Proceedings of the National Academy of Sciences of the United States of America最新文献

{"title":"Taylor's law beyond finite moments: A route to dynamic financial risk.","authors":"Svetlozar T Rachev","doi":"10.1073/pnas.2632396123","DOIUrl":"https://doi.org/10.1073/pnas.2632396123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2632396123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168339","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":"A multiscale framework for heme crystallization inhibition: From single-molecule step-capping to parasite suppression.","authors":"Huan-Jui Lee, Sandra Massih, Mahnoor Abdullah, Hariharan Annadurai, Jeffrey D Rimer, David J Sullivan, Peter G Vekilov","doi":"10.1073/pnas.2613405123","DOIUrl":"https://doi.org/10.1073/pnas.2613405123","url":null,"abstract":"<p><p>Heme crystallization is central to malaria parasites' survival during the erythrocytic stage of the disease, yet how clinically relevant antimalarial drugs modulate this process at the molecular level remains unclear. Here we employ stage-resolved parasite assays and multiscale in vitro approaches to explore the interactions between lumefantrine (LF), one of the popular components of current combination therapies, and hematin crystallization. Pulse LF suppresses <i>Plasmodium falciparum</i> during both ring and trophozoite stages. Under biomimetic conditions, LF markedly reduces β-hematin crystal growth rates. High-resolution atomic force microscopy reveals that individual LF molecules bind directly to crystal steps, physically constraining step motion through a previously unreported step-capping mechanism. This localized inhibition propagates to the mesoscale, producing step broadening, reduced interstep spacing, and causing surface kinetic roughening. In contrast to its strong inhibition of crystal growth, LF enhances hematin nucleation by promoting the formation of mesoscopic hematin-rich clusters, as detected by a combination of scattering and microscopy techniques. Attachment of the nucleated crystallites to larger crystal surfaces initiates a nonclassical inhibition sequence by straining the crystal interface, which further impedes step growth.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2613405123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169873","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":"Modulation of avian iridescence via melanogenesis.","authors":"Soraia Barbosa, Carina Bittner, Roberto Arbore, Pedro M Araújo, Paulo Pereira, Pedro Andrade, Csaba Fekete, Rita Afonso, Sandra Afonso, M Francisca Amorim, Cristiana I Marques, Michaël P J Nicolaï, João Carita, Jindřich Brejcha, Ricardo J Lopes, Joel M Alves, Fernando Cruz, Jèssica Gómez-Garrido, Cristina Zamarreño, Marta Gut, Tyler Alioto, Muhammad Akhtar Ali, Andrea Hilpert, Anita Hecht, Erdmann Spiecker, Benjamin Apeleo Zubiri, Shosuke Ito, Kazumasa Wakamatsu, Leif Andersson, Joseph C Corbo, Nicolas Vogel, Miguel Carneiro","doi":"10.1073/pnas.2614444123","DOIUrl":"https://doi.org/10.1073/pnas.2614444123","url":null,"abstract":"<p><p>The iridescent colors of birds originate in nanoscale feather structures that interact with light. Although the physical principles governing avian iridescence are well established, the molecular mechanisms assembling these nanostructures into photonic materials remain unknown. Here, we integrated genomic, cellular, and optical approaches to investigate the molecular basis of iridescent color formation in birds. We leveraged mutations that arose in the domesticated Indian peafowl and natural color variation in wild birds. In peafowl, we identified eight genes underlying gains, losses, and shifts of iridescence, whereas in two wild species, we used single-cell transcriptomics to profile asymmetric feathers in which iridescent and noniridescent barbules develop on opposite sides of the same feather. We found that all peafowl mutations mapped to melanogenesis genes, showing that variation in this pathway can modify diverse geometric features of feather photonic nanostructures. Mutations altering melanin composition collapsed multilayered photonic systems and yielded noniridescent tissues, whereas changes in melanosome abundance, elongation, or deposition timing generated multilayer architectures with variable periodicity and color. We further show in peafowl that transitions from noniridescent to iridescent plumage were associated with single-nucleotide mutations in a melanogenesis gene, suggesting that, in species already capable of forming multilayered nanostructures, iridescence can be gained by relatively small genetic changes. Single-cell transcriptomes from wild species also supported extensive melanocyte-centered regulatory rewiring associated with iridescence, including changes in melanosome maturation, trafficking, and intercellular signaling. Together, these results show that the nanoscale order underlying iridescence is developmentally plastic and highly responsive to the melanogenic environment.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2614444123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207547","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":"<i>S</i>-adenosyl-L-homocysteine triggers an adaptive response that extends lifespan through the <i>YBT1</i> ABC transporter.","authors":"Koji Masumura, Sayaka Kawasaki, Mayu Tsutsumi, Hiiro Yamashita, Muneyoshi Kanai, Haruto Nakajo, Wakaba Yagi, Shoma Katsunoi, Kaori Yoneyama, Miyuki Kawano-Kawada, Takayuki Sekito, Takafumi Ogawa, Tomoyoshi Soga, Masaki Mizunuma","doi":"10.1073/pnas.2621286123","DOIUrl":"https://doi.org/10.1073/pnas.2621286123","url":null,"abstract":"<p><p><i>S</i>-adenosyl-L-methionine (SAM) is a fundamental methyl donor; however, the physiological role of its byproduct and competitive inhibitor, <i>S</i>-adenosyl-L-homocysteine (SAH), remains unclear. Here, we show that transient reactive oxygen species (ROS) production triggered by SAH during the early logarithmic phase mimics partial SAH hydrolase inhibition, extending the yeast chronological lifespan (CLS) through a hormetic mechanism. This study reveals that the dual nature of ROS in aging is determined by the specific degree of SAH hydrolase activity. We identified the adenosine 5'-triphosphate-binding cassette (ABC) transporter Ybt1 as a key downstream effector of SAH. Ybt1 localizes to the vacuolar membrane and facilitates the sequestration of SAM from the cytosol into the vacuole. Notably, <i>YBT1</i> overexpression extends CLS, mimicking SAH effects through an integrated pathway involving target of rapamycin complex 1 downregulation, autophagy, and adenosine 5'-monophosphate-activated protein kinase activation. Our findings establish that SAH acts as a metabolic signal coupling nutrient and energy availability to longevity via Ybt1, defining an adaptive/hormetic response for lifespan regulation in yeast.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2621286123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207827","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":"Reply to Roff: Ecological readiness must evolve with AI.","authors":"Gayatri Mishra","doi":"10.1073/pnas.2627861123","DOIUrl":"https://doi.org/10.1073/pnas.2627861123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2627861123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149491","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":"Structural insights into the coupling mechanism of vectorial CO₂ uptake by DAB1.","authors":"Naiya R Phillips, Luke M Oltrogge, Jonathan P Remis, David F Savage","doi":"10.1073/pnas.2616712123","DOIUrl":"https://doi.org/10.1073/pnas.2616712123","url":null,"abstract":"<p><p>CO₂ transporters enable bacterial CO₂-concentrating mechanisms by catalyzing directional hydration of CO₂, yet the basis of this vectorial carbonic anhydrase (CA) activity remains an open question. We used cryoelectron microscopy to determine the structure of the DAB1 complex from <i>Thermocrinis albus</i> to 2.29 Å, revealing a heterotrimer in which a deeply buried β-CA active site in DabA is structurally coupled to the proton-translocating subunit DabB. Two conformational states define distinct solvent channels for substrate entry and product exit. A suppressor screen identifies mutations that disrupt coupling while retaining CA activity, underlying the importance of conserved residues that link proton translocation to active-site remodeling. These results support a model in which proton-driven conformational changes regulate substrate access to the active site, enabling vectorial CO₂ hydration.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2616712123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166444","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":"A water-pinning hot spot drives templated tau aggregation.","authors":"Chung-Ta Han, Karen Tsay, Samuel Lobo, Saeed Najafi, Kieran Monahan, Erica Hong, M Scott Shell, Joan-Emma Shea, Songi Han","doi":"10.1073/pnas.2611158123","DOIUrl":"https://doi.org/10.1073/pnas.2611158123","url":null,"abstract":"<p><p>Tau assembles into fibrillar aggregates that are pathological hallmarks of a group of neurodegenerative diseases collectively called tauopathies. Templated aggregation of naïve tau to seeding-competent fibrils that proceed from cell to cell is a key driver of prion-like progression of tauopathies. This study tests the hypothesis that tau, an intrinsically disordered protein, achieves in-register stacking to form seed-competent fibrils by a pinning action of tau to each other and/or the seed surface via a single dominant hotspot to avoid mismatch in tau stacking to fibrils. Structured solvation water has been proposed to be a signature of such hot spots at both the tau fibril-end surface and soluble tau monomers. Although jR2R3-P301L tau exhibits a heterogeneous hydration landscape in its intrinsically disordered state, with enhanced water structuring near the P301L mutation site, it is unclear whether a localized hotspot exists at the fibril end surface and surface water facilitates the initial contacts in templated aggregation. Using rapid ¹H-¹⁵N SOFAST-HMQC NMR to track seed-induced aggregation of jR2R3-P301L in real time, complemented by molecular dynamics simulation of fibril surface hydration, we identify a residue-specific pinning hotspot that is prone to dewetting followed by sequential folding and incorporation of the remaining segment in a two-step dock-and-lock process. Site-specific spin labeling further demonstrates that blocking this pinning hotspot disrupts templated aggregation, leading to shorter fibrils. The identification of a dominant pinning site will facilitate the rational design of binders to effectively disrupt fibril extension or serve as diagnostic or therapeutic strategies.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2611158123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169616","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":"Phylogenomics confirms Palaeoptera monophyly and illuminates the origin of winged insects.","authors":"Shiyu Du, Yehao Wang, Feng Zhang, Michael S Engel, Xuhongyi Zheng, Dewen Gong, Changfa Zhou, Chenyang Cai","doi":"10.1073/pnas.2614706123","DOIUrl":"https://doi.org/10.1073/pnas.2614706123","url":null,"abstract":"<p><p>The origin and early radiation of winged insects (Pterygota) represent one of the most transformative events in terrestrial evolution, yet phylogenetic relationships among their basalmost lineages (Ephemeroptera, Odonata and Neoptera) continue to be a central debate within insect systematics. Here, we present the most taxonomically comprehensive phylogenomic analysis to date, leveraging genomic and transcriptomic data from 101 species, including 16 sequenced ephemeropteran genomes. Employing 1,367 universal single-copy orthologs across two supermatrices, we used concatenation- and coalescent-based frameworks under homogeneous and heterogeneous, and multispecies coalescent models. Our analyses support Palaeoptera monophyly. Although coalescent-based methods initially suggested a Chiastomyaria (Ephemeroptera + Neoptera) topology, subsequent signal dissection and topology tests confirm that the preponderance of genomic signal favors a monophyletic Palaeoptera. Furthermore, we identify incomplete lineage sorting and gene tree estimation error as the primary drivers of previous topological conflicts. Our molecular dating results point to an Early Devonian origin of crown-Pterygota, whereas crown-Palaeoptera first emerged in the Late Devonian. By reconciling molecular evidence with morphological synapomorphies, such as wing-base sclerite homologies, this study provides a coherent framework for the early evolution of winged insects, supports a single origin of wings, and identifies the neopteran wing-folding mechanism as a singular evolutionary innovation.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2614706123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169890","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":"A neural operator framework for data-driven discovery of stability and receptivity in physical systems.","authors":"Chengyun Wang, Liwei Chen, Nils Thuerey","doi":"10.1073/pnas.2526451123","DOIUrl":"https://doi.org/10.1073/pnas.2526451123","url":null,"abstract":"<p><p>Understanding how complex systems respond to perturbations, such as whether they will remain stable or what their most sensitive patterns are, is a fundamental challenge across science and engineering. Traditional stability and receptivity (resolvent) analyses are powerful but rely on known equations and linearization, limiting their use in nonlinear or poorly modeled systems. Here, we introduce a data-driven framework that automatically identifies stability properties of both equilibrium points and periodic orbits, as well as optimal forcing responses from observation data alone, without requiring governing equations. By training a neural network as a dynamics emulator and using automatic differentiation to extract its Jacobian, we can perform stability and receptivity analyses directly from data. We demonstrate the method on systems of increasing complexity, from canonical models to high-dimensional fluid flows and a real-world climate dataset, employing model reduction where needed and successfully identifying dominant instability modes and optimal input-output structures, even in strongly nonlinear regimes. By leveraging a neural network emulator, we readily obtain a nonlinear representation of system dynamics while additionally retrieving intricate dynamical patterns that were previously difficult to resolve. This equation-free methodology establishes a broadly applicable tool for analyzing complex, high-dimensional datasets, with potential relevance to grand challenges in fields such as climate science, neuroscience, and fluid engineering.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2526451123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207517","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":"Loss of tRNA uridine thiolation affects mRNA translation, protein production, and metabolite accumulation in <i>Arabidopsis</i>.","authors":"Arnaud Dannfald, Adrien Cadoudal, Marie-Christine Carpentier, Rémy Merret, Quentin Rigal, Jérôme Vialaret, Aurore Attina, Jana Kindermans, Sonia Garcia Llorens, Christina Berrissou, Lisa Tritsch, Anna Koprivova, Bastian Welter, Virginie Marchand, Philipp Westhoff, Alexandre David, Christophe Hirtz, Yuri Motorin, Jean-Jacques Favory, Stanislav Kopriva, Laurence Drouard, Jean-Marc Deragon","doi":"10.1073/pnas.2604945123","DOIUrl":"https://doi.org/10.1073/pnas.2604945123","url":null,"abstract":"<p><p>It is well established in yeast and animal system that the level of uridine thiolation at position 34 of tRNA anticodon loops can impact the decoding potential of the corresponding codons. Using <i>Arabidopsis thaliana</i>, we confirm that the ability of the plant ribosome to decode AAA, GAA, and CAA codons is impaired when this thiol group is lost, leading to a reduction in protein production, especially for genes enriched in these codons. Interestingly, we observed that loss of tRNA thiolation results in variations in the levels of numerous proteins involved in sulfur-compound metabolism and amino acid biosynthesis. These variations, in turn, affect the accumulation of several sulfur-containing metabolites and amino acids, suggesting that the level of tRNA thiolation has a direct and profound impact on plant metabolism. We also demonstrate that U₃₄ thiolation is essential for adjusting plant growth in response to sulfur limitation and that its absence directly affects the plant's interaction with bacteria, including both pathogens and beneficial organisms. Our results support the hypothesis that the level of tRNA thiolation can be used in plant to link nutritional status to translation.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 42","pages":"e2604945123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207569","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}