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

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Coordinated stomatal, mesophyll, and biochemical functions in photosynthetic responses to heat and dryness. 光合作用对热和干燥的响应中气孔、叶肉和生化功能的协调。
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.2605032123
Xingyu Hu, Suan Chin Wong, Graham D Farquhar
{"title":"Coordinated stomatal, mesophyll, and biochemical functions in photosynthetic responses to heat and dryness.","authors":"Xingyu Hu, Suan Chin Wong, Graham D Farquhar","doi":"10.1073/pnas.2605032123","DOIUrl":"https://doi.org/10.1073/pnas.2605032123","url":null,"abstract":"<p><p>The intrinsic link between temperature and leaf-to-air vapor pressure difference (Δ<i>e</i>) complicates isolation of their individual effects on photosynthesis. Consequently, how CO<sub>2</sub> diffusion changes under heat and high evaporative demand, particularly through mesophyll conductance (<i>g</i><sub>m</sub>) responses, remains poorly understood. The conditions under which biochemical colimitation occurs, meaning Rubisco carboxylation and RuBP regeneration capacities match, are also unclear. To advance understanding of plant responses to climate change, we separated temperature and Δ<i>e</i> effects by holding Δ<i>e</i> at 1 and 2 kPa while varying leaf temperature (<i>T</i><sub>leaf</sub>) from 20 to 40 °C across five CO<sub>2</sub> levels (150 to 800 μmol mol<sup>-1</sup>) in cotton, sunflower, and dwarf bean. Gas exchange and chlorophyll fluorescence measurements showed that <i>g</i><sub>m</sub> responses partly counteract increases in stomatal conductance to CO<sub>2</sub> (<i>g</i><sub>sc</sub>) at high temperatures and declines in <i>g</i><sub>sc</sub> at elevated Δ<i>e</i>. Coordination between <i>g</i><sub>sc</sub> and <i>g</i><sub>m</sub> buffers effects of heat and dryness on CO<sub>2</sub> diffusion and stabilizes chloroplast-to-ambient CO<sub>2</sub> ratio (<i>C</i><sub>c</sub>/<i>C</i><sub>a</sub>) across measured <i>T</i><sub>leaf</sub> and Δ<i>e</i> ranges. <i>C</i><sub>c</sub>/<i>C</i><sub>a</sub> is more conservative with increasing <i>T</i><sub>leaf</sub> at <i>C</i><sub>a</sub> ≤ 400 μmol mol<sup>-1</sup> than at elevated <i>C</i><sub>a</sub>. Across tested <i>T</i><sub>leaf</sub> and Δ<i>e</i> conditions, the transition from Rubisco carboxylation to RuBP regeneration limitation remains near <i>C</i><sub>a</sub> of 400 μmol mol<sup>-1</sup>, indicating that biochemical colimitation occurs near current atmospheric CO<sub>2</sub> levels. Our findings reveal that plants alleviate diffusional limitations under heat and dryness through coordinated responses of <i>g</i><sub>sc</sub> and <i>g</i><sub>m</sub>, and maintain biochemical colimitation over broad <i>T</i><sub>leaf</sub> and Δ<i>e</i> conditions to efficiently utilize Rubisco carboxylation and RuBP regeneration capacities at near-atmospheric CO<sub>2</sub> levels.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2605032123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842094","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
Convergent antibody solutions revealed by focused humanized repertoires. 集中人源化库揭示的收敛抗体解决方案。
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.2606253123
Maria Maddalena Perra, Jayanta Chaudhuri
{"title":"Convergent antibody solutions revealed by focused humanized repertoires.","authors":"Maria Maddalena Perra, Jayanta Chaudhuri","doi":"10.1073/pnas.2606253123","DOIUrl":"https://doi.org/10.1073/pnas.2606253123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2606253123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842108","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
Reconstructing ancient genomes from gene counts: A robust likelihood framework with sampling bias correction. 从基因计数重建古代基因组:具有抽样偏差校正的鲁棒似然框架。
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.2537812123
Miklós Csűrös
{"title":"Reconstructing ancient genomes from gene counts: A robust likelihood framework with sampling bias correction.","authors":"Miklós Csűrös","doi":"10.1073/pnas.2537812123","DOIUrl":"https://doi.org/10.1073/pnas.2537812123","url":null,"abstract":"<p><p>Deducing the makeup of ancient genomes is a fundamental challenge in evolutionary biology. While vast genomic datasets exist that span the entire tree of life, current methods for ancestral reconstructions struggle to resolve the inherent ambiguities of gene-sequence evolution at scale. Here, we present a numerically robust computational framework that overcomes the topological uncertainty of gene trees. Instead of tracking every single event, our phylogenetic gain-loss-duplication (GLD) model is based on birth-death processes over gene copies along the species tree. We show that the likelihood and its gradient can be computed efficiently under an adjustable observation bias of minimum gene family size. The framework facilitates unconstrained numerical likelihood maximization and ancestral inference by posterior probabilities. We apply this framework to kingdom-level reconstructions over a 269-genome archaeal dataset and demonstrate that GLD recovers ancestral states with high accuracy. We compare GLD inference with phylogenetic reconciliation from gene sequences (ALE method) and show that implausibly frequent horizontal gene transfer inferred by ALE are often statistical artifacts of collapsing phylogenetic signals in large alignments. In contrast, GLD inferences reveal how two layers of opposing evolutionary mechanics shape microbial genomes: a high-frequency tension between genome streamlining and the pervasive influx of transient genes, complemented by an adaptive counterbalance of recurrent, modular losses, and punctuated massive gains. The GLD framework provides a statistically sound foundation for hypothesizing about gene content evolution across the diversity of entire kingdoms.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 19","pages":"e2537812123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856658","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
Spontaneous Coulomb fissions of drops on lubricated surfaces. 润滑表面上液滴的自发库仑裂变。
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 : 2026-05-05 Epub Date: 2026-04-30 DOI: 10.1073/pnas.2538161123
Marcus Lin, Peng Zhang, Aaron D Ratschow, Oscar Li, Sankara Arunachalam, Dan Daniel
{"title":"Spontaneous Coulomb fissions of drops on lubricated surfaces.","authors":"Marcus Lin, Peng Zhang, Aaron D Ratschow, Oscar Li, Sankara Arunachalam, Dan Daniel","doi":"10.1073/pnas.2538161123","DOIUrl":"10.1073/pnas.2538161123","url":null,"abstract":"<p><p>Charged water drops are more widespread than commonly acknowledged. For example, raindrops typically carry charges of order [Formula: see text] pC, while routine pipetting in the laboratory produces drops with [Formula: see text] pC. Here, we show that such modest charging can spontaneously generate periodic Coulomb fissions for evaporating water drops on lubricated surfaces, with more than 60 successive cycles observed over 30 min. Interestingly, the underlying instability can be quantitatively predicted by two fissility thresholds: one marking the onset of drop elongation and another triggering fission. Each fission culminates with a fine liquid jet that disintegrates into 40 to 50 microdroplets, expelled within microseconds. The phenomenon spans an extraordinary range of length scales (from millimeters to microns) and time scales (hours to microseconds), with broad potential applications ranging from nanoscale fabrication to electrospray ionization.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2538161123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neural correlates of perceptual decision-making in the primary somatosensory cortex. 初级体感皮层中知觉决策的神经关联。
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 : 2026-05-05 Epub Date: 2026-04-29 DOI: 10.1073/pnas.2514107123
Alex G Armstrong, Yurii Vlasov
{"title":"Neural correlates of perceptual decision-making in the primary somatosensory cortex.","authors":"Alex G Armstrong, Yurii Vlasov","doi":"10.1073/pnas.2514107123","DOIUrl":"10.1073/pnas.2514107123","url":null,"abstract":"<p><p>The brain is thought to produce decisions by gradual accumulation of sensory evidence through a hierarchically organized feedforward cascade of neuronal activities that transforms early stimulus representations in the primary somatosensory cortex (S1) to a perceptual decision processed in premotor areas. Recently, this prevailing view has been challenged by observation of choice-correlated neural activity as early in the hierarchy as S1. Here, to reconcile these seemingly controversial observations, we employ ethological whisker-guided navigation of mice in a tactile virtual reality paradigm combined with dense electrophysiological recordings in whisker-related wS1. Leaving only a pair of C2 whiskers for mice to navigate with, we effectively designed an information bottleneck for sensory input to decision-making. We show that neural activity during sensory evidence accumulation exhibits dramatic collapse of the high-dimensional spiking activity to just a single latent variable followed by a slower and almost synchronous ramping up across the whole cortical column. We show that this variable is consistent with models of gradual accumulation of noisy sensory evidence to a decision bound. These observations indicate that S1 may directly participate in a categorical coding of all-or-none decision variable via cortico-cortical feedback loops through which sensory information reverberates to be transformed into perception and action.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2514107123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted knockout of a host peroxisomal peptidase confers field resistance to maize lethal necrosis. 靶向敲除宿主过氧化物酶体肽酶赋予玉米致命坏死的田间抗性。
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 : 2026-05-05 Epub Date: 2026-04-30 DOI: 10.1073/pnas.2535202123
Mark Jung, Zhengyu Wen, Sabrina Humbert, Fengzhong Lu, Alyssa DeLeon, Lisa Marshall, Craig Hastings, Heather Cartwright, Katherine Thilges, Ning Wang, Kassandra Breckenridge, Emily Wu, Larisa Ryan, Kevin Fengler, Kevin Simcox, Shawn Thatcher, Victor Llaca, Grace Woollums, Jeffry Sander, Deping Xu, Mary Beatty, Kent Brink, Maria Fedorova, Mark Jones, Erik Ohlson, L M Suresh, Yoseph Beyene, Michael Olsen, Veronica Ogugo, Amos Alakonya, Ann Murithi, Stephen Mugo, James Karanja, Prasanna Boddupalli, Kevin Pixley, Marc Albertsen, Todd Jones, Robert Meeley, Neal Gutterson, Barbara Mazur, Kanwarpal S Dhugga
{"title":"Targeted knockout of a host peroxisomal peptidase confers field resistance to maize lethal necrosis.","authors":"Mark Jung, Zhengyu Wen, Sabrina Humbert, Fengzhong Lu, Alyssa DeLeon, Lisa Marshall, Craig Hastings, Heather Cartwright, Katherine Thilges, Ning Wang, Kassandra Breckenridge, Emily Wu, Larisa Ryan, Kevin Fengler, Kevin Simcox, Shawn Thatcher, Victor Llaca, Grace Woollums, Jeffry Sander, Deping Xu, Mary Beatty, Kent Brink, Maria Fedorova, Mark Jones, Erik Ohlson, L M Suresh, Yoseph Beyene, Michael Olsen, Veronica Ogugo, Amos Alakonya, Ann Murithi, Stephen Mugo, James Karanja, Prasanna Boddupalli, Kevin Pixley, Marc Albertsen, Todd Jones, Robert Meeley, Neal Gutterson, Barbara Mazur, Kanwarpal S Dhugga","doi":"10.1073/pnas.2535202123","DOIUrl":"10.1073/pnas.2535202123","url":null,"abstract":"<p><p>Maize lethal necrosis (MLN) is a severe disease caused by the combined infection of maize chlorotic mottle virus (MCMV) and a potyvirus, most often sugarcane mosaic virus (SCMV). This disease seriously threatens food security across sub-Saharan Africa (SSA). We investigated a major-effect quantitative trait locus for resistance on chromosome 6, named the <i>maize lethal necrosis susceptibility locus 1</i> (<i>qMLNS1</i>), derived from the Thai line KS23-6. Fine mapping and CRISPR-Cas9 editing of the candidate genes within the narrowed 105 kb interval revealed a peroxisomal <i>peptidase</i> as the underlying cause of susceptibility. Confocal microscopy confirmed the localization of the MLNS1 protein within peroxisomes. Targeted knockout of the <i>Mlns1</i> gene in the susceptible elite line CML536 from SSA conferred resistance comparable to KS23-6 in field trials conducted in Naivasha, Kenya. This knockout specifically blocked MCMV accumulation without affecting SCMV. The edited lines showed no yield penalty or agronomic defects under disease-free conditions. Our findings uncover a mechanistic link between a peroxisomal enzyme and viral susceptibility. They also establish a rapid, scalable gene editing strategy for incorporating MLN resistance into elite germplasm, offering a model for combating similar viral diseases in staple crops globally.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2535202123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Ad5-vectored platform generating self-assembling VLPs elicits potent mucosal immunity against influenza A virus and SARS-CoV-2. ad5载体平台生成自组装VLPs可诱导对甲型流感病毒和SARS-CoV-2的有效粘膜免疫。
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 : 2026-05-05 Epub Date: 2026-04-29 DOI: 10.1073/pnas.2519857123
Yuan Zhang, Caiqian Wang, Yanhong Zheng, Feiyu Chen, Yaya Feng, Lingying Fang, Zongmei Wang, Ming Zhou, Zhen F Fu, Ling Zhao
{"title":"An Ad5-vectored platform generating self-assembling VLPs elicits potent mucosal immunity against influenza A virus and SARS-CoV-2.","authors":"Yuan Zhang, Caiqian Wang, Yanhong Zheng, Feiyu Chen, Yaya Feng, Lingying Fang, Zongmei Wang, Ming Zhou, Zhen F Fu, Ling Zhao","doi":"10.1073/pnas.2519857123","DOIUrl":"10.1073/pnas.2519857123","url":null,"abstract":"<p><p>Integrating complementary vaccine modalities is essential for combating emerging pathogens. Although the recent mRNA-VLP hybrids enable spontaneous virus-like particles (VLPs) self-assembly, thereby enhancing immunogenicity, they fail to elicit robust pulmonary mucosal immunity against respiratory pathogens. Here, we developed Ad5-Envp-VLP, a chimeric adenoviral platform enabling spontaneous in vivo assembly of envelope protein-displaying VLPs using advanced technology that recruits ESCRT (endosomal sorting complex required for transport) via the EABR (ESCRT and ALIX-binding region). Compared with the intramuscular route, intranasal administration of a single-dose Ad5-HA-VLP confers long-lasting protection against both homologous and heterologous influenza A strains. Integrated single-cell RNA sequencing and flow cytometry analyses reveal that intranasal delivery of Ad5-HA-VLP recruits and functionally reprograms lung innate immune cells, promoting antigen presentation and driving robust mucosal secretory IgA (sIgA) secretion and cytotoxic T lymphocyte responses. Similarly, intranasal delivery of Ad5-S-VLP elicits potent cross-neutralizing antibody titers against SARS-CoV-2 variants. Importantly, intranasal immunization with Ad5-S-HA-VLP (coexpressing S- and HA-VLPs) generates dual influenza and SARS-CoV-2 neutralizing antibodies, alongside pulmonary antigen-specific sIgA, confirming Ad5-Envp-VLP as a promising \"single-dose multiplexed mucosal vaccine\" against respiratory pathogens. Further extended applications show that Ad5-RVDG-VLP also induces broad protective immunity in mouse, dog, and cat models, verifying its feasibility as an efficient rabies vaccine. Collectively, the Ad5-Envp-VLP platform represents a universal and versatile mucosal vaccine strategy, leveraging pulmonary delivery of vectors that encode in vivo-assembling VLPs to concurrently elicit robust mucosal and systemic immunity against a wide spectrum of pathogens.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2519857123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exercise works-if mitochondria do. 运动起作用——如果线粒体起作用的话。
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 : 2026-05-05 Epub Date: 2026-04-27 DOI: 10.1073/pnas.2609146123
Jianing Xu
{"title":"Exercise works-if mitochondria do.","authors":"Jianing Xu","doi":"10.1073/pnas.2609146123","DOIUrl":"10.1073/pnas.2609146123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2609146123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resource availability structures microbial competition through genomic niche partitioning. 资源可用性通过基因组生态位分配来构建微生物竞争。
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 : 2026-05-05 Epub Date: 2026-04-29 DOI: 10.1073/pnas.2526391123
Célio Dias Santos-Júnior, Maria Camila Escobar, Paula Huber, Juan Pablo Niño-Garcia, Gladys Inés Cardona, Raul Costa-Pereira, Hugo Sarmento
{"title":"Resource availability structures microbial competition through genomic niche partitioning.","authors":"Célio Dias Santos-Júnior, Maria Camila Escobar, Paula Huber, Juan Pablo Niño-Garcia, Gladys Inés Cardona, Raul Costa-Pereira, Hugo Sarmento","doi":"10.1073/pnas.2526391123","DOIUrl":"10.1073/pnas.2526391123","url":null,"abstract":"<p><p>Microbial competition for scarce resources shapes biodiversity patterns and ecosystem function across global biomes, yet quantifying this process from genomic data has remained elusive. Here, we introduce CaCo, a scalable metric that transforms metagenomic carbohydrate-active enzyme profiles into precise measures of niche overlap and competition potential (Resource Partitioning Score, RPS). Analyzing 14,691 high-quality metagenome-assembled genomes spanning Ocean, freshwater, soil, and human gut microbiomes, we reveal a striking macroecological pattern: Niche overlap increases from partitioned specialists in oligotrophic oceans to overlapping generalists in carbon-rich environments, including the human gut. This gradient aligns with classic niche theory, as phylogenetic signals indicate that closely related taxa may compete most intensely. Multitiered validation, spanning BIOLOG phenotypes, synthetic cocultures, and interaction gradients, confirms CaCo's predictive power and captures competitive exclusion. CaCo bridges genomic potential and ecological reality, providing niche-breadth metrics and enabling testable predictions of how resource availability shapes microbial competition and community structure.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2526391123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural rewiring of IL-7R dimerization by an oncogenic transmembrane mutation can be reversed by rational design. 通过合理的设计,可以逆转由致癌跨膜突变引起的IL-7R二聚化的结构重组。
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 : 2026-05-05 Epub Date: 2026-04-28 DOI: 10.1073/pnas.2601748123
Qian Wang, Min Chen, Asma Lasram, Saana Vihuri, Angela Z Chou, Weixin Bian, Zhiming Dai, Outi Haapanen, Giray Enkavi, Christoph Pollmann, Ilpo Vattulainen, Tiantian Cai, Jacob Piehler, James J Chou
{"title":"Structural rewiring of IL-7R dimerization by an oncogenic transmembrane mutation can be reversed by rational design.","authors":"Qian Wang, Min Chen, Asma Lasram, Saana Vihuri, Angela Z Chou, Weixin Bian, Zhiming Dai, Outi Haapanen, Giray Enkavi, Christoph Pollmann, Ilpo Vattulainen, Tiantian Cai, Jacob Piehler, James J Chou","doi":"10.1073/pnas.2601748123","DOIUrl":"10.1073/pnas.2601748123","url":null,"abstract":"<p><p>Mutations within the transmembrane domains (TMDs) of single-pass transmembrane receptors often cause aberrant, ligand-independent receptor signaling associated with diverse malignancies, but their mechanism of action remains largely unknown. These TMD mutations are generally not targetable as they are buried in the membrane. Here, we determined the mechanism of a gain-of-function (GOF) TMD mutation of interleukin-7 receptor (IL-7R) associated with T cell acute lymphoblastic leukemia and addressed the possibility of directly targeting the TMD mutation by using rationally designed transmembrane helices to restore order to uncontrolled signaling. We find that the GOF mutation of IL-7R severely shifts the TMD homodimerization interface, causing the receptor to homodimerize in a geometry that activates downstream signaling independent of ligand. Designed transmembrane helices that interfere with the new interface, delivered with mRNA technology, selectively block ligand-independent but not ligand-dependent signaling. Our study provides a conceptual framework for understanding and repairing disease-causing TMD mutations of single-pass cytokine receptors.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 18","pages":"e2601748123"},"PeriodicalIF":9.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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