Nature Communications最新文献_第10页

Structural insights into S-lignin O-demethylation via a rare class of heme peroxygenase enzymes

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57129-6

Alix C. Harlington, Tuhin Das, Keith E. Shearwin, Stephen G. Bell, Fiona Whelan

{"title":"Structural insights into S-lignin O-demethylation via a rare class of heme peroxygenase enzymes","authors":"Alix C. Harlington, Tuhin Das, Keith E. Shearwin, Stephen G. Bell, Fiona Whelan","doi":"10.1038/s41467-025-57129-6","DOIUrl":"https://doi.org/10.1038/s41467-025-57129-6","url":null,"abstract":"The O-demethylation of lignin aromatics is a rate-limiting step in their bioconversion to higher-value compounds. A recently discovered cytochrome P450, SyoA, demethylates the S-lignin aromatic syringol. In this work, we solve high-resolution X-ray crystal structures of substrate-free and substrate-bound SyoA and evaluate demethylation of para-substituted S-lignin aromatics via monooxygenase and peroxide shunt pathways. We find that SyoA demethylates S-lignin aromatics exclusively using the peroxide shunt pathway. The atomic-resolution structures reveal the position of non-canonical residues in the I-helix (Gln252, Glu253). Mutagenesis of this amide-acid pair in SyoA shows they are critical for catalytic activity. This work expands the enzymatic toolkit for improving the capacity to funnel lignin derived aromatics towards higher value compounds and defines the chemistry within the active site of the enzyme that enables peroxygenase activity. These insights provide a framework for engineering peroxygenase activity in other heme enzymes to generate easier to use biocatalysts.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"47 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462163","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

Olaparib combined to metronomic cyclophosphamide and metformin in women with recurrent advanced/metastatic endometrial cancer: the ENDOLA phase I/II trial

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-56914-7

Max Piffoux, Alexandra Leary, Philippe Follana, Cyril Abdeddaim, Florence Joly, Sylvie Bin, Maxime Bonjour, Anais Boulai, Celine Callens, Laurent Villeneuve, Marine Alexandre, Verane Schwiertz, Gilles Freyer, Manuel Rodrigues, Benoit You

{"title":"Olaparib combined to metronomic cyclophosphamide and metformin in women with recurrent advanced/metastatic endometrial cancer: the ENDOLA phase I/II trial","authors":"Max Piffoux, Alexandra Leary, Philippe Follana, Cyril Abdeddaim, Florence Joly, Sylvie Bin, Maxime Bonjour, Anais Boulai, Celine Callens, Laurent Villeneuve, Marine Alexandre, Verane Schwiertz, Gilles Freyer, Manuel Rodrigues, Benoit You","doi":"10.1038/s41467-025-56914-7","DOIUrl":"https://doi.org/10.1038/s41467-025-56914-7","url":null,"abstract":"Endometrial cancers are characterized by frequent alterations in the PI3K-AKT-mTor, IGF1 and DNA repair signaling pathways. Concomitant inhibition of these pathways was warranted. ENDOLA phase I/II trial (NCT02755844) was designed to assess the safety/efficacy of the triplet combination of the PARP inhibitor olaparib, metronomic cyclophosphamide (50 mg daily), and PI3K-AKT-mTor inhibitor metformin (1500 mg daily) in women with recurrent endometrial carcinomas. Olaparib dose-escalation (100-300 mg twice-a-day (bid)) was used to determine the recommended-phase II-trial-dose (RP2D, primary endpoint), followed by an expansion cohort to determine the non-progression rate at 10 weeks (NPR-10w, secondary endpoint). 31 patients were treated. Olaparib RP2D was defined as 300 mg bid. The tolerability was acceptable, and grade 3-4 adverse events (51% patients) were mainly hematological. The NPR-10w was 61.5%, and the median progression-free survival (mPFS) was 5.2 months. In a post-hoc analysis, when explored by molecular subtypes/alterations, longer PFS were observed in patients with tumors characterized by a non-specific-molecular-profile (NSMP, n = 4; mPFS, 9.1 months), and by both TP53 altered & high number of large genomic alterations (LGA ≥ 8)(n = 10, mPFS, 8.6 months)). The analyses about kinetics of circulating biomarkers and pharmacodynamic effects are not reported here. In total, the benefit/toxicity ratio of the all-oral olaparib/cyclophosphamide/metformin regimen was favorable in heavily pretreated patients with recurrent endometrial cancer.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"12 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462190","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

Molecular basis of foreign DNA recognition by BREX anti-phage immunity system

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57006-2

Alena Drobiazko, Myfanwy C. Adams, Mikhail Skutel, Kristina Potekhina, Oksana Kotovskaya, Anna Trofimova, Mikhail Matlashov, Daria Yatselenko, Karen L. Maxwell, Tim R. Blower, Konstantin Severinov, Dmitry Ghilarov, Artem Isaev

{"title":"Molecular basis of foreign DNA recognition by BREX anti-phage immunity system","authors":"Alena Drobiazko, Myfanwy C. Adams, Mikhail Skutel, Kristina Potekhina, Oksana Kotovskaya, Anna Trofimova, Mikhail Matlashov, Daria Yatselenko, Karen L. Maxwell, Tim R. Blower, Konstantin Severinov, Dmitry Ghilarov, Artem Isaev","doi":"10.1038/s41467-025-57006-2","DOIUrl":"https://doi.org/10.1038/s41467-025-57006-2","url":null,"abstract":"Anti-phage systems of the BREX (BacteRiophage EXclusion) superfamily rely on site-specific epigenetic DNA methylation to discriminate between the host and invading DNA. We demonstrate that in Type I BREX systems, defense and methylation require BREX site DNA binding by the BrxX (PglX) methyltransferase employing S-adenosyl methionine as a cofactor. We determined 2.2-Å cryoEM structure of Escherichia coli BrxX bound to target dsDNA revealing molecular details of BREX DNA recognition. Structure-guided engineering of BrxX expands its DNA specificity and dramatically enhances phage defense. We show that BrxX alone does not methylate DNA, and BREX activity requires an assembly of a supramolecular BrxBCXZ immune complex. Finally, we present a cryoEM structure of BrxX bound to a phage-encoded inhibitor Ocr that sequesters BrxX in an inactive dimeric form. We propose that BrxX-mediated foreign DNA sensing is a necessary first step in activation of BREX defense.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"127 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462195","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

A neural implementation model of feedback-based motor learning

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-024-54738-5

Barbara Feulner, Matthew G. Perich, Lee E. Miller, Claudia Clopath, Juan A. Gallego

{"title":"A neural implementation model of feedback-based motor learning","authors":"Barbara Feulner, Matthew G. Perich, Lee E. Miller, Claudia Clopath, Juan A. Gallego","doi":"10.1038/s41467-024-54738-5","DOIUrl":"https://doi.org/10.1038/s41467-024-54738-5","url":null,"abstract":"Animals use feedback to rapidly correct ongoing movements in the presence of a perturbation. Repeated exposure to a predictable perturbation leads to behavioural adaptation that compensates for its effects. Here, we tested the hypothesis that all the processes necessary for motor adaptation may emerge as properties of a controller that adaptively updates its policy. We trained a recurrent neural network to control its own output through an error-based feedback signal, which allowed it to rapidly counteract external perturbations. Implementing a biologically plausible plasticity rule based on this same feedback signal enabled the network to learn to compensate for persistent perturbations through a trial-by-trial process. The network activity changes during learning matched those from populations of neurons from monkey primary motor cortex — known to mediate both movement correction and motor adaptation — during the same task. Furthermore, our model natively reproduced several key aspects of behavioural studies in humans and monkeys. Thus, key features of trial-by-trial motor adaptation can arise from the internal properties of a recurrent neural circuit that adaptively controls its output based on ongoing feedback.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"71 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462794","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

Emergent patterns of patchiness differ between physical and planktonic properties in the ocean

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-56794-x

Patrick Clifton Gray, Emmanuel Boss, Guillaume Bourdin, Yoav Lehahn

{"title":"Emergent patterns of patchiness differ between physical and planktonic properties in the ocean","authors":"Patrick Clifton Gray, Emmanuel Boss, Guillaume Bourdin, Yoav Lehahn","doi":"10.1038/s41467-025-56794-x","DOIUrl":"https://doi.org/10.1038/s41467-025-56794-x","url":null,"abstract":"While a rich history of patchiness research has explored spatial structure in the ocean, there is no consensus over the controls on biological patchiness and how physical-ecological-biogeochemical processes and patchiness relate. The prevailing thought is that physics structures biology, but this has not been tested at basin scale with consistent in situ measurements. Here we use the slope of the relationship between variance vs spatial scale to quantify patchiness and ~650,000 nearly continuous (dx ~ 200 m) measurements - representing the Atlantic, Pacific, and Southern Oceans - and find that patchiness of biological parameters and physical parameters are uncorrelated. We show variance slope is an emergent property with unique patterns in biogeochemical properties distinct from physical tracers, yet correlated with other biological tracers. These results provide context for decades of observations with different interpretations, suggest the use of spatial tests of biogeochemical model parameterizations, and open the way for studies into processes regulating the observed patterns.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"26 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462903","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

Activity-based sensing reveals elevated labile copper promotes liver aging via hepatic ALDH1A1 depletion

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-56585-4

Zhenxiang Zhao, Melissa Y. Lucero, Shengzhang Su, Eric J. Chaney, Jiajie Jessica Xu, Michael Myszka, Jefferson Chan

引用次数: 0

Predictable recovery rates in near-surface materials after earthquake damage

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57151-8

Luc Illien, Jens M. Turowski, Christoph Sens-Schönfelder, Clément Berenfeld, Niels Hovius

引用次数: 0

Crystal symmetry modification enables high-ranged in-plane thermoelectric performance in n-type SnSe crystals

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57125-w

Haonan Shi, Yi Wen, Shulin Bai, Cheng Chang, Lizhong Su, Tian Gao, Shibo Liu, Dongrui Liu, Bingchao Qin, Yongxin Qin, Huiqiang Liang, Xin Qian, Zhenghao Hou, Xiang Gao, Tianhang Zhou, Qing Tan, Li-Dong Zhao

{"title":"Crystal symmetry modification enables high-ranged in-plane thermoelectric performance in n-type SnSe crystals","authors":"Haonan Shi, Yi Wen, Shulin Bai, Cheng Chang, Lizhong Su, Tian Gao, Shibo Liu, Dongrui Liu, Bingchao Qin, Yongxin Qin, Huiqiang Liang, Xin Qian, Zhenghao Hou, Xiang Gao, Tianhang Zhou, Qing Tan, Li-Dong Zhao","doi":"10.1038/s41467-025-57125-w","DOIUrl":"https://doi.org/10.1038/s41467-025-57125-w","url":null,"abstract":"SnSe crystal has witnessed significant advancements as a promising thermoelectric material over the past decade. Its in-plane direction shows robust mechanical strength for practical thermoelectric applications. Herein, we optimize the in-plane thermoelectric performance of n-type SnSe by crystal symmetry modification. In particular, we find that Te and Mo alloying continuously enhances the crystal symmetry, thereby increasing the carrier mobility to ~ 422 cm2 V−1 s−1. Simultaneously, the conduction bands converge with the symmetry modification, further improving the electrical transport. Additionally, the lattice thermal conductivity is limited to ~ 1.1 W m−1 K−1 due to the softness of both acoustic and optical branches. Consequently, we achieve a power factor of ~ 28 μW cm−1 K−2 and ZT of ~ 0.6 in n-type SnSe at 300 K. The average ZT reaches ~ 0.89 at 300−723 K. The single-leg device based on the obtained n-type SnSe shows a remarkable efficiency of ~ 5.3% under the ΔT of ~ 300 K, which is the highest reported in n-type SnSe. This work demonstrates the substantial potential of SnSe for practical applications of power generation and waste heat recovery.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452173","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

Oscillations in fluid pressure caused by silica precipitation in a fracture

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57199-6

Atsushi Okamoto, Edward Vinis

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Anthropogenic nutrient inputs cause excessive algal growth for nearly half the world’s population

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-02-20 DOI: 10.1038/s41467-025-57054-8

Richard W. McDowell, Dongwen Luo, Peter Pletnyakov, Martin Upsdell, Walter K. Dodds

{"title":"Anthropogenic nutrient inputs cause excessive algal growth for nearly half the world’s population","authors":"Richard W. McDowell, Dongwen Luo, Peter Pletnyakov, Martin Upsdell, Walter K. Dodds","doi":"10.1038/s41467-025-57054-8","DOIUrl":"https://doi.org/10.1038/s41467-025-57054-8","url":null,"abstract":"Reference conditions pertain to conditions without anthropogenic influence and serve to gauge the degree of river pollution and identify the best attainable water quality. Here we show estimates of the global human footprint of nitrogen and phosphorus concentrations and potential for related nuisance or harmful algal growth in rivers. We use statistical models based on 1.2 million stream nutrient measurements (from 2005 to 2013) and find global human enrichment of river total nitrogen and total phosphorus is 35% and 14% respectively. The greatest enrichment is in Europe (86 and 30% respectively) and the least in Oceania (9 and 2% respectively). The levels of enrichment translated into an almost doubling of the catchment areas with rivers predicted to have anthropogenically elevated levels of potentially harmful or nuisance algae, affecting ~40% of the world’s population. Focusing management on the difference between current and reference conditions can help protect good water quality while avoiding unrealistic goals where nitrogen and phosphorus are naturally high.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"25 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462118","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