综合性期刊最新文献

{"title":"Compensate peer reviewers; do not conscript them.","authors":"Daniel A Gorelick, Jonas Kunst","doi":"10.1073/pnas.2619714123","DOIUrl":"https://doi.org/10.1073/pnas.2619714123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2619714123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207843","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":"Identification and characterization of neoplastic cells in keratin-positive giant cell-rich tumors.","authors":"Maarten van der Linde, John S A Chrisinger, Elizabeth G Demicco, Carina A Dehner, Gregory W Charville, Inge H Briaire-de Bruijn, Sushama Varma, ChunFang Zhu, Magdalena Matusiak, Judith V M G Bovée, Matt van de Rijn, David Gp van IJzendoorn","doi":"10.1073/pnas.2611959123","DOIUrl":"https://doi.org/10.1073/pnas.2611959123","url":null,"abstract":"<p><p>Keratin-positive giant cell-rich tumor (KPGCT) is a newly described bone and soft tissue tumor. The tumor is characterized by scattered keratin-positive cells and the presence of <i>HMGA2::NCOR2</i> fusions. It is not known if the <i>HMGA2::NCOR2</i> fusion is located in the keratin-positive cells, and little is known about how KPGCT develops. KPGCT shares some histologic features with tenosynovial giant cell tumor (TGCT), a soft tissue tumor with <i>CSF1</i> rearrangements. Single-nuclei RNA sequencing and Xenium spatial transcriptomics were used to elucidate the most likely mechanisms driving KPGCT and compare KPGCT to TGCT. We identified a population of cells coexpressing keratin, <i>HMGA2</i>, and <i>CSF1</i> as the likely neoplastic cells; these cells constitute the minority of the cells in the tumor. These cells express no synovial markers, confirming KPGCT as a distinct entity, separate from TGCT. The bulk of the tumor consists of <i>CSF1R</i>-expressing macrophages and multinucleated giant cells (MNGCs), suggesting an important role for CSF1-CSF1R signaling. In addition, we find that the likely neoplastic cell population shows activation of the hippo signaling pathway, a possible central pathway in KPGCT tumorigenesis. The CSF1-CSF1R axis likely stimulates the migration and proliferation of macrophages, which form the majority of cells in the tumor, as well as their differentiation into MNGCs. These results provide a rationale for the use of CSF1R inhibitors, which have already shown efficacy in TGCT, as a therapy for KPGCT.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2611959123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224327","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":"Understory diversity is positively associated with overstory carbon sequestration.","authors":"Yakun Zhang, Rui Zhang, Scott X Chang, Han Y H Chen, Anthony R Taylor, Masumi Hisano, Chen Chen, Sai Peng, Ya Wang, Xin Chen, Jiasheng Wu, Xinli Chen, Peter B Reich","doi":"10.1073/pnas.2615624123","DOIUrl":"https://doi.org/10.1073/pnas.2615624123","url":null,"abstract":"<p><p>Forests are a major terrestrial carbon sink, and higher overstory diversity is often associated with greater carbon accrual in trees and soils. Yet the contribution of the understory vegetation, the most species-rich forest stratum, to tree and soil carbon accumulation remains largely unknown. Here, we analyzed Canada's National Forest Inventory database to explore whether understory diversity (richness and evenness of shrubs, herbs, and bryophytes) is associated with carbon accumulation in overstory trees and soils across environmental gradients of air temperature, climate moisture, and nitrogen deposition. We found that herb and bryophyte species richness were positively associated with decadal tree carbon accumulation, with the strongest effects at warmer, drier, and nitrogen-limited sites. In contrast, understory diversity showed no consistent association with soil carbon accumulation. On a decadal scale, increasing herb and bryophyte species richness from their minimum to median values corresponded to 15% and 6% increases in tree carbon accumulation, respectively. These results provide large-scale observational evidence that diversity in lower vegetation layers is positively associated with overstory carbon sequestration and reveal strong environmental modulation of these multistratal biodiversity-ecosystem functioning relationships. These findings suggest that species-rich herb and bryophyte communities should be considered in strategies for sustaining forest carbon sinks, especially under warmer, drier conditions and nutrient limitation.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2615624123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224598","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":"Climate-driven rodent demography provides a general, transferable basis for predicting arenavirus spillover.","authors":"John M Drake, Nia W Carroll","doi":"10.1073/pnas.2631478123","DOIUrl":"https://doi.org/10.1073/pnas.2631478123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2631478123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224784","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":"Biotic response networks are an important organizer of the transcriptome in wild <i>Arabidopsis thaliana</i> populations.","authors":"Ana Paula Leite Montalvão, Kevin D Murray, Ilja Bezrukov, Natalie Betz, Lucas P Henry, Paloma Duran, Patrick Boppert, Martina Kolb, Fabrice Roux, Joy Bergelson, Detlef Weigel, Wei Yuan","doi":"10.1073/pnas.2611539123","DOIUrl":"https://doi.org/10.1073/pnas.2611539123","url":null,"abstract":"<p><p>Extensive laboratory experimentation has revealed conserved molecular pathways controlling growth and stress responses in plants, yet how these programs operate in natural settings remains poorly understood. We have investigated the organization of the transcriptome in wild populations of <i>Arabidopsis thaliana</i> by sampling plants across 60 natural sites in Europe and North America over two seasons. Transcriptomes varied extensively among individuals and were only weakly structured by geography or season. No groups of plants stood out due to clear biotic or abiotic stress signatures known from the laboratory. While only a small portion of transcriptome variance was explained by disease symptoms or environmental and phenotypic variables, infection-associated signals accounted for the largest share of the explainable fraction. Biotic-response networks identified in controlled laboratory conditions were well conserved in wild transcriptomes, while other networks, including abiotic-response networks were substantially reorganized in wild plants. Together, these results indicate that while certain transcriptional modules are easily reidentified when moving from the wild to controlled conditions, many regulatory relationships differ in these two contexts, highlighting how ecological complexity shapes transcriptome organization in natural populations.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2611539123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224817","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":"Mediator-associated proteins and the small RNA-guided Polycomb repressive complex enhance cryptic transcription for transposon exclusion.","authors":"Zhihao Zhai, Haoyu He, Tomoko Noto, Mingmei Liucong, Jialuo Li, Julie Saksouk, Yike Liu, Xue Wang, Yujie Liu, Kazufumi Mochizuki, Miao Tian","doi":"10.1073/pnas.2606005123","DOIUrl":"https://doi.org/10.1073/pnas.2606005123","url":null,"abstract":"<p><p>Suppression of transposable elements (TEs) is critical for maintaining genome integrity. The evolutionary arms race between TEs and their eukaryotic host organisms has driven the development of small RNA-dependent mechanisms that specifically suppress TEs while leaving non-TE regions unperturbed. In the binucleated ciliate <i>Tetrahymena</i>, small RNAs (sRNAs) are generated from both TE and non-TE regions of the germline genome, whereas noncoding RNAs (ncRNAs) from the TE-free somatic genome target and eliminate non-TE sRNAs, thereby selectively preserving TE-specific sRNAs for guiding TE recognition. Since sRNAs are produced from both strands, the counteracting ncRNAs must also occur bidirectionally. However, the mechanism by which the somatic genome generates ncRNAs from both strands remains unresolved. Here, we show that these ncRNAs arise from widespread cryptic transcription initiated outside canonical promoters and dependent on the developmentally specific Mediator complex-associated proteins Dima1 and Emit2. We further demonstrate that sRNA-guided recruitment of the <i>Tetrahymena</i> Polycomb repressive complex 2 and Dima1 occupancy are mutually reinforcing, promoting local accumulation of RNA polymerase II, which may facilitate cryptic transcription from these loci in a histone methyltransferase-independent manner. Disruption of Dima1 abolishes cryptic transcription, leads to aberrant accumulation of non-TE sRNAs, and results in erroneous genome elimination and cell death. These findings reveal a regulatory circuit involving sRNAs, Polycomb, and the Mediator-associated protein Dima1 that promotes cryptic transcription, thereby ensuring accurate TE exclusion and genome integrity.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2606005123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228664","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":"mechanoLight: A genetically encoded fluorescent biosensor for visualizing 5-HT2AR mechanotransduction in live cells.","authors":"In-Yeop Baek, Hyunbin Kim, Duwan Kwon, Hahnbeom Park, Jihye Seong","doi":"10.1073/pnas.2610816123","DOIUrl":"https://doi.org/10.1073/pnas.2610816123","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are pivotal sensors of the mechanical environment, yet how they sense and transduce physical stimuli into biochemical signals within live cells remains largely elusive. Here we introduce mechanoLight, a genetically encoded red fluorescent biosensor designed to report the mechanical activation of the 5-hydroxytryptamine 2A receptor (5-HT2AR). By incorporating a circularly permuted mApple (cp-mApple) into the third intracellular loop of 5-HT2AR with the optimized linker (m-linker), mechanoLight selectively detects conformational changes of 5-HT2AR in response to fluid shear stress while exhibiting minimal sensitivity to 5-HT. In sharp contrast, psychLight2, the previously developed green 5-HT2AR biosensor, primarily detects ligand-induced 5-HT2AR activation, suggesting that mechanoLight and psychLight2 capture distinct conformational modes of 5-HT2AR activation. Integrated analysis of linker-swapping experiments, structural modeling, and molecular dynamics simulations revealed that the flexibility of the m-linker underlies the mechanosensitivity of mechanoLight. We further extend this strategy to other mechanosensitive GPCRs, enabling visualization of their mechanoreactivity in live cells. The mechanoLight signal reflects the mechanosensitivity of 5-HT2AR, as shear stress-induced 5-HT2AR activation triggers Gα_q-dependent signaling pathways, including phospholipase C (PLC) activation, intracellular Ca²⁺ mobilization, and ERK phosphorylation. Mutational analysis further identifies N-terminal glycosylation and helix 8 as structural determinants of 5-HT2AR mechanotransduction. Together, our findings establish 5-HT2AR as a mechanotransducer and introduce mechanoLight as a powerful tool for deciphering the molecular principles of GPCR mechanotransduction in live cells.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2610816123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224642","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":"Calibration, accuracy, and domain variation across one million collective forecasts from prediction platforms.","authors":"Justin Dickerson, Hilla Shinitzky, Maayan Peer, Mattan S Ben-Shachar, Michael Gilead","doi":"10.1073/pnas.2615627123","DOIUrl":"https://doi.org/10.1073/pnas.2615627123","url":null,"abstract":"<p><p>Using approximately one million resolved contracts and questions across four collective forecasting platforms, twelve domains, and time horizons ranging from hours to years, we evaluate the calibration and accuracy of collective forecasts in real-world settings. We found that forecast probabilities were overall highly calibrated: events assigned a probability of <i>p</i>% occurred approximately <i>p</i>% of the time. This broad pattern was evident across platforms and many domains, although fine-grained analyses revealed systematic tendencies toward over- or underestimation in highly consequential areas. While this does not mean that forecasting platforms provide certainty about individual events, our findings suggest that large-scale aggregation of judgments contains meaningful information about real-world uncertainty; when examined in aggregate, the predictions generated by the platforms provided informative estimates of event likelihood.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2615627123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224808","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":"Scientists disrupt less but more persistently with career aging.","authors":"Nan Deng, Liying Yang, Shlomo Havlin, An Zeng","doi":"10.1073/pnas.2626763123","DOIUrl":"https://doi.org/10.1073/pnas.2626763123","url":null,"abstract":"<p><p>Disruption describes the extent to which a scientific work overturns the prior knowledge on which it builds and leads to a new line of research. A scientist's tendency to produce disruptive work has been found recently to decline over the career. However, the disruption index captures only how strongly a paper overturns prior work and ignores whether that disruption is later accepted or overturned by subsequent research. The persistent disruption (PD) framework adds this second perspective, identifying work that disrupts prior research and is then consolidated rather than displaced by later work. We examine how PD evolves over the career and find the opposite pattern: The probability of producing a persistent disruptive paper increases with career age. Senior scientists disrupt prior work less often compared to young, but once they do, the disruption tends to persist rather than being quickly superseded. Our results suggest that this reversal feature is due to the experience and we corroborate it across several dimensions of recognition. We also show that, at a fixed level of disruptiveness, the more senior the scientist is, it attracts more citations, social-media attention, and research grants. Nobel laureates also show delayed persistent disruptions. They exhibit high disruptive ability early in their careers, yet their prize-winning work appears years later. This lag further indicates that experience is needed to turn disruptive ability into the field's most celebrated contributions.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2626763123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224613","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":"Bridging spatial scales in respiratory viral infection.","authors":"Ulrik Hvid, Bjarke Frost Nielsen, Kim Sneppen","doi":"10.1073/pnas.2614436123","DOIUrl":"https://doi.org/10.1073/pnas.2614436123","url":null,"abstract":"<p><p>Respiratory viruses spread within the host through a combination of local expansion and occasional long-range dissemination that seeds new infection foci. We present LEAP (Lotka-Euler Airway Pathogen model), an analytically tractable within-host model that captures this two-scale process. The model takes the form of an age-dependent branching process and yields a closed-form expression for the exponential growth rate during early infection. Using empirical data to parameterize the model, we find that productive dissemination requires only a small number of successful long-range seeding events per infected cell, with distinct values for SARS-CoV-2 and influenza A virus. LEAP further predicts that, in these well-adapted viruses, interferon-mediated restriction only weakly affects exponential growth, while remaining decisive for poorly adapted pathogens. More broadly, the model provides a flexible framework for experimentally testable predictions of early infection dynamics.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2614436123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228539","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}