Nian-Feng Wan, Ben A. Woodcock, Christoph Scherber, Kris A. G. Wyckhuys, Zhong Li, Xuhong Qian
{"title":"Leaving synthetic pesticides behind","authors":"Nian-Feng Wan, Ben A. Woodcock, Christoph Scherber, Kris A. G. Wyckhuys, Zhong Li, Xuhong Qian","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074798","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}
Ruchao Peng, Xin Xu, Binod Nepal, Yikang Gong, Fenglin Li, Max B. Ferretti, Mingyang Zhou, Kristen W. Lynch, George M. Burslem, Sandhya Kortagere, Ronen Marmorstein, Yi-Wei Chang
{"title":"Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis","authors":"Ruchao Peng, Xin Xu, Binod Nepal, Yikang Gong, Fenglin Li, Max B. Ferretti, Mingyang Zhou, Kristen W. Lynch, George M. Burslem, Sandhya Kortagere, Ronen Marmorstein, Yi-Wei Chang","doi":"","DOIUrl":"","url":null,"abstract":"<div >Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074799","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":"Watching electronic ice melt","authors":"Sandeep Joy, Brian Skinner","doi":"","DOIUrl":"","url":null,"abstract":"<div >One of the most familiar phase transitions on Earth is the freezing and melting of water. Underlying this transition is the competition between the kinetic energy of water molecules and the potential energy arising from their mutual interactions. When the temperature falls below the freezing point, the interaction energy wins this competition and water freezes. A two-dimensional (2D) system of electrons exhibits a similar competition between kinetic and potential energies that also gives rise to a freezing–melting transition. However, the nature of this transition in an electron system has remained mysterious for decades. On page 736 of this issue, Xiang <i>et al.</i> (<i>1</i>) report direct imaging of the melting and freezing of a Wigner crystal—a periodic 2D lattice of strongly interacting electrons. The observed intricate spatial patterns raise fascinating questions about the nature of this fundamental phase transition in the quantum realm.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074809","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}
Isaac P. Witte, George D. Lampe, Simon Eitzinger, Shannon M. Miller, Kiara N. Berríos, Amber N. McElroy, Rebeca T. King, Olivia G. Stringham, Diego R. Gelsinger, Phuc Leo H. Vo, Albert T. Chen, Jakub Tolar, Mark J. Osborn, Samuel H. Sternberg, David R. Liu
{"title":"Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase","authors":"Isaac P. Witte, George D. Lampe, Simon Eitzinger, Shannon M. Miller, Kiara N. Berríos, Amber N. McElroy, Rebeca T. King, Olivia G. Stringham, Diego R. Gelsinger, Phuc Leo H. Vo, Albert T. Chen, Jakub Tolar, Mark J. Osborn, Samuel H. Sternberg, David R. Liu","doi":"","DOIUrl":"","url":null,"abstract":"<div >Programmable gene integration in human cells has the potential to enable mutation-agnostic treatments for loss-of-function genetic diseases and facilitate many applications in the life sciences. CRISPR-associated transposases (CASTs) catalyze RNA-guided DNA integration but thus far demonstrate minimal activity in human cells. Using phage-assisted continuous evolution (PACE), we generated CAST variants with >200-fold average improved integration activity. The evolved CAST system (evoCAST) achieves ~10 to 30% integration efficiencies of kilobase-size DNA cargoes in human cells across 14 tested genomic target sites, including safe harbor loci, sites used for immunotherapy, and genes implicated in loss-of-function diseases, with undetected indels and low levels of off-target integration. Collectively, our findings establish a platform for the laboratory evolution of CASTs and advance a versatile system for programmable gene integration in living systems.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074806","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.adq5729
Kevin A Guttenplan, Isa Maxwell, Erin Santos, Luke A Borchardt, Ernesto Manzo, Leire Abalde-Atristain, Rachel D Kim, Marc R Freeman
{"title":"GPCR signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity.","authors":"Kevin A Guttenplan, Isa Maxwell, Erin Santos, Luke A Borchardt, Ernesto Manzo, Leire Abalde-Atristain, Rachel D Kim, Marc R Freeman","doi":"10.1126/science.adq5729","DOIUrl":"10.1126/science.adq5729","url":null,"abstract":"<p><p>How astrocytes regulate neuronal circuits is a fundamental question in neurobiology. Specifically, how astrocytes respond to different neurotransmitters in vivo and how they affect downstream circuit modulation are questions that remain to be fully elucidated. Here, we report a mechanism in <i>Drosophila</i> by which G protein-coupled adrenergic signaling in astrocytes can control-or \"gate\"-their ability to respond to other neurotransmitters. Further, we show that manipulating this pathway potently regulates neuronal circuit activity and animal behavior. This gating mechanism is conserved in cultured primary mammalian astrocytes, suggesting that it might be an ancient feature of astrocyte circuit function. Our work establishes a mechanism by which astrocytes dynamically respond to and modulate neuronal activity in different brain regions and in different behavioral states.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"763-768"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079797","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.adq5480
Katheryn B Lefton, Yifan Wu, Yanchao Dai, Takao Okuda, Yufen Zhang, Allen Yen, Gareth M Rurak, Sarah Walsh, Rachel Manno, Bat-Erdene Myagmar, Joseph D Dougherty, Vijay K Samineni, Paul C Simpson, Thomas Papouin
{"title":"Norepinephrine signals through astrocytes to modulate synapses.","authors":"Katheryn B Lefton, Yifan Wu, Yanchao Dai, Takao Okuda, Yufen Zhang, Allen Yen, Gareth M Rurak, Sarah Walsh, Rachel Manno, Bat-Erdene Myagmar, Joseph D Dougherty, Vijay K Samineni, Paul C Simpson, Thomas Papouin","doi":"10.1126/science.adq5480","DOIUrl":"10.1126/science.adq5480","url":null,"abstract":"<p><p>Locus ceruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit functional connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is completely independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and calcium dynamics fully gate the effect of NE on synapses. Additionally, we found that NE suppression of synaptic strength results from an adenosine 5'-triphosphate (ATP)-derived and A1 adenosine receptor-mediated control of presynaptic efficacy. These findings suggest that astrocytes are a core component of neuromodulatory systems and the circuit effector through which NE produces network and behavioral adaptations.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"776-783"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079930","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.abn7811
Yan Xu, Lei Tian, Jinyi Tan, Weijie Huang, Josh Li, Nigel O'Neil, Martin Hirst, Phil Hieter, Yuelin Zhang, Xin Li
{"title":"Distribution of haploid chromosomes into separate nuclei in two pathogenic fungi.","authors":"Yan Xu, Lei Tian, Jinyi Tan, Weijie Huang, Josh Li, Nigel O'Neil, Martin Hirst, Phil Hieter, Yuelin Zhang, Xin Li","doi":"10.1126/science.abn7811","DOIUrl":"10.1126/science.abn7811","url":null,"abstract":"<p><p>Nuclei define eukaryotes, enabling macromolecular compartmentalization and cellular regulation. Each nucleus is believed to contain one or more haploid sets of chromosomes (1N). However, we discovered that haploid cells of the pathogenic fungi <i>Sclerotinia sclerotiorum</i> and <i>Botrytis cinerea</i> distribute their chromosomes such that each of their nuclei contains only a subset of the haploid chromosomes (≤½N). The unusual chromosomal distribution was confirmed by cellular and molecular methods including chromosome counting, fluorescence in situ hybridization, flow cytometry-based DNA measurements, and single-nucleus polymerase chain reaction experiments. This phenomenon challenges fundamental assumptions about nuclear organization and opens fresh avenues in chromosome biology.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"784-788"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080148","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.adt1438
Hyunjoon Kim, Seo-Young Heo, Young-Il Kim, Dongbin Park, Suhee Hwang, Yong-Ki Lee, Hobin Jang, Jae-Woo Ahn, Jeongmin Ha, Sujin Park, Ho Young Ji, Semi Kim, Isaac Choi, Woohyun Kwon, Jaemoo Kim, Kanghee Kim, Juryeon Gil, Boyeong Jeong, Josea Carmel D Lazarte, Rare Rollon, Jeong Ho Choi, Eun Ha Kim, Seung-Gyu Jang, Hye Kwon Kim, Bo-Young Jeon, Ghazi Kayali, Richard J Webby, Bon-Kyoung Koo, Young Ki Choi
{"title":"Diverse bat organoids provide pathophysiological models for zoonotic viruses.","authors":"Hyunjoon Kim, Seo-Young Heo, Young-Il Kim, Dongbin Park, Suhee Hwang, Yong-Ki Lee, Hobin Jang, Jae-Woo Ahn, Jeongmin Ha, Sujin Park, Ho Young Ji, Semi Kim, Isaac Choi, Woohyun Kwon, Jaemoo Kim, Kanghee Kim, Juryeon Gil, Boyeong Jeong, Josea Carmel D Lazarte, Rare Rollon, Jeong Ho Choi, Eun Ha Kim, Seung-Gyu Jang, Hye Kwon Kim, Bo-Young Jeon, Ghazi Kayali, Richard J Webby, Bon-Kyoung Koo, Young Ki Choi","doi":"10.1126/science.adt1438","DOIUrl":"10.1126/science.adt1438","url":null,"abstract":"<p><p>Bats are important reservoirs of zoonotic pathogens, but suitable model systems for comprehensively exploring host-pathogen interactions and assessing spillover risks remain limited. To address this gap, we developed a collection of bat organoid models spanning five species and four organ types. This multispecies, multiorgan organoid panel showed species- and tissue-specific replication patterns for several viruses, offering robust pathophysiological models for studying respiratory, renal, and enteric zoonotic viruses. Using this platform, we successfully isolated and characterized bat-borne mammalian orthoreoviruses and paramyxoviruses, demonstrating the utility of these organoid panels for virome surveillance. Furthermore, we successfully tested known antiviral drugs for their efficacy against bat virus isolates.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"756-762"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080150","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.adv8619
Diego J Arévalo-Ayala, Guillermo Funes, José D Pablo-Cea
{"title":"El Salvador revives metallic mining risks.","authors":"Diego J Arévalo-Ayala, Guillermo Funes, José D Pablo-Cea","doi":"10.1126/science.adv8619","DOIUrl":"https://doi.org/10.1126/science.adv8619","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"714"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080152","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}
SciencePub Date : 2025-05-15DOI: 10.1126/science.ady7976
{"title":"Erratum for the Report \"Recognition of a ubiquitous self antigen by prostate cancer-infiltrating CD8<sup>+</sup> T lymphocytes\" by P. A. Savage <i>et al</i>.","authors":"","doi":"10.1126/science.ady7976","DOIUrl":"https://doi.org/10.1126/science.ady7976","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"388 6748","pages":"eady7976"},"PeriodicalIF":44.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080156","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}