick Yan,Fangyi Wang,Zhuang Miao,Katalin Sandor,Bence Daniel,Vincent Liu,Paul L Mendez,Petra Knaus,Manpreet Meyer,William J Greenleaf,Anshul Kundaje,Redmond P Smyth,Mathias Munschauer,Leif S Ludwig,Ansuman T Satpathy","doi":"10.1073/pnas.2505704122","DOIUrl":"https://doi.org/10.1073/pnas.2505704122","url":null,"abstract":"While somatic variants are well-characterized drivers of tumor evolution, their influence on cellular fitness in nonmalignant contexts remains understudied. We identified a mosaic synonymous variant (m.7076A > G) in the mitochondrial DNA (mtDNA)-encoded cytochrome c-oxidase subunit 1 (MT-CO1, p.Gly391=), present at homoplasmy in 47% of immune cells from a healthy donor. Single-cell multiomics revealed strong, lineage-specific selection against the m.7076G allele in CD8+ effector memory T cells, but not other T cell subsets, mirroring patterns of purifying selection of pathogenic mtDNA alleles. The limited anticodon diversity of mitochondrial tRNAs forces m.7076G translation to rely on wobble pairing, unlike the Watson-Crick-Franklin pairing used for m.7076A. Mitochondrial ribosome profiling confirmed stalled translation of the m.7076G allele. Functional analyses demonstrated that the elevated translational and metabolic demands of short-lived effector T cells (SLECs) amplify dependence on MT-CO1, driving this selective pressure. These findings suggest that synonymous variants can alter codon syntax, impacting mitochondrial physiology in a cell type-specific manner.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"115 1","pages":"e2505704122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic instability and hypofunctionality of fetal Tregs allow a permissive regulatory environment for T effector memory maturation. 胎儿treg的表观遗传不稳定性和功能低下为T效应记忆成熟提供了一个宽松的调节环境。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2506673122

Jing Yao Leong,Naomi McGovern,Archita Mishra,Martin Wasser,Pavanish Kumar,Shi Huan Tay,Sharifah Nur Hazirah,Joo Guan Yeo,Xiu Qi Tan,Nursyuhadah Sutamam,Farah Nadiah Azman,Camillus Jian Hui Chua,Phyllis ZiXuan Chen,Fauziah Ally,Charles-Antoine Dutertre,Lakshmi Ramakrishna,Su Li Poh,Liang Xie,Yiping Fan,Catherine Donner,Maria Papadopoulou,David Vermijlen,Thaschawee Arkachaisri,Jerry Kok Yen Chan,Florent Ginhoux,Salvatore Albani

{"title":"Epigenetic instability and hypofunctionality of fetal Tregs allow a permissive regulatory environment for T effector memory maturation.","authors":"Jing Yao Leong,Naomi McGovern,Archita Mishra,Martin Wasser,Pavanish Kumar,Shi Huan Tay,Sharifah Nur Hazirah,Joo Guan Yeo,Xiu Qi Tan,Nursyuhadah Sutamam,Farah Nadiah Azman,Camillus Jian Hui Chua,Phyllis ZiXuan Chen,Fauziah Ally,Charles-Antoine Dutertre,Lakshmi Ramakrishna,Su Li Poh,Liang Xie,Yiping Fan,Catherine Donner,Maria Papadopoulou,David Vermijlen,Thaschawee Arkachaisri,Jerry Kok Yen Chan,Florent Ginhoux,Salvatore Albani","doi":"10.1073/pnas.2506673122","DOIUrl":"https://doi.org/10.1073/pnas.2506673122","url":null,"abstract":"The human gestational environment is commonly perceived to be predominantly suppressive and incompatible for T effector maturation. However, evidence of a competent effector fetal environment is mounting in the field. Here, we employed a high parametric, mass cytometry-based approach to study the fetal circulatory and microenvironmental immunomes, with the aim to understand the inception and extent of fetal effector T cell priming and its relation with regulatory mechanisms. We found evidence of fetal thymic immune imprinting, coupled with both circulatory and tissue effector memory development. Correspondingly, in the regulatory compartment, we detected the presence of Tbet+Treg in fetal tissues at elevated levels compared to adult tissues. Fetal Tregs, though capable of suppression, were hyposuppressive as compared with adult counterparts. We found that a proportion of fetal Tregs lost FoxP3 commitment during proliferation and exhibited higher TCR clonotype sharing with effector T cells, indicating higher plasticity in fetal Tregs than adult. Epigenetic profiling of the FoxP3 promoter locus reveals that fetal Tregs were only partially demethylated, possibly explaining the observed instability. In summary, our data provide evidence of a regulatory environment in the 2nd trimester permissive for T effector maturation, in part contributed by the relative instability and hypofunctionality in fetal Tregs.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"98 1","pages":"e2506673122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soil nitrogen drives inverse acclimation of xylem growth cessation to rising temperature in Northern Hemisphere conifers. 土壤氮驱动北半球针叶树木质部停止生长对温度升高的反向驯化。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-24 DOI: 10.1073/pnas.2421834122

Yaling Zhang,Jian-Guo Huang,Minhuang Wang,Wenjin Wang,Feiyu Yang,Annie Deslauriers,Patrick Fonti,Eryuan Liang,Harri Mäkinen,Walter Oberhuber,Cyrille B K Rathgeber,Roberto Tognetti,Václav Treml,Bao Yang,Lihong Zhai,Serena Antonucci,Valentina Buttò,J Julio Camarero,Filipe Campelo,Katarina Čufar,Martin De Luis,Marek Fajstavr,Alessio Giovannelli,Jožica Gričar,Andreas Gruber,Vladimír Gryc,Aylin Güney,Tuula Jyske,Jakub Kašpar,Gregory King,Cornelia Krause,Audrey Lemay,Fabio Lombardi,Edurne Martinez Del Castillo,Hubert Morin,Cristina Nabais,Pekka Nöjd,Richard L Peters,Peter Prislan,Antonio Saracino,Vladimir V Shishov,Hanuš Vavrčík,Joana Vieira,Qiao Zeng,Sergio Rossi

{"title":"Soil nitrogen drives inverse acclimation of xylem growth cessation to rising temperature in Northern Hemisphere conifers.","authors":"Yaling Zhang,Jian-Guo Huang,Minhuang Wang,Wenjin Wang,Feiyu Yang,Annie Deslauriers,Patrick Fonti,Eryuan Liang,Harri Mäkinen,Walter Oberhuber,Cyrille B K Rathgeber,Roberto Tognetti,Václav Treml,Bao Yang,Lihong Zhai,Serena Antonucci,Valentina Buttò,J Julio Camarero,Filipe Campelo,Katarina Čufar,Martin De Luis,Marek Fajstavr,Alessio Giovannelli,Jožica Gričar,Andreas Gruber,Vladimír Gryc,Aylin Güney,Tuula Jyske,Jakub Kašpar,Gregory King,Cornelia Krause,Audrey Lemay,Fabio Lombardi,Edurne Martinez Del Castillo,Hubert Morin,Cristina Nabais,Pekka Nöjd,Richard L Peters,Peter Prislan,Antonio Saracino,Vladimir V Shishov,Hanuš Vavrčík,Joana Vieira,Qiao Zeng,Sergio Rossi","doi":"10.1073/pnas.2421834122","DOIUrl":"https://doi.org/10.1073/pnas.2421834122","url":null,"abstract":"Controlled experiments suggest that the seasonal build-up of nitrogen (N) limitation constrains the responses of forest autumn phenology to elevated temperatures. Therefore, rising soil N is expected to increase the delaying effects of elevated temperature on the end of the season, i.e., leaf senescence. However, the interactive effects of temperature, soil N, and aridity on xylem autumn phenology remain unknown. We conducted a wide spatial analysis from 75 conifer sites in the Northern Hemisphere and found that rising soil N increases the delaying effects of elevated temperature on the end of xylem cell wall thickening but reduced the delaying effects on the cessation of cell enlargement, especially in humid regions. The contrasting effects of elevated soil N on cell enlargement versus cell wall thickening could affect xylem cell anatomy, thereby induce changes in wood density, and induce a decoupling of stem size growth from photosynthate production. These analyses extend previous findings on forest autumn phenology by systematically investigating the spatial variation in the interactive effects of temperature and soil N on xylem autumn phenology at the cellular scale.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"53 1","pages":"e2421834122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementation science aims to improve healthcare by validating effective interventions. 实施科学旨在通过验证有效的干预措施来改善医疗保健。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-23 DOI: 10.1073/pnas.2517704122

John Carey

引用次数: 0

Interfacial effects determine nonequilibrium phase behaviors in chemically driven fluids 界面效应决定了化学驱动流体中的非平衡相行为

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-23 DOI: 10.1073/pnas.2501145122

Yongick Cho, William M. Jacobs

{"title":"Interfacial effects determine nonequilibrium phase behaviors in chemically driven fluids","authors":"Yongick Cho, William M. Jacobs","doi":"10.1073/pnas.2501145122","DOIUrl":"https://doi.org/10.1073/pnas.2501145122","url":null,"abstract":"Coupling between chemical fuel consumption and phase separation can lead to condensation at a nonequilibrium steady state, resulting in phase behaviors that are not described by equilibrium thermodynamics. Theoretical models of such “chemically driven fluids” typically invoke near-equilibrium approximations at small length scales. However, because dissipation occurs due to both molecular-scale chemical reactions and mesoscale diffusive transport, it has remained unclear which properties of phase-separated reaction–diffusion systems can be assumed to be at an effective equilibrium. Here, we use microscopic simulations to show that mesoscopic fluxes are dependent on nonequilibrium fluctuations at phase-separated interfaces. We further develop a first-principles theory to predict nonequilibrium coexistence curves, localization of mesoscopic fluxes near phase-separated interfaces, and droplet size-scaling relations in good agreement with simulations. Our findings highlight the central role of interfacial properties in governing nonequilibrium condensation and have broad implications for droplet nucleation, coarsening, and size control in chemically driven fluids.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"9 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Can we still use the Michaelis-Menten model for enzymatic microneedle sensors? 我们还能将Michaelis-Menten模型用于酶微针传感器吗？

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-23 DOI: 10.1073/pnas.2418168122

Marco Fratus,Muhammad A Alam

{"title":"Can we still use the Michaelis-Menten model for enzymatic microneedle sensors?","authors":"Marco Fratus,Muhammad A Alam","doi":"10.1073/pnas.2418168122","DOIUrl":"https://doi.org/10.1073/pnas.2418168122","url":null,"abstract":"Since the 1960s, enzymatic sensors have been vital in healthcare and environmental monitoring due to their high selectivity. Traditionally, their performance is interpreted using the Michaelis-Menten (MM) equation, which assumes idealized, homogeneous, well-mixed laboratory conditions. However, integrating these sensors with microneedle (MN) patches for wearable applications introduces challenges such as spatial and temporal variations and limited reactant availability. Applying the MM model in such scenarios can lead to dramatic errors in enzyme kinetics and biomarker estimates, risking inaccurate substrate measurements and potentially life-threatening decisions. Here, we generalize the reaction-diffusion framework for enzymatic sensors and integrate it with analytical models for MN sensors. Our approach captures time-dependent MM variables, quantifies the rate of product formation, accounts for mass transport limitations, and provides expressions for response time and active substrate levels. This physics-based framework enables a) quantification of otherwise inaccessible parameters such as active substrate levels, b) accurate response-time predictions to reach steady-state conditions, c) improved data interpretation, and d) projection of enzymatic responses across various conditions. The study highlights the need for careful application of MM model in wearable microneedle sensors, where key assumptions may not hold. Our model can also extend to sensor degradation, inactivation, and hypoxia, making it broadly applicable to enzymatic sensors in diverse environments.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"4 1","pages":"e2418168122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydrogen cyanide and hydrocarbons mix on Titan. 土卫六上氰化氢和碳氢化合物混合在一起。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-07-23 DOI: 10.1073/pnas.2507522122

Fernando Izquierdo-Ruiz,Morgan L Cable,Robert Hodyss,Tuan H Vu,Hilda Sandström,Alvaro Lobato,Martin Rahm

引用次数: 0