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

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 )

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 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 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

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

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

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

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

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

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

Crystalline materials with uniform molecular-sized pores are desirable for a broad range of applications, such as sensors, catalysis, and separations. However, it is challenging to tune the pore size of a single material continuously and to reversibly distinguish small molecules (below 4 angstroms). We synthesized a series of ionic covalent organic frameworks using a tetraphenoxyborate linkage that

In the face of rapid global changes, the agricultural sector in Latin America and the Caribbean (LAC) stands at a crossroads. The region, known for its rich biodiversity and considerable agricultural output, is increasingly challenged by climate change, political and economic pressures, and the need for efficient and effective innovations to sustain the transformation of agrifood systems toward more

Despite declines in transportation emissions, urban North America and Europe still face unhealthy air pollution levels. This has challenged conventional understanding of the sources of their volatile organic compound (VOC) precursors. Using airborne flux measurements to map emissions of a wide range of VOCs, we demonstrate that biogenic terpenoid emissions contribute ~60% of emitted VOC OH reactivity

Dark clouds loom on the nuclear horizon, with threats from all directions: Russia’s nuclear bombast in its war on Ukraine, China’s construction of hundreds of nuclear missile silos, North Korea’s missile testing, India and Pakistan’s ongoing nuclear competition, and Iran’s push toward nuclear weapons capability. In response, US policy-makers are discussing whether a further American nuclear arms buildup

High dynamic strength is of fundamental importance for fibrous materials that are used in high–strain rate environments. Carbon nanotube fibers are one of the most promising candidates. Using a strategy to optimize hierarchical structures, we fabricated carbon nanotube fibers with a dynamic strength of 14 gigapascals (GPa) and excellent energy absorption. The dynamic performance of the fibers is attributed

Heart rate (HR) can be voluntarily regulated when individuals receive real-time feedback. In a rat model of HR biofeedback, the neocortex and medial forebrain bundle were stimulated as feedback and reward, respectively. The rats reduced their HR within 30 minutes, achieving a reduction of approximately 50% after 5 days of 3-hour feedback. The reduced HR persisted for at least 10 days after training

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti–PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non–small

The interplay of topology and optics provides a route to pursue robust photonic devices, with the application to photonic quantum computation in its infancy. However, the possibilities of harnessing topological structures to process quantum information with linear optics, through the quantum interference of photons, remain largely uncharted. Here, we present a Hong-Ou-Mandel interference effect of

Directional liquid transport has been widely observed in various species including cacti, spiders, lizards, the pitcher plant Nepenthes alata , and Araucaria leaves. However, in all these examples the liquid transport for a specific liquid is completely restricted in a fixed direction. We demonstrate that Crassula muscosa shoot surfaces have the ability to transport a specific liquid unidirectionally

Intercellular communication in the nervous system occurs through the release of neurotransmitters into the synaptic cleft between neurons. In the presynaptic neuron, the proton pumping vesicular- or vacuolar-type ATPase (V-ATPase) powers neurotransmitter loading into synaptic vesicles (SVs), with the V 1 complex dissociating from the membrane region of the enzyme before exocytosis. We isolated SVs

On-chip generation of optical frequency combs using nonlinear ring resonators has enabled numerous applications of combs that were otherwise limited to mode-locked lasers. Nevertheless, on-chip frequency combs have relied predominantly on single-ring resonators. In this study, we experimentally demonstrate the generation of a novel class of frequency combs, the topological frequency combs, in a two-dimensional

Using CRISPR/Cas9 nicking enzymes, we examine the interaction between the replication machinery and single strand breaks, one of the most common forms of endogenous DNA damage. We show that replication fork collapse at leading strand nicks generates resected single-ended double-strand breaks (seDSBs) that are repaired by homologous recombination (HR). If these seDSBs are not promptly repaired, arrival

Photosystem II starts the photosynthetic electron transport chain that converts solar energy into chemical energy and thus sustains life on Earth. It catalyzes two chemical reactions: water oxidation to molecular oxygen and plastoquinone reduction. Coupling of electron and proton transfer is crucial for efficiency; however, the molecular basis of these processes remains speculative owing to uncertain

Vegetation and soils are taking up approximately 30% of anthropogenic carbon dioxide emissions because of small imbalances in large gross carbon exchanges from productivity and turnover that are poorly constrained. We combined a new budget of radiocarbon produced by nuclear bomb testing in the 1960s with model simulations to evaluate carbon cycling in terrestrial vegetation. We found that most state-of-the-art

Control over quantum systems is typically achieved by time-dependent electric or magnetic fields. Alternatively, electronic spins can be controlled by spin-polarized currents. Here, we demonstrate coherent driving of a single spin by a radiofrequency spin-polarized current injected from the tip of a scanning tunneling microscope into an organic molecule. With the excitation of electron paramagnetic

Extreme weather events radically alter ecosystems. When ecological damage persists, selective pressures on individuals can change, leading to phenotypic adjustments. For group-living animals, social relationships may be a mechanism enabling adaptation to ecosystem disturbance. Yet whether such events alter selection on sociality and whether group-living animals can, as a result, adaptively change their

Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti–PD-1 antibody

The oxygen evolution reaction is the bottleneck to energy-efficient water-based electrolysis for the production of hydrogen and other solar fuels. In proton exchange membrane water electrolysis (PEMWE), precious metals have generally been necessary for the stable catalysis of this reaction. In this work, we report that delamination of cobalt tungstate enables high activity and durability through the

The field-effect transistor (FET) is a cornerstone of modern electronics, pivotal in the development of compact and efficient integrated microprocessors and memory storage devices capable of low-power operation. At the heart of a FET is a semiconductor channel, typically made of materials such as silicon, which links the source to the drain. Positioned directly beneath an insulator that overlays the

The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral or calvarial bone marrow and meninges, bypassing the blood-brain barrier. This

Jonathan Haidt’s new book, The Anxious Generation: How the Great Rewiring of Childhood Is Causing an Epidemic of Mental Illness , is a hot seller that makes the case that smartphones and social media are largely responsible for the current mental health crisis among young people and that restricting their use below certain ages (14 for smartphones and 16 for social media) can have a positive effect

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

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

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’

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

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

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

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

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

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 structures of two different heteromeric odorant receptor complexes containing

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

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

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

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

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

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

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 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

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

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). In this work, 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

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

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

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 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

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

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

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

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

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