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

{"title":"eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer","authors":"Jacob A. Boyer, Ezra Y. Rosen, Malvika Sharma, Madeline A. Dorso, Nicholas Mai, Corina Amor, Jason M. Reiter, Ram Kannan, Sunyana Gadal, Jianing Xu, Matthew Miele, Zhuoning Li, Xiaoping Chen, Qing Chang, Fresia Pareja, Stephan Worland, Douglas Warner, Sam Sperry, Gary G. Chiang, Peggy A. Thompson, Guangli Yang, Ouathek Ouerfelli, Alexander Drilon, Elisa de Stanchina, Hans-Guido Wendel, Sarat Chandarlapaty, Neal Rosen","doi":"10.1073/pnas.2424286122","DOIUrl":"https://doi.org/10.1073/pnas.2424286122","url":null,"abstract":"Most breast cancers depend on hormone-stimulated estrogen receptor alpha (ER) activity and are sensitive to ER inhibition. Resistance can arise from activating mutations in the gene encoding ER ( <jats:italic toggle=\"yes\">ESR1</jats:italic> ) or from reactivation of downstream targets. Newer ER antagonists occasionally show efficacy but are largely ineffective as single agents in the long term. Here, we show that ER translation is eIF4E/cap-independent yet sensitive to inhibitors of the translation initiation factor eIF4A. EIF4A inhibition reduces the expression of ER and cell cycle regulators such as cyclin D1. This leads to growth suppression in ligand-independent breast cancer models, including those driven by ER mutants and fusion proteins. Efficacy is enhanced by adding the ER degrader, fulvestrant. The combination further lowers ER expression and blocks tumor growth in vitro and in vivo. In an early clinical trial (NCT04092673), the eIF4A inhibitor zotatifin was combined with either fulvestrant or fulvestrant plus CDK4 inhibitor, abemaciclib, in patients with acquired resistance to these agents. Multiple clinical responses including a handful of durable regressions were observed, with little toxicity. Thus, eIF4A inhibition could be useful for treating ER+ breast cancer resistant to other modalities.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"21 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677613","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":"Tautomerism induces bending and twisting of biogenic crystals","authors":"Weiwei Tang, Taimin Yang, Qing Tu, Hector A. Calderon, Francisco C. Robles Hernandez, Padraic O’Reilly, Yun Jing, Sung Park, Jeffrey D. Rimer","doi":"10.1073/pnas.2426814122","DOIUrl":"https://doi.org/10.1073/pnas.2426814122","url":null,"abstract":"Understanding and exploiting material flexibility through phenomena such as the bending and twisting of molecular crystals has been a subject of increased interest owing to the number of applications that benefit from these properties, such as optoelectronics, mechanophotonics, soft robotics, and smart sensors. Here, we report the growth of spontaneously bent and twisted ammonium urate crystals induced by the keto–enol tautomerism of the urate molecule. The major tautomer is native to biogenic crystals, whereas the minor tautomer functions as an effective crystal growth modifier to induce naturally bent and twisted ammonium urate crystals. We show that the degree of curvature can be tailored based on the judicious selection of growth conditions. A combination of state-of-the-art microscopy and spectroscopy techniques are used to characterize the origin of bending. Spatially resolved nano-electron diffraction and high-resolution electron microscopy of naturally bent crystals show nearly single crystallinity with local lattice deformations generated by a combination of screw and edge dislocations. These observations are consistent with photoinduced force microscopy and contact resonance atomic force microscopy, which confirmed spatially resolved changes in the intermolecular interactions and the mechanical properties throughout the cross-sectional and axial regions of bent crystals. A mechanism of bending involving the generation of regionally specific dislocations is proposed as an alternative to more commonly reported models. These findings highlight a unique characteristic of tautomeric crystals that may have broader implications for other biogenic materials.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"11 18 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678061","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 histone tail electrostatic potentials in nucleosome core particles by acetylation and PARylation","authors":"Nicolas Bolik-Coulon, Philip Rößler, Michael L. Nosella, Tae Hun Kim, Lewis E. Kay","doi":"10.1073/pnas.2511507122","DOIUrl":"https://doi.org/10.1073/pnas.2511507122","url":null,"abstract":"Cellular DNA is wrapped about an octamer composed of four histone proteins forming the fundamental unit of chromatin structure, the nucleosome core particle (NCP). The intrinsically disordered tails of the histones serve as scaffolds for binding an array of proteins that regulate the fidelity of the genome and gene expression. A variety of posttranslational modifications (PTMs) on the tails have been characterized, including some that alter their overall charge; however, per-residue changes in tail electrostatic potentials for different PTMs have not been reported. Here, using a solution NMR approach in which enhancements of transverse relaxation rates of tail amide and methyl group protons are quantified through the addition of paramagnetic cosolutes, we examine how acetylation and PARylation modulate histone tail electrostatic potentials. Notably, even though both PTMs decrease the net positive charge carried by each tail, their electrostatic potentials either increase or decrease in a tail-specific manner relative to an unmodified NCP. A simple model of tail–DNA interactions is presented to explain these results.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"665 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678145","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":"Lipid residue analysis reveals divergent culinary practices in Japan and Korea at the dawn of intensive agriculture","authors":"Oliver E. Craig, Jasmine Lundy, Manon Bondetti, Sesha Nicholson-Lailey, Natsuki Murakami, Miho Suzuki, Chris Stevens, Alexandre Lucquin, Helen M. Talbot, Joon-ho Son, Shinichiro Fujio, Minoru Sakamoto, Yusuke Yamashita, Kenichi Kobayashi, Enrico R. Crema, Shinya Shoda","doi":"10.1073/pnas.2504414122","DOIUrl":"https://doi.org/10.1073/pnas.2504414122","url":null,"abstract":"The dispersal of millet and rice agriculture from Korea to Japan from around 3,000 y ago has been well documented through radiocarbon analysis of botanical remains and surveying seed impressions on pottery. Much less is known about the extent to which these novel crops were consumed and incorporated into everyday culinary practices. In Japan, agriculturalists moving from Korea would have encountered large, sedentary Final Jomon populations who had well-established hunting, foraging, and cultivation strategies for exploiting indigenous fauna and flora. The degree to which these encounters hindered or enhanced the emergence of agriculture is a key question. To investigate potential changes in food exploitation, we analyzed the contents of pottery through lipid residue analysis of 260 vessels from Bronze Age (Mumun) Korea and contemporary Jomon and Yayoi pottery from Northern Kyushu. A lipid biomarker for broomcorn millet was only found in samples from Korea, suggesting that this crop was not routinely prepared in early agricultural pottery from Japan, despite some botanical evidence for its cultivation. Instead, aquatic products continued to be used in early agricultural pottery, pointing to continuity from the Jomon period despite the arrival of new “continental” ceramic forms. Rice remains difficult to identify conclusively, but by modeling carbon isotope values, we were able to determine the maximum extent that rice may have contributed. Overall, we show that there was a change in culinary practices as agriculture dispersed from Korea to Japan, most likely influenced by different long-standing traditions of preparing and cooking foods in each locality.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"115 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678062","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":"Electroreception in treehoppers: How extreme morphologies can increase electrical sensitivity","authors":"Sam J. England, Ryan A. Palmer, Liam J. O’Reilly, Isaac V. Chenchiah, Daniel Robert","doi":"10.1073/pnas.2505253122","DOIUrl":"https://doi.org/10.1073/pnas.2505253122","url":null,"abstract":"The link between form and function of an organism’s morphology is usually apparent or intuitive. However, some clades of organisms show remarkable diversity in their form, often exhibiting extreme morphologies, but with no obvious functional explanation. Treehoppers (Membracidae) are a family of insects that exemplify this, displaying an astounding morphological diversity, resulting in a plethora of extreme forms. The function of these morphological extremities and the reasons for their evolution have thus far remained largely enigmatic. However, this mystery can be considered in light of the capacity of many animals to detect electric fields in air via electrostatic actuation of mechanosensory structures on their body. Importantly, the strength of the electric field experienced by these mechanosensory structures is expected by physics to depend on the animal’s geometry, with sharp and elongated features producing the highest electric fields. Therefore, we hypothesize that the extreme morphologies of treehoppers increase their electrical sensitivity. Here, we show that treehoppers, along with their predators and mutualists, produce electric fields and that the treehopper <jats:italic toggle=\"yes\">Poppea capricornis</jats:italic> can detect electric fields, responding behaviorally. We also demonstrate that predatory wasps and mutualist bees differ significantly in their electrostatic profiles, pointing to the sophistication of electrical information potentially available to treehoppers. Biophysical, computational, and mathematical techniques are then utilized to provide evidence that the pronotum of treehoppers is the site of electroreception and that its extreme shapes may enhance its sensitivity to electricity.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678063","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":"Correction for Gao et al., Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling.","authors":"","doi":"10.1073/pnas.2516674122","DOIUrl":"https://doi.org/10.1073/pnas.2516674122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"14 1","pages":"e2516674122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677743","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":"Unprecedentedly high global forest disturbance due to fire in 2023 and 2024.","authors":"Peter Potapov,Alexandra Tyukavina,Svetlana Turubanova,Matthew C Hansen,Louis Giglio,Andres Hernandez-Serna,André Lima,Nancy Harris,Fred Stolle","doi":"10.1073/pnas.2505418122","DOIUrl":"https://doi.org/10.1073/pnas.2505418122","url":null,"abstract":"Global forests provide key ecosystem services, from climate regulation to biodiversity habitat, but are under increasing pressure from the combined impacts of climate and land use change. Here, we show that forest disturbance due to fire is growing globally, with the most dramatic increases in intact forest landscapes, highlighting an existential threat to remaining high biomass, high biodiversity forests. The global annual area of forest disturbance due to fire for 2023 and 2024 was highest since the beginning of monitoring in 2001. Compared to 2002-2022 average annual forest disturbance due to fire, the 2023-2024 average was 2.2 times higher globally and 3 times higher in the Tropics. More than ¼ of all 2024 forest disturbance from fire occurred in tropical forests. We found a statistically significant increasing trend of forest disturbance due to fire from 2002 to 2024 in all climate domains except Subtropical. High forest, low deforestation tropical countries were not exempt, with Guyana and the Republic of the Congo experiencing record forest disturbance due to fire. Our results agree with recently estimated increases in global forest fire emissions and active fire detections. The unprecedented scale of fires in the world's most remote forests is a potential harbinger of ecosystem tipping points. Protecting these remaining unfragmented high conservation value forests from this threat poses a daunting and as yet undeveloped policy and capacity challenge.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"24 1","pages":"e2505418122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677909","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":"Retraction for Kundu et al., Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-γ.","authors":"","doi":"10.1073/pnas.2516531122","DOIUrl":"https://doi.org/10.1073/pnas.2516531122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"665 1","pages":"e2516531122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677741","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":"Previous epidemiological studies support the idea of ileal microbiota triggering multiple sclerosis.","authors":"Marian Simka","doi":"10.1073/pnas.2514491122","DOIUrl":"https://doi.org/10.1073/pnas.2514491122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"14 1","pages":"e2514491122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677793","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":"Mutualism between degraders and nondegraders stabilizes the function of a natural biopolymer-degrading community","authors":"Liang Liu, Changfu Tian, Miaoxiao Wang, Ying Luo, Yaru Huang, Tingting Jiang, Hongwen Zhao, Qijun Yu, Entao Wang, Jinshui Yang, Hongli Yuan","doi":"10.1073/pnas.2500664122","DOIUrl":"https://doi.org/10.1073/pnas.2500664122","url":null,"abstract":"Natural biopolymer-degrading microbial communities drive carbon biogeochemical cycling. Within these communities, polymer degraders facilitate the growth of nondegraders by breaking down polymers through extracellular enzymes. However, the contributions of nondegraders to community dynamics, as well as the mechanisms that limit their access to degradation products, remain poorly understood. Here, we investigate EMSD5, a lignocellulose-degrading microbial community that efficiently converts corncob into isopropanol. We demonstrate that nondegraders, such as <jats:italic toggle=\"yes\">Escherichia coli</jats:italic> , enable the growth of degraders (e.g., <jats:italic toggle=\"yes\">Lachnoclostridium</jats:italic> sp. and <jats:italic toggle=\"yes\">Clostridium beijerinckii</jats:italic> ) by creating anaerobic conditions and supplying biotin. Within such expanded niches, lignocellulose degradation proceeds sequentially, and the availability of breakdown products to <jats:italic toggle=\"yes\">E</jats:italic> . <jats:italic toggle=\"yes\">coli</jats:italic> is constrained by two interlinked processes. Specifically, <jats:italic toggle=\"yes\">Lachnoclostridium</jats:italic> sp. produces oligosaccharides that are largely inaccessible to <jats:italic toggle=\"yes\">E</jats:italic> . <jats:italic toggle=\"yes\">coli</jats:italic> . A subset of these oligosaccharides is utilized by <jats:italic toggle=\"yes\">C</jats:italic> . <jats:italic toggle=\"yes\">beijerinckii</jats:italic> to produce monosaccharides that support <jats:italic toggle=\"yes\">E</jats:italic> . <jats:italic toggle=\"yes\">coli</jats:italic> growth, while glycosidase secretion by <jats:italic toggle=\"yes\">C</jats:italic> . <jats:italic toggle=\"yes\">beijerinckii</jats:italic> is reduced under coculture conditions. Building on these findings, we designed a synthetic consortium by coculturing <jats:italic toggle=\"yes\">C. beijerinckii</jats:italic> with an engineered <jats:italic toggle=\"yes\">E</jats:italic> . <jats:italic toggle=\"yes\">coli</jats:italic> strain that expresses xylanase genes from an unculturable <jats:italic toggle=\"yes\">Lachnoclostridium</jats:italic> . This consortium achieved isopropanol production from hemicellulose without requiring anaerobic conditions. Our findings reveal the niche-expanding role of nondegraders and the processes that constrain their access to degradation products, offering insights into maintaining stable cooperation in biopolymer-degrading communities and designing efficient consortia for biopolymer conversion.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"12 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678177","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}