Mariarosaria De Rosa, Ryan P. Barnes, Ariana C. Detwiler, Prasanth R. Nyalapatla, Peter Wipf, Patricia L. Opresko
{"title":"OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts","authors":"Mariarosaria De Rosa, Ryan P. Barnes, Ariana C. Detwiler, Prasanth R. Nyalapatla, Peter Wipf, Patricia L. Opresko","doi":"10.1038/s41467-024-55638-4","DOIUrl":"https://doi.org/10.1038/s41467-024-55638-4","url":null,"abstract":"<p>Telomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts. Glycosylase deficiency also suppresses 8oxoG-induced telomere fragility and dysfunction, indicating that downstream single-stranded break (SSB) repair intermediates impair telomere replication. Preventing BER initiation suppresses PARylation and confers resistance to the synergistic effects of PARP inhibitors on 8oxoG-induced senescence. However, OGG1 activity is essential for preserving cell growth after chronic telomeric 8oxoG formation, whereas MUTYH promotes senescence to prevent chromosomal instability from unrepaired damage. Our studies reveal that inefficient completion of 8oxoG BER at telomeres triggers cellular senescence via SSB intermediates which disrupt telomere function.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"52 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990630","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}
Yina Wu, Jinwon Park, Quoc-Viet Le, Junho Byun, Jaehyun Choi, Enzhen Xu, Jaiwoo Lee, Yu-Kyoung Oh
{"title":"Publisher Correction: NET formation-mediated in situ protein delivery to the inflamed central nervous system","authors":"Yina Wu, Jinwon Park, Quoc-Viet Le, Junho Byun, Jaehyun Choi, Enzhen Xu, Jaiwoo Lee, Yu-Kyoung Oh","doi":"10.1038/s41467-025-56288-w","DOIUrl":"https://doi.org/10.1038/s41467-025-56288-w","url":null,"abstract":"<p>Correction to: <i>Nature Communications</i> https://doi.org/10.1038/s41467-024-54817-7, published online 30 December 2024</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990968","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}
Francesco Hoch, Eugenio Caruccio, Giovanni Rodari, Tommaso Francalanci, Alessia Suprano, Taira Giordani, Gonzalo Carvacho, Nicolò Spagnolo, Seid Koudia, Massimiliano Proietti, Carlo Liorni, Filippo Cerocchi, Riccardo Albiero, Niki Di Giano, Marco Gardina, Francesco Ceccarelli, Giacomo Corrielli, Ulysse Chabaud, Roberto Osellame, Massimiliano Dispenza, Fabio Sciarrino
{"title":"Quantum machine learning with Adaptive Boson Sampling via post-selection","authors":"Francesco Hoch, Eugenio Caruccio, Giovanni Rodari, Tommaso Francalanci, Alessia Suprano, Taira Giordani, Gonzalo Carvacho, Nicolò Spagnolo, Seid Koudia, Massimiliano Proietti, Carlo Liorni, Filippo Cerocchi, Riccardo Albiero, Niki Di Giano, Marco Gardina, Francesco Ceccarelli, Giacomo Corrielli, Ulysse Chabaud, Roberto Osellame, Massimiliano Dispenza, Fabio Sciarrino","doi":"10.1038/s41467-025-55877-z","DOIUrl":"https://doi.org/10.1038/s41467-025-55877-z","url":null,"abstract":"<p>The implementation of large-scale universal quantum computation represents a challenging and ambitious task on the road to quantum processing of information. In recent years, an intermediate approach has been pursued to demonstrate quantum computational advantage via non-universal computational models. A relevant example for photonic platforms has been provided by the Boson Sampling paradigm and its variants, which are known to be computationally hard while requiring at the same time only the manipulation of the generated photonic resources via linear optics and detection. Beside quantum computational advantage demonstrations, a promising direction towards possibly useful applications can be found in the field of quantum machine learning, considering the currently almost unexplored intermediate scenario between non-adaptive linear optics and universal photonic quantum computation. Here, we report the experimental implementation of quantum machine learning protocols by adding adaptivity via post-selection to a Boson Sampling platform based on universal programmable photonic circuits fabricated via femtosecond laser writing. Our experimental results demonstrate that Adaptive Boson Sampling is a viable route towards dimension-enhanced quantum machine learning with linear optical devices.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"6 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992578","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":"Anomalous entropy-driven kinetics of dislocation nucleation","authors":"Soumendu Bagchi, Danny Perez","doi":"10.1038/s41467-025-56272-4","DOIUrl":"https://doi.org/10.1038/s41467-025-56272-4","url":null,"abstract":"<p>The kinetics of dislocation reactions, such as dislocation multiplication, controls the plastic deformation in crystals beyond their elastic limit, therefore critical mechanisms in a number of applications in materials science. We present a series of large-scale molecular dynamics simulations that shows that one such type of reactions, the nucleation of dislocation at free surfaces, exhibit unconventional kinetics, including unexpectedly large nucleation rates under compression, very strong entropic stabilization under tension, as well as strong non-Arrhenius behavior. These unusual kinetics are quantitatively rationalized using a variational transition state theory approach coupled with an efficient numerical scheme for the estimation of vibrational entropy changes. These results highlight the need for a variational treatment of the kinetics to quantitatively capture dislocation reaction kinetics, especially at low-to-moderate strains where large deformations are required to activate reactions. These observations suggest possible explanations to previously observed unconventional deformation kinetics in both molecular dynamics simulations and experiments.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"18 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992423","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}
Yi Wang, Shuo Wang, Yunfan Fu, Jiaqi Sang, Pengfei Wei, Rongtan Li, Dunfeng Gao, Guoxiong Wang, Xinhe Bao
{"title":"Ammonia electrosynthesis from nitrate using a stable amorphous/crystalline dual-phase Cu catalyst","authors":"Yi Wang, Shuo Wang, Yunfan Fu, Jiaqi Sang, Pengfei Wei, Rongtan Li, Dunfeng Gao, Guoxiong Wang, Xinhe Bao","doi":"10.1038/s41467-025-55889-9","DOIUrl":"https://doi.org/10.1038/s41467-025-55889-9","url":null,"abstract":"<p>Renewable energy-driven electrocatalytic nitrate reduction reaction presents a low-carbon and sustainable route for ammonia synthesis under mild conditions. Yet, the practical application of this process is currently hindered by unsatisfactory electrocatalytic activity and long-term stability. Herein we achieve high-rate ammonia electrosynthesis using a stable amorphous/crystalline dual-phase Cu catalyst. The ammonia partial current density and formation rate reach 3.33 ± 0.005 A cm<sup>−2</sup> and 15.5 ± 0.02 mmol h<sup>−1</sup> cm<sup>−2</sup> at a low cell voltage of 2.6 ± 0.01 V, respectively. Remarkably, the dual-phase Cu catalyst can maintain stable ammonia production with a Faradaic efficiency of around 90% at a high current density of 1.5 A cm<sup>−2</sup> for up to 300 h. A scale-up demonstration with an electrode size of 100 cm<sup>2</sup> achieves an ammonia formation rate as high as 11.9 ± 0.5 g h<sup>−1</sup> at a total current of 160 A. The impressive electrocatalytic performance is ascribed to the presence of stable amorphous Cu domains which promote the adsorption and hydrogenation of nitrogen-containing intermediates, thus improving reaction kinetics for ammonia formation. This work underscores the importance of stabilizing metastable amorphous structures for improving electrocatalytic reactivity and long-term stability.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"30 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990612","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}
Duck Gyun Kim, Boncheol Gu, Yujin Cha, Jeonghan Ha, Yongjae Lee, Gahyeon Kim, Byung-Kwan Cho, Min-Kyu Oh
{"title":"Engineered CRISPR-Cas9 for Streptomyces sp. genome editing to improve specialized metabolite production","authors":"Duck Gyun Kim, Boncheol Gu, Yujin Cha, Jeonghan Ha, Yongjae Lee, Gahyeon Kim, Byung-Kwan Cho, Min-Kyu Oh","doi":"10.1038/s41467-025-56278-y","DOIUrl":"https://doi.org/10.1038/s41467-025-56278-y","url":null,"abstract":"<p>The CRISPR-Cas9 system has frequently been used for genome editing in <i>Streptomyces</i>; however, cytotoxicity, caused by off-target cleavage, limits its application. In this study, we implement innovative modification to Cas9, strategically addressing challenges encountered during gene manipulation using Cas9 within strains possessing high GC content genome. The Cas9-BD, a modified Cas9 with the addition of polyaspartate to its N- and C-termini, is developed with decreased off-target binding and cytotoxicity compared with wild-type Cas9. Cas9-BD and similarly modified dCas9-BD have been successfully employed for simultaneous biosynthetic gene cluster (BGC) refactoring, multiple BGC deletions, or multiplexed gene expression modulations in <i>Streptomyces</i>. We also demonstrate improved secondary metabolite production using multiplexed genome editing with multiple single guide RNA libraries in several <i>Streptomyces</i> strains. Cas9-BD is also used to capture large BGCs using a developed in vivo cloning method. The modified CRISPR-Cas9 system is successfully applied to many <i>Streptomyces</i> sp., providing versatile and efficient genome editing tools for strain engineering of actinomycetes with high GC content genome.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990631","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":"Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides","authors":"Wenqian Huang, Yaru Yan, Weisheng Tian, Xiaoxue Cui, Yingxia Wang, Yuelin Song, Ting Mo, Xiping Xu, Saijing Zhao, Yuyu Liu, Xiaohui Wang, Juan Wang, Yong Jiang, Jun Li, She-po Shi, Xiao Liu, Pengfei Tu","doi":"10.1038/s41467-025-56243-9","DOIUrl":"https://doi.org/10.1038/s41467-025-56243-9","url":null,"abstract":"<p>Echinacoside (ECH), one of the most representative phenylethanoid glycosides (PhGs), has considerable neuroprotective effects and is an effective ingredient in numerous commercial drugs. Here, we elucidate the complete ECH biosynthetic pathway in the medicinal plant <i>Cistanche tubulosa</i>. In total, 14 related genes are cloned and functionally characterized. Two upstream pathways for tyrosol biosynthesis from L-tyrosine are identified: one includes separate decarboxylation, deamination and reduction steps; the other uses microbial-like transamination, decarboxylation and reduction steps. In addition, a distinct downstream assembly process from tyrosol to ECH is revealed that includes sequential glucosylation, acylation, hydroxylation, and rhamnosylation to form acteoside, and ends with a final glucosylation converting acteoside to ECH. Furthermore, the de novo synthesis of 23 PhG derivatives is achieved via the heterologous expression of different combinations of the functional genes in tobacco. Our findings provide insights into the biosynthesis of ECH and a platform for alternative production of complex PhGs.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"84 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990615","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}
Antonia Habich, Verónica Chaves Vargas, Luca A. Robinson, Luke P. Allsopp, Daniel Unterweger
{"title":"Distribution of the four type VI secretion systems in Pseudomonas aeruginosa and classification of their core and accessory effectors","authors":"Antonia Habich, Verónica Chaves Vargas, Luca A. Robinson, Luke P. Allsopp, Daniel Unterweger","doi":"10.1038/s41467-024-54649-5","DOIUrl":"https://doi.org/10.1038/s41467-024-54649-5","url":null,"abstract":"<p>Bacterial type VI secretion systems (T6SSs) are puncturing molecular machines that transport effector proteins to kill microbes, manipulate eukaryotic cells, or facilitate nutrient uptake. How and why T6SS machines and effectors differ within a species is not fully understood. Here, we applied molecular population genetics to the T6SSs in a global population of the opportunistic pathogen <i>Pseudomonas aeruginosa</i>. We reveal varying occurrence of up to four distinct T6SS machines. Moreover, we define conserved core T6SS effectors, likely critical for the biology of <i>P. aeruginosa</i>, and accessory effectors that can exhibit mutual exclusivity between strains. By ancestral reconstruction, we observed dynamic changes in the gain and loss of effector genes in the species’ evolutionary history. Our work highlights the potential importance of T6SS intraspecific diversity in bacterial ecology and evolution.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"74 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990616","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":"NuFold: end-to-end approach for RNA tertiary structure prediction with flexible nucleobase center representation","authors":"Yuki Kagaya, Zicong Zhang, Nabil Ibtehaz, Xiao Wang, Tsukasa Nakamura, Pranav Deep Punuru, Daisuke Kihara","doi":"10.1038/s41467-025-56261-7","DOIUrl":"https://doi.org/10.1038/s41467-025-56261-7","url":null,"abstract":"<p>RNA plays a crucial role not only in information transfer as messenger RNA during gene expression but also in various biological functions as non-coding RNAs. Understanding mechanical mechanisms of function needs tertiary structure information; however, experimental determination of three-dimensional RNA structures is costly and time-consuming, leading to a substantial gap between RNA sequence and structural data. To address this challenge, we developed NuFold, a novel computational approach that leverages state-of-the-art deep learning architecture to accurately predict RNA tertiary structures. NuFold is a deep neural network trained end-to-end for the output structure from the input sequence. NuFold incorporates a nucleobase center representation, which enables flexible conformation of ribose rings. Benchmark study showed that NuFold clearly outperformed energy-based methods and demonstrated comparable results with existing state-of-the-art deep-learning-based methods. NuFold exhibited a particular advantage in building correct local geometries of RNA. Analyses of individual components in the NuFold pipeline indicated that the performance improved by utilizing metagenome sequences for multiple sequence alignment and increasing the number of recycling. NuFold is also capable of predicting multimer complex structures of RNA by linking the input sequences.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"47 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990694","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}
Yu Zhao, Ran Zhou, Bingqing Xie, Cambrian Y. Liu, Martin Kalski, Candace M. Cham, Zhiwei Jiang, Jason Koval, Christopher R. Weber, David T. Rubin, Mitch Sogin, Sean Crosson, Mengjie Chen, Jun Huang, Aretha Fiebig, Sushila Dalal, Eugene B. Chang, Anindita Basu, Sebastian Pott
{"title":"Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients","authors":"Yu Zhao, Ran Zhou, Bingqing Xie, Cambrian Y. Liu, Martin Kalski, Candace M. Cham, Zhiwei Jiang, Jason Koval, Christopher R. Weber, David T. Rubin, Mitch Sogin, Sean Crosson, Mengjie Chen, Jun Huang, Aretha Fiebig, Sushila Dalal, Eugene B. Chang, Anindita Basu, Sebastian Pott","doi":"10.1038/s41467-025-56212-2","DOIUrl":"https://doi.org/10.1038/s41467-025-56212-2","url":null,"abstract":"<p>Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including <i>CEACAM5</i> and <i>CD24</i>. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992579","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}