Proceedings of the National Academy of Sciences of the United States of America最新文献_第2页

Can privacy technologies replace cookies? Ad revenue in a field experiment. 隐私技术能取代cookie吗？实地试验中的广告收入。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-05 DOI: 10.1073/pnas.2603752123

Zhengrong Gu, Garrett A Johnson, Shunto J Kobayashi

{"title":"Can privacy technologies replace cookies? Ad revenue in a field experiment.","authors":"Zhengrong Gu, Garrett A Johnson, Shunto J Kobayashi","doi":"10.1073/pnas.2603752123","DOIUrl":"https://doi.org/10.1073/pnas.2603752123","url":null,"abstract":"Digital advertising finances much of the open web, yet relies on tracking technologies that regulators increasingly seek to restrict. In response, industry has developed privacy-enhancing technologies intended to preserve advertising performance while limiting data collection, but their economic effects remain largely untested. We study this question using an open, industry-wide field experiment jointly overseen by Google and the UK Competition and Markets Authority, in which Chrome users were randomly assigned to browse with third-party cookies enabled, with cookies disabled, or with Google's Privacy Sandbox replacing cookies. Combining this experimental variation with proprietary data from a major ad management firm, we analyze more than 200 million ad impressions across over 5,000 publishers worldwide. Removing third-party cookies reduces publisher advertising revenue by 29.1%. Privacy Sandbox recovers only 4.2% of this lost revenue; this estimate reflects observed adoption and performance during the study period and may reflect modest industry adoption. Privacy-preserving auctions also increase ad latency, reducing impression delivery and further limiting revenue performance. Together, these findings provide a large-scale experimental benchmark for evaluating privacy-preserving reforms and demonstrate the difficulty of reconciling privacy protection with the economics of online content provision.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2603752123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841988","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

Timing and origins of Mexican and Central American oak diversity. 墨西哥和中美洲橡树多样性的时间和起源。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-04 DOI: 10.1073/pnas.2537040123

Kieran N Althaus, Marlene Hahn, Silvia Alvarez-Clare, Jeannine Cavender-Bares, Allen J Coombes, María Del Socorro González-Elizondo, Antonio González-Rodríguez, Paul S Manos, Hernando Rodríguez-Correa, Susana Valencia-Ávalos, Andrew L Hipp

{"title":"Timing and origins of Mexican and Central American oak diversity.","authors":"Kieran N Althaus, Marlene Hahn, Silvia Alvarez-Clare, Jeannine Cavender-Bares, Allen J Coombes, María Del Socorro González-Elizondo, Antonio González-Rodríguez, Paul S Manos, Hernando Rodríguez-Correa, Susana Valencia-Ávalos, Andrew L Hipp","doi":"10.1073/pnas.2537040123","DOIUrl":"https://doi.org/10.1073/pnas.2537040123","url":null,"abstract":"The origins and assembly of temperate biodiversity hotspots remain poorly understood. This knowledge gap is particularly evident in low-latitude montane regions of the Americas, where northern lineages have repeatedly colonized and diversified. Here we investigate the evolutionary history of oaks (Quercus) in the Americas, with a focus on their parallel radiation into Mexican and Central American montane forests. Using a time-calibrated phylogeny, we show that white oaks (Q. section Quercus) and red oaks (Q. sect. Lobatae) independently colonized Mexico c. 25 Mya. This coincides with a variety of ecosystem changes at the Oligocene-Miocene boundary, including aridification. Diversification analyses reveal that montane habitats acted as cradles of oak diversity, with higher speciation rates associated with movement into topographically complex, higher-elevation landscapes. Despite 20 Ma of independent evolution in Mexico and Central America, red and white oaks show remarkable convergent evolution in climate niche. Our results highlight how extrinsic factors-migration into novel environments-coupled with intrinsic niche lability can facilitate rapid diversification. Our study thus provides insights into the origins of temperate biodiversity and the evolutionary processes shaping species-rich montane ecosystems.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2537040123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842022","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

The electoral choice context and support for democratic norms. 选举选择的背景和对民主规范的支持。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-06 DOI: 10.1073/pnas.2521380123

Kang Huang, Mitchell Lovett, Gretchen Helmke

{"title":"The electoral choice context and support for democratic norms.","authors":"Kang Huang, Mitchell Lovett, Gretchen Helmke","doi":"10.1073/pnas.2521380123","DOIUrl":"https://doi.org/10.1073/pnas.2521380123","url":null,"abstract":"In this paper, we explore whether different choice environments affect voters' willingness to put democracy over party and policy. Using a series of candidate choice experiments in which we manipulate not only candidate attributes, but also the number of races on the ballot, we find that when voters are able to vote in multiple races on a ballot they are substantially more likely to punish antidemocratic candidates than when they are only given the opportunity to cast one vote. We refer to this effect as \"democratic balancing.\" Substantively, our experiments show that the magnitude of the total punishment effect increases from 11% in single-race ballot settings to 17.9% in multirace ballot settings. Such effects remain largely consistent across different candidate platforms, separate waves of the survey, different types of norm violations, and are robust to different electoral race combinations and different information environments. Observational data from the 2022 U.S. midterm elections further corroborates our experimental findings. For researchers, our results underscore the importance of taking into account the institutional context in which voters make decisions. For citizens concerned with democratic backsliding, our results offer some reassurance: Moving to a more realistic electoral context in which multiple races appear on the ballot tempers the willingness of respondents to trade off democracy for their preferred policies and party.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2521380123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842030","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

Developmental landmarks and cellular transitions during extravillous trophoblast cell differentiation. 外滋养细胞分化过程中的发育标志和细胞转变。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-06 DOI: 10.1073/pnas.2529836123

Ayelen Moreno-Irusta, Malay Kumar Basu, Esteban M Dominguez, Thomas S Chen, Sawyer H Smith, Kaela M Varberg, Hiroaki Okae, Takahiro Arima, Michael J Soares

{"title":"Developmental landmarks and cellular transitions during extravillous trophoblast cell differentiation.","authors":"Ayelen Moreno-Irusta, Malay Kumar Basu, Esteban M Dominguez, Thomas S Chen, Sawyer H Smith, Kaela M Varberg, Hiroaki Okae, Takahiro Arima, Michael J Soares","doi":"10.1073/pnas.2529836123","DOIUrl":"https://doi.org/10.1073/pnas.2529836123","url":null,"abstract":"Human trophoblast stem (TS) can be captured, maintained in vitro under specific conditions, and differentiated into extravillous trophoblast (EVT) cells. The regulatory mechanisms that govern the self-renewal and differentiation of human TS cells into EVT cells are largely unknown. In this study, bulk RNA-sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) were performed on human TS cells maintained in the stem state and on cells progressing from the stem state into EVT cells (differentiation days 3, 6, and 8). Distinct bulk and single cell transcript profiles were identified for each day of analysis. Day 3 of EVT cell differentiation represented a striking transition point and was readily distinguished from stem state and days 6 and 8 of EVT cell differentiation. Analysis of scRNA-seq led to the identification of several unique cell populations, trophoblast cell developmental state-specific regulons, and trajectories. We elucidated functional roles of key regulators of EVT cell development: cyclin B1, CCAAT/enhancer-binding protein beta, and A Disintegrin And Metalloproteinase (ADAM) metallopeptidase with thrombospondin type 1 motif 20. Collectively, we have defined developmental landmarks and transitional cell populations during EVT cell differentiation. These findings provide a valuable resource and foundation for future investigations into regulatory mechanisms controlling TS cell differentiation into the EVT cell lineage.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2529836123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842049","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 Osvatic et al., Global biogeography of chemosynthetic symbionts reveals both localized and globally distributed symbiont groups. 对Osvatic等人的修正，全球生物地理学的化学合成共生体揭示了局部和全球分布的共生体群体。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-04 DOI: 10.1073/pnas.2611059123

引用次数: 0

Correction for Konstantoulea et al., Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity. 对Konstantoulea等人的更正，吞噬细胞作为斑块催化剂：人类巨噬细胞产生具有交叉播种活性的具有播种能力的Aβ42原纤维。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-06 DOI: 10.1073/pnas.2613397123

引用次数: 0

Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes. 鞘磷脂与胆固醇在脂质双分子层膜上相互作用的可视化。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-05 DOI: 10.1073/pnas.2528400123

Jared C Smothers, Chieu H B Nguyen, Yan Han, Yang Li, Zhe Chen, Arun Radhakrishnan

{"title":"Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes.","authors":"Jared C Smothers, Chieu H B Nguyen, Yan Han, Yang Li, Zhe Chen, Arun Radhakrishnan","doi":"10.1073/pnas.2528400123","DOIUrl":"https://doi.org/10.1073/pnas.2528400123","url":null,"abstract":"Biomembranes are complex two-dimensional liquids composed of hundreds of lipid species that interact in a myriad of ways. One such interaction, that between sphingomyelin (SM) and cholesterol in plasma membranes of animal cells, provides many functional benefits, including protection from microbial infection, prevention of unrestrained cell growth, and proper maintenance of cellular lipid composition. Owing to the liquid nature of membranes, the structure of the SM/cholesterol interaction, or any other functionally critical lipid-lipid interaction, has remained elusive. Here, we overcome this challenge using a fungal toxin called Ostreolysin A (OlyA), that has been shown to specifically bind to SM/cholesterol complexes in membranes. We used OlyA to stabilize the SM/cholesterol interaction much in the same way as antibodies are used to stabilize preexisting protein complexes. Cryoelectron microscopy analysis of OlyA bound to SM/cholesterol membranes reveals the details of the tight interaction between these two lipids-the steroid nucleus of cholesterol packs against the acyl chains of SM, and a hydrogen bond forms between the nitrogen on SM's ceramide base and the oxygen on cholesterol's hydroxyl group, thus sequestering this key functional group of cholesterol. The importance of hydrogen bonding in stabilizing the SM/cholesterol interaction is supported by structural analysis of a mutant form of OlyA that binds free SM in a cholesterol-independent manner. These results provide structural insights into the organization of cholesterol in membranes.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2528400123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842110","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

Intramolecular bonding as a design strategy for robust intermolecular binding of oligomers. 分子内键作为低聚物分子间稳定结合的设计策略。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-05 DOI: 10.1073/pnas.2534579123

Mohammed Suliman Alshammasi, R Kenton Weigel, Christopher A Alabi, Fernando A Escobedo

{"title":"Intramolecular bonding as a design strategy for robust intermolecular binding of oligomers.","authors":"Mohammed Suliman Alshammasi, R Kenton Weigel, Christopher A Alabi, Fernando A Escobedo","doi":"10.1073/pnas.2534579123","DOIUrl":"https://doi.org/10.1073/pnas.2534579123","url":null,"abstract":"In this study, a combined multiscale-modeling and experimental framework is presented to elucidate design rules to optimize the binding thermodynamics and kinetics of sequence-defined oligomers. It is shown that, contrary to conventional notions, entropy can be designed to favor not only binding affinity but also the rapid hybridization of stable complementary complexes. This entropic gain of binding arises from a strategic interplay between intermolecular contacts and intramolecular interactions that maintain restricted oligomer conformations when unbound. Furthermore, our analysis underscores the important role that solvent quality plays in modulating this interplay through structural changes upon binding in both the oligomers and their solvation shells. While these insights are in principle chemistry-agnostic and can be deployed for a wide range of materials platforms and applications, oligocarbamates are used as testbeds for experimental validation. Oligocarbamates are economical DNA-mimics that, unlike DNA-based constructs, form stable Watson-Crick bonds in common nonaqueous solvents, are not susceptible to enzymatic degradation and can be economically produced at scale.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2534579123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841600","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

MiR-155-driven loss of ICOSL and SOCS1 in EBV+ gastric cancers renders abundant cytotoxic T cells ineffective, enabling immune evasion. 在EBV+胃癌中，mir -155驱动的ICOSL和SOCS1缺失使大量的细胞毒性T细胞无效，从而实现免疫逃避。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-08 DOI: 10.1073/pnas.2536375123

Gerard J Nuovo, Koshi Mimori, Hajime Otsu, Esmerina Tili, Carlo M Croce

{"title":"MiR-155-driven loss of ICOSL and SOCS1 in EBV+ gastric cancers renders abundant cytotoxic T cells ineffective, enabling immune evasion.","authors":"Gerard J Nuovo, Koshi Mimori, Hajime Otsu, Esmerina Tili, Carlo M Croce","doi":"10.1073/pnas.2536375123","DOIUrl":"https://doi.org/10.1073/pnas.2536375123","url":null,"abstract":"Poorly differentiated gastric carcinomas (PDGC) comprise 30% of gastric cancers and are associated with poor prognosis, correlating with tumor size and microvascular invasion. PDGC may be subcategorized as Epstein-Barr virus (EBV)-positive or EBV-negative. Based on prior work with EBV-positive nasopharyngeal carcinomas, we interrogated 33 PDGC samples for EBV DNA/RNA/protein, CD8, PDL1, PD1, Inducible T cell Co-Stimulator Ligand (ICOSL), ICOS, MHC-I, Suppressor of cytokine signaling 1 (SOCS1), and miR-155. The 13 EBV-positive tumors each showed intense PD1, PDL1, and CD8+ T cell responses that were largely absent in EBV-negative tumors. EBV EBER-1/2 RNA strongly colocalized with miR-155 in cancer cells with a concomitant loss of ICOSL expression as well as downregulation of cytokine signaling suppressor, SOCS1. In contrast, the 20 EBV-negative PDGCs showed weak to no miR-155 expression, with strong ICOSL and SOCS1 expression. On the other hand, the MHC-I expression was lost in both PDGC types. These data suggest that, despite the similar histological patterns of the cancer cells, EBV-driven induction of miR-155 suppresses SOCS1 expression, resulting in intense cytotoxic T cell infiltration, but also loss of the other miR-155 target, ICOSL, making tumor cells invisible to the surrounding intense T cell infiltration. Conversely, EBV-negative tumors retain ICOSL/SOCS1 expression, but exhibit minimal T cell infiltration, partly due to high SOCS1 expression, preventing immune-mediated clearance. Overall, our data indicate that SOCS1 expression, regulated by EBV-induced miR-155, along with ICOSL status determines whether tumors attract T cells and whether those T cells can effectively eradicate cancer cells.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2536375123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857019","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

Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture. 灵长类松果体的单细胞多组学和空间景观揭示了昼夜节律和褪黑激素调节结构。

IF 9.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-05-12 Epub Date: 2026-05-05 DOI: 10.1073/pnas.2524839123

Jihong Zheng, Yuchen Xiao, Jianjun Lyu, Hongtao Xu, Yaqun Zhang, Yanchuan Li, Yihao Li, Tianjun Wang, Liu Liu, Lingjing Jin, Xuhui Zhou, Chao Zhang

{"title":"Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture.","authors":"Jihong Zheng, Yuchen Xiao, Jianjun Lyu, Hongtao Xu, Yaqun Zhang, Yanchuan Li, Yihao Li, Tianjun Wang, Liu Liu, Lingjing Jin, Xuhui Zhou, Chao Zhang","doi":"10.1073/pnas.2524839123","DOIUrl":"https://doi.org/10.1073/pnas.2524839123","url":null,"abstract":"The mammalian pineal gland maintains normal circadian rhythms and homeostasis by secreting melatonin. However, the lack of a single-cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated. Here, we constructed a multiomics atlas of the pineal gland from Macaca fascicularis by integrating snRNA-seq, snATAC-seq, and spatial transcriptomics. We identified pinealocytes as the predominant cell type, alongside six glial and vascular lineages. Chromatin accessibility analysis delineated cell-type-specific regions enriched for melatonin synthesis and phototransduction genes. Notably, we resolved a dual-layer regulatory architecture: While melatonin synthesis programs are robustly organized, circadian clock regulators exhibit a distinct, sparse spatial pattern. Coexpression networks further identified core modules and regulatory hubs-including CRX/OTX2, LHX4, and RORA-that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as PTN-ALK/SDC2, RA-RORB, and NRG1-ERBB4, that potentially coordinate this spatial functional organization. Integrating genetic traits showed that sleep and neuropsychiatric risk variants preferentially map to these pineal regulatory modules. Specifically, sleep-associated loci converged on MEIS1-linked elements, while bipolar disorder-associated loci highlighted candidate genes of RDH12 and SDK2. Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a physiological foundation for investigating circadian and neuroendocrine regulation in healthy and disease models.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2524839123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841869","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