Proceedings of the National Academy of Sciences of the United States of America最新文献_第4页

Stag2-mediated chromatin dynamics regulates antibody class switch recombination. stag2介导的染色质动力学调节抗体类开关重组。

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.2536391123

Zhichen Wan, Leyi Yu, Zifan Yang, Sha Luo, Yutao Zhou, Ruolin Qiao, Hailiang Zha, Xiaoling Shan, Yifan Wang, Shuchan Li, Xuefei Zhang

{"title":"Stag2-mediated chromatin dynamics regulates antibody class switch recombination.","authors":"Zhichen Wan, Leyi Yu, Zifan Yang, Sha Luo, Yutao Zhou, Ruolin Qiao, Hailiang Zha, Xiaoling Shan, Yifan Wang, Shuchan Li, Xuefei Zhang","doi":"10.1073/pnas.2536391123","DOIUrl":"https://doi.org/10.1073/pnas.2536391123","url":null,"abstract":"Class switch recombination (CSR) in B lymphocytes switches immunoglobulin heavy chain (Igh) constant regions (CHs) to generate different functional antibody isotypes and chromatin loop extrusion has been proposed to regulate CSR. Stag1 and Stag2 are key components for stabilizing cohesin during chromatin loop extrusion, but the regulatory mechanism of Stag1 and Stag2 in CSR is unknown. Here, we reported that Stag2 is a specific cohesin component playing critical roles in promoting CSR. In contrast to the dispensable roles of Stag1 in CSR, Stag2 deficiency significantly decreases CSR without affecting DNA damage repair pathways. Mechanistically, loss of Stag2, not Stag1, significantly decreases the chromatin interaction of acceptor CH with CSR center, leading to decreased synapsis of donor and acceptor CH units, decreased transcription of acceptor CH, and impaired CSR. Notably, Stag2 deficiency significantly decreases Stag1 binding within Igh, while Stag2 could compensate for Stag1 binding within Igh upon Stag1 deficiency. Interestingly, Stag2 expression is higher than Stag1 during both mouse and human germinal center (GC) B cell development and Stag2 expression has a high correlation with CSR level in vaccinated and SARS-CoV-2-infected patients. Furthermore, Stag2 is also highly expressed in the GC B cells within different cancers, corresponding to the high level of CSR. Our findings uncover the unrecognized specific roles of Stag2 in regulating CSR.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2536391123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841953","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

Transmembrane ROOM proteins ensure rooms for germ cells by maintaining intercellular bridges. 跨膜ROOM蛋白通过维持细胞间的桥梁来保证生殖细胞的生存空间。

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.2522264123

Kenta Sugiura, Ichiro Kawasaki, Hidetaka Kosako, Ken Sato

引用次数: 0

A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit. PKA选择性抑制剂捕获PKA催化亚基的开放但更有序的构象。

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: 2026-05-07 DOI: 10.1073/pnas.2536312123

Jessica G H Bruystens, Jian Wu, Gerald Tan, Daniela Bertinetti, Hans-Michael Zenn, Bastian Zimmermann, Lisa Chen, Johannes Köckenberger, Federica Massaro, Banumathi Sankaran, Matthew S Walters, Gianluigi Veglia, Fleur M Ferguson, Friedrich W Herberg, Susan S Taylor

{"title":"A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit.","authors":"Jessica G H Bruystens, Jian Wu, Gerald Tan, Daniela Bertinetti, Hans-Michael Zenn, Bastian Zimmermann, Lisa Chen, Johannes Köckenberger, Federica Massaro, Banumathi Sankaran, Matthew S Walters, Gianluigi Veglia, Fleur M Ferguson, Friedrich W Herberg, Susan S Taylor","doi":"10.1073/pnas.2536312123","DOIUrl":"https://doi.org/10.1073/pnas.2536312123","url":null,"abstract":"The structure of the catalytic subunit of cAMP-dependent protein kinase (PKA-C), a prototype for the protein kinase superfamily, laid the foundation for the development of targeted kinase inhibitors. Here we describe the structure and biophysical characterization of a PKA-C complex with BLU0588, a small PKA-selective inhibitor. The high-resolution crystal structure not only captures the inhibitor's unusual T-shaped geometry, but also shows how the four rings of BLU0588 serve as surrogates for ATP's adenosine and phosphate-organizing sites. Each site contains two subsites. BLU0588's planar azaindole and pyridine rings, which are buried beneath the glycine-rich loop in a hydrophobic shell at the base of the active site cleft, fill the adenine and ribose subsites. In contrast, BLU0588's indane and pyrrolidine rings fill the phosphate-organizing site. The indane ring occupies the α/β-phosphate organizing site while the pyrrolidine ring fills the Mg/γ-phosphate organizing site. The structure also shows how BLU0588 nucleates an open but stable conformation of the entire hydrophobic architecture of the N- and C-lobes. In addition to potently blocking phosphoryl transfer activity, BLU0588 also abolishes the synergistic high-affinity binding of the physiological pseudosubstrate inhibitor, protein kinase inhibitor. The residence time of BLU0588, measured by surface plasmon residence, contributes to its picomolar affinity and is distinct from H89, a commonly used but more promiscuous PKA inhibitor. These molecular insights provide a valuable framework for dissecting the organization of the active site cleft as well as different strategies for the rational design of more potent and selective kinase inhibitors in general.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2536312123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841958","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

Vertical conveyor driving the integration of moisture transported by the westerlies to the Asian water towers' atmospheric water cycle. 垂直传送带驱动西风带输送的水汽整合进入亚洲水塔的大气水循环。

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.2529749123

Jing Gao, Tandong Yao, Valérie Masson-Delmotte, Martin Werner, Jean Jouzel, Lonnie Thompson, Mathieu Casado, Hans Christian Steen-Larsen, Alexandre Cauquoin, Ellen Mosley-Thompson, Zeqing He, Rong Cai, Taihua Zhang, Yigang Liu, Gebanruo Chen, Baiqing Xu, Guangjian Wu, Hongxi Pang, Maosheng He

{"title":"Vertical conveyor driving the integration of moisture transported by the westerlies to the Asian water towers' atmospheric water cycle.","authors":"Jing Gao, Tandong Yao, Valérie Masson-Delmotte, Martin Werner, Jean Jouzel, Lonnie Thompson, Mathieu Casado, Hans Christian Steen-Larsen, Alexandre Cauquoin, Ellen Mosley-Thompson, Zeqing He, Rong Cai, Taihua Zhang, Yigang Liu, Gebanruo Chen, Baiqing Xu, Guangjian Wu, Hongxi Pang, Maosheng He","doi":"10.1073/pnas.2529749123","DOIUrl":"https://doi.org/10.1073/pnas.2529749123","url":null,"abstract":"The westerlies moisture transport underpins water security for over two billion people dependent on the Asian water towers (AWTs). However, the mechanisms by which large-scale westerlies-advected moisture is integrated into the AWTs' atmospheric water budget remain poorly understood due to observational gaps. Here, we combine three-dimensional observations of atmospheric water vapor stable isotopes with isotope-enabled modeling. We identify the conveyor mechanism that regulates the vertical moisture transport under calm conditions during the winter-spring period when the westerlies are dominant. Sharp vertical isotopic gradients show that large-scale westerlies-advected moisture is predominantly confined aloft, while local residual moisture persists near the surface. Our results show the interplay of the westerlies' subsidence at night with thermodynamically distinct local residual air, yielding thermal inversions and condensation that suppresses vertical mixing and decouples moisture between the free troposphere and the atmospheric boundary layer. This process constitutes a primary pathway for integrating westerlies-advected moisture into the local moisture budget without precipitation, sustaining near-surface moisture accumulation. Our results provide critical benchmarks for improving atmospheric models, refining climate projections of the intensifying water cycle over the AWTs, and advancing interpretations of isotopic records in regional climatic archives.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2529749123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841985","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

Force patterning drives quasistratification and graded tissue-scale spatial order in auditory epithelia. 力模式驱动听觉上皮的准分层和分级组织尺度空间秩序。

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: 2026-05-07 DOI: 10.1073/pnas.2519341123

Julian Weninger, Anubhav Prakash, Sukanya Raman, Raj K Ladher, Madan Rao, Karsten Kruse

{"title":"Force patterning drives quasistratification and graded tissue-scale spatial order in auditory epithelia.","authors":"Julian Weninger, Anubhav Prakash, Sukanya Raman, Raj K Ladher, Madan Rao, Karsten Kruse","doi":"10.1073/pnas.2519341123","DOIUrl":"https://doi.org/10.1073/pnas.2519341123","url":null,"abstract":"During development, coordinated cell behaviors drive epithelial morphogenesis toward precise three-dimensional architectures essential for physiological function. How such coordination arises in epithelia composed of multiple cell types remains unclear. Here, we study development of the avian auditory epithelium comprising sensory hair cells (HCs) and nonsensory supporting cells (SCs). Initially, HCs and SCs are arranged into mosaics by Notch-Delta signaling. As development proceeds, HCs partially extrude from the epithelium, establish a tenfold gradient in apical surface area across the tissue, and rearrange with SCs to form near-hexagonal order. Using experiments combined with a three-dimensional vertex model, we show that increased contractility at apical junctions between SCs relative to HC-SC junctions drives spatial organization both within the epithelial plane and along the apical-basal axis. Consistent with experimental findings, our simulation shows systematic differences in HC apical area expansion generate opposing coordinated movements of HCs and SCs, establishing gradients in HC apical surface area and density while maintaining uniform hexagonal order. Together, these results demonstrate that spatial patterning of junctional contractility coordinates cell behavior across both the plane and depth of a mixed epithelium, producing quasi-stratified architecture and tissue-scale three-dimensional order.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2519341123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842085","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

Genomic ancestry predicts rapid responses to drought across spatiotemporal scales. 基因组祖先预测了对干旱在时空尺度上的快速反应。

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.2531142123

Rozenn M Pineau, Natalia Bercovich, Loren H Rieseberg, Julia M Kreiner

{"title":"Genomic ancestry predicts rapid responses to drought across spatiotemporal scales.","authors":"Rozenn M Pineau, Natalia Bercovich, Loren H Rieseberg, Julia M Kreiner","doi":"10.1073/pnas.2531142123","DOIUrl":"https://doi.org/10.1073/pnas.2531142123","url":null,"abstract":"How genetic diversity responds to environmental change across spatiotemporal scales remains poorly understood despite its importance for species persistence in changing landscapes. Agricultural weeds offer ideal models for studying these adaptive dynamics as they rapidly evolve under both the intensive management practices designed to eliminate them and increasingly severe climate challenges such as drought. Here, we combine experimental and herbarium genomic approaches spanning within-generation to century-long timescales to understand how genome-wide variation responds to drought in Amaranthus tuberculatus. In this native species, a history of divergent selection between two ancestral lineages followed by secondary contact is thought to have facilitated its invasion into agriculture. A drought survival experiment on accessions from paired agricultural and natural populations across its range revealed substantial phenotypic variation differentiated by habitat, geography, and ancestry. Admixture mapping revealed 43 independent loci across nearly all chromosomes that confer protective effects under drought, demonstrate particularly rapid allele frequency changes, and exhibit duration-specific selection over the course of the imposed drought. Observation of allele frequencies across the past century reveals evidence for climate-dependent fluctuating selection governing the evolution of drought-associated loci. Selection favors drought alleles during hot/dry years and selects against them in cool/wet years-a pattern more evident in long-term trends than in shorter temporal intervals, suggestive of adaptive lag in rapidly changing environments. By combining short and long-term spatiotemporal data, we demonstrate that fluctuating selection has preserved the polygenic variation underlying population responses to drought, enabling ongoing adaptive responses to contemporary land use and climate change.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2531142123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842088","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

IL-33-induced ILC2 effector cytokine responses promote the expansion of red pulp macrophages. il -33诱导的ILC2效应细胞因子反应促进了红髓巨噬细胞的扩张。

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.2609716123

Irina R Iten, Nikolaos D Sidiropoulos, Lucas Onder, Aneta Jończy, Christoph S N Klose, Philippe Krebs, Katarzyna Mleczko-Sanecka, Burkhard Ludewig, Christoph Schneider, Manfred Kopf

引用次数: 0

Design of an ultrabright biosensor for dynamic imaging of kinase activity in cells. 用于细胞中激酶活性动态成像的超亮生物传感器的设计。

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.2523631123

Xiaoquan Li, Sophia K Tan, Chan-I Chung, A Katherine Hatstat, Qian Zhao, Jingyu Luo, William F DeGrado, Xiaokun Shu

引用次数: 0

Conserved regulatory core and lineage-specific diversification of light-temperature integration in plants. 植物光温整合的保守调控核心和谱系特异性多样化。

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.2601574123

Bruno Catarino, Fernando Rodríguez-Marín, Cristina Úrbez, Christina Arvanitidou, Eva Álvarez, Federico Valverde, José Manuel Franco-Zorrilla, Francisco Romero-Campero, Miguel A Blázquez

{"title":"Conserved regulatory core and lineage-specific diversification of light-temperature integration in plants.","authors":"Bruno Catarino, Fernando Rodríguez-Marín, Cristina Úrbez, Christina Arvanitidou, Eva Álvarez, Federico Valverde, José Manuel Franco-Zorrilla, Francisco Romero-Campero, Miguel A Blázquez","doi":"10.1073/pnas.2601574123","DOIUrl":"https://doi.org/10.1073/pnas.2601574123","url":null,"abstract":"Plants rely on environmental information such as light and temperature to control growth and development. Integrating these cues improves developmental precision, yet it remains unclear how this capacity is distributed across major plant lineages and how it diversified during evolution. We investigated light-temperature integration across major green plant lineages with particular attention to the origin and early diversification of land plants. Using comparative phenotypic and transcriptomic analyses, we examined responses to combined light and temperature signals in a chlorophyte alga, a streptophyte alga, a bryophyte, and a flowering plant. Streptophytes showed synergistic developmental and transcriptional responses, whereas the chlorophyte representative displayed predominantly additive behavior, indicating that the streptophyte lineage underwent a significant elaboration in environmental signal integration. Functional genetic analyses revealed that phytochromes and the transcription factors PHYTOCHROME INTERACTING FACTOR and ELONGATED HYPOCOTYL 5 are conserved regulators of this integration in land plants. Cistromic analyses further showed that diversification of downstream transcriptional responses is associated with lineage-specific redistribution of conserved cis-regulatory elements. Together, these results support the view that the capacity for light-temperature integration was established early during streptophyte evolution and diversified through lineage-specific changes in gene regulatory landscapes.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2601574123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842125","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 Andrews et al., Tropism of SARS-CoV-2 for human cortical astrocytes. 对Andrews等人关于SARS-CoV-2对人类皮质星形胶质细胞的趋向性的更正。

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.2613717123

引用次数: 0