Science Advances最新文献

{"title":"Sustainable regeneration of 20 aminoacyl-tRNA synthetases in a reconstituted system toward self-synthesizing artificial systems","authors":"Katsumi Hagino,&nbsp;Keiko Masuda,&nbsp;Yoshihiro Shimizu,&nbsp;Norikazu Ichihashi","doi":"10.1126/sciadv.adt6269","DOIUrl":"10.1126/sciadv.adt6269","url":null,"abstract":"<div >In vitro construction of self-reproducible artificial systems is a major challenge in bottom-up synthetic biology. Here, we developed a reconstituted system capable of sustainably regenerating all 20 aminoacyl-transfer RNA synthetases (AARS), which are major components of the translation system. To achieve this, we needed five types of improvements: (i) optimization of AARS sequences for efficient translation, (ii) optimization of the composition of the translation system to enhance translation, (iii) employment of another bacterial AlaRS and SerRS to improve each aminoacylation activity, (iv) diminishing the translational inhibition caused by certain AARS sequences by codon optimization and EF-P addition, and (v) balancing the DNA concentrations of 20 AARS to match each requirement. After these improvements, we succeeded in the sustainable regeneration of all 20 AARS for up to 20 cycles of 2.5-fold serial dilutions. These methodologies and results provide a substantial advancement toward the realization of self-reproducible artificial systems.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 14","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt6269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762426","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}

{"title":"A predatory gene drive for targeted control of self-transmissible plasmids","authors":"Ryan Tsoi,&nbsp;Hye-In Son,&nbsp;Grayson S. Hamrick,&nbsp;Katherine Tang,&nbsp;Jonathan H. Bethke,&nbsp;Jia Lu,&nbsp;Rohan Maddamsetti,&nbsp;Lingchong You","doi":"10.1126/sciadv.ads4735","DOIUrl":"10.1126/sciadv.ads4735","url":null,"abstract":"<div >Suppressing plasmid transfer in microbial communities has profound implications due to the role of horizontal gene transfer (HGT) in spreading and maintaining diverse functional traits such as metabolic functions, virulence factors, and antibiotic resistance. However, existing tools for inhibiting HGT are limited in their modes of delivery, efficacy, and scalability. Here, we present a versatile denial-of-spread (DoS) strategy to target and eliminate specific conjugative plasmids. Our strategy exploits retrotransfer, whereby an engineered DoS plasmid is introduced into host cells containing a target plasmid. Acting as a predatory gene drive, DoS propagates itself at the expense of the target plasmid, through competition or active elimination. Once the target plasmid is eradicated, DoS is removed via induced plasmid suicide, resulting in a community containing neither plasmid. The strategy is tunable and scalable for various conjugative plasmids, different mechanisms of plasmid inheritance interruption, and diverse environmental contexts. DoS represents a new tool for precise control of gene persistence in microbial communities.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 14","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762430","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}

{"title":"Reconstructing historical climate fields with deep learning","authors":"Nils Bochow,&nbsp;Anna Poltronieri,&nbsp;Martin Rypdal,&nbsp;Niklas Boers","doi":"10.1126/sciadv.adp0558","DOIUrl":"10.1126/sciadv.adp0558","url":null,"abstract":"<div >Historical records of climate fields are often sparse because of missing measurements, especially before the introduction of large-scale satellite missions. Several statistical and model-based methods have been introduced to fill gaps and reconstruct historical records. Here, we use a recently introduced deep learning approach based on Fourier convolutions, trained on numerical climate model output, to reconstruct historical climate fields. Using this approach, we are able to realistically reconstruct large and irregular areas of missing data and to reproduce known historical events, such as strong El Niño or La Niña events, with very little given information. Our method outperforms the widely used statistical kriging method, as well as other recent machine learning approaches. The model generalizes to higher resolutions than the ones it was trained on and can be used on a variety of climate fields. Moreover, it allows inpainting of masks never seen before during the model training.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 14","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp0558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762441","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}

{"title":"Structural dynamics-guided engineering of a riboswitch RNA for evolving c-di-AMP synthases","authors":"Dian Chen,&nbsp;Jun Li,&nbsp;You Wu,&nbsp;Liang Hong,&nbsp;Yu Liu","doi":"10.1126/sciadv.adt8165","DOIUrl":"10.1126/sciadv.adt8165","url":null,"abstract":"<div >Cyclic diadenosine monophosphate (C-di-AMP) synthases are key enzymes for synthesizing c-di-AMP, a potent activator of the stimulator of interferon genes (STING) immune pathway. However, characterizing these enzymes has been hampered by the lack of effective sensors. While c-di-AMP riboswitches, as natural aptamers, hold the potential as RNA biosensors, their poorly comprehended structural dynamics and inherent \"OFF\" genetic output pose substantial challenges. To address these limitations, we synthesized over 10 fluorophore-labeled samples to probe the conformational changes of the riboswitch at the single-molecule level. By integrating these dynamic findings with steady-state fluorescence titration, mutagenesis, in vivo assays, and strand displacement strategy, we transformed the natural aptamer into a c-di-AMP biosensor. This engineered biosensor reversed its genetic output from \"OFF\" to \"ON\" upon c-di-AMP binding, exhibiting a 50-fold improvement in the c-di-AMP detection limit. Leveraging this refined biosensor, we developed a robust strategy for high-throughput in vivo evolution of c-di-AMP synthases.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 14","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt8165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762445","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}

{"title":"Neuroecology of alcohol risk and reward: Methanol boosts pheromones and courtship success in Drosophila melanogaster","authors":"Ian W. Keesey,&nbsp;Georg Doll,&nbsp;Sudeshna Das Chakraborty,&nbsp;Amelie Baschwitz,&nbsp;Marion Lemoine,&nbsp;Martin Kaltenpoth,&nbsp;Aleš Svatoš,&nbsp;Silke Sachse,&nbsp;Markus Knaden,&nbsp;Bill S. Hansson","doi":"10.1126/sciadv.adi9683","DOIUrl":"10.1126/sciadv.adi9683","url":null,"abstract":"<div >Attraction of <i>Drosophila melanogaster</i> toward by-products of alcoholic fermentation, especially ethanol, has been extensively studied. Previous research has provided several interpretations of this attraction, including potential drug abuse, or a self-medicating coping strategy after mate rejection. We posit that the ecologically adaptive value of alcohol attraction has not been fully explored. Here, we assert a simple yet vital biological rationale for this alcohol preference. Flies display attraction to fruits rich in alcohol, specifically ethanol and methanol, where contact results in a rapid amplification of fatty acid–derived pheromones that enhance courtship success. We also identify olfactory sensory neurons that detect these alcohols, where we reveal roles in both attraction and aversion, and show that valence is balanced around alcohol concentration. Moreover, we demonstrate that methanol can be deadly, and adult flies must therefore accurately weigh the trade-off between benefits and costs for exposure within their naturally fermented and alcohol-rich environments.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 14","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adi9683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762427","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}

{"title":"Current crowding–free superconducting nanowire single-photon detectors","authors":"Stefan Strohauer,&nbsp;Fabian Wietschorke,&nbsp;Christian Schmid,&nbsp;Stefanie Grotowski,&nbsp;Lucio Zugliani,&nbsp;Björn Jonas,&nbsp;Kai Müller,&nbsp;Jonathan J. Finley","doi":"10.1126/sciadv.adt0502","DOIUrl":"10.1126/sciadv.adt0502","url":null,"abstract":"<div >Detecting single photons is essential for applications such as dark matter detection, quantum science and technology, and biomedical imaging. Superconducting nanowire single-photon detectors (SNSPDs) excel in this task due to their near-unity detection efficiency, subhertz dark count rates, and picosecond timing jitter. However, a local increase of current density (current crowding) in the bends of meander-shaped SNSPDs limits these performance metrics. By locally irradiating the SNSPD’s straight segments with helium ions while leaving the bends unirradiated, we realize current crowding–free SNSPDs with simultaneously enhanced sensitivity: After irradiation with 800 ions nm⁻², locally irradiated SNSPDs showed a relative saturation plateau width of 37%, while fully irradiated SNSPDs reached only 10%. This larger relative plateau width allows operation at lower relative bias currents, thereby reducing the dark count rate while still detecting single photons efficiently. We achieve an internal detection efficiency of 94% with 7 mHz dark count rate near the onset of saturating detection efficiency for a wavelength of 780 nm.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt0502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726955","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}

{"title":"Preemptive optimization of a clinical antibody for broad neutralization of SARS-CoV-2 variants and robustness against viral escape","authors":"Fangqiang Zhu,&nbsp;Saravanan Rajan,&nbsp;Conor F. Hayes,&nbsp;Ka Yin Kwong,&nbsp;Andre R. Goncalves,&nbsp;Adam T. Zemla,&nbsp;Edmond Y. Lau,&nbsp;Yi Zhang,&nbsp;Yingyun Cai,&nbsp;John W. Goforth,&nbsp;Mikel Landajuela,&nbsp;Pavlo Gilchuk,&nbsp;Michael Kierny,&nbsp;Andrew Dippel,&nbsp;Bismark Amofah,&nbsp;Gilad Kaplan,&nbsp;Vanessa Cadevilla Peano,&nbsp;Christopher Morehouse,&nbsp;Ben Sparklin,&nbsp;Vancheswaran Gopalakrishnan,&nbsp;Kevin M. Tuffy,&nbsp;Amy Nguyen,&nbsp;Jagadish Beloor,&nbsp;Gustavo Kijak,&nbsp;Chang Liu,&nbsp;Aiste Dijokaite-Guraliuc,&nbsp;Juthathip Mongkolsapaya,&nbsp;Gavin R. Screaton,&nbsp;Brenden K. Petersen,&nbsp;Thomas A. Desautels,&nbsp;Drew Bennett,&nbsp;Simone Conti,&nbsp;Brent W. Segelke,&nbsp;Kathryn T. Arrildt,&nbsp;Samantha Kaul,&nbsp;Emilia A. Grzesiak,&nbsp;Felipe Leno da Silva,&nbsp;Thomas W. Bates,&nbsp;Christopher G. Earnhart,&nbsp;Svetlana Hopkins,&nbsp;Shivshankar Sundaram,&nbsp;Mark T. Esser,&nbsp;Joseph R. Francica,&nbsp;Daniel M. Faissol,&nbsp;LLNL Generative Unconstrained Intelligent Drug Engineering (GUIDE) consortium","doi":"10.1126/sciadv.adu0718","DOIUrl":"10.1126/sciadv.adu0718","url":null,"abstract":"<div >Most previously authorized clinical antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lost neutralizing activity to recent variants due to rapid viral evolution. To mitigate such escape, we preemptively enhance AZD3152, an antibody authorized for prophylaxis in immunocompromised individuals. Using deep mutational scanning (DMS) on the SARS-CoV-2 antigen, we identify AZD3152 vulnerabilities at antigen positions F456 and D420. Through two iterations of computational antibody design that integrates structure-based modeling, machine-learning, and experimental validation, we co-optimize AZD3152 against 24 contemporary and previous SARS-CoV-2 variants, as well as 20 potential future escape variants. Our top candidate, 3152-1142, restores full potency (100-fold improvement) against the more recently emerged XBB.1.5+F456L variant that escaped AZD3152, maintains potency against previous variants of concern, and shows no additional vulnerability as assessed by DMS. This preemptive mitigation demonstrates a generalizable approach for optimizing existing antibodies against potential future viral escape.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu0718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726960","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}

{"title":"Anatomy of a foreseeable disaster: Lessons from the 2023 dam-breaching flood in Derna, Libya","authors":"Moshe Armon,&nbsp;Yuval Shmilovitz,&nbsp;Elad Dente","doi":"10.1126/sciadv.adu2865","DOIUrl":"10.1126/sciadv.adu2865","url":null,"abstract":"<div >Was the catastrophic flooding in Derna, Libya—one of the deadliest hydrometeorological disasters on record—an inevitable outcome of rare weather conditions, or did the design of the infrastructure fail to account for probable risks? On 10 to 11 September 2023, Storm Daniel, a Mediterranean tropical-like cyclone, caused heavy rainfall that led to the collapse of two dams and more than 5000 casualties in Derna. Using a combination of atmospheric reanalysis, satellite data, and hydrologic modeling, we overcame key limitations typical of data-scarce, high-variability regions and revealed that despite the catastrophic impact, the return periods of the rainfall and flood were only a few decades. Hydraulic simulations revealed that the dam failures amplified the damage nearly 20-fold compared to a dam-free scenario. With extensive and timely implications, our findings underscore the importance of uncertainty-aware risk assessment and highlight the value of distributed flood prevention and early warning systems in mitigating risks in vulnerable regions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu2865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723898","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}

{"title":"Scalable fabrication of Chip-integrated 3D-nanostructured electronic devices via DNA-programmable assembly","authors":"Aaron Michelson,&nbsp;Lior Shani,&nbsp;Jason S. Kahn,&nbsp;Daniel C. Redeker,&nbsp;Won-Il Lee,&nbsp;Katerina R. DeOlivares,&nbsp;Kim Kisslinger,&nbsp;Nikhil Tiwale,&nbsp;Hanfei Yan,&nbsp;Ajith Pattammattel,&nbsp;Chang-Yong Nam,&nbsp;Vlad S. Pribiag,&nbsp;Oleg Gang","doi":"10.1126/sciadv.adt5620","DOIUrl":"10.1126/sciadv.adt5620","url":null,"abstract":"<div >DNA-based self-assembly methods have demonstrated powerful and unique capabilities to encode nanomaterial structures through the prescribed placement of inorganic and biological nanocomponents. However, the challenge of selectively growing DNA superlattices on specific locations of surfaces and their integration with conventional nanofabrication has hindered the fabrication of three-dimensional (3D) DNA-assembled functional devices. Here, we present a scalable nanofabrication technique that combines bottom-up and top-down approaches for selective growth of 3D DNA superlattices on gold microarrays. This approach allows for the fabrication of self-assembled 3D-nanostructured electronic devices. DNA strands are bound onto the gold arrays, which anchor DNA origami frames and promote ordered framework growth on the specific areas of the surface, enabling control of the lateral placement and orientation of superlattices. DNA frameworks selectively grown on the pads are subsequently templated to nanoscale silica and tin oxide (SnO_x) that follow the architecture, as confirmed by structural and chemical characterizations. The fabricated SnO_x superlattices are integrated into devices that demonstrate photocurrent response.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt5620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723911","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}

{"title":"Untethered subcentimeter flying robots","authors":"Fanping Sui,&nbsp;Wei Yue,&nbsp;Kamyar Behrouzi,&nbsp;Yuan Gao,&nbsp;Mark Mueller,&nbsp;Liwei Lin","doi":"10.1126/sciadv.ads6858","DOIUrl":"10.1126/sciadv.ads6858","url":null,"abstract":"<div >The miniaturization of insect-scale flying robots with untethered flights is extremely challenging as the tradeoff between mass and power becomes problematic. Here, a subcentimeter rotating-wing robot of 21 mg in weight and 9.4 mm in wingspan driven by a single-axis alternating magnetic field has accomplished navigable flights. This artificial flying robot is the lightest and smallest to realize untethered and controllable aerial travels including hovering, collision recovery, and route adjustments. Experimentally, it has achieved a high aerodynamic efficacy with a measured lift-to-drag ratio of 0.7 and lift–to–flying power ratio of 7.2 × 10⁻² N/W at a Reynolds number of ~2500. The wireless driving mechanism, system operation principle, and flight characteristics can be further optimized for the advancement and miniaturization of subcentimeter scale flying robots.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads6858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723912","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}