Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing

Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell–mediated killing. This is driven by succinate-mediated

Pregnancy confers partner-specific protection against complications in future pregnancy that parallel persistence of fetal microchimeric cells (FMcs) in mothers after parturition. We show that preexisting FMcs become displaced by new FMcs during pregnancy and that FMc tonic stimulation is essential for expansion of protective fetal-specific forkhead box P3 (FOXP3)–positive regulatory T cells (T reg

Mixed-matrix membranes (MMMs) that combine processable polymer with more permeable and selective filler have potential for molecular separation, but it remains difficult to control their interfacial compatibility and achieve ultrathin selective layers during processing, particularly at high filler loading. We present a solid-solvent processing strategy to fabricate an ultrathin MMM (thickness less

Jupiter’s moon Europa has a subsurface ocean beneath an icy crust. Conditions within the ocean are unknown, and it is unclear whether it is connected to the surface. We observed Europa with the James Webb Space Telescope (JWST) to search for active release of material by probing its surface and atmosphere. A search for plumes yielded no detection of water, carbon monoxide, methanol, ethane, or methane

Solid-state batteries with lithium metal anodes have the potential for higher energy density, longer lifetime, wider operating temperature, and increased safety. Although the bulk of the research has focused on improving transport kinetics and electrochemical stability of the materials and interfaces, there are also critical challenges that require investigation of the mechanics of materials. In batteries

Jupiter’s moon Europa has a subsurface ocean, the chemistry of which is largely unknown. Carbon dioxide (CO 2 ) has previously been detected on the surface of Europa, but it was not possible to determine whether it originated from subsurface ocean chemistry, was delivered by impacts, or was produced on the surface by radiation processing of impact-delivered material. We mapped the distribution of CO

Early in August this year, a high-profile summit was held in Belém, Brazil, where the eight Amazonian countries discussed the future of the Amazon. The nations recognized that the Amazon is very close to reaching a tipping point for turning into a degraded ecosystem. The result of their discussions was the Belém Declaration, an ambitious plan to protect and conserve the Amazon forests and to support

Mexican cartels lose many members as a result of conflict with other cartels and incarcerations. Yet, despite their losses, cartels manage to increase violence for years. We address this puzzle by leveraging data on homicides, missing persons, and incarcerations in Mexico for the past decade along with information on cartel interactions. We model recruitment, state incapacitation, conflict, and saturation

From surfboard-stealing sea otters to sailboat-chomping killer whales, the summer of 2023 was a landmark year of wild animal antics. Why is wildlife suddenly interacting with humans and their toys in this way? Speculation and headlines have espoused theories about learned behaviors due to enticements with food, increased intrusion, and proximity of humans in wild habitats, as well as aberrant animal

An estimated 23 million people live on floodplains affected by potentially dangerous concentrations of toxic waste derived from past and present metal mining activity. We analyzed the global dimensions of this hazard, particularly in regard to lead, zinc, copper, and arsenic, using a georeferenced global database detailing all known metal mining sites and intact and failed tailings storage facilities

Short tandem repeats (STRs) are enriched in eukaryotic cis -regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)–DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number

Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E -to- Z isomerization by using light of

Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-Å-resolution cryo–electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2

The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of

Insects perform feats of strength and endurance that belie their small stature. Insect-scale robots—although subject to the same scaling laws—demonstrate reduced performance because existing microactuator technologies are driven by low–energy density power sources and produce small forces and/or displacements. The use of high–energy density chemical fuels to power small, soft actuators represents a

Inactivation of the ubiquitin ligase Ube3a causes the developmental disorder Angelman syndrome, whereas increased Ube3a dosage is associated with autism spectrum disorders. Despite the enriched localization of Ube3a in the axon terminals including presynapses, little is known about the presynaptic function of Ube3a and mechanisms underlying its presynaptic localization. We show that developmental synapse

Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103.

Neuronal cell loss is a defining feature of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was

The mitogen-activated protein kinase (MAPK) p38α is a central component of signaling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double phosphorylation from MAPK kinases (MAP2Ks), because of the challenge of trapping a transient and dynamic heterokinase complex. We applied a multidisciplinary

Machines don’t have eyes, but you wouldn’t know that if you followed the progression of deep learning models for accurate interpretation of medical images, such as x-rays, computed tomography (CT) and magnetic resonance imaging (MRI) scans, pathology slides, and retinal photos. Over the past several years, there has been a torrent of studies that have consistently demonstrated how powerful “machine

Complex vocal learning, a critical component of human spoken language, has been assumed to be associated with more-advanced cognitive abilities. Tests of this hypothesis between individuals within a species have been inconclusive and have not been done across species. In this work, we measured an array of cognitive skills—namely, problem-solving, associative and reversal learning, and self-control—across

In many ways, the current US scientific enterprise is the intellectual descendant of 87 scientists who gathered in Philadelphia 175 years ago to establish the American Association for the Advancement of Science (AAAS, the publisher of Science ). They joined disparate, scattered scientific disciplines to identify and address key challenges of the day. Today’s research community and AAAS itself are reflections

Learning is highly important for edge intelligence devices to adapt to different application scenes and owners. Current technologies for training neural networks require moving massive amounts of data between computing and memory units, which hinders the implementation of learning on edge devices. We developed a fully integrated memristor chip with the improvement learning ability and low energy cost

Eosinophils are granulocytes that play an essential role in type 2 immunity and regulate multiple homeostatic processes in the small intestine (SI). However, the signals that regulate eosinophil activity in the SI at steady state remain poorly understood. Through transcriptome profiling of eosinophils from various mouse tissues, we found that a subset of SI eosinophils expressed neuromedin U (NMU)

Coarse-grained materials are widely accepted to display the highest strain hardening and the best tensile ductility. We experimentally report an attractive strain hardening rate throughout the deformation stage at 77 kelvin in a stable single-phase alloy with gradient dislocation cells, that even surpasses coarse-grained counterparts. Contrary to conventional understanding, the exceptional strain hardening

At the beginning of the 77th session of the United Nations General Assembly (UNGA 77) in September 2022, UN members agreed to design and implement solutions to guarantee food, water, and education for all; improve human development; reform the global financial system; secure a healthy environment; and embark on a path toward a less unjust global society. Transformative solutions are needed to respond

Lysosomes critically rely on bis(monoacylglycero)phosphate (BMP) to stimulate lipid catabolism, cholesterol homeostasis, and lysosomal function. Alterations in BMP levels in monogenic and complex neurodegeneration suggest an essential function in human health. However, the site and mechanism responsible for BMP synthesis have been subject to debate for decades. Here, we report that the Batten disease

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response

Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid

The cerebellum contains most of the neurons in the human brain and exhibits distinctive modes of development and aging. In this work, by developing our single-cell three-dimensional (3D) genome assay—diploid chromosome conformation capture, or Dip-C—into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we resolved the first 3D genome structures of single cerebellar cells, created life-spanning

Early-stage organ transplant rejection can be difficult to detect. Percutaneous biopsies occur infrequently and are risky, and measuring biomarker levels in blood can lead to false-negative and -positive outcomes. We developed an implantable bioelectronic system capable of continuous, real-time, long-term monitoring of the local temperature and thermal conductivity of a kidney for detecting inflammatory

Rising consumer demand for online food delivery has increased the consumption of disposable cutlery, leading to plastic pollution worldwide. In this work, we investigate the impact of green nudges on single-use cutlery consumption in China. In collaboration with Alibaba’s food-delivery platform, Eleme (which is similar to Uber Eats and DoorDash), we analyzed detailed customer-level data and found that

There are no cures for the most common neurodegenerative diseases. None of the currently approved treatments cure or halt these conditions; rather, they address symptoms or slow disease progression. A focus on protein deposits in the brain—a hallmark of Alzheimer’s disease (AD) and Parkinson’s disease (PD)—has led to the development of immunotherapy drugs. Other promising avenues of investigation include

The social benefit of technologies is frequently unevenly realized across the United States. Rural communities, individuals with disabilities, and historically marginalized groups face out-of-reach costs or lack access to products that meet their needs. Blame is typically placed on complicated regulatory processes or complex delivery systems, but this response neglects the problem that equity is not

Biotic responses to global change include directional shifts in organismal traits. Body size, an integrative trait that determines demographic rates and ecosystem functions, is thought to be shrinking in the Anthropocene. Here, we assessed the prevalence of body size change in six taxon groups across 5025 assemblage time series spanning 1960 to 2020. Using the Price equation to partition this change

The step that cleaves the carbon-halogen bond in copper-catalyzed cross-coupling reactions remains ill defined because of the multiple redox manifolds available to copper and the instability of the high-valent copper product formed. We report the oxidative addition of α-haloacetonitrile to ionic and neutral copper(I) complexes to form previously elusive but here fully characterized copper(III) complexes

Copper complexes are widely used in the synthesis of fine chemicals and materials to catalyze couplings of heteroatom nucleophiles with aryl halides. We show that cross-couplings catalyzed by some of the most active catalysts occur by a mechanism not previously considered. Copper(II) [Cu(II)] complexes of oxalamide ligands catalyze Ullmann coupling to form the C–O bond in aryl ethers by concerted oxidative

Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal cells to maintain their identity and serve as the body’s central bacterial filter. Liver cirrhosis drastically alters vascular architecture, but how KCs adapt is unclear. We used a mouse model of liver fibrosis and human tissue to examine immune adaptation. Fibrosis forced KCs to lose contact with parenchymal

Membranes with molecular-sized, high-density nanopores, which are stable under industrially relevant conditions, are needed to decrease energy consumption for separations. Interfacial polymerization has demonstrated its potential for large-scale production of organic membranes, such as polyamide desalination membranes. We report an analogous ultrafast interfacial process to generate inorganic, nanoporous

Enhanced warm, salty subarctic inflows drive high-latitude atlantification, which weakens oceanic stratification, amplifies heat fluxes, and reduces sea ice. In this work, we show that the atmospheric Arctic Dipole (AD) associated with anticyclonic winds over North America and cyclonic winds over Eurasia modulates inflows from the North Atlantic across the Nordic Seas. The alternating AD phases create

Human and environmental health are inextricably linked. Yet ocean ecosystem health is declining because of anthropogenic pollution, overexploitation, and the effects of global climate change. These problems affect billions of people dependent on oceans for their lives, livelihoods, and cultural practices. The importance of ocean health is recognized by scientists, managers, policy-makers, nongovernmental

Accretion of material onto a black hole drags any magnetic fields present inwards, increasing their strength. Theory predicts that sufficiently strong magnetic fields can halt the accretion flow, producing a magnetically arrested disk (MAD). We analyzed archival multiwavelength observations of an outburst from the black hole x-ray binary MAXI J1820+070 in 2018. The radio and optical fluxes were delayed

Phylogeny-based estimates suggesting a low germline mutation rate (μ) in baleen whales have influenced research ranging from assessments of whaling impacts to evolutionary cancer biology. We estimated μ directly from pedigrees in four baleen whale species for both the mitochondrial control region and nuclear genome. The results suggest values higher than those obtained through phylogeny-based estimates

Machine-learning methods have great potential to accelerate the identification of reaction conditions for chemical transformations. A tool that gives substrate-adaptive conditions for palladium (Pd)–catalyzed carbon-nitrogen (C–N) couplings is presented. The design and construction of this tool required the generation of an experimental dataset that explores a diverse network of reactant pairings across

Plant mitochondria represent the largest group of respiring organelles on the planet. Plant mitochondrial messenger RNAs (mRNAs) lack Shine-Dalgarno-like ribosome-binding sites, so it is unknown how plant mitoribosomes recognize mRNA. We show that “mitochondrial translation factors” mTRAN1 and mTRAN2 are land plant–specific proteins, required for normal mitochondrial respiration chain biogenesis. Our

Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals. Results showed that

Apolipoprotein B (apoB)–lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the

A long-standing problem associated with silicone synthesis is contamination of the polymer products with 10 to 15% cyclic oligosiloxanes that results from backbiting reactions at the polymer chain ends. This process, in competition with chain propagation through ring-opening polymerization (ROP) of cyclic monomers, was thought to be unavoidable and routinely leads to a thermodynamically controlled

Chromatin inheritance entails de novo nucleosome assembly after DNA replication by chromatin assembly factor-1 (CAF-1). Yet direct knowledge about CAF-1’s histone binding mode and nucleosome assembly process is lacking. In this work, we report the crystal structure of human CAF-1 in the absence of histones and the cryo–electron microscopy structure of CAF-1 in complex with histones H3 and H4. One histone

Plant cell surface pattern recognition receptors (PRRs) and intracellular immune receptors cooperate to provide immunity to microbial infection. Both receptor families have coevolved at an accelerated rate, but the evolution and diversification of PRRs is poorly understood. We have isolated potato surface receptor Pep-13 receptor unit (PERU) that senses Pep-13, a conserved immunogenic peptide pattern

While the world recovers from the COVID-19 pandemic, another crisis continues to spiral at a much faster speed than was expected. Climate change is dominating our lives and causing a high level of distress . Countries all over the world are struggling to survive the damage caused by extreme events. They are trying to control wildfires, rebuild roads and houses damaged by floods, and learn to survive

Carbon offsets from voluntary avoided-deforestation projects are generated on the basis of performance in relation to ex ante deforestation baselines. We examined the effects of 26 such project sites in six countries on three continents using synthetic control methods for causal inference. We found that most projects have not significantly reduced deforestation. For projects that did, reductions were

Driven by fierce winds and dry, hot conditions, the fire that consumed Maui’s Lahaina—the deadliest US fire in more than a century—is a sad, stark reminder of the environmental pressures on the Hawaiian islands caused by overdevelopment and industrial tourism. As Maui emerges from the ashes, there is an opportunity to reimagine the governance of habitats through sustainable and equitable processes

On a flat map of the Earth, continents are inevitably distorted. Reciprocally, curving a plate simultaneously in two directions requires a modification of in-plane distances, as Gauss stated in his seminal theorem. Although emerging architectured materials with programmed in-plane distortions are capable of such shape morphing, an additional control of local bending is required to precisely set the

Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. We explored how mechanosensation affords exquisite awareness of the genitals and controls reproduction in mice and humans. Using genetic strategies and in vivo functional imaging, we demonstrated that the mechanosensitive ion channel PIEZO2 (piezo-type mechanosensitive

Coronal holes are areas on the Sun with open magnetic field lines. They are a source region of the solar wind, but how the wind emerges from coronal holes is not known. We observed a coronal hole using the Extreme Ultraviolet Imager on the Solar Orbiter spacecraft. We identified jets on scales of a few hundred kilometers, which last 20 to 100 seconds and reach speeds of ~100 kilometers per second.

Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp 3 )–C(sp 2 ) σ bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp 3 )–C(sp 2 ) σ bond–rupturing cross-coupling reactions for the construction of new C(sp 3 )–N bonds. We have used this unconventional transformation

The intestinal microbiota regulates mammalian lipid absorption, metabolism, and storage. We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA (lncRNA) Snhg9 (small nucleolar RNA host gene 9) in small intestinal epithelial cells. Snhg9 suppressed the activity of peroxisome proliferator–activated receptor γ (PPARγ)—a central regulator

Ultracool dwarfs are a category of astronomical objects including brown dwarfs and very low-mass stars. Radio observations of ultracool dwarfs have measured their brightness as a function of time (light-curves) and spectral energy distributions, providing insight into their magnetic fields. We present spatially resolved radio observations of the brown dwarf LSR J1835+3259 using very long baseline interferometry