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  •   High-temperature quantum valley Hall effect with quantized resistance and a topological switch
    Science (IF 44.7) Pub Date : 2024-07-18
    Ke Huang, Hailong Fu, Kenji Watanabe, Takashi Taniguchi, Jun Zhu

    Edge states of a topological insulator can be used to explore fundamental science emerging at the interface of low dimensionality and topology. Achieving a robust conductance quantization, however, has proven challenging for helical edge states. Here we show wide resistance plateaus in kink states – a manifestation of the quantum valley Hall effect in Bernal bilayer graphene – quantized to the predicted

  •   Dynamics of high-speed electrical tree growth in electron-irradiated polymethyl methacrylate
    Science (IF 44.7) Pub Date : 2024-07-18
    Kathryn M. Sturge, Noah Hoppis, Ariana M. Bussio, Jonathan Barney, Brian Beaudoin, Cameron Brown, Bruce Carlsten, Carolyn Chun, Bryson C. Clifford, John Cumings, Nicholas Dallmann, Jack Fitzgibbon, Emily H. Frashure, Ashley E. Hammell, José Hannan, Samuel L. Henderson, Miriam E. Hiebert, James Krutzler, Joseph Lichthardt, Mark Marr-Lyon, Thomas Montano, Nathan Moody, Alexander Mueller, Patrick O’Shea

    Dielectric materials are foundational to our modern-day communications, defense, and commerce needs. Although dielectric breakdown is a primary cause of failure of these systems, we do not fully understand this process. We analyzed the dielectric breakdown channel propagation dynamics of two distinct types of electrical trees. One type of these electrical trees has not been formally classified. We

  •   We need better and more PopSci by scientists
    Science (IF 44.7) Pub Date : 2024-07-18
    Agustín Fuentes

    Any scientist knows that to be a good scientist, they must conduct thoughtful research; generate high-quality, verifiable results and analyses; and get them into circulation in the scientific community. However, what often goes underappreciated is that this good science will likely remain ignored by most of the world if one doesn’t find a way to get it out beyond the scientific community. Unfortunately

  •   Synthesis and reactivity of an N-heterocyclic carbene–stabilized diazoborane
    Science (IF 44.7) Pub Date : 2024-07-18
    Chonghe Zhang, Christopher C. Cummins, Robert J. Gilliard

    Diazo compounds and organic azides are widely used as reagents for accessing valuable molecules in multiple areas of fundamental and applied chemistry. Their capacity to undergo versatile chemical transformations arises from the reactive nature of an incipient dinitrogen molecule at the terminal position. In this work, we report the synthesis and characterization of an N-heterocyclic carbene (NHC)–stabilized

  •   Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases
    Science (IF 44.7) Pub Date : 2024-07-18
    Peter H. Yoon, Zeyuan Zhang, Kenneth J. Loi, Benjamin A. Adler, Arushi Lahiri, Kamakshi Vohra, Honglue Shi, Daniel Bellieny Rabelo, Marena Trinidad, Ron S. Boger, Muntathar J. Al-Shimary, Jennifer A. Doudna

    The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an), and further trace Cas13 origins to defense-associated

  •   Defective TiO x overlayers catalyze propane dehydrogenation promoted by base metals
    Science (IF 44.7) Pub Date : 2024-07-18
    Sai Chen, Yiyi Xu, Xin Chang, Yue Pan, Guodong Sun, Xianhui Wang, Donglong Fu, Chunlei Pei, Zhi-Jian Zhao, Dong Su, Jinlong Gong

    The industrial catalysts utilized for propane dehydrogenation (PDH) to propylene, an important alternative to petroleum-based cracking processes, either use expensive metals or metal oxides that are environmentally unbenign. We report that a typically less-active oxide, titanium oxide (TiO 2 ), can be combined with earth-abundant metallic nickel (Ni) to form an unconventional Ni@TiO x catalyst for

  •   Go/no-go for a Mars samples return
    Science (IF 44.7) Pub Date : 2024-07-18
    David Southwood

    Last month’s return to Earth of China’s lunar lander Chang’e-6 with samples from the far side of the Moon is a reminder that there are “firsts” in robotic space exploration still to be achieved. Unfortunately, this year has seen a major setback for the prospects of an even more extensive plan to collect samples from Mars. In April, the US National Aeronautics and Space Administration (NASA) made clear

  •   Birds optimize fruit size consumed near their geographic range limits
    Science (IF 44.7) Pub Date : 2024-07-18
    Lucas P. Martins, Daniel B. Stouffer, Pedro G. Blendinger, Katrin Böhning-Gaese, José Miguel Costa, D. Matthias Dehling, Camila I. Donatti, Carine Emer, Mauro Galetti, Ruben Heleno, Ícaro Menezes, José Carlos Morante-Filho, Marcia C. Muñoz, Eike Lena Neuschulz, Marco Aurélio Pizo, Marta Quitián, Roman A. Ruggera, Francisco Saavedra, Vinicio Santillán, Matthias Schleuning, Luís Pascoal da Silva, Fernanda

    Animals can adjust their diet to maximize energy or nutritional intake. For example, birds often target fruits that match their beak size because those fruits can be consumed more efficiently. We hypothesized that pressure to optimize diet—measured as matching between fruit and beak size—increases under stressful environments, such as those that determine species’ range edges. Using fruit-consumption

  •   Sculpting conducting nanopore size and shape through de novo protein design
    Science (IF 44.7) Pub Date : 2024-07-18
    Samuel Berhanu, Sagardip Majumder, Thomas Müntener, James Whitehouse, Carolin Berner, Asim K. Bera, Alex Kang, Binyong Liang, Nasir Khan, Banumathi Sankaran, Lukas K. Tamm, David J. Brockwell, Sebastian Hiller, Sheena E. Radford, David Baker, Anastassia A. Vorobieva

    Transmembrane β-barrels have considerable potential for a broad range of sensing applications. Current engineering approaches for nanopore sensors are limited to naturally occurring channels, which provide suboptimal starting points. By contrast, de novo protein design can in principle create an unlimited number of new nanopores with any desired properties. Here we describe a general approach to designing

  •   Binding and sensing diverse small molecules using shape-complementary pseudocycles
    Science (IF 44.7) Pub Date : 2024-07-18
    Linna An, Meerit Said, Long Tran, Sagardip Majumder, Inna Goreshnik, Gyu Rie Lee, David Juergens, Justas Dauparas, Ivan Anishchenko, Brian Coventry, Asim K. Bera, Alex Kang, Paul M. Levine, Valentina Alvarez, Arvind Pillai, Christoffer Norn, David Feldman, Dmitri Zorine, Derrick R. Hicks, Xinting Li, Mariana Garcia Sanchez, Dionne K. Vafeados, Patrick J. Salveson, Anastassia A. Vorobieva, David Baker

    We describe an approach for designing high-affinity small molecule–binding proteins poised for downstream sensing. We use deep learning–generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying shapes that depend on the geometry and number of the repeat units. We dock small molecules of interest into the most shape complementary of these pseudocycles

  •   Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells
    Science (IF 44.7) Pub Date : 2024-07-18
    Zhi Lin, Kaitlin Schaefer, Irene Lui, Zi Yao, Andrea Fossati, Danielle L. Swaney, Ajikarunia Palar, Andrej Sali, James A. Wells

    Proximity labeling proteomics (PLP) strategies are powerful approaches to yield snapshots of protein neighborhoods. Here, we describe a multiscale PLP method with adjustable resolution that uses a commercially available photocatalyst, Eosin Y, which upon visible light illumination activates different photo-probes with a range of labeling radii. We applied this platform to profile neighborhoods of the

  •   Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
    Science (IF 44.7) Pub Date : 2024-07-18
    Anurag Verma, Jennifer E. Huffman, Alex Rodriguez, Mitchell Conery, Molei Liu, Yuk-Lam Ho, Youngdae Kim, David A. Heise, Lindsay Guare, Vidul Ayakulangara Panickan, Helene Garcon, Franciel Linares, Lauren Costa, Ian Goethert, Ryan Tipton, Jacqueline Honerlaw, Laura Davies, Stacey Whitbourne, Jeremy Cohen, Daniel C. Posner, Rahul Sangar, Michael Murray, Xuan Wang, Daniel R. Dochtermann, Poornima Devineni

    One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program

  •   Ph 3 PCN 2 : A stable reagent for carbon-atom transfer
    Science (IF 44.7) Pub Date : 2024-07-18
    Taichi Koike, Jhen-Kuei Yu, Max M. Hansmann

    Precise modification of a chemical site in a molecule at the single-atom level is one of the most elegant yet difficult transformations in chemistry. A reagent specifically designed for chemoselective introduction of monoatomic carbon is a particularly formidable challenge. Here, we report a straightforward, azide-free synthesis of a crystalline and isolable diazophosphorus ylide, Ph 3 PCN 2 , a stable

  •   Host control of the microbiome: Mechanisms, evolution, and disease
    Science (IF 44.7) Pub Date : 2024-07-18
    Jacob Wilde, Emma Slack, Kevin R. Foster

    Many species, including humans, host communities of symbiotic microbes. There is a vast literature on the ways these microbiomes affect hosts, but here we argue for an increased focus on how hosts affect their microbiomes. Hosts exert control over their symbionts through diverse mechanisms, including immunity, barrier function, physiological homeostasis, and transit. These mechanisms enable hosts to

  •   Two-dimensional chiral perovskites with large spin Hall angle and collinear spin Hall conductivity
    Science (IF 44.7) Pub Date : 2024-07-18
    Ibrahim Abdelwahab, Dushyant Kumar, Tieyuan Bian, Haining Zheng, Heng Gao, Fanrui Hu, Arthur McClelland, Kai Leng, William L. Wilson, Jun Yin, Hyunsoo Yang, Kian Ping Loh

    Two-dimensional hybrid organic-inorganic perovskites with chiral spin texture are emergent spin-optoelectronic materials. Despite the wealth of chiro-optical studies on these materials, their charge-to-spin conversion efficiency is unknown. We demonstrate highly efficient electrically driven charge-to-spin conversion in enantiopure chiral perovskites (R/S-MB) 2 (MA) 3 Pb 4 I 13 (〈 n 〉 = 4), where MB

  •   Periodic cytokinin responses in Lotus japonicus rhizobium infection and nodule development
    Science (IF 44.7) Pub Date : 2024-07-18
    Takashi Soyano, Akira Akamatsu, Naoya Takeda, Masaaki K. Watahiki, Tatsuaki Goh, Nao Okuma, Norio Suganuma, Mikiko Kojima, Yumiko Takebayashi, Hitoshi Sakakibara, Keiji Nakajima, Masayoshi Kawaguchi

    Host plants benefit from legume root nodule symbiosis with nitrogen-fixing bacteria under nitrogen-limiting conditions. In this interaction, the hosts must regulate nodule numbers and distribution patterns to control the degree of symbiosis and maintain root growth functions. The host response to symbiotic bacteria occurs discontinuously but repeatedly at the region behind the tip of the growing roots

  •   Live chromosome identifying and tracking reveals size-based spatial pathway of meiotic errors in oocytes
    Science (IF 44.7) Pub Date : 2024-07-18
    Osamu Takenouchi, Yogo Sakakibara, Tomoya S. Kitajima

    Meiotic errors of relatively small chromosomes in oocytes result in egg aneuploidies that cause miscarriages and congenital diseases. Unlike somatic cells, which preferentially mis-segregate larger chromosomes, aged oocytes preferentially mis-segregate smaller chromosomes through unclear processes. Here, we provide a comprehensive three-dimensional chromosome identifying-and-tracking dataset throughout

  •   The human mitochondrial mRNA structurome reveals mechanisms of gene expression
    Science (IF 44.7) Pub Date : 2024-07-18
    J. Conor Moran, Amir Brivanlou, Michele Brischigliaro, Flavia Fontanesi, Silvi Rouskin, Antoni Barrientos

    The human mitochondrial genome encodes crucial oxidative phosphorylation system proteins, pivotal for aerobic energy transduction. They are translated from nine monocistronic and two bicistronic transcripts whose native structures remain unexplored, posing a gap in understanding mitochondrial gene expression. In this work, we devised the mitochondrial dimethyl sulfate mutational profiling with sequencing

  •   A crystal capping layer for formation of black-phase FAPbI 3 perovskite in humid air
    Science (IF 44.7) Pub Date : 2024-07-11
    Yu Zou, Wenjin Yu, Haoqing Guo, Qizhi Li, Xiangdong Li, Liang Li, Yueli Liu, Hantao Wang, Zhenyu Tang, Shuang Yang, Yanrun Chen, Bo Qu, Yunan Gao, Zhijian Chen, Shufeng Wang, Dongdong Zhang, Yihua Chen, Qi Chen, Shaik M. Zakeeruddin, Yingying Peng, Huanping Zhou, Qihuang Gong, Mingyang Wei, Michael Grätzel, Lixin Xiao

    Black-phase formamidinium lead iodide (α-FAPbI 3 ) perovskites are the desired phase for photovoltaic applications, but water can trigger formation of photoinactive impurity phases such as δ-FAPbI 3 . We show that the classic solvent system for perovskite fabrication exacerbates this reproducibility challenge. The conventional coordinative solvent dimethyl sulfoxide (DMSO) promoted δ-FAPbI 3 formation

  •   Stratospheric air intrusions promote global-scale new particle formation
    Science (IF 44.7) Pub Date : 2024-07-11
    Jiaoshi Zhang, Xianda Gong, Ewan Crosbie, Glenn Diskin, Karl Froyd, Samuel Hall, Agnieszka Kupc, Richard Moore, Jeff Peischl, Andrew Rollins, Joshua Schwarz, Michael Shook, Chelsea Thompson, Kirk Ullmann, Christina Williamson, Armin Wisthaler, Lu Xu, Luke Ziemba, Charles A. Brock, Jian Wang

    New particle formation in the free troposphere is a major source of cloud condensation nuclei globally. The prevailing view is that in the free troposphere, new particles are formed predominantly in convective cloud outflows. We present another mechanism using global observations. We find that during stratospheric air intrusion events, the mixing of descending ozone-rich stratospheric air with more

  •   Rat poison’s long reach
    Science (IF 44.7) Pub Date : 2024-07-11
    Dina Fine Maron

    Supertoxic rodenticides are building up inside unintended targets, including birds, mammals, and insects. Scientists want to understand the damage—and limit it

  •   Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity
    Science (IF 44.7) Pub Date : 2024-07-11
    Meng-Ju Wu, Hiroshi Kondo, Ashwin V. Kammula, Lei Shi, Yi Xiao, Sofiene Dhiab, Qin Xu, Chloe J Slater, Omar I. Avila, Joshua Merritt, Hiroyuki Kato, Prabhat Kattel, Jonathan Sussman, Ilaria Gritti, Jason Eccleston, Yi Sun, Hyo Min Cho, Kira Olander, Takeshi Katsuda, Diana D. Shi, Milan R. Savani, Bailey C. Smith, James M Cleary, Raul Mostoslavsky, Vindhya Vijay, Yosuke Kitagawa, Hiroaki Wakimoto, Russell

    Isocitrate dehydrogenase 1 ( IDH1 ) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1 -mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores antitumor immunity. Here, we define a cell-autonomous

  •   Programmed alternating current optimization of Cu-catalyzed C-H bond transformations
    Science (IF 44.7) Pub Date : 2024-07-11
    Li Zeng, Qinghong Yang, Jianxing Wang, Xin Wang, Pengjie Wang, Shengchun Wang, Shide Lv, Shabbir Muhammad, Yichang Liu, Hong Yi, Aiwen Lei

    Direct current (DC) electrosynthesis, which has undergone optimization over the past century, plays a pivotal role in a variety of industrial processes. Alternating current (AC) electrosynthesis, characterized by polarity reversal and periodic fluctuations, may be advantageous for multiple chemical reactions, but apparatus, principles, and application scenarios remain underdeveloped. In this work,

  •   Recurrent gene flow between Neanderthals and modern humans over the past 200,000 years
    Science (IF 44.7) Pub Date : 2024-07-11
    Liming Li, Troy J. Comi, Rob F. Bierman, Joshua M. Akey

    Although it is well known that the ancestors of modern humans and Neanderthals admixed, the effects of gene flow on the Neanderthal genome are not well understood. We develop methods to estimate the amount of human-introgressed sequences in Neanderthals and apply it to whole-genome sequence data from 2000 modern humans and three Neanderthals. We estimate that Neanderthals have 2.5 to 3.7% human ancestry

  •   Natural selection drives emergent genetic homogeneity in a century-scale experiment with barley
    Science (IF 44.7) Pub Date : 2024-07-11
    Jacob B. Landis, Angelica M. Guercio, Keely E. Brown, Christopher J. Fiscus, Peter L. Morrell, Daniel Koenig

    Direct observation is central to our understanding of adaptation, but evolution is rarely documented in a large, multicellular organism for more than a few generations. In this study, we observed evolution across a century-scale competition experiment, barley composite cross II (CCII). CCII was founded in 1929 in Davis, California, with thousands of genotypes, but we found that natural selection has

  •   Integrated translation and metabolism in a partially self-synthesizing biochemical network
    Science (IF 44.7) Pub Date : 2024-07-11
    Simone Giaveri, Nitin Bohra, Christoph Diehl, Hao Yuan Yang, Martine Ballinger, Nicole Paczia, Timo Glatter, Tobias J. Erb

    One of the hallmarks of living organisms is their capacity for self-organization and regeneration, which requires a tight integration of metabolic and genetic networks. We sought to construct a linked metabolic and genetic network in vitro that shows such lifelike behavior outside of a cellular context and generates its own building blocks from nonliving matter. We integrated the metabolism of the

  •   Pathogenic strategies of Pseudogymnoascus destructans during torpor and arousal of hibernating bats
    Science (IF 44.7) Pub Date : 2024-07-11
    Marcos Isidoro-Ayza, Bruce S. Klein

    Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus, Pseudogymnoascus destructans , that invades their skin. Mechanisms of P. destructans invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat ( Myotis lucifugus

  •   Drivers of epidemic dynamics in real time from daily digital COVID-19 measurements
    Science (IF 44.7) Pub Date : 2024-07-11
    Michelle Kendall, Luca Ferretti, Chris Wymant, Daphne Tsallis, James Petrie, Andrea Di Francia, Francesco Di Lauro, Lucie Abeler-Dörner, Harrison Manley, Jasmina Panovska-Griffiths, Alice Ledda, Xavier Didelot, Christophe Fraser

    Understanding the drivers of respiratory pathogen spread is challenging, particularly in a timely manner during an ongoing epidemic. Here we present insights obtained using daily data from the NHS COVID-19 app for England and Wales and shared with health authorities in almost real time. Our indicator of the reproduction number R(t) was available days earlier than other estimates, with a novel capability

  •   Antagonistic conflict between transposon-encoded introns and guide RNAs
    Science (IF 44.7) Pub Date : 2024-07-11
    Rimantė Žedaveinytė, Chance Meers, Hoang C. Le, Edan E. Mortman, Stephen Tang, George D. Lampe, Sanjana R. Pesari, Diego R. Gelsinger, Tanner Wiegand, Samuel H. Sternberg

    TnpB nucleases represent the evolutionary precursors to CRISPR-Cas12 and are widespread in all domains of life. IS605-family TnpB homologs function as programmable RNA-guided homing endonucleases in bacteria, driving transposon maintenance through DNA double-strand break–stimulated homologous recombination. In this work, we uncovered molecular mechanisms of the transposition life cycle of IS607-family

  •   Resetting tropospheric OH and CH 4 lifetime with ultraviolet H 2 O absorption
    Science (IF 44.7) Pub Date : 2024-07-11
    Michael J. Prather, Lei Zhu

    The decay of methyl chloroform, a banned ozone-depleting substance, has provided a clear observational metric of mean tropospheric hydroxyl radical (OH) abundance. Almost all current global chemistry models calculate about 15% too much OH and thus too rapid methane loss. Methane is a short-lived climate forcer, critical to achieving global warming targets, and this error affects our model projections

  •   Structured electrons with chiral mass and charge
    Science (IF 44.7) Pub Date : 2024-07-11
    Yiqi Fang, Joel Kuttruff, David Nabben, Peter Baum

    Chirality is a phenomenon with widespread relevance in fundamental physics, material science, chemistry, optics, and spectroscopy. In this work, we show that a free electron can be converted by the field cycles of laser light into a right-handed or left-handed coil of mass and charge. In contrast to phase-vortex beams, our electrons maintained a flat de Broglie wave but obtained their chirality from

  •   A quantum-network register assembled with optical tweezers in an optical cavity
    Science (IF 44.7) Pub Date : 2024-07-11
    Lukas Hartung, Matthias Seubert, Stephan Welte, Emanuele Distante, Gerhard Rempe

    Quantum computation and quantum communication are expected to provide users with capabilities inaccessible by classical physics. However, scalability to larger systems with many qubits is challenging. One solution is to develop a quantum network consisting of small-scale quantum registers containing computation qubits that are reversibly interfaced to communication qubits. In this study, we report

  •   Stop H5N1 influenza in US cattle now
    Science (IF 44.7) Pub Date : 2024-07-11
    Nicola Lewis, Martin Beer

    The relentless march of a highly pathogenic avian influenza virus (HPAIV) strain, known as H5N1, to become an unprecedented panzootic continues unchecked. The leap of H5N1 clade from Eurasia and Africa to North America in 2021 and its further spread to South America and the Antarctic have exposed new avian and mammalian populations to the virus and led to outbreaks on an unrivaled scale. The

  •   Partitioning polar-slush strategy in relaxors leads to large energy-storage capability
    Science (IF 44.7) Pub Date : 2024-07-11
    Liang Shu, Xiaoming Shi, Xin Zhang, Ziqi Yang, Wei Li, Yunpeng Ma, Yi-Xuan Liu, Lisha Liu, Yue-Yu-Shan Cheng, Liyu Wei, Qian Li, Houbing Huang, Shujun Zhang, Jing-Feng Li

    Relaxor ferroelectric (RFE) films are promising energy-storage candidates for miniaturizing high-power electronic systems, which is credited to their high energy density ( U e ) and efficiency. However, advancing their U e beyond 200 joules per cubic centimeter is challenging, limiting their potential for next-generation energy-storage devices. We implemented a partitioning polar-slush strategy in

  •   Unsupervised evolution of protein and antibody complexes with a structure-informed language model
    Science (IF 44.7) Pub Date : 2024-07-04
    Varun R. Shanker, Theodora U. J. Bruun, Brian L. Hie, Peter S. Kim

    Large language models trained on sequence information alone can learn high-level principles of protein design. However, beyond sequence, the three-dimensional structures of proteins determine their specific function, activity, and evolvability. Here, we show that a general protein language model augmented with protein structure backbone coordinates can guide evolution for diverse proteins without the

  •   An intron endonuclease facilitates interference competition between coinfecting viruses
    Science (IF 44.7) Pub Date : 2024-07-04
    Erica A. Birkholz, Chase J. Morgan, Thomas G. Laughlin, Rebecca K. Lau, Amy Prichard, Sahana Rangarajan, Gabrielle N. Meza, Jina Lee, Emily Armbruster, Sergey Suslov, Kit Pogliano, Justin R. Meyer, Elizabeth Villa, Kevin D. Corbett, Joe Pogliano

    Introns containing homing endonucleases are widespread in nature and have long been assumed to be selfish elements that provide no benefit to the host organism. These genetic elements are common in viruses, but whether they confer a selective advantage is unclear. In this work, we studied intron-encoded homing endonuclease gp210 in bacteriophage ΦPA3 and found that it contributes to viral competition

  •   A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction
    Science (IF 44.7) Pub Date : 2024-07-04
    Pamela Y. Ting, Sneha Borikar, John Ryan Kerrigan, Noel M. Thomsen, Eamon Aghania, Amelia E. Hinman, Alejandro Reyes, Nicolas Pizzato, Barna D. Fodor, Fabian Wu, Muluken S. Belew, Xiaohong Mao, Jian Wang, Shripad Chitnis, Wei Niu, Amanda Hachey, Jennifer S. Cobb, Nikolas A. Savage, Ashley Burke, Joshiawa Paulk, Dustin Dovala, James Lin, Matthew C. Clifton, Elizabeth Ornelas, Xiaolei Ma, Nathaniel F

    Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to a heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate disease complications and has been intently pursued. However, safe and effective small-molecule inducers of HbF remain elusive. We report the discovery of dWIZ-1 and dWIZ-2, molecular glue degraders of the WIZ transcription

  •   Ultrastrong MXene film induced by sequential bridging with liquid metal
    Science (IF 44.7) Pub Date : 2024-07-04
    Wei Li, Tianzhu Zhou, Zejun Zhang, Lei Li, Wangwei Lian, Yanlei Wang, Junfeng Lu, Jia Yan, Huagao Wang, Lei Wei, Qunfeng Cheng

    Assembling titanium carbide (Ti 3 C 2 T x ) MXene nanosheets into macroscopic films presents challenges, including voids, low orientation degree, and weak interfacial interactions, which reduce mechanical performance. We demonstrate an ultrastrong macroscopic MXene film using liquid metal (LM) and bacterial cellulose (BC) to sequentially bridge MXene nanosheets (an LBM film), achieving a tensile strength

  •   American academic freedom is in peril
    Science (IF 44.7) Pub Date : 2024-07-04
    Ryan Calo, Kate Starbird

    Academics researching online misinformation in the US are learning a hard lesson: Academic freedom cannot be taken for granted. They face a concerted effort—including by members of Congress—to undermine or silence their work documenting false and misleading internet content. The claim is that online misinformation researchers are trying to silence conservative voices. The evidence suggests just the

  •   Trees have overlapping potential niches that extend beyond their realized niches
    Science (IF 44.7) Pub Date : 2024-07-04
    Daniel C. Laughlin, Brian J. McGill

    Tree species appear to prefer distinct climatic conditions, but the true nature of these preferences is obscured by species interactions and dispersal, which limit species’ ranges. We quantified realized and potential thermal niches of 188 North American tree species to conduct a continental-scale test of the architecture of niches. We found strong and consistent evidence that species occurring at

  •   Evolution and host-specific adaptation of Pseudomonas aeruginosa
    Science (IF 44.7) Pub Date : 2024-07-04
    Aaron Weimann, Adam M. Dinan, Christopher Ruis, Audrey Bernut, Stéphane Pont, Karen Brown, Judy Ryan, Lúcia Santos, Louise Ellison, Emem Ukor, Arun P. Pandurangan, Sina Krokowski, Tom L. Blundell, Martin Welch, Beth Blane, Kim Judge, Rachel Bousfield, Nicholas Brown, Josephine M. Bryant, Irena Kukavica-Ibrulj, Giordano Rampioni, Livia Leoni, Patrick T. Harrison, Sharon J. Peacock, Nicholas R. Thomson

    The major human bacterial pathogen Pseudomonas aeruginosa causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over

  •   Wigner molecular crystals from multielectron moiré artificial atoms
    Science (IF 44.7) Pub Date : 2024-07-04
    Hongyuan Li, Ziyu Xiang, Aidan P. Reddy, Trithep Devakul, Renee Sailus, Rounak Banerjee, Takashi Taniguchi, Kenji Watanabe, Sefaattin Tongay, Alex Zettl, Liang Fu, Michael F. Crommie, Feng Wang

    Semiconductor moiré superlattices provide a versatile platform to engineer quantum solids composed of artificial atoms on moiré sites. Previous studies have mostly focused on the simplest correlated quantum solid—the Fermi-Hubbard model—in which intra-atom interactions are simplified to a single onsite repulsion energy U . Here we report the experimental observation of Wigner molecular crystals emerging

  •   Interfacial epitaxy of multilayer rhombohedral transition-metal dichalcogenide single crystals
    Science (IF 44.7) Pub Date : 2024-07-04
    Biao Qin, Chaojie Ma, Quanlin Guo, Xiuzhen Li, Wenya Wei, Chenjun Ma, Qinghe Wang, Fang Liu, Mengze Zhao, Guodong Xue, Jiajie Qi, Muhong Wu, Hao Hong, Luojun Du, Qing Zhao, Peng Gao, Xinqiang Wang, Enge Wang, Guangyu Zhang, Can Liu, Kaihui Liu

    Rhombohedral-stacked transition-metal dichalcogenides (3R-TMDs), which are distinct from their hexagonal counterparts, exhibit higher carrier mobility, sliding ferroelectricity, and coherently enhanced nonlinear optical responses. However, surface epitaxial growth of large multilayer 3R-TMD single crystals is difficult. We report an interfacial epitaxy methodology for their growth of several compositions

  •   Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model
    Science (IF 44.7) Pub Date : 2024-07-04
    Martin Kaag Rasmussen, Kjeld Møllgård, Peter A. R. Bork, Pia Weikop, Tina Esmail, Lylia Drici, Nicolai J. Wewer Albrechtsen, Jonathan Frederik Carlsen, Nguyen P. T. Huynh, Nima Ghitani, Matthias Mann, Steven A. Goldman, Yuki Mori, Alexander T. Chesler, Maiken Nedergaard

    Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between

  •   Ice sheet–free West Antarctica during peak early Oligocene glaciation
    Science (IF 44.7) Pub Date : 2024-07-04
    J. P. Klages, C.-D. Hillenbrand, S. M. Bohaty, U. Salzmann, T. Bickert, G. Lohmann, H. S. Knahl, P. Gierz, L. Niu, J. Titschack, G. Kuhn, T. Frederichs, J. Müller, T. Bauersachs, R. D. Larter, K. Hochmuth, W. Ehrmann, G. Nehrke, F. J. Rodríguez-Tovar, G. Schmiedl, S. Spezzaferri, A. Läufer, F. Lisker, T. van de Flierdt, A. Eisenhauer, G. Uenzelmann-Neben, O. Esper, J. A. Smith, H. Pälike, C. Spiegel

    One of Earth’s most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition—a critical knowledge gap for assessing feedbacks between permanently

  •   A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling
    Science (IF 44.7) Pub Date : 2024-07-04
    Jian-Wen Ma, Fu-Rong Zeng, Xin-Cen Lin, Yan-Qin Wang, Yi-Heng Ma, Xu-Xu Jia, Jin-Cheng Zhang, Bo-Wen Liu, Yu-Zhong Wang, Hai-Bo Zhao

    Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered

  •   Preventing bad behavior in academia
    Science (IF 44.7) Pub Date : 2024-07-04
    Rayane da Cruz Albino, Mark Allen Brimble, Christina Zdenek, Katrien Vandenbroeck, Sarah Masud, Xuan Zhang, Mel Cosentino, Ankita Gupta, Rashad Abdul-Ghani, Casimiro Gerarduzzi, Pamela Jackson, Rebekah Oomen, Bram Servais, Akshatha Manjunatha, Nick Bulthuis, Carmen Romero-Molina, Dequn Teng, Aleksandra Kosanic, Daniela de Angeli Dutra, Demos Alekkou, Andressa M. Venturini, Edgar Virguez, Adetayo Emmanuel

    We gave young scientists this prompt: Describe one change to scientific policy or culture that would substantially decrease incidents of scientific misconduct or other unethical behavior.

  •   Slow rupture in a fluid-rich fault zone initiated the 2024 M w 7.5 Noto earthquake
    Science (IF 44.7) Pub Date : 2024-07-04
    Zhangfeng Ma, Hongyu Zeng, Haipeng Luo, Zemin Liu, Yu Jiang, Yosuke Aoki, Weitao Wang, Yuji Itoh, Mingzhe Lyu, Yan Cui, Sang-Ho Yun, Emma M. Hill, Shengji Wei

    The 2024 moment magnitude ( M w ) 7.5 Noto Peninsula (Japan) earthquake caused devastation to communities and was generated by a complex rupture process. Using space geodetic and seismic observations, we show that the event deformed the peninsula with a peak uplift reaching 5 m at the west coast. Shallow slip exceeded 10 m on an offshore fault. Peak stress drop was greater than 10 MPa. This devastating

  •   Genomic investigation of 18,421 lines reveals the genetic architecture of rice
    Science (IF 44.7) Pub Date : 2024-07-04
    Xin Wei, Mengjiao Chen, Qi Zhang, Junyi Gong, Jie Liu, Kaicheng Yong, Qin Wang, Jiongjiong Fan, Suhui Chen, Hua Hua, Zhaowei Luo, Xiaoyan Zhao, Xuan Wang, Wei Li, Jia Cong, Xiting Yu, Zhihan Wang, Ruipeng Huang, Jiaxin Chen, Xiaoyi Zhou, Jie Qiu, Ping Xu, Jeremy Murray, Hai Wang, Yang Xu, Chenwu Xu, Gen Xu, Jinliang Yang, Bin Han, Xuehui Huang

    Understanding how numerous quantitative trait loci (QTL) shape phenotypic variation is an important question in genetics. To address this, we established a permanent population of 18,421 (18K) rice lines with reduced population structure. We generated reference-level genome assemblies of the founders and genotyped all 18K-rice lines through whole-genome sequencing. Through high-resolution mapping,

  •   A neutralizing antibody prevents postfusion transition of measles virus fusion protein
    Science (IF 44.7) Pub Date : 2024-06-27
    Dawid S. Zyla, Roberta Della Marca, Gele Niemeyer, Gillian Zipursky, Kyle Stearns, Cameron Leedale, Elizabeth B. Sobolik, Heather M. Callaway, Chitra Hariharan, Weiwei Peng, Diptiben Parekh, Tara C. Marcink, Ruben Diaz Avalos, Branka Horvat, Cyrille Mathieu, Joost Snijder, Alexander L. Greninger, Kathryn M. Hastie, Stefan Niewiesk, Anne Moscona, Matteo Porotto, Erica Ollmann Saphire

    Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced

  •   Structure of methylaluminoxane (MAO): Extractable [Al(CH 3 ) 2 ] + for precatalyst activation
    Science (IF 44.7) Pub Date : 2024-06-27
    Lubin Luo, Jarod M. Younker, Alexander V. Zabula

    Methylaluminoxane (MAO) is used as a precatalyst activator for million ton–scale production of commercial polyolefins, but its precise structure and associated activation mechanisms have been a fundamental research puzzle for more than 40 years. We report here the crystallographic characterization of an active MAO component, which reveals a discrete two-dimensional sheet cluster [Al 33 O 26 (CH 3 )

  •   Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites
    Science (IF 44.7) Pub Date : 2024-06-27
    Abderrazak El Albani, Arnaud Mazurier, Gregory D. Edgecombe, Abdelfattah Azizi, Asmaa El Bakhouch, Harry O. Berks, El Hafid Bouougri, Ibtissam Chraiki, Philip C. J. Donoghue, Claude Fontaine, Robert R. Gaines, Mohamed Ghnahalla, Alain Meunier, Alain Trentesaux, John R. Paterson

    Knowledge of Cambrian animal anatomy is limited by preservational processes that result in compaction, size bias, and incompleteness. We documented pristine three-dimensional (3D) anatomy of trilobites fossilized through rapid ash burial from a pyroclastic flow entering a shallow marine environment. Cambrian ellipsocephaloid trilobites from Morocco are articulated and undistorted, revealing exquisite

  •   GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans
    Science (IF 44.7) Pub Date : 2024-06-27
    Kyu Sik Kim, Joon Seok Park, Eunsang Hwang, Min Jung Park, Hwa Yun Shin, Young Hee Lee, Kyung Min Kim, Laurent Gautron, Elizabeth Godschall, Bryan Portillo, Kyle Grose, Sang-Ho Jung, So Lin Baek, Young Hyun Yun, Doyeon Lee, Eunseong Kim, Jason Ajwani, Seong Ho Yoo, Ali D. Güler, Kevin W. Williams, Hyung Jin Choi

    GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic

  •   Ephemeral stream water contributions to United States drainage networks
    Science (IF 44.7) Pub Date : 2024-06-27
    Craig B. Brinkerhoff, Colin J. Gleason, Matthew J. Kotchen, Douglas A. Kysar, Peter A. Raymond

    Ephemeral streams flow only in direct response to precipitation and are ubiquitous landscape features. However, little is known about their influence on downstream rivers. Here, we modeled ephemeral stream water contributions to the contiguous United States network of more than 20 million rivers, lakes, and reservoirs, finding that ephemeral streams contribute, on average, 55% of the discharge exported

  •   Homeocurvature adaptation of phospholipids to pressure in deep-sea invertebrates
    Science (IF 44.7) Pub Date : 2024-06-27
    Jacob R. Winnikoff, Daniel Milshteyn, Sasiri J. Vargas-Urbano, Miguel A. Pedraza-Joya, Aaron M. Armando, Oswald Quehenberger, Alexander Sodt, Richard E. Gillilan, Edward A. Dennis, Edward Lyman, Steven H. D. Haddock, Itay Budin

    Hydrostatic pressure increases with depth in the ocean, but little is known about the molecular bases of biological pressure tolerance. We describe a mode of pressure adaptation in comb jellies (ctenophores) that also constrains these animals’ depth range. Structural analysis of deep-sea ctenophore lipids shows that they form a nonbilayer phase at pressures under which the phase is not typically stable

  •   Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer
    Science (IF 44.7) Pub Date : 2024-06-27
    Krishnan K. Mahadevan, Allison M. Dyevoich, Yang Chen, Bingrui Li, Hikaru Sugimoto, Amari M. Sockwell, Kathleen M. McAndrews, Lakshmi Kavitha Sthanam, Huamin Wang, Shabnam Shalapour, Stephanie S. Watowich, Raghu Kalluri

    Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8 + T cell activation and elimination of ptPDAC

  •   Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor
    Science (IF 44.7) Pub Date : 2024-06-27
    Edwin N. Neumann, Tessa M. Bertozzi, Elaine Wu, Fiona Serack, John W. Harvey, Pamela P. Brauer, Catherine P. Pirtle, Alissa Coffey, Michael Howard, Nikita Kamath, Kenney Lenz, Kenia Guzman, Michael H. Raymond, Ahmad S. Khalil, Benjamin E. Deverman, Eric Vallabh Minikel, Sonia M. Vallabh, Jonathan S. Weissman

    Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts prion disease progression. In this study, we describe Coupled Histone tail for Autoinhibition Release of Methyltransferase (CHARM), a compact, enzyme-free epigenetic editor capable of silencing transcription

  •   Visible light–mediated aza Paternò–Büchi reaction of acyclic oximes and alkenes to azetidines
    Science (IF 44.7) Pub Date : 2024-06-27
    Emily R. Wearing, Yu-Cheng Yeh, Gianmarco G. Terrones, Seren G. Parikh, Ilia Kevlishvili, Heather J. Kulik, Corinna S. Schindler

    The aza Paternò–Büchi reaction is a [2+2]-cycloaddition reaction between imines and alkenes that produces azetidines, four-membered nitrogen-containing heterocycles. Currently, successful examples rely primarily on either intramolecular variants or cyclic imine equivalents. To unlock the full synthetic potential of aza Paternò–Büchi reactions, it is essential to extend the reaction to acyclic imine

  •   Mef2d potentiates type-2 immune responses and allergic lung inflammation
    Science (IF 44.7) Pub Date : 2024-06-27
    Aydan C. H. Szeto, Paula A. Clark, Ana C. F. Ferreira, Morgan Heycock, Emma L. Griffiths, Eric Jou, Jonathan Mannion, Shi-Lu Luan, Sophie Storrar, Martin D. Knolle, Patrycja Kozik, Helen E. Jolin, Padraic G. Fallon, Andrew N. J. McKenzie

    Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood

  •   Heterogeneous field response of hierarchical polar laminates in relaxor ferroelectrics
    Science (IF 44.7) Pub Date : 2024-06-27
    Hao Zheng, Tao Zhou, Dina Sheyfer, Jieun Kim, Jiyeob Kim, Travis D. Frazer, Zhonghou Cai, Martin V. Holt, Zhan Zhang, J. F. Mitchell, Lane W. Martin, Yue Cao

    Understanding the microscopic origin of the superior electromechanical response in relaxor ferroelectrics requires knowledge not only of the atomic-scale formation of polar nanodomains (PNDs) but also the rules governing the arrangements and stimulated response of PNDs over longer distances. Using x-ray coherent nanodiffraction, we show the staggered self-assembly of PNDs into unidirectional mesostructures

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