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  •   Remedy hope for polycystic ovary syndrome
    Science (IF 56.9) Pub Date : 2024-06-14
    Elisabet Stener-Victorin

    Polycystic ovary syndrome (PCOS) remains a major public health problem that affects millions of women worldwide during their reproductive years (1). This syndrome is characterized by elevated androgen levels, which leads to excessive hair growth, acne, thinning hair, ovulatory disorder, irregular menstrual cycles, and/or the presence of polycystic ovaries. PCOS and hyperandrogenemia are associated

  •   Molecular mechanism of plasmid elimination by the DdmDE defense system
    Science (IF 56.9) Pub Date : 2024-06-13
    Luuk Loeff, David W. Adams, Christelle Chanez, Sandrine Stutzmann, Laurie Righi, Melanie Blokesch, Martin Jinek

    Seventh pandemic Vibrio cholerae strains contain two pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. Here we use cryogenic electron microscopy to reveal the mechanistic basis for plasmid defense by DdmDE. A structure of the DdmD helicase-nuclease reveals it adopts an auto-inhibited dimeric architecture. The prokaryotic Argonaute protein DdmE uses a DNA guide to target plasmid

  •   Synthesis of a stable crystalline nitrene
    Science (IF 56.9) Pub Date : 2024-06-13
    Marvin Janssen, Thomas Frederichs, Marian Olaru, Enno Lork, Emanuel Hupf, Jens Beckmann

    Nitrenes are a highly reactive, yet fundamental compound class. They possess a mono-valent nitrogen atom and usually a short life span, typically in the nanosecond range. Here, we report on the synthesis of a stable nitrene by photolysis of the arylazide M S FluindN 3 ( 1 ), which gave rise to the quantitative formation of the arylnitrene M S FluindN ( 2 ) (M S Fluind = dispiro[fluorene-9,3′-(1’,1’

  •   Metabolic inflexibility promotes mitochondrial health during liver regeneration
    Science (IF 56.9) Pub Date : 2024-06-13
    Xun Wang, Cameron J. Menezes, Yuemeng Jia, Yi Xiao, Siva Sai Krishna Venigalla, Feng Cai, Meng-Hsiung Hsieh, Wen Gu, Liming Du, Jessica Sudderth, Dohun Kim, Spencer D. Shelton, Claire B. Llamas, Yu-Hsuan Lin, Min Zhu, Salma Merchant, Divya Bezwada, Sherwin Kelekar, Lauren G. Zacharias, Thomas P. Mathews, Gerta Hoxhaj, R. Max Wynn, Uttam K. Tambar, Ralph J. DeBerardinis, Hao Zhu, Prashant Mishra

    Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)–dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative

  •   Integrated platform for multiscale molecular imaging and phenotyping of the human brain
    Science (IF 56.9) Pub Date : 2024-06-13
    Juhyuk Park, Ji Wang, Webster Guan, Lars A. Gjesteby, Dylan Pollack, Lee Kamentsky, Nicholas B. Evans, Jeff Stirman, Xinyi Gu, Chuanxi Zhao, Slayton Marx, Minyoung E. Kim, Seo Woo Choi, Michael Snyder, David Chavez, Clover Su-Arcaro, Yuxuan Tian, Chang Sin Park, Qiangge Zhang, Dae Hee Yun, Mira Moukheiber, Guoping Feng, X. William Yang, C. Dirk Keene, Patrick R. Hof, Satrajit S. Ghosh, Matthew P. Frosch

    Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ–scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells

  •   Two-dimensional perovskite templates for durable, efficient formamidinium perovskite solar cells
    Science (IF 56.9) Pub Date : 2024-06-13
    Siraj Sidhik, Isaac Metcalf, Wenbin Li, Tim Kodalle, Connor J. Dolan, Mohammad Khalili, Jin Hou, Faiz Mandani, Andrew Torma, Hao Zhang, Rabindranath Garai, Jessica Persaud, Amanda Marciel, Itzel Alejandra Muro Puente, G. N. Manjunatha Reddy, Adam Balvanz, Muhammad A. Alam, Claudine Katan, Esther Tsai, David Ginger, David P. Fenning, Mercouri G. Kanatzidis, Carolin M. Sutter-Fella, Jacky Even, Aditya

    We present a design strategy for fabricating ultrastable phase-pure films of formamidinium lead iodide (FAPbI 3 ) by lattice templating using specific two-dimensional (2D) perovskites with FA as the cage cation. When a pure FAPbI 3 precursor solution is brought in contact with the 2D perovskite, the black phase forms preferentially at 100°C, much lower than the standard FAPbI 3 annealing temperature

  •   Digitalization paving the ways for sustainable chemistry: switching on more green lights
    Science (IF 56.9) Pub Date : 2024-06-13
    Vânia Zuin Zeidler

    The world is facing an interconnected crisis caused by a variety of factors including climate change, water scarcity, biodiversity loss, and chemical waste. One of most prominent factors is the exploitation of limited resources to convert them into chemical products based on the traditional linear approach. This has been provocatively described as rubbish chemistry , a “bad, old-school” system that

  •   Biogenic-to-lithogenic handoff of particulate Zn affects the Zn cycle in the Southern Ocean
    Science (IF 56.9) Pub Date : 2024-06-13
    J. Duan, R. Cloete, J. C. Loock, A. Lanzirotti, M. Newville, A. Martínez-García, D. M. Sigman, P. J. Lam, A. N. Roychoudhury, S. C. B. Myneni

    Zinc (Zn) is vital to marine organisms. Its active uptake by phytoplankton results in a substantial depletion of dissolved Zn, and Zn bound to particulate organic matter replenishes dissolved Zn in the ocean through remineralization. However, we found that particulate Zn changes from Zn bound to phosphoryls in cells to recalcitrant inorganic pools that include biogenic silica, clays, and iron, manganese

  •   Structural basis of odor sensing by insect heteromeric odorant receptors
    Science (IF 56.9) Pub Date : 2024-06-13
    Jiawei Zhao, Andy Q. Chen, Jaewook Ryu, Josefina del Mármol

    Most insects, including human-targeting mosquitoes, detect odors through odorant-activated ion channel complexes consisting of a divergent odorant-binding subunit (OR) and a conserved co-receptor subunit (Orco). As a basis for understanding how odorants activate these heteromeric receptors, we report here cryo–electron microscopy (cryo-EM) structures of two different heteromeric odorant receptor complexes

  •   Probing structural superlubricity of two-dimensional water transport with atomic resolution
    Science (IF 56.9) Pub Date : 2024-06-13
    Da Wu, Zhengpu Zhao, Bo Lin, Yizhi Song, Jiajie Qi, Jian Jiang, Zifeng Yuan, Bowei Cheng, Mengze Zhao, Ye Tian, Zhichang Wang, Muhong Wu, Ke Bian, Kai-Hui Liu, Li-Mei Xu, Xiao Cheng Zeng, En-Ge Wang, Ying Jiang

    Low-dimensional water transport can be drastically enhanced under atomic-scale confinement. However, its microscopic origin is still under debate. In this work, we directly imaged the atomic structure and transport of two-dimensional water islands on graphene and hexagonal boron nitride surfaces using qPlus-based atomic force microscopy. The lattice of the water island was incommensurate with the graphene

  •   Highly pure DNA-encoded chemical libraries by dual-linker solid-phase synthesis
    Science (IF 56.9) Pub Date : 2024-06-13
    Michelle Keller, Dimitar Petrov, Andreas Gloger, Bastien Dietschi, Kilian Jobin, Timon Gradinger, Adriano Martinelli, Louise Plais, Yuichi Onda, Dario Neri, Jörg Scheuermann

    The first drugs discovered using DNA-encoded chemical library (DEL) screens have entered late-stage clinical development. However, DEL technology as a whole still suffers from poor chemical purity resulting in suboptimal performance. In this work, we report a technique to overcome this issue through self-purifying release of the DEL after magnetic bead–based synthesis. Both the first and last building

  •   Scientists in exile
    Science (IF 56.9) Pub Date : 2024-06-13
    Gary E. Machlis, Franklin A. Carrero-Martinez

    Since 2001, the United Nations has designated 20 June as World Refugee Day. It seeks to raise awareness of refugees—currently estimated to be more than 114 million persons internally displaced, exiled, or on the move—and the often-harsh conditions they confront around the world. Among them are scientists, giving the scientific community a special responsibility to protect and support these colleagues

  •   YABBY and diverged KNOX1 genes shape nodes and internodes in the stem
    Science (IF 56.9) Pub Date : 2024-06-13
    Katsutoshi Tsuda, Akiteru Maeno, Ayako Otake, Kae Kato, Wakana Tanaka, Ken-Ichiro Hibara, Ken-Ichi Nonomura

    Plant stems comprise nodes and internodes that specialize in solute exchange and elongation. However, their boundaries are not well defined, and how these basic units arise remains elusive. In rice with clear nodes and internodes, we found that one subclade of class I knotted1-like homeobox ( KNOX1 ) genes for shoot meristem indeterminacy restricts node differentiation and allows internode formation

  •   Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction
    Science (IF 56.9) Pub Date : 2024-06-13
    Yang Liu, Jing-jing Jiang, Shao-yue Du, Liang-shan Mu, Jian-jun Fan, Jun-chi Hu, Yao Ye, Meng Ding, Wei-yu Zhou, Qiu-han Yu, Yi-fan Xia, Hong-yu Xu, Yi-jie Shi, Shu-wen Qian, Yan Tang, Wei Li, Yong-jun Dang, Xi Dong, Xiao-ying Li, Cong-jian Xu, Qi-qun Tang

    Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating

  •   Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I
    Science (IF 56.9) Pub Date : 2024-06-13
    Daniel N. Grba, John J. Wright, Zhan Yin, William Fisher, Judy Hirst

    Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and cellular damage. Ischemic conditions switch complex I from rapid, reversible catalysis into a dormant state that protects upon reoxygenation, but the molecular basis for the switch is unknown. We combined precise

  •   Spectrally engineered textile for radiative cooling against urban heat islands
    Science (IF 56.9) Pub Date : 2024-06-13
    Ronghui Wu, Chenxi Sui, Ting-Hsuan Chen, Zirui Zhou, Qizhang Li, Gangbin Yan, Yu Han, Jiawei Liang, Pei-Jan Hung, Edward Luo, Dmitri V. Talapin, Po-Chun Hsu

    Radiative cooling textiles hold promise for achieving personal thermal comfort under increasing global temperature. However, urban areas have heat island effects that largely diminish the effectiveness of cooling textiles as wearable fabrics because they absorb emitted radiation from the ground and nearby buildings. We developed a mid-infrared spectrally selective hierarchical fabric (SSHF) with emissivity

  •   In vivo editing of lung stem cells for durable gene correction in mice
    Science (IF 56.9) Pub Date : 2024-06-13
    Yehui Sun, Sumanta Chatterjee, Xizhen Lian, Zachary Traylor, Sandhya R. Sattiraju, Yufen Xiao, Sean A. Dilliard, Yun-Chieh Sung, Minjeong Kim, Sang M. Lee, Stephen Moore, Xu Wang, Di Zhang, Shiying Wu, Pratima Basak, Jialu Wang, Jing Liu, Rachel J. Mann, David F. LePage, Weihong Jiang, Shadaan Abid, Mirko Hennig, Anna Martinez, Brandon A. Wustman, David J. Lockhart, Raksha Jain, Ronald A. Conlon, Mitchell

    In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell

  •   A phage tail–like bacteriocin suppresses competitors in metapopulations of pathogenic bacteria
    Science (IF 56.9) Pub Date : 2024-06-13
    Talia Backman, Sergio M. Latorre, Efthymia Symeonidi, Artur Muszyński, Ella Bleak, Lauren Eads, Paulina I. Martinez-Koury, Sarita Som, Aubrey Hawks, Andrew D. Gloss, David M. Belnap, Allison M. Manuel, Adam M. Deutschbauer, Joy Bergelson, Parastoo Azadi, Hernán A. Burbano, Talia L. Karasov

    Bacteria can repurpose their own bacteriophage viruses (phage) to kill competing bacteria. Phage-derived elements are frequently strain specific in their killing activity, although there is limited evidence that this specificity drives bacterial population dynamics. Here, we identified intact phage and their derived elements in a metapopulation of wild plant–associated Pseudomonas genomes. We discovered

  •   Structural basis for odorant recognition of the insect odorant receptor OR-Orco heterocomplex
    Science (IF 56.9) Pub Date : 2024-06-13
    Yidong Wang, Liang Qiu, Bing Wang, Zeyuan Guan, Zhi Dong, Jie Zhang, Song Cao, Lulu Yang, Bo Wang, Zhou Gong, Liwei Zhang, Weihua Ma, Zhu Liu, Delin Zhang, Guirong Wang, Ping Yin

    Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). Here, we report structures of the Ap OR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand geranyl acetate. In these structures

  •   Strong-bonding hole-transport layers reduce ultraviolet degradation of perovskite solar cells
    Science (IF 56.9) Pub Date : 2024-06-06
    Chengbin Fei, Anastasia Kuvayskaya, Xiaoqiang Shi, Mengru Wang, Zhifang Shi, Haoyang Jiao, Timothy J. Silverman, Michael Owen-Bellini, Yifan Dong, Yeming Xian, Rebecca Scheidt, Xiaoming Wang, Guang Yang, Hangyu Gu, Nengxu Li, Connor J. Dolan, Zhewen J. D. Deng, Deniz N. Cakan, David P. Fenning, Yanfa Yan, Matthew C. Beard, Laura T. Schelhas, Alan Sellinger, Jinsong Huang

    The light-emitting diodes (LEDs) used in indoor testing of perovskite solar cells do not expose them to the levels of ultraviolet (UV) radiation that they would receive in actual outdoor use. We report degradation mechanisms of p-i-n–structured perovskite solar cells under unfiltered sunlight and with LEDs. Weak chemical bonding between perovskites and polymer hole-transporting materials (HTMs) and

  •   Rare codon recoding for efficient noncanonical amino acid incorporation in mammalian cells
    Science (IF 56.9) Pub Date : 2024-06-06
    Wenlong Ding, Wei Yu, Yulin Chen, Lihui Lao, Yu Fang, Chengzhu Fang, Hongxia Zhao, Bo Yang, Shixian Lin

    The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, we developed a rare codon recoding strategy that takes advantage of the relative

  •   Ultrafast high-endurance memory based on sliding ferroelectrics
    Science (IF 56.9) Pub Date : 2024-06-06
    Kenji Yasuda, Evan Zalys-Geller, Xirui Wang, Daniel Bennett, Suraj S Cheema, Kenji Watanabe, Takashi Taniguchi, Efthimios Kaxiras, Pablo Jarillo-Herrero, Raymond Ashoori

    The persistence of voltage-switchable collective electronic phenomena down to the atomic scale has extensive implications for area-efficient and energy-efficient electronics, especially in emerging nonvolatile memory technology. We investigate the performance of a ferroelectric field-effect transistor (FeFET) based on sliding ferroelectricity in bilayer boron nitride at room temperature. Sliding ferroelectricity

  •   Spontaneous chiral symmetry breaking in polar fluid–heliconical ferroelectric nematic phase
    Science (IF 56.9) Pub Date : 2024-06-06
    Jakub Karcz, Jakub Herman, Natan Rychłowicz, Przemysław Kula, Ewa Górecka, Jadwiga Szydlowska, Pawel W. Majewski, Damian Pociecha

    Spontaneous mirror symmetry breaking by formation of chiral structures from achiral building blocks and emergent polar order are phenomena rarely observed in fluids. Separately, they have both been found in certain nematic liquid crystalline phases; however, they have never been observed simultaneously. Here, we report a heliconical arrangement of achiral molecules in the ferroelectric nematic phase

  •   WS 2 ribbon arrays with defined chirality and coherent polarity
    Science (IF 56.9) Pub Date : 2024-06-06
    Guodong Xue, Ziqi Zhou, Quanlin Guo, Yonggang Zuo, Wenya Wei, Jiashu Yang, Peng Yin, Shuai Zhang, Ding Zhong, Yilong You, Xin Sui, Chang Liu, Muhong Wu, Hao Hong, Zhu-Jun Wang, Peng Gao, Qunyang Li, Libo Zhang, Dapeng Yu, Feng Ding, Zhongming Wei, Can Liu, Kaihui Liu

    One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley–Queisser limit efficiency in solar energy harvest within p - n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS 2 ribbon arrays with defined chirality and coherent

  •   Molecular mechanism of substrate recognition and cleavage by human γ-secretase
    Science (IF 56.9) Pub Date : 2024-06-06
    Xuefei Guo, Haotian Li, Chuangye Yan, Jianlin Lei, Rui Zhou, Yigong Shi

    Successive cleavages of amyloid precursor protein C-terminal fragment with 99 residues (APP-C99) by γ-secretase result in amyloid-β (Aβ) peptides of varying lengths. Most cleavages have a step size of three residues. To elucidate the underlying mechanism, we determined the atomic structures of human γ-secretase bound individually to APP-C99, Aβ49, Aβ46, and Aβ43. In all cases, the substrate displays

  •   Connecting lab, clinic, and community
    Science (IF 56.9) Pub Date : 2024-06-06
    Monica M. Bertagnolli

    Despite great progress in biomedical research, the health of the US population appears to be getting worse. The United States spends substantially more per capita on health care than other wealthy countries, yet US life expectancy ranks low among its peers. Mortality rates have been increasing for segments of the US population, including those in rural areas, certain racial and ethnic groups, and individuals

  •   Developing fatigue-resistant ferroelectrics using interlayer sliding switching
    Science (IF 56.9) Pub Date : 2024-06-06
    Renji Bian, Ri He, Er Pan, Zefen Li, Guiming Cao, Peng Meng, Jiangang Chen, Qing Liu, Zhicheng Zhong, Wenwu Li, Fucai Liu

    Ferroelectric materials have switchable electrical polarization that is appealing for high density non-volatile memories. However, inevitable fatigue hinders practical applications of these materials. Fatigue-free ferroelectric switching could dramatically improve the endurance of devices. We report a fatigue-free ferroelectric system based on the sliding ferroelectricity of bilayer 3R-MoS 2 . The

  •   Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer
    Science (IF 56.9) Pub Date : 2024-06-06
    Jennifer E. Klomp, J. Nathaniel Diehl, Jeffrey A. Klomp, A. Cole Edwards, Runying Yang, Alexis J. Morales, Khalilah E. Taylor, Kristina Drizyte-Miller, Kirsten L. Bryant, Antje Schaefer, Jared L. Johnson, Emily M. Huntsman, Tomer M. Yaron, Mariaelena Pierobon, Elisa Baldelli, Alex W. Prevatte, Natalie K. Barker, Laura E. Herring, Emanuel F. Petricoin, Lee M. Graves, Lewis C. Cantley, Adrienne D. Cox

    To delineate the mechanisms by which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS–driven cancer growth, we determined the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We determined that ERK1 and ERK2 share near-identical signaling and transforming outputs and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK. We identified 4666

  •   Cellular architecture shapes the naïve T cell response
    Science (IF 56.9) Pub Date : 2024-06-06
    Benjamin D. Hale, Yannik Severin, Fabienne Graebnitz, Dominique Stark, Daniel Guignard, Julien Mena, Yasmin Festl, Sohyon Lee, Jacob Hanimann, Nathan S. Zangger, Michelle Meier, David Goslings, Olga Lamprecht, Beat M. Frey, Annette Oxenius, Berend Snijder

    After antigen stimulation, naïve T cells display reproducible population-level responses, which arise from individual T cells pursuing specific differentiation trajectories. However, cell-intrinsic predeterminants controlling these single-cell decisions remain enigmatic. We found that the subcellular architectures of naïve CD8 T cells, defined by the presence (T Ø ) or absence (T O ) of nuclear envelope

  •   Abundant hydrocarbons in the disk around a very-low-mass star
    Science (IF 56.9) Pub Date : 2024-06-06
    A. M. Arabhavi, I. Kamp, Th. Henning, E. F. van Dishoeck, V. Christiaens, D. Gasman, A. Perrin, M. Güdel, B. Tabone, J. Kanwar, L. B. F. M. Waters, I. Pascucci, M. Samland, G. Perotti, G. Bettoni, S. L. Grant, P. O. Lagage, T. P. Ray, B. Vandenbussche, O. Absil, I. Argyriou, D. Barrado, A. Boccaletti, J. Bouwman, A. Caratti o Garatti, A. M. Glauser, F. Lahuis, M. Mueller, G. Olofsson, E. Pantin, S

    Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI

  •   Curved crease origami and topological singularities enable hyperextensibility of L. olor
    Science (IF 56.9) Pub Date : 2024-06-06
    Eliott Flaum, Manu Prakash

    Fundamental limits of cellular deformations, such as hyperextension of a living cell, remain poorly understood. Here, we describe how the single-celled protist Lacrymaria olor , a 40-micrometer cell, is capable of reversibly and repeatably extending its necklike protrusion up to 1200 micrometers in 30 seconds. We discovered a layered cortical cytoskeleton and membrane architecture that enables hyperextensions

  •   Electric nuclear quadrupole coupling reveals dissociation of HCl with a few water molecules
    Science (IF 56.9) Pub Date : 2024-06-06
    Fan Xie, Denis S. Tikhonov, Melanie Schnell

    Investigating the dissociation of acids in the presence of a limited number of water molecules is crucial for understanding various elementary chemical processes. In our study focusing on HCl(H 2 O) n clusters formed in a cold and isolated jet expansion, we utilized the nuclear quadrupole coupling tensor obtained via rotational spectroscopy to decipher the nature of the H-Cl chemical bond in a micro-aqueous

  •   Axis formation in annual killifish: Nodal and β-catenin regulate morphogenesis without Huluwa prepatterning
    Science (IF 56.9) Pub Date : 2024-06-06
    Philip B. Abitua, Laura M. Stump, Deniz C. Aksel, Alexander F. Schier

    Axis formation in fish and amphibians typically begins with a prepattern of maternal gene products. Annual killifish embryogenesis, however, challenges prepatterning models as blastomeres disperse and then aggregate to form the germ layers and body axes. We show that huluwa , a prepatterning factor thought to break symmetry by stabilizing β-catenin, is truncated and inactive in Nothobranchius furzeri

  •   Localized thermal emission from topological interfaces
    Science (IF 56.9) Pub Date : 2024-06-06
    M. Said Ergoktas, Ali Kecebas, Konstantinos Despotelis, Sina Soleymani, Gokhan Bakan, Askin Kocabas, Alessandro Principi, Stefan Rotter, Sahin K. Ozdemir, Coskun Kocabas

    The control of thermal radiation by shaping its spatial and spectral emission characteristics plays a key role in many areas of science and engineering. Conventional approaches to tailoring thermal emission using metamaterials are hampered both by the limited spatial resolution of the required subwavelength material structures and by the materials’ strong absorption in the infrared. In this work, we

  •   Two-stage evolution of mammalian adipose tissue thermogenesis
    Science (IF 56.9) Pub Date : 2024-06-06
    Susanne Keipert, Michael J. Gaudry, Maria Kutschke, Michaela Keuper, Margeoux A. S. Dela Rosa, Yiming Cheng, José M. Monroy Kuhn, Rutger Laterveer, Camila A. Cotrim, Peter Giere, Fabiana Perocchi, Regina Feederle, Paul G. Crichton, Dominik Lutter, Martin Jastroch

    Brown adipose tissue (BAT) is a heater organ that expresses thermogenic uncoupling protein 1 (UCP1) to maintain high body temperatures during cold stress. BAT thermogenesis is considered an overarching mammalian trait, but its evolutionary origin is unknown. We show that adipose tissue of marsupials, which diverged from eutherian mammals ~ 150 million years ago, expresses a nonthermogenic UCP1 variant

  •   Unpacking climate policy
    Science (IF 56.9) Pub Date : 2024-06-06
    Navroz K. Dubash

    As temperatures and evidence of climate impacts mount, so too do pressures to enhance climate policy ambition and implementation. In a previous piece, I have argued that to respond to these pressures requires rebalancing focus from target setting to implementation through policy formulation and enactment. But following through on policy and its implementation brings its own challenges. One size seldom

  •   Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers
    Science (IF 56.9) Pub Date : 2024-06-06
    Jeffrey A. Klomp, Jennifer E. Klomp, Clint A. Stalnecker, Kirsten L. Bryant, A. Cole Edwards, Kristina Drizyte-Miller, Priya S. Hibshman, J. Nathaniel Diehl, Ye S. Lee, Alexis J. Morales, Khalilah E. Taylor, Sen Peng, Nhan L. Tran, Laura E. Herring, Alex W. Prevatte, Natalie K. Barker, Laura D. Hover, Jill Hallin, Saikat Chowdhury, Oluwadara Coker, Hey Min Lee, Craig M. Goodwin, Prson Gautam, Peter

    How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal–regulated kinase (ERK)–dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark

  •   A master regulator of opioid reward in the ventral prefrontal cortex
    Science (IF 56.9) Pub Date : 2024-06-06
    Alexander C. W. Smith, Soham Ghoshal, Samuel W. Centanni, Mary P. Heyer, Alberto Corona, Lauren Wills, Emma Andraka, Ye Lei, Richard M. O’Connor, Stephanie P. B. Caligiuri, Sohail Khan, Kristin Beaumont, Robert P. Sebra, Brigitte L. Kieffer, Danny G. Winder, Masago Ishikawa, Paul J. Kenny

    In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling

  •   Breaking down microdroplet chemistry
    Science (IF 56.9) Pub Date : 2024-05-31
    R. Graham Cooks, Dylan T. Holden

    Charged microdroplets are commonly observed in clouds, sea spray, and other natural aerosols. The chemistry that occurs at the air-water interface of these droplets is often distinct from that observed in bulk solution, which is of considerable interest because chemical reactions can be accelerated at this boundary (1, 2). This may have implications for environmental processes such as the weathering

  •   Human activities shape global patterns of decomposition rates in rivers
    Science (IF 56.9) Pub Date : 2024-05-30
    S. D. Tiegs, K. A. Capps, D. M. Costello, J. P. Schmidt, C. J. Patrick, J. J. Follstad Shah, C. J. LeRoy, the CELLDEX Consortium‡, Vicenç Acuña, Ricardo Albariño, Daniel C. Allen, Cecilia Alonso, Patricio Andino, Clay Arango, Jukka Aroviita, Marcus V.M. Barbosa, Leon A. Barmuta, Colden Baxter, Brent Bellinger, Luz Boyero, Lyubov Bragina, Lee E. Brown, Andreas Bruder, Denise A. Bruesewitz, Francis Burdon

    Rivers and streams contribute to global carbon cycling by decomposing immense quantities of terrestrial plant matter. However, decomposition rates are highly variable and large-scale patterns and drivers of this process remain poorly understood. Using a cellulose-based assay to reflect the primary constituent of plant detritus, we generated a predictive model (81% variance explained) for cellulose

  •   Living bioelectronics resolve inflammation
    Science (IF 56.9) Pub Date : 2024-05-31
    Peder S. Olofsson

    Although inflammation is an integral part of animal physiology and promotes homeostasis, unrestrained inflammation is linked to numerous diseases (1, 2). Recent advances have improved outcomes in several inflammatory diseases—for example, the introduction of anti-cytokine therapy to treat rheumatoid arthritis (3). However, side effects and therapy failure remain common. Medicines that adapt to individual

  •   Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer’s disease
    Science (IF 56.9) Pub Date : 2024-05-30
    Katrien Princen, Tom Van Dooren, Marit van Gorsel, Nikolaos Louros, Xiaojuan Yang, Michael Dumbacher, Ilse Bastiaens, Kristel Coupet, Shana Dupont, Eva Cuveliers, Annick Lauwers, Mohamed Laghmouchi, Thomas Vanwelden, Sofie Carmans, Nele Van Damme, Hein Duhamel, Seppe Vansteenkiste, Jovan Prerad, Karolien Pipeleers, Olivier Rodiers, Liese De Ridder, Sofie Claes, Yoni Busschots, Lentel Pringels, Vanessa

    Abnormal calcium signaling is a central pathological component of Alzheimer’s disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex

  •   Supersharers of fake news on Twitter
    Science (IF 56.9) Pub Date : 2024-05-30
    Sahar Baribi-Bartov, Briony Swire-Thompson, Nir Grinberg

    Governments may have the capacity to flood social media with fake news, but little is known about the use of flooding by ordinary voters. In this work, we identify 2107 registered US voters who account for 80% of the fake news shared on Twitter during the 2020 US presidential election by an entire panel of 664,391 voters. We found that supersharers were important members of the network, reaching a

  •   Heinrich event ice discharge and the fate of the Atlantic Meridional Overturning Circulation
    Science (IF 56.9) Pub Date : 2024-05-30
    Yuxin Zhou, Jerry F. McManus

    During Heinrich events, great armadas of icebergs episodically flooded the North Atlantic Ocean and weakened overturning circulation. The ice discharges of these episodes constrain the sensitivity of overturning circulation to iceberg melting. We reconstructed these ice discharges to be as high as 0.13 sverdrup (Sv) (1 Sv = 1 million cubic meters per second) during Heinrich event 4 and to average 0

  •   Melting entropy of crystals determined by electron-beam–induced configurational disordering
    Science (IF 56.9) Pub Date : 2024-05-30
    Dongxin Liu, Jiarui Fu, Oren Elishav, Masaya Sakakibara, Kaoru Yamanouchi, Barak Hirshberg, Takayuki Nakamuro, Eiichi Nakamura

    Upon melting, the molecules in a crystal explore numerous configurations, reflecting an increase in disorder. The molar entropy of disorder can be defined by Boltzmann’s formula Δ S d = R ln( W d ), where W d is the increase in the number of microscopic states, so far inaccessible experimentally. We found that the Arrhenius frequency factor A of the electron diffraction signal decay provides W d through

  •   Quantifying the impact of misinformation and vaccine-skeptical content on Facebook
    Science (IF 56.9) Pub Date : 2024-05-30
    Jennifer Allen, Duncan J. Watts, David G. Rand

    Low uptake of the COVID-19 vaccine in the US has been widely attributed to social media misinformation. To evaluate this claim, we introduce a framework combining lab experiments (total N = 18,725), crowdsourcing, and machine learning to estimate the causal effect of 13,206 vaccine-related URLs on the vaccination intentions of US Facebook users ( N ≈ 233 million). We estimate that the impact of unflagged

  •   Molecular templating of layered halide perovskite nanowires
    Science (IF 56.9) Pub Date : 2024-05-30
    Wenhao Shao, Jeong Hui Kim, Jeffrey Simon, Zhichen Nian, Sung-Doo Baek, Yuan Lu, Colton B. Fruhling, Hanjun Yang, Kang Wang, Jee Yung Park, Libai Huang, Yi Yu, Alexandra Boltasseva, Brett M. Savoie, Vladimir M. Shalaev, Letian Dou

    Layered metal-halide perovskites, or two-dimensional perovskites, can be synthesized in solution, and their optical and electronic properties can be tuned by changing their composition. We report a molecular templating method that restricted crystal growth along all crystallographic directions except for [110] and promoted one-dimensional growth. Our approach is widely applicable to synthesize a range

  •   Simulations predict intermediate-mass black hole formation in globular clusters
    Science (IF 56.9) Pub Date : 2024-05-30
    Michiko S. Fujii, Long Wang, Ataru Tanikawa, Yutaka Hirai, Takayuki R. Saitoh

    Intermediate-mass black holes (IMBHs) are those between 100 and 10 5 solar masses ( M ⨀ ); their formation process is debated. One potential origin is the growth of less massive black holes, by merging with stars and compact objects within globular clusters (GCs). However, previous simulations have indicated that this process only produces IMBHs <500 M ⨀ , before gravitational wave recoil ejects them

  •   Solid-state continuous time crystal in a polariton condensate with a built-in mechanical clock
    Science (IF 56.9) Pub Date : 2024-05-30
    I. Carraro-Haddad, D. L. Chafatinos, A. S. Kuznetsov, I. A. Papuccio-Fernández, A. A. Reynoso, A. Bruchhausen, K. Biermann, P. V. Santos, G. Usaj, A. Fainstein

    Time crystals (TCs) are many-body systems that display spontaneous breaking of time translation symmetry. We demonstrate a TC by using driven-dissipative condensates of microcavity exciton-polaritons, spontaneously formed from an incoherent particle bath. The TC phases are controlled by the power of a continuous-wave nonresonant optical drive exciting the condensate and the interaction with cavity

  •   Coevolution with hosts underpins speciation in brood-parasitic cuckoos
    Science (IF 56.9) Pub Date : 2024-05-30
    N. E. Langmore, A. Grealy, H.-J. Noh, I. Medina, A. Skeels, J. Grant, K. D. Murray, R. M. Kilner, C. E. Holleley

    Coevolution between interacting species is thought to increase biodiversity, but evidence linking microevolutionary processes to macroevolutionary patterns is scarce. We leveraged two decades of behavioral research coupled with historical DNA analysis to reveal that coevolution with hosts underpins speciation in brood-parasitic bronze-cuckoos. At a macroevolutionary scale, we show that highly virulent

  •   Shearing brittle intermetallics enhances cryogenic strength and ductility of steels
    Science (IF 56.9) Pub Date : 2024-05-30
    Feng Wang, Miao Song, Mohamed N. Elkot, Ning Yao, Binhan Sun, Min Song, Zhangwei Wang, Dierk Raabe

    Precipitates are crucial for crafting mechanically strong metallic materials. In this work, we report the dislocation cutting of B2 (ordered body-centered cubic) nanoprecipitates, typically considered nonshearable intermetallics, in a lightweight compositionally complex steel during cryogenic tensile loading. Shearing is enabled by the high strength level for dislocation glide within the austenitic

  •   A three-dimensionally architected electronic skin mimicking human mechanosensation
    Science (IF 56.9) Pub Date : 2024-05-30
    Zhi Liu, Xiaonan Hu, Renheng Bo, Youzhou Yang, Xu Cheng, Wenbo Pang, Qing Liu, Yuejiao Wang, Shuheng Wang, Shiwei Xu, Zhangming Shen, Yihui Zhang

    Human skin sensing of mechanical stimuli originates from transduction of mechanoreceptors that converts external forces into electrical signals. Although imitating the spatial distribution of those mechanoreceptors can enable developments of electronic skins capable of decoupled sensing of normal/shear forces and strains, it remains elusive. We report a three-dimensionally (3D) architected electronic

  •   Imbalanced speciation pulses sustain the radiation of mammals
    Science (IF 56.9) Pub Date : 2024-05-30
    Ignacio Quintero, Nicolas Lartillot, Hélène Morlon

    The evolutionary histories of major clades, including mammals, often comprise changes in their diversification dynamics, but how these changes occur remains debated. We combined comprehensive phylogenetic and fossil information in a new “birth-death diffusion” model that provides a detailed characterization of variation in diversification rates in mammals. We found an early rising and sustained diversification

  •   Bridging two views of autism
    Science (IF 56.9) Pub Date : 2024-05-30
    H. Holden Thorp

    Last week, Science , Science Advances , and Science Translational Medicine published an extensive set of papers from the PsychENCODE Consortium, a multi-institutional collaboration whose aim is to study the genetics of neuropsychiatric disorders such as bipolar disorder, autism spectrum disorder, and schizophrenia. The papers, collectively called PsychENCODE2, apply advances in single-cell and multi-omic

  •   Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity
    Science (IF 56.9) Pub Date : 2024-05-30
    Kathleen E. Houlahan, Aziz Khan, Noah F. Greenwald, Cristina Sotomayor Vivas, Robert B. West, Michael Angelo, Christina Curtis

    Tumors with the same diagnosis can have different molecular profiles and response to treatment. It remains unclear when and why these differences arise. Somatic genomic aberrations occur within the context of a highly variable germline genome. Interrogating 5870 breast cancer lesions, we demonstrated that germline-derived epitopes in recurrently amplified genes influence somatic evolution by mediating

  •   Active biointegrated living electronics for managing inflammation
    Science (IF 56.9) Pub Date : 2024-05-30
    Jiuyun Shi, Saehyun Kim, Pengju Li, Fuying Dong, Chuanwang Yang, Bryan Nam, Chi Han, Ethan Eig, Lewis L. Shi, Simiao Niu, Jiping Yue, Bozhi Tian

    Seamless interfaces between electronic devices and biological tissues stand to revolutionize disease diagnosis and treatment. However, biological and biomechanical disparities between synthetic materials and living tissues present challenges at bioelectrical signal transduction interfaces. We introduce the active biointegrated living electronics (ABLE) platform, encompassing capabilities across the

  •   Spontaneous weathering of natural minerals in charged water microdroplets forms nanomaterials
    Science (IF 56.9) Pub Date : 2024-05-30
    B. K. Spoorthi, Koyendrila Debnath, Pallab Basuri, Ankit Nagar, Umesh V. Waghmare, Thalappil Pradeep

    In this work, we show that particles of common minerals break down spontaneously to form nanoparticles in charged water microdroplets within milliseconds. We transformed micron-sized natural minerals like quartz and ruby into 5- to 10-nanometer particles when integrated into aqueous microdroplets generated via electrospray. We deposited the droplets on a substrate, which allowed nanoparticle characterization

  •   Stem-cell states converge in multistage cutaneous squamous cell carcinoma development
    Science (IF 56.9) Pub Date : 2024-05-30
    Mark A. Taylor, Eve Kandyba, Kyle Halliwill, Reyno Delrosario, Matvei Khoroshkin, Hani Goodarzi, David Quigley, Yun Rose Li, Di Wu, Saumya R. Bollam, Olga K. Mirzoeva, Rosemary J. Akhurst, Allan Balmain

    Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks from hundreds of mouse tissue samples (both normal and tumor) and integrated these with lineage tracing and single-cell RNA-seq, to identify convergence of cell states in premalignant tumor cells expressing markers of lineage plasticity

  •   Synthesis and characterization of low-dimensional N-heterocyclic carbene lattices
    Science (IF 56.9) Pub Date : 2024-05-24
    Boyu Qie, Ziyi Wang, Jingwei Jiang, Zisheng Zhang, Peter H. Jacobse, Jiaming Lu, Xinheng Li, Fujia Liu, Anastassia N. Alexandrova, Steven G. Louie, Michael F. Crommie, Felix R. Fischer

    The covalent interaction of N-heterocyclic carbenes (NHCs) with transition metal atoms gives rise to distinctive frontier molecular orbitals (FMOs). These emergent electronic states have spurred the widespread adoption of NHC ligands in chemical catalysis and functional materials. Although formation of carbene-metal complexes in self-assembled monolayers on surfaces has been explored, design and electronic

  •   Mapping the brain’s gene-regulatory maze
    Science (IF 56.9) Pub Date : 2024-05-24
    Gaia Novarino, Christoph Bock

    Genetic research has contributed greatly to the molecular diagnostics of neurodevelopmental and neuropsychiatric disorders. Nevertheless, the precise molecular causes underlying these disorders have often remained elusive, even in cases with clearly genetic causes. One of the reasons is the difficulty of linking genetic variants to genes and biological processes. On pages 862, 868, and 869 of this

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