综合性期刊最新文献

{"title":"Reply to Gillan et al.: What should be the null hypothesis in computational psychiatry?","authors":"Noam Sarna, Reuven Dar, Matan Mazor","doi":"10.1073/pnas.2628596123","DOIUrl":"https://doi.org/10.1073/pnas.2628596123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2628596123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207917","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}

{"title":"Disentangling the evolving effects of climate change and technology diffusion on building electricity demand.","authors":"Mai Shi, Ziqi Wei, Flavio Lehner, Michael T Craig","doi":"10.1073/pnas.2612343123","DOIUrl":"https://doi.org/10.1073/pnas.2612343123","url":null,"abstract":"<p><p>Climate change and technology diffusion will jointly drive future growth in building electricity demand. How this nonadditive response evolves over time with the pace of climate change and technology diffusion has not previously been examined, despite its importance for maintaining reliable power systems. We estimate electricity demand from residential and commercial buildings under climate change and/or technology diffusion across 183 counties in the United States through 2060. Our framework drives 209,352 machine learning models of building electricity demand with 100 spatiotemporally downscaled climate realizations across four climate models and three emissions scenarios, and 18 technology diffusion pathways of air source heat pumps and insulation. We find that the combined response of peak demand to climate change and technology diffusion diverges substantially from the sum of their individual responses, with distinct patterns across hot and cold grid regions. In cold regions, climate change and technology diffusion drive roughly up to 10 times larger peak demand growth than climate change alone by 2060. Conversely, in hot regions, technology diffusion counteracts climate-change-driven peak demand growth. Across regions, climate-change-induced warming reduces or eliminates a shift toward winter peaking driven by technology diffusion. Via uncertainty partitioning, we find climate-related uncertainty dominates near-term peak demand uncertainty, while technology-diffusion-related uncertainty increases to 10 to 80% of uncertainty by 2060. Internal variability accounts for a much larger share of climate-related uncertainty in peak demand than in temperature itself. Our results demonstrate that capturing nonadditive responses between climate change and technology diffusion is important for planning reliable power systems.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2612343123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228486","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}

{"title":"Methanogenic archaea <i>Methanobrevibacter smithii</i> and <i>Methanosphaera stadtmanae</i> promote mucosal homeostasis and protect from colitis.","authors":"Emily E Byrd, Benjamin W Harris, Hongpan Zhang, W Elise Warren, Sree H Kolli, Audrey M Putelo, Mitchell T McGinty, Michael D Solga, Melanie R Rutkowski, Melissa M Kendall","doi":"10.1073/pnas.2610622123","DOIUrl":"https://doi.org/10.1073/pnas.2610622123","url":null,"abstract":"<p><p>The intestinal microbiota is a critical determinant of mucosal homeostasis, yet the functional contributions of Archaea-which constitute up to 10% of the anaerobic community-remain largely undefined. Here, we provide evidence that the human methanogens <i>Methanobrevibacter smithii</i> (MSm) and <i>Methanosphaera stadtmanae</i> (MSt) promote colonic health. Transcriptomic analysis of germ-free mice reveals that MSm and MSt induce distinct colonic programs important for epithelial integrity. Using gnotobiotic and antibiotic-treated specific-pathogen-free mouse models, we show that MSm and MSt reinforce the epithelial barrier, characterized by increased goblet cell expansion, mucus thickening, and enhanced epithelial regeneration. Furthermore, methanogens expand Foxp3⁺ regulatory T cell (T_reg) populations without inducing pro-inflammatory T_H17 responses. Notably, MSm and MSt protect against dextran sodium sulfate-induced colitis. While MSt-mediated protection requires adaptive immunity, MSm retains partial efficacy in lymphocyte-deficient mice, revealing nonredundant protective mechanisms. These findings indicate that methanogenic archaea promote mucosal integrity during host association and suggest that methanogens may hold therapeutic potential for inflammatory bowel disease, though translation to human disease remains to be established.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2610622123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228629","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}

{"title":"Molecular basis for discrimination of cGAMP linkage isomers by a c-di-GMP-II riboswitch variant.","authors":"Xiaochen Xu, Wang Cheng, Huiqin You, Zejia Hu, Xinyue Bao, Hongcheng Li, Jinzhu Zhang, Dinshaw J Patel, Aiming Ren","doi":"10.1073/pnas.2621568123","DOIUrl":"https://doi.org/10.1073/pnas.2621568123","url":null,"abstract":"<p><p>Riboswitches are noncoding RNA regulatory motifs predominantly found in bacteria. Signaling molecules such as c-di-GMP, c-di-AMP, and 3',3'-cGAMP have been reported to be recognized by riboswitches. In contrast, 2',3'-cGAMP functions as a second messenger in mammalian cells, yet its interaction with RNA molecules remains unclear. Here, we report the crystal structures of a c-di-GMP-II riboswitch variant, c-di-GMP-II-Bh, bound to 2',3'-cGAMP and 3',3'-cGAMP. Both complexes adopt a similar overall RNA scaffold with an identical binding pocket composition. However, the ligand bases adopt inverted orientations in the binding pocket, resulting in distinct interaction patterns with residues A64 and G68 and differences in base-pair stacking against the phosphodiester backbone. Structural comparison together with ligand-binding assays of structure-guided mutants using isothermal titration calorimetry reveals the molecular principles by which an RNA riboswitch discriminates among cyclic dinucleotide linkage isomers, highlighting the remarkable sensitivity of RNA binding pockets to subtle ligand structural variations and provides a mechanistic framework for understanding ligand specificity in RNA-small molecule recognition.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2621568123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228667","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}

{"title":"Causality in liquid water as a hallmark of emergent glassy dynamics.","authors":"Léon Huet, Vittorio Del Tatto, Debarshi Banerjee, Alessandro Laio, Ali A Hassanali","doi":"10.1073/pnas.2616852123","DOIUrl":"https://doi.org/10.1073/pnas.2616852123","url":null,"abstract":"<p><p>In molecular liquids such as water, time-delayed influences between microscopic or mesoscopic variables are typically probed using time-correlation functions, which are symmetric under detailed balance and therefore blind to dynamical asymmetries. Here, we characterize water's dynamics using a causal inference metric that captures asymmetric couplings between collective variables. Analyzing equilibrium molecular dynamics simulations at ambient conditions and in the high-density liquid (HDL) regime of supercooled water, we uncover pronounced asymmetries in the couplings between orientational and translational degrees of freedom across multiple time and length scales. At room temperature, rotational modes exert a modest directional influence on translational dynamics. In contrast, in the supercooled HDL regime, translational motions emerge as the primary drivers of the dynamics, suggesting facilitation-like relaxation mechanisms characteristic of glassy systems. These results reveal a qualitative reorganization of dynamical couplings across thermodynamic conditions, implying that molecular liquids at thermal equilibrium can exhibit an emergent directionality in their fluctuation couplings. As a consequence, our analysis reveals that external perturbations acting on specific degrees of freedom can induce a stronger arrow of time in the causal relations between translational and orientational modes.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2616852123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228507","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}

{"title":"Evolution of the arbuscular mycorrhizal regulatory network through differential GRAS gene retention and protein interaction in land plants.","authors":"Wen-Shen Wu, Peng Zhao, Zhen Zeng, Xiao-Tong Li, Ping Wu, Qian Ding, Xing-Yu Feng, Yan-Mei Zhang, Shuai-Ya Hu, Jia-Yu Xue, Qiang Wang, Yang Liu, Jian-Qun Chen, Zhu-Qing Shao","doi":"10.1073/pnas.2607793123","DOIUrl":"https://doi.org/10.1073/pnas.2607793123","url":null,"abstract":"<p><p>Plants rely on an ancient genetic \"toolkit\" to establish arbuscular mycorrhizal symbiosis (AMS) with fungal partners. However, the symbiotic outcomes vary among AMS hosts, indicating divergence in downstream transcriptional reprogramming after the perception of symbiotic signals. To uncover the cross-species variation of the AMS regulatory network, we traced the evolutionary trajectory of the GRAS gene family, which encodes the major group of transcription factors in AMS regulation. Phylogenetic analysis of the GRAS family across land plants placed known symbiotic GRAS members within 12 anciently diverged lineages, with multiple lineages showing pronounced gene loss in nonmycorrhizal plants. This pattern pointed to three additional GRAS lineages as candidates for AMS regulation. Given that tomato harbors single-copy, AMS-induced genes in these lineages, we selected it for functional validation. CRISPR-Cas9 mutagenesis, combined with detailed phenotyping of fungal colonization and arbuscule morphology, and transcriptome profiling of mutant roots, confirmed that all three tomato genes are individually required for AMS development, designated Symbiosis-Required GRAS (SRG) 1 to 3. Large-scale phylogenomic analysis and protein interaction assays (by yeast two-hybrid and bimolecular fluorescence complementation) further showed that both the repertoire and interaction networks of symbiotic GRAS members vary among AMS hosts. In summary, together with 12 previously characterized lineages, the three SRGs identified in this study bring the total number of GRAS lineages with known symbiotic members across land plants to fifteen. Furthermore, our findings demonstrate that the symbiotic GRAS network has been dynamically reshaped by gene loss and rewiring of protein interactions during land plant evolution.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2607793123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228538","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}

{"title":"Conformational flexibility of the nitrogenase-like reductase CfbC/D involved in coenzyme F₄₃₀ biosynthesis.","authors":"Lin Zhang, Florian Schuhmacher, Alena Kussler, Oliver Einsle, Gunhild Layer","doi":"10.1073/pnas.2611794123","DOIUrl":"https://doi.org/10.1073/pnas.2611794123","url":null,"abstract":"<p><p>The nitrogenase-like reductase CfbC/D catalyzes the six-electron reduction of the tetrapyrrole macrocycle of Ni²⁺-sirohydrochlorin <i>a,c</i>-diamide during the biosynthesis of coenzyme F₄₃₀, an essential cofactor for biological methane formation and consumption. The individual dimeric protein components, CfbC₂ and CfbD₂, form a complex to allow for electron transfer from the [4Fe:4S] cluster in CfbC₂ to the [4Fe:4S] cluster in CfbD₂ and onto the substrate. The overall process is ATP-dependent. Although CfbC/D belongs to the family of nitrogenase-like enzymes, there are several intriguing differences between CfbC/D, other nitrogenase-like enzymes and nitrogenase itself. In contrast to the other enzymes, CfbC/D exhibits a simpler molecular architecture, forming a heterotetrameric CfbC₂D₂ assembly. Furthermore, the interaction of the CfbC and CfbD components does not depend on the presence of adenosine triphosphate (ATP). Here we report cryoelectron microscopy structures of the CfbC/D complex prepared in the absence and presence of substrates. These structures not only shed light on the molecular architecture of the CfbC/D complex but also reveal a high degree of structural flexibility within the CfbD₂ component, which undergoes a large conformational change in the presence of an ATP analog and the tetrapyrrole substrate. The interplay of CfbD with its reductase CfbC also strongly suggests an evolutionary pathway toward the modern nitrogenase from methanogenic archaea.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2611794123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228561","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}

{"title":"Natural product biosynthesis by guanidine prenyltransferases in plants and bacteria","authors":"Dominik Kolling, Katharina Konzok, Daghan Taser, Tom Jentsch, Svenja Schwoerer, Henry Struwe, Arne Bültemeier, Jonas Freiberg, Claus-Peter Witte, Jakob Franke, Andriy Luzhetskyy, Andreas Kirschning, Sophia Rudorf, Jesko Koehnke","doi":"10.1126/science.aeg1821","DOIUrl":"https://doi.org/10.1126/science.aeg1821","url":null,"abstract":"Guanidine exists almost exclusively as a resonance-stabilized cation, making its direct enzymatic functionalization challenging. We identified the cyanobacterial enzyme NosH, which catalyzes direct prenyl transfer to free guanidine. Structural and mechanistic analyses revealed guanidine activation by a two-aspartate clamp coupled to prenyl-donor binding through a distinct catalytic architecture. Guided by these features, we identified a large family of guanidine prenyltransferases across bacteria and plants. Plant enzymes produced guanidine alkaloids such as galegine in vitro and heterologous expression of a plant ortholog in <jats:italic toggle=\"yes\">Nicotiana benthamiana</jats:italic> produced galegine in planta, providing a direct enzymatic link to plant-specialized metabolism.","PeriodicalId":21678,"journal":{"name":"Science","volume":"12 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229947","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}

{"title":"Visualizing symmetry-broken Chern insulators and their quantum melting","authors":"Minhao He, Yen-Chen Tsui, Ran Peng, Kenji Watanabe, Takashi Taniguchi, Oskar Vafek, Ali Yazdani","doi":"10.1126/science.aef0940","DOIUrl":"https://doi.org/10.1126/science.aef0940","url":null,"abstract":"In the presence of a magnetic field, electronic states of moiré quantum materials develop a Hofstadter spectrum that provides a distinctive setting for studying the interplay between band topology and strong electron-electron interaction. Using scanning tunneling microscopy, we studied Hofstadter’s states in bilayer graphene aligned with hexagonal boron nitride and directly visualized the formation of interaction-driven symmetry breaking Chern insulators. Our measurements revealed the formation of phases that double, triple, or quadruple the moiré unit cell at fractional filling of the Hofstadter bands as well as states with complex intra–unit cell wave functions. We visualized two distinct quantum phenomena in different Chern states, including quantum melting driven by the appearance and proliferation of topological defects and a quantum transition co-occurring with phase competition and separation.","PeriodicalId":21678,"journal":{"name":"Science","volume":"31 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229949","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}

{"title":"The AI debate is missing half the system","authors":"Pietro Michelucci","doi":"10.1126/science.aen2722","DOIUrl":"https://doi.org/10.1126/science.aen2722","url":null,"abstract":"Last month, leading executives of artificial intelligence (AI) companies warned the United Nations Security Council about the risks of losing human control over this rapidly advancing technology. Their recommendations focused heavily on safeguards, evaluation, and governance of AI models and systems, largely overlooking the risks that arise from the interactions of AI with people and institutions. AI safety needs to be addressed at the level of the human–AI system, not the AI model alone.","PeriodicalId":21678,"journal":{"name":"Science","volume":"76 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229946","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}