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Fixing the US statistical infrastructure Science (IF 44.7) Pub Date : 2025-05-29
Nancy Potok, Erica L. GroshenOfficial government statistics are critical infrastructure for the information age. Reliable, relevant, statistical information helps businesses to invest and flourish; governments at the local, state, and national levels to make critical decisions on policy and public services; and individuals and families to invest in their futures. Yet surrounded by all manner of digitized data, one can still feel
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Glacier preservation doubled by limiting warming to 1.5°C versus 2.7°C Science (IF 44.7) Pub Date : 2025-05-29
Harry Zekollari, Lilian Schuster, Fabien Maussion, Regine Hock, Ben Marzeion, David R. Rounce, Loris Compagno, Koji Fujita, Matthias Huss, Megan James, Philip D. A. Kraaijenbrink, William H. Lipscomb, Samar Minallah, Moritz Oberrauch, Lander Van Tricht, Nicolas Champollion, Tamsin Edwards, Daniel Farinotti, Walter Immerzeel, Gunter Leguy, Akiko SakaiGlaciers adapt slowly to changing climatic conditions, with long-term implications for sea-level rise and water supply. Using eight glacier models, we simulated global glacier evolution over multicentennial timescales, allowing glaciers to equilibrate with climate under various constant global temperature scenarios. We estimate that glaciers globally will lose 39 (range, 15 to 55)% of their mass relative
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Pair wave function symmetry in UTe 2 from zero-energy surface state visualization Science (IF 44.7) Pub Date : 2025-05-29
Qiangqiang Gu, Shuqiu Wang, Joseph P. Carroll, Kuanysh Zhussupbekov, Christopher Broyles, Sheng Ran, Nicholas P. Butch, Jarryd A. Horn, Shanta Saha, Johnpierre Paglione, Xiaolong Liu, J. C. Séamus Davis, Dung-Hai LeeAlthough nodal spin-triplet topological superconductivity appears probable in uranium ditelluride (UTe 2 ), its superconductive order parameter Δ k remains unestablished. In theory, a distinctive identifier would be the existence of a superconductive topological surface band, which could facilitate zero-energy Andreev tunneling to an s-wave superconductor and also distinguish a chiral from a nonchiral
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Conserved brain-wide emergence of emotional response from sensory experience in humans and mice Science (IF 44.7) Pub Date : 2025-05-29
Isaac Kauvar, Ethan B. Richman, Tony X. Liu, Chelsea Li, Sam Vesuna, Adelaida Chibukhchyan, Lisa Yamada, Adam Fogarty, Ethan Solomon, Eun Young Choi, Leili Mortazavi, Gustavo Chau Loo Kung, Pavithra Mukunda, Cephra Raja, Dariana Gil-Hernández, Kishandra Patron, Xue Zhang, Jacob Brawer, Shenandoah Wrobel, Zoe Lusk, Dian Lyu, Anish Mitra, Laura Hack, Liqun Luo, Logan Grosenick, Peter van Roessel, LeanneEmotional responses to sensory experience are central to the human condition in health and disease. We hypothesized that principles governing the emergence of emotion from sensation might be discoverable through their conservation across the mammalian lineage. We therefore designed a cross-species neural activity screen, applicable to humans and mice, combining precise affective behavioral measurements
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Attenuation of virulence in Yersinia pestis across three plague pandemics Science (IF 44.7) Pub Date : 2025-05-29
Ravneet Kaur Sidhu, Guillem Mas Fiol, Pierre Lê-Bury, Christian E. Demeure, Emelyne Bougit, Rémi Beau, Charlotte Balière, Aurelia Kwasiborski, Valérie Caro, Jennifer Klunk, Daniel J. Salkeld, Ann Carmichael, Nükhet Varlık, Debi Poinar, David J. D. Earn, Benjamin M. Bolker, Jonathan Dushoff, G. Brian Golding, Nicolas Rascovan, Olivier Dussurget, Edward C. Holmes, Javier Pizarro-Cerdá, Hendrik N. PoinarYersinia pestis has spilled over from wild rodent reservoirs to commensal rodents and humans, causing three historically recorded pandemics. Depletion in the copy number of the plasmid-encoded virulence gene pla occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the pla deletion has been difficult to test. We identified modern Y. pestis strains that independently
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Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation Science (IF 44.7) Pub Date : 2025-05-29
Ajay S. Labade, Zachary D. Chiang, Caroline Comenho, Paul L. Reginato, Andrew C. Payne, Andrew S. Earl, Rojesh Shrestha, Fabiana M. Duarte, Ehsan Habibi, Ruochi Zhang, George M. Church, Edward S. Boyden, Fei Chen, Jason D. BuenrostroMicroscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. Applying ExIGS to progeria-derived fibroblasts
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Vapor-assisted surface reconstruction enables outdoor-stable perovskite solar modules Science (IF 44.7) Pub Date : 2025-05-29
Xiangnan Sun, Wenda Shi, Tianjun Liu, Jinzhan Cheng, Xin Wang, Peng Xu, Wei Zhang, Xiaoming Zhao, Wanlin GuoNatural illumination variations in light-dark cycles induce irreversible ion migration in perovskite solar cells, posing substantial challenges to their long-term outdoor operational stability. We addressed this issue by isolating defective octahedra at the perovskite surface using a vapor-deposited polydentate ligand. Surface octahedra isolation suppresses ion migration into the charge transport layer
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Ecological and evolutionary consequences of changing seasonality Science (IF 44.7) Pub Date : 2025-05-29
Daniel Hernández-Carrasco, Jason M. Tylianakis, David A. Lytle, Jonathan D. TonkinClimate change and other anthropogenic drivers alter seasonal regimes across freshwater, terrestrial, and marine biomes. Seasonal patterns affect ecological and evolutionary processes at different ecological levels through changes to gene frequencies, species traits, population dynamics, species interactions, and different facets of biodiversity. We synthesize the mechanisms that determine biological
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Deep learning–guided design of dynamic proteins Science (IF 44.7) Pub Date : 2025-05-29
Amy B. Guo, Deniz Akpinaroglu, Christina A. Stephens, Michael Grabe, Colin A. Smith, Mark J. S. Kelly, Tanja KortemmeDeep learning has advanced the design of static protein structures, but the controlled conformational changes that are hallmarks of natural signaling proteins have remained inaccessible to de novo design. Here, we describe a general deep learning–guided approach for de novo design of dynamic changes between intradomain geometries of proteins, similar to switch mechanisms prevalent in nature, with atomic-level
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Arctic bird nesting traces back to the Cretaceous Science (IF 44.7) Pub Date : 2025-05-29
Lauren N. Wilson, Daniel T. Ksepka, John P. Wilson, Jacob D. Gardner, Gregory M. Erickson, Donald Brinkman, Caleb M. Brown, Jaelyn J. Eberle, Chris L. Organ, Patrick S. DruckenmillerPolar ecosystems are structured and enriched by birds, which nest there seasonally and serve as keystone ecosystem members. Despite the ecological importance of polar birds, the origins of high-latitude nesting strategies remain obscured by a sparse fossil record. We report an extreme-latitude Arctic avialan assemblage from the Prince Creek Formation of Alaska—the northernmost Late Cretaceous terrestrial
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Predicting and preventing Alzheimer’s disease Science (IF 44.7) Pub Date : 2025-05-29
Eric TopolWith all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer’s disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded β-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that
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Enamel proteins reveal biological sex and genetic variability in southern African Paranthropus Science (IF 44.7) Pub Date : 2025-05-29
Palesa P. Madupe, Claire Koenig, Ioannis Patramanis, Patrick L. Rüther, Nomawethu Hlazo, Meaghan Mackie, Mirriam Tawane, Johanna Krueger, Alberto J. Taurozzi, Gaudry Troché, Job Kibii, Robyn Pickering, Marc R. Dickinson, Yonatan Sahle, Dipuo Kgotleng, Charles Musiba, Fredrick Manthi, Liam Bell, Michelle DuPlessis, Catherine Gilbert, Bernhard Zipfel, Lukas F. K. Kuderna, Esther Lizano, Frido WelkerParanthropus robustus is a morphologically well-documented Early Pleistocene hominin species from southern Africa with no genetic evidence reported so far. In this work, we describe the mass spectrometric sequencing of enamel peptides from four ~2 million–year-old dental specimens attributed morphologically to P. robustus from the site of Swartkrans in South Africa. The identification of AMELY-specific
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Predicting expression-altering promoter mutations with deep learning Science (IF 44.7) Pub Date : 2025-05-29
Kishore Jaganathan, Nicole Ersaro, Gherman Novakovsky, Yuchuan Wang, Terena James, Jeremy Schwartzentruber, Petko Fiziev, Irfahan Kassam, Fan Cao, Johann Hawe, Henry Cavanagh, Ashley Lim, Grace Png, Jeremy McRae, Abhimanyu Banerjee, Arvind Kumar, Jacob Ulirsch, Yan Zhang, Francois Aguet, Pierrick Wainschtein, Laksshman Sundaram, Adriana Salcedo, Sofia Kyriazopoulou Panagiotopoulou, Delasa AghamirzaieOnly a minority of patients with rare genetic diseases are currently diagnosed by exome sequencing, suggesting that additional unrecognized pathogenic variants may reside in non-coding sequence. Here, we describe PromoterAI, a deep neural network that accurately identifies non-coding promoter variants which dysregulate gene expression. We show that promoter variants with predicted expression-altering
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Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems Science (IF 44.7) Pub Date : 2025-05-29
Baptiste Darracq, Eloi Littner, Manon Brunie, Julia Bos, Pierre Alexandre Kaminski, Florence Depardieu, Weronika Slesak, Kevin Debatisse, Marie Touchon, Aude Bernheim, David Bikard, Frédérique Le Roux, Didier Mazel, Eduardo P. C. Rocha, Céline LootIntegrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, the functions of the hundreds of cassettes carried by sedentary integrons remain largely unexplored. We show that many of these cassettes encode small variants of known antiphage systems that favor their
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A single domestication origin of adzuki bean in Japan and the evolution of domestication genes Science (IF 44.7) Pub Date : 2025-05-29
Chih-Cheng Chien, Takashi Seiko, Chiaki Muto, Hirotaka Ariga, Yen-Chiao Wang, Chuan-Hsin Chang, Hiroaki Sakai, Ken Naito, Cheng-Ruei LeeAdzuki is a central legume in East Asian culinary culture, yet its domestication origin remains debated. Using ~700 accessions across Asia, we show that the initial domestication happened three to five thousand years ago in central Japan during the Jomon period, followed by a range expansion into China and secondary hybridization with Chinese wild populations. We mapped, validated, and dated key genes
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Mobile integrons encode phage defense systems Science (IF 44.7) Pub Date : 2025-05-29
Nicolas Kieffer, Alberto Hipólito, Laura Ortiz-Miravalles, Paula Blanco, Thomas Delobelle, Patricia Vizuete, Francisco Manuel Ojeda, Thomas Jové, Dukas Jurenas, Meritxell García-Quintanilla, André Carvalho, Pilar Domingo-Calap, José Antonio EscuderoIntegrons are bacterial genetic elements that capture, stockpile, and modulate the expression of genes encoded in integron cassettes. Mobile integrons (MIs) are borne on plasmids, acting as a vehicle for hundreds of antimicrobial resistance genes among key pathogens. These elements also carry gene cassettes of unknown function ( gcu s) whose role and adaptive value remain unexplored. In this work,
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Testing interelectronic interaction in lithium-like tin Science (IF 44.7) Pub Date : 2025-05-29
Jonathan Morgner, Vladimir A. Yerokhin, Charlotte M. König, Fabian Heiße, Bingsheng Tu, Tim Sailer, Bastian Sikora, Zoltán Harman, José R. Crespo López-Urrutia, Christoph H. Keitel, Sven Sturm, Klaus BlaumMagnetic moments of bound-electron systems are a sensitive tool for testing fundamental interactions. The g factors of lithium-like ions have been rigorously studied in recent years, enabling insights into the relativistic interelectronic effects. In this work, we present the g -factor measurement of lithium-like tin, accurate to 0.5 parts per billion, as well as ab initio theoretical calculations
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ASB7 is a negative regulator of H3K9me3 homeostasis Science (IF 44.7) Pub Date : 2025-05-29
Liwen Zhou, Zhenxuan Chen, Yezi Zou, Xia Zhang, Zifeng Wang, Hongwen Zhu, Jiahui Lin, Ziyao Huang, Lisi Zheng, Jiali Chen, Miner Xie, Meifang Zhang, Ruhua Zhang, Minglu Zhu, Ziwen Wang, Hu Zhou, Song Gao, Yuxin Yin, Yuanzhong Wu, Tiebang KangThe maintenance of H3K9me3 involves the recognition of pre-existing modifications by HP1, which recruits methyltransferase SUV39H1 to methylate the adjacent newly incorporated histones, thereby establishing a positive feedback loop. However, how this positive feedback is restricted to maintain H3K9me3 homeostasis remains largely unknown. Here, we performed an unbiased genome-scale CRISPR-Cas9 screen
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Functional polymorphism of CYCLE underlies the diapause variation in moths Science (IF 44.7) Pub Date : 2025-05-29
Shirui Zheng, Yaohui Wang, Guiyun Li, Sheng Qin, Zhi Dong, Xu Yang, Xiaomiao Xu, Gangqi Fang, Muwang Li, Shuai ZhanDiapause is a common seasonal adaptive strategy that regulates annual timing in insects. Very few causal loci underlying diapause variation have yet been identified. By leveraging cross-mapping and genome-wide association analysis, we identified the N terminus of the clock protein CYCLE as a major causal effector underlying embryonic diapause differences in the silk moth. We found that the nondiapause
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BRAF oncogenic mutants evade autoinhibition through a common mechanism Science (IF 44.7) Pub Date : 2025-05-29
Hugo Lavoie, Ting Jin, Driss Lajoie, Marion Decossas, Patrick Gendron, Bing Wang, Frantisek Filandr, Malha Sahmi, Chang Hwa Jo, Sandra Weber, Geneviève Arseneault, Sasmita Tripathy, Pierre Beaulieu, Doris A. Schuetz, David C. Schriemer, Anne Marinier, William J. Rice, Pierre Maisonneuve, Marc TherrienUncontrolled activation of the rat sarcoma (RAS)–extracellular signal–regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain unclear. By using cryo–electron microscopy, we solved
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Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins Science (IF 44.7) Pub Date : 2025-05-29
Jenna N. Beyer, Yevgeniy V. Serebrenik, Kaitlyn Toy, Mohd. Altaf Najar, Emily Feierman, Nicole R. Raniszewski, Erica Korb, Ophir Shalem, George M. BurslemThe ability to study proteins in their native cellular context is crucial to our understanding of biology. In this work, we report a technology for intracellular protein editing, drawing from split intein–mediated protein splicing, genetic code expansion, and endogenous protein tagging. This approach enables us to rapidly and site-specifically install residues and chemical handles into a protein. We
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Mind reader? Science (IF 44.7) Pub Date : 2025-05-29
Jonathan MoensA forensic technology developed in India sifts brain recordings for clues to a suspect’s guilt or innocence. Many neuroscientists are skeptical, but it is catching on in other countries
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Prehistoric genomes from Yunnan reveal ancestry related to Tibetans and Austroasiatic speakers Science (IF 44.7) Pub Date : 2025-05-29
Tianyi Wang, Melinda A. Yang, Zhonghua Zhu, Minmin Ma, Han Shi, Leo Speidel, Rui Min, Haibing Yuan, Zhilong Jiang, Changcheng Hu, Xiaorui Li, Dongyue Zhao, Fan Bai, Peng Cao, Feng Liu, Qingyan Dai, Xiaotian Feng, Ruowei Yang, Xiaohong Wu, Xu Liu, Ming Zhang, Wanjing Ping, Yichen Liu, Yang Wan, Fan Yang, Ranchao Zhou, Lihong Kang, Guanghui Dong, Mark Stoneking, Qiaomei FuThe human landscape in East and Southeast Asia is vastly complex, and successful retrieval of genome-wide data from prehistoric humans of southern East Asia is sparse. We successfully sampled 127 ancient human genomes from southwestern China. A 7100-year-old female individual from central Yunnan shows a previously unsampled Basal Asian ancestry related to a ghost population that contributed to Tibetan
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Pre-European contact leprosy in the Americas and its current persistence Science (IF 44.7) Pub Date : 2025-05-29
Maria Lopopolo, Charlotte Avanzi, Sebastian Duchene, Pierre Luisi, Alida de Flamingh, Gabriel Yaxal Ponce-Soto, Gaetan Tressieres, Sarah Neumeyer, Frédéric Lemoine, Elizabeth A. Nelson, Miren Iraeta-Orbegozo, Jerome S. Cybulski, Joycelynn Mitchell, Vilma T. Marks, Linda B. Adams, John Lindo, Michael DeGiorgio, Nery Ortiz, Carlos Wiens, Juri Hiebert, Alexandro Bonifaz, Griselda Montes de Oca, VanessaLeprosy, primarily caused by Mycobacterium leprae , is considered a disease introduced into the Americas during European colonization. However, the recent discovery of a second pathogen causing leprosy, M. lepromatosis , mainly found in the Americas, challenges this view. Here, we show that M. lepromatosis infected humans in the Americas before European contact. By screening 389 ancient and 408 contemporary
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Resiliency, morphology, and entropic transformations in high-entropy oxide nanoribbons Science (IF 44.7) Pub Date : 2025-05-29
Hessam Shahbazi, Pardis Seraji, Husam Farraj, Taimin Yang, Allen Kim, Seyyedfaridoddin Fattahpour, Ilias Papailias, Matthew Diamond, Shahriar Namvar, Alireza Ahmadiparidari, Shuxi Wang, Zhenxian Liu, Shihui Feng, Khagesh Kumar, Muhtar Ahart, Jordi Cabana, Sara Kadkhodaei, Junlan Wang, Zhehao Huang, Russell J. Hemley, Amin Salehi-KhojinWe present the successful synthesis and characterization of a one-dimensional high-entropy oxide (1D-HEO) exhibiting nanoribbon morphology. These 1D-HEO nanoribbons exhibit high structural stability at elevated temperatures (to 1000°C), elevated pressures (to 12 gigapascals), and long exposure to harsh acid or base chemical environments. Moreover, they exhibit notable mechanical properties, with an
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Thermal acclimation of stem respiration implies a weaker carbon-climate feedback Science (IF 44.7) Pub Date : 2025-05-29
Han Zhang, Han Wang, Ian J. Wright, I. Colin Prentice, Sandy P. Harrison, Nicholas G. Smith, Andrea C. Westerband, Lucy Rowland, Lenka Plavcová, Hugh Morris, Peter B. Reich, Steven Jansen, Trevor Keenan, Ngoc Bao NguyenThe efflux of carbon dioxide (CO 2 ) from woody stems, a proxy for stem respiration, is a critical carbon flux from ecosystems to the atmosphere, which increases with temperature on short timescales. However, plants acclimate their respiratory response to temperature on longer timescales, potentially weakening the carbon-climate feedback. The magnitude of this acclimation is uncertain despite its importance
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Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo Science (IF 44.7) Pub Date : 2025-05-29
Blake Hernandez, Piotr Tetlak, Ana Domingo-Muelas, Hiroki Akizawa, Robin M. Skory, Goli Ardestani, Mate Biro, Xiaolei Liu, Stephanie Bissiere, Denny Sakkas, Nicolas PlachtaFollowing fertilization, the preimplantation embryo undergoes successive rounds of cell division and must accurately propagate the genetic material to ensure successful development. However, early mammalian embryos lack efficient spindle assembly mechanisms, and it remains unclear how error-free chromosome segregation is achieved. In this work, we imaged early mouse embryos and identified a network
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3D laminar flow–assisted crystallization of perovskites for square meter–sized solar modules Science (IF 44.7) Pub Date : 2025-05-29
Buyi Yan, Wanlei Dai, Zheng Wang, Zhiming Zhong, Lei Zhang, Mingqiang Yu, Qianjin Zhou, Qianling Ma, Kangrong Yan, Lu Zhang, Yang (Michael) Yang, Jizhong YaoTransforming laboratory-scale perovskite solar cells to large-scale production will require uniform crystallization of the perovskite film. We designed a method to aid the crystallization process by generating well-defined three-dimensional (3D) laminar airflow over square meter–sized perovskite films using a customized 3D-printed structure. The resultant perovskite solar modules with areas of 0.7906
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Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis Science (IF 44.7) Pub Date : 2025-05-29
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 ChangInfluenza 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
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Admixture’s impact on Brazilian population evolution and health Science (IF 44.7) Pub Date : 2025-05-29
Kelly Nunes, Marcos Araújo Castro e Silva, Maíra R. Rodrigues, Renan Barbosa Lemes, Patricio Pezo-Valderrama, Lilian Kimura, Lucas Schenatto de Sena, José Eduardo Krieger, Margareth Catoia Varela, Luiz Otávio de Azevedo, Luis Marcelo Aranha Camargo, Ricardo G. M. Ferreira, Henrique Krieger, Maria Cátira Bortolini, José Geraldo Mill, Putira Sacuena, João F. Guerreiro, Celia M. B. de Souza, FranciscoBrazil, the largest Latin American country, is underrepresented in genomic research despite boasting the world’s largest recently admixed population. In this study, we generated 2723 high-coverage whole-genome sequences from the Brazilian population, including urban, rural, and riverine communities representing diverse ethnic backgrounds. We reveal the impressive genomic diversity of Brazilians, identifying
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Activation dynamics traced through a G protein–coupled receptor by 81 1 H- 15 N NMR probes Science (IF 44.7) Pub Date : 2025-05-29
Feng-Jie Wu, Pascal S. Rieder, Layara Akemi Abiko, Anne Grahl, Daniel Häussinger, Stephan GrzesiekThe regulation of G protein–coupled receptor signaling by different orthosteric ligands is thought to occur through shifts in dynamically interconverting, conformational distributions. Such changes in dynamical distributions have been detected so far only by very sparse, often non-native experimental probes at low resolution. Using a recently developed paramagnetic nuclear magnetic resonance (NMR)
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From North Asia to South America: Tracing the longest human migration through genomic sequencing Science (IF 44.7) Pub Date : 2025-05-29
Elena S. Gusareva, Amit Gourav Ghosh, Vladimir N. Kharkov, Seik-Soon Khor, Aleksei Zarubin, Nikita Moshkov, Namrata Kalsi, Aakrosh Ratan, Cassie E. Heinle, Niall Cooke, Claudio M. Bravi, Marina V. Smolnikova, Sergey Yu. Tereshchenko, Eduard W. Kasparov, Irina Khitrinskaya, Andrey Marusin, Magomed O. Razhabov, Maria V. Golubenko, Maria Swarovskaya, Nikita A. Kolesnikov, Ksenia V. Vagaitseva, Elena RGenome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represented by the Kets and Nenets, contributed to the genetic ancestry of most Siberian populations. West Beringians, including the Koryaks, Inuit, and Luoravetlans, exhibit genetic adaptation
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Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase Science (IF 44.7) Pub Date : 2025-05-29
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. LiuProgrammable 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
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Measurements of molecular size and shape on a chip Science (IF 44.7) Pub Date : 2025-05-29
Xin Zhu, Timothy J. D. Bennett, Konstantin C. Zouboulis, Dimitrios Soulias, Michal Grzybek, Justin L. P. Benesch, Afaf H. El-Sagheer, Ünal Coskun, Madhavi KrishnanSize and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude and down to two carbon atoms in small molecules. We quantify the
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Pancreatic cancer–restricted cryptic antigens are targets for T cell recognition Science (IF 44.7) Pub Date : 2025-05-29
Zackery A. Ely, Zachary J. Kulstad, Gurcan Gunaydin, Sudarsana Addepalli, Eva K. Verzani, Marta Casarrubios, Karl R. Clauser, Xilin Wang, Isabelle E. Lippincott, Cedric Louvet, Thomas Schmitt, Kevin S. Kapner, Miles P. Agus, Connor J. Hennessey, James M. Cleary, Sine R. Hadrup, Susan Klaeger, Jennifer Su, Alex M. Jaeger, Brian M. Wolpin, Srivatsan Raghavan, Eric L. Smith, Philip D. Greenberg, AndrewTranslation of the noncoding genome in cancer can generate cryptic (noncanonical) peptides capable of presentation by human leukocyte antigen class I (HLA-I); however, the cancer specificity and immunogenicity of noncanonical HLA-I–bound peptides (ncHLAp) are incompletely understood. Using high-resolution immunopeptidomics, we discovered that cryptic peptides are abundant in the pancreatic cancer immunopeptidome
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Reducing emissions and air pollution from informal brick kilns: Evidence from Bangladesh Science (IF 44.7) Pub Date : 2025-05-29
Nina Brooks, Debashish Biswas, Sameer Maithel, Grant Miller, Aprajit Mahajan, M. Rofi Uddin, Shoeb Ahmed, Moogdho Mahzab, Mahbubur Rahman, Stephen P. LubyWe present results from a randomized controlled trial in Bangladesh that introduced operational practices to improve energy efficiency and reduce emissions in 276 “zigzag” brick kilns. Of all intervention kilns, 65% adopted the improved practices. Treatment assignment reduced energy use by 10.5% ( P -value <0.001) and decreased CO 2 and PM 2.5 emissions by 171 and 0.45 metric tons, respectively, per
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Interphase cell morphology defines the mode, symmetry, and outcome of mitosis Science (IF 44.7) Pub Date : 2025-05-29
Holly E. Lovegrove, Georgia E. Hulmes, Sabrina Ghadaouia, Christopher Revell, Marta Giralt-Pujol, Zain Alhashem, Andreia Pena, Damian D. Nogare, Ellen Appleton, Guilherme Costa, Richard L. Mort, Christoph Ballestrem, Gareth W. Jones, Cerys S. Manning, Ajay B. Chitnis, Claudio A. Franco, Claudia Linker, Katie Bentley, Shane P. HerbertDuring tissue formation, dynamic cell shape changes drive morphogenesis while asymmetric divisions create cellular diversity. We found that the shifts in cell morphology that shape tissues could concomitantly act as conserved instructive cues that trigger asymmetric division and direct core identity decisions underpinning tissue building. We performed single-cell morphometric analyses of endothelial
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Ancient Borrelia genomes document the evolutionary history of louse-borne relapsing fever Science (IF 44.7) Pub Date : 2025-05-28
Pooja Swali, Thomas Booth, Cedric C. S. Tan, Jesse McCabe, Kyriaki Anastasiadou, Christopher Barrington, Matteo Borrini, Adelle Bricking, Jo Buckberry, Lindsey Büster, Rea Carlin, Alexandre Gilardet, Isabelle Glocke, Joel D. Irish, Monica Kelly, Megan King, Fiona Petchey, Jessica Peto, Marina Silva, Leo Speidel, Frankie Tait, Adelina Teoaca, Satu Valoriani, Mia Williams, Richard Madgwick, Graham MullanSeveral bacterial pathogens have transitioned from tick-borne to louse-borne transmission, which often involves genome reduction and increasing virulence. However, the timing of such transitions remains unclear. We sequenced four ancient Borrelia recurrentis genomes, the agent of louse-borne relapsing fever, dating from 2300 to 600 years ago. We estimated the divergence from its closest tick-borne
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Sequence-based prediction of intermolecular interactions driven by disordered regions Science (IF 44.7) Pub Date : 2025-05-28
Garrett M. Ginell, Ryan J. Emenecker, Jeffrey M. Lotthammer, Alex T. Keeley, Stephen P. Plassmeyer, Nicholas Razo, Emery T. Usher, Jaqueline F. Pelham, Alex S. HolehouseIntrinsically disordered regions (IDRs) in proteins play essential roles in cellular function. A growing body of work has shown that IDRs often interact with partners in a manner that does not depend on the precise order of amino acids but is instead driven by complementary chemical interactions, leading to disordered bound-state complexes. However, these chemically specific dynamic interactions are
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Erasure cooling, control, and hyperentanglement of motion in optical tweezers Science (IF 44.7) Pub Date : 2025-05-23
Adam L. Shaw, Pascal Scholl, Ran Finkelstein, Richard Bing-Shiun Tsai, Joonhee Choi, Manuel EndresCoherently controlling the motion of single atoms in optical tweezers would enable new applications in quantum information science. To demonstrate this, we first prepared atoms in their motional ground state using a species-agnostic cooling mechanism that converts motional excitations into erasures, errors with a known location. This cooling mechanism fundamentally outperforms idealized traditional
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Functional biogeography of marine microbial heterotrophs Science (IF 44.7) Pub Date : 2025-05-23
Emily J. Zakem, Jesse McNichol, J. L. Weissman, Yubin Raut, Liang Xu, Elisa R. Halewood, Craig A. Carlson, Stephanie Dutkiewicz, Jed A. Fuhrman, Naomi M. LevineHeterotrophic bacteria and archaea (“heteroprokaryotes”) drive global carbon cycling, but how to quantitatively organize their functional complexity remains unclear. We generated a global-scale understanding of marine heteroprokaryotic functional biogeography by synthesizing genetic sequencing data with a mechanistic marine ecosystem model. We incorporated heteroprokaryotic diversity into the trait-based
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A vector calculus for neural computation in the cerebellum Science (IF 44.7) Pub Date : 2025-05-23
Mohammad Amin Fakharian, Alden M. Shoup, Paul Hage, Hisham Y. Elseweifi, Reza ShadmehrNull space theory predicts that neurons generate spikes not only to produce behavior but also to prevent the undesirable effect of other neurons on behavior. In this work, we show that this competitive cancellation is essential for understanding computation in the cerebellum. In marmosets, we identified a vector for each Purkinje cell (P cell) along which its spikes displaced the eyes. Two spikes in
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Brain drain or brain gain? Effects of high-skilled international emigration on origin countries Science (IF 44.7) Pub Date : 2025-05-23
Catia Batista, Daniel Han, Johannes Haushofer, Gaurav Khanna, David McKenzie, Ahmed Mushfiq Mobarak, Caroline Theoharides, Dean YangHow does emigration of highly educated citizens of low-income countries to high-income countries affect the economies of the origin countries? The direct effect is “brain drain”—a decrease in the country’s human capital stock. However, there may also be indirect “brain gain” effects. This review summarizes evidence that uses causal inference methods to reveal mechanisms that may lead to brain drain
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A pulsar-helium star compact binary system formed by common envelope evolution Science (IF 44.7) Pub Date : 2025-05-23
Z. L. Yang, J. L. Han, D. J. Zhou, W. C. Jing, W. C. Chen, T. Wang, X. D. Li, S. Wang, B. Wang, H. W. Ge, Y. L. Guo, L. H. Li, Y. Shao, J. F. Liu, W. Q. Su, L. G. Hou, W. J. Huang, J. C. Jiang, P. Jiang, J. H. Sun, B. J. Wang, C. Wang, H. G. Wang, J. B. Wang, N. Wang, P. F. Wang, S. Q. Wang, H. Xu, J. Xu, R. X. Xu, W. M. Yan, Y. Yan, X. P. You, D. J. Yu, Z. S. Yuan, C. F. ZhangA stellar common envelope occurs in a binary system when the atmosphere of an evolving star expands to encompass an orbiting companion object. Such systems are predicted to evolve rapidly, ejecting the stellar envelope and leaving the companion in a tighter orbit around a stripped star. We used radio timing to identify a pulsar, PSR J1928+1815, with a spin period of 10.55 ms in a compact binary system
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Microporous polyimine membranes for efficient separation of liquid hydrocarbon mixtures Science (IF 44.7) Pub Date : 2025-05-23
Tae Hoon Lee, Marcel Balcik, Zain Ali, Taigyu Joo, Matthew P. Rivera, Ingo Pinnau, Zachary P. SmithInterfacial polymerization has been an industrial standard for preparing desalination membranes. Extending the same concept to molecular separation of organic solvents would be a key enabler for the decarbonization of the chemical and petrochemical industries through energy-efficient crude or biocrude oil fractionation. Here, we report a molecular engineering approach based on acid-catalyzed interfacial
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Turf algae redefine the chemical landscape of temperate reefs, limiting kelp forest recovery Science (IF 44.7) Pub Date : 2025-05-23
Shane P. Farrell, Daniel Petras, Paolo Stincone, Dara S. Yiu, John A. Burns, Abzer Kelminal Pakkir Shah, Aaron C. Hartmann, Damian C. Brady, Douglas B. RasherIn temperate regions experiencing rapid ocean warming, kelp forests are being replaced by chemically rich turf algae. However, the extent to which these turf algae alter the surrounding chemical environment or affect the rebound potential of kelp forests (through chemically mediated interactions) remains unknown. Here, we used underwater visual surveys, comprehensive chemical profiling, and laboratory
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CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade Science (IF 44.7) Pub Date : 2025-05-23
Cody M. Rogers, Hardeep Kaur, Michelle L. Swift, Vivek B. Raina, Shuo Zhou, Ajinkya S. Kawale, Shahrez Syed, Korilynn G. Kelly, Angela M. Jasper, Sameer Salunkhe, Youngho Kwon, Jeffrey Wang, Aida Badamchi Shabestari, James M. Daley, Adam Sacks, Maria E. Gaczynska, Pawel A. Osmulski, Yashpal Rawal, Nozomi Tomimatsu, Simon A. Gayther, Kate Lawrenson, Sandeep Burma, Elizabeth V. Wasmuth, Shaun K. OlsenAntagonistic activities of the 53BP1 axis and the tumor suppressor BRCA1-BARD1 determine whether DNA double-strand breaks (DSBs) are repaired by end joining or homologous recombination. We show that the CTC1-STN1-TEN1 (CST) complex, a central 53BP1 axis component, suppresses DNA end resection by EXO1 and the BLM-DNA2 helicase-nuclease complex but acts by distinct mechanisms in restricting these entities
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The emergence and demise of giant sloths Science (IF 44.7) Pub Date : 2025-05-23
Alberto Boscaini, Daniel M. Casali, Néstor Toledo, Juan L. Cantalapiedra, M. Susana Bargo, Gerardo De Iuliis, Timothy J. Gaudin, Max C. Langer, Rachel Narducci, François Pujos, Eduardo M. Soto, Sergio F. Vizcaíno, Ignacio M. SotoThe emergence of multi-tonne herbivores is a recurrent aspect of the Cenozoic mammalian radiation. Several of these giants have vanished within the past 130,000 years, but the timing and macroevolutionary drivers behind this pattern of rise and collapse remain unclear for some megaherbivore lineages. Using trait modeling that combines total-evidence evolutionary trees and a comprehensive size dataset
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Alpha and helion particle charge radius difference determined from quantum-degenerate helium Science (IF 44.7) Pub Date : 2025-05-23
Y. van der Werf, K. Steinebach, R. Jannin, H. L. Bethlem, K. S. E. EikemaAccurate spectroscopic measurements of calculable systems provide a powerful method for testing the Standard Model and extracting fundamental constants. Recently, spectroscopic measurements of finite nuclear size effects in normal and muonic hydrogen resulted in unexpectedly large adjustments of the proton charge radius and the Rydberg constant. We measured the 2 3 S →2 1 S transition frequency in
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Safeguarding against biological weapons Science (IF 44.7) Pub Date : 2025-05-22
Sonia Ben Ouagrham-GormleyThe Biological Weapons Convention turned 50 this year. Since 1975, the intent of this international treaty has been to prohibit the development, production, and stockpiling of biological and toxin weapons. Global commitment to these objectives is reflected by the treaty’s total membership of 188 states. However, member states have thus far been unable to raise strong barriers against illicit bioweapons
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Norepinephrine changes behavioral state through astroglial purinergic signaling Science (IF 44.7) Pub Date : 2025-05-22
Alex B. Chen, Marc Duque, Altyn Rymbek, Mahalakshmi Dhanasekar, Vickie M. Wang, Xuelong Mi, Loeva Tocquer, Sujatha Narayan, Emmanuel Marquez Legorreta, Mark Eddison, Guoqiang Yu, Claire Wyart, David A. Prober, Florian Engert, Misha B. AhrensBoth neurons and glia communicate through diffusible neuromodulators; however, how neuron-glial interactions in such neuromodulatory networks influence circuit computation and behavior is unclear. During futility-induced behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine (NE) drives fast excitation and delayed inhibition of behavior and circuit activity. We found that
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GPCR signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity Science (IF 44.7) Pub Date : 2025-05-22
Kevin A. Guttenplan, Isa Maxwell, Erin Santos, Luke A. Borchardt, Ernesto Manzo, Leire Abalde-Atristain, Rachel D. Kim, Marc R. FreemanHow 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 Drosophila by which G protein–coupled adrenergic signaling in astrocytes can control—or “gate”—their ability
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Norepinephrine signals through astrocytes to modulate synapses Science (IF 44.7) Pub Date : 2025-05-22
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 PapouinLocus 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
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Distribution of haploid chromosomes into separate nuclei in two pathogenic fungi Science (IF 44.7) Pub Date : 2025-05-22
Yan Xu, Lei Tian, Jinyi Tan, Weijie Huang, Josh Li, Nigel O’Neil, Martin Hirst, Phil Hieter, Yuelin Zhang, Xin LiNuclei 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 Sclerotinia sclerotiorum and Botrytis cinerea distribute their chromosomes such that each of their nuclei contains only a subset of the haploid chromosomes (≤½N)
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Physical synchronization of soft self-oscillating limbs for fast and autonomous locomotion Science (IF 44.7) Pub Date : 2025-05-22
Alberto Comoretto, Harmannus A. H. Schomaker, Johannes T. B. OverveldeAnimals achieve robust locomotion by offloading regulation from the brain to physical couplings within the body. In contrast, locomotion in artificial systems often depends on centralized processors. Here, we introduce a rapid and autonomous locomotion strategy with synchronized gaits emerging through physical interactions between self-oscillating limbs and the environment, without control signals
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Silencing mitochondrial gene expression in living cells Science (IF 44.7) Pub Date : 2025-05-22
Luis Daniel Cruz-Zaragoza, Drishan Dahal, Mats Koschel, Angela Boshnakovska, Aiturgan Zheenbekova, Mehmet Yilmaz, Marcel Morgenstern, Jan-Niklas Dohrke, Julian Bender, Anusha Valpadashi, Kristine A Henningfeld, Silke Oeljeklaus, Laura Sophie Kremer, Mirjam Breuer, Oliver Urbach, Sven Dennerlein, Michael Lidschreiber, Stefan Jakobs, Bettina Warscheid, Peter RehlingMitochondria fulfill central functions in metabolism and energy supply. They express their own genome, which encodes key subunits of the oxidative phosphorylation system. However, central mechanisms underlying mitochondrial gene expression remain enigmatic. A lack of suitable technologies to target mitochondrial protein synthesis in cells has limited experimental access. Here, we silenced the translation
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Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense Science (IF 44.7) Pub Date : 2025-05-22
Rocky M. Barilla, Clara Berard, Linyu Sun, Sumiti Sandhu, Sarah Zaghouani, Krishna S. Iyer, Gizem Altun, Chien-Wen Su, Jacques Deguine, Vasundhara Singh, Yu Hou, Kanupriya Kusumakar, Michael L. Rutlin, Meenakshi Rao, Habib Zaghouani, Hai Ning Shi, Ramnik J. Xavier, Vijay K. KuchrooEnteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is considerably lacking. Here, we characterized a primary enteric sensory neuron (PSN) subset producing the neuropeptides neuromedin U (NMU) and calcitonin gene-related peptide β (CGRPβ) and coexpressing receptors
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Systemic failure of European fisheries management. Science (IF 44.7) Pub Date : 2025-05-22
Rainer Froese,Noa Steiner,Eva Papaioannou,Liam MacNeil,Thorsten B H Reusch,Marco ScottiOvercoming shortsighted interests with politically independent ecosystem-based catch limits may end overfishing in EU waters.
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Rewriting the rules of cell division. Science (IF 44.7) Pub Date : 2025-05-22
William BementMicrotubules get help from actin filaments during mitosis.
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