Glaciers populate the mountain ranges of the western conterminous United States and despite their importance to alpine hydrology, their area and volume change have never been comprehensively evaluated. Our study shows that since the mid-twentieth century about one-quarter of the glaciers have disappeared and the overall area and volume are reduced by one-third. The pattern of glacier shrinkage suggests most glaciers in the conterminous United States are largely maintained by local topographic in
Capturing enzymes under native turnover conditions remains a grand challenge in structural biology. Here, we develop a reaction-based cryo-electron microscopy (cryo-EM) strategy that directly samples Drosophila melanogaster cytidine triphosphate synthase (CTPS) from actively catalyzing mixtures containing only natural substrates and allosteric effectors. By integrating reaction-based sampling with three-dimensional variability analysis, we resolve a continuous conformational spectrum of CTPS dur
Cytidine triphosphate (CTP), a fundamental building block of RNA, plays vital roles in diverse biological processes. CTP synthase (CTPS) is the only known enzyme for de novo synthesis of CTP. Efficient CTPS catalysis requires guanosine triphosphate (GTP) in a dose-dependent, nonconsumptive manner; however, the precise mechanism by which GTP drives CTP formation remains unclear. Here, we integrate a series of cryo-EM structures of Drosophila melanogaster CTPS captured from actively catalyzing sam
Antiferromagnetism and superconductivity are often viewed as competing orders in correlated electron systems. Here, we demonstrate that kinetic frustration in hole motion facilitates their coexistence within the square-lattice repulsive Hubbard model. Combining exact analytical solutions on tailored geometries with large-scale numerical simulations, we reveal a robust pairing mechanism: Holes on opposite sublattices behave as if they carry opposite effective charges due to spin singlet formation
Evolutionary shape changes of the vertebrate semicircular canals (SCCs) are often ascribed to evolutionary transitions in locomotion, including the origin of flight during the dinosaur-bird transition. However, the potential for transformations of braincase architecture to influence SCC shape independent of sensory-functional adaptation has generally been overlooked. We evaluate the influence of both factors using a large dataset of 146 living and recently extinct crown birds, including taxa rep
Brain network formation unfolds on a nonuniform developmental timetable, with different cortical regions generating connections at different developmental phases. Generative network models (GNMs) aim to uncover the principles underpinning the organization of connectomes by creating synthetic networks according to simple computational rules. These models capture the connectome's topology, operationalized here as the cumulative distributions of network metrics (e.g., modularity, small-worldness, r
Limited selenium (Se) accumulation in agricultural products contributes to widespread dietary Se deficiency, posing a global nutritional threat. Efficient agronomic strategies to enhance Se biofortification in crops are still lacking. Here, we reveal the synergistic effects of shading and Se nanoparticles application on Se biofortification in tea leaves. Field experiments demonstrate that shading enhances Se accumulation in tea leaves under sufficient Se supply, through activating Se metabolism
Tetrapods arose from lobe-finned fishes with a notochord-dominated axial column 1-3 . During this transition, the skull became separated from the shoulder girdle 4-6 , giving rise to a neck region. This head-shoulder separation has generated hypotheses suggesting that neck mobility increased during the origin of tetrapods, facilitating the ecological transition towards more terrestrial habitats 4,5,7-9 . However, incompletely co-ossified vertebral components 10 have posed a challenge to mod
Cryptovivipary and vivipary, referred to as (crypto)vivipary, occur across multiple angiosperm lineages and enable embryos to continue developing before dispersal. Yet, this trait raises a fundamental question: how are seed-specific abscisic acid (ABA) responses modulated to support continuous embryonic growth without compromising ABA-dependent vegetative stress tolerance? Here, integrating phylogenomic analyses of independently evolved (crypto)viviparous lineages with spatiotemporal transcripto
The Benjamini-Hochberg (BH) procedure is the standard method for controlling the false discovery rate (FDR) in large-scale studies involving testing multiple hypotheses. Whether the BH procedure controls the FDR for every correlation structure among two-sided Gaussian tests has been a long-standing question, and a positive answer has been believed. Here, we settle the question negatively, by providing examples of Gaussian factor models for which the BH method fails to control the FDR at the nomi
Understanding the structural conformation and dynamics of nucleic acids in solution is critical for the development of nucleic acid therapeutics involving antisense or mRNA therapies, where controlling stability, efficacy, and manufacturability are important. Circular dichroism (CD) spectroscopy allows rapid and nondestructive solution analysis of the spatial arrangements of nucleic acids. While widely used to analyze protein structure, the potential of CD for DNA- and RNA-based pharmaceutical a
Existing models of learning in the brain explain how given circuits learn, but not how biology could assemble those circuits in the first place. To address this gap, we formulate Self-Assembling Learning-the study of how learning systems can emerge from lower-level interactions-and introduce one example mechanism, the Self-Assembling Motif (SAM). SAM is self-assembling at two scales: The motif emerges from initially random connectivity under heterosynaptic plasticity rules, and networks of SAMs,
A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO 2 ) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Althoug
Transposable elements (TEs) are epigenetically silenced through multiple mechanisms, including heterochromatin formation and DNA methylation. Prior studies have implicated SETDB1 and the Human Silencing Hub (HUSH) complex in heterochromatin formation-based TE repression, but precise characterization of repeat subclass and locus-specific effects for SETDB1 and related mechanisms has been limited by short-read transcriptome mapping. Here, we use long-read RNA sequencing mapped to a telomere-to-tel
Quantum Fisher information (QFI) sets the ultimate precision of optical phase measurements and can reveal multiphoton entanglement. Yet the photon-number fluctuations that encode this sensitivity are difficult to convert into an electrical signal. We theoretically predict that a photodetector utilizing the shot noise of the quantum-geometric shift current of exciton polaritons can measure photon-number statistics and, for pure states, infer the QFI. By solving the Lindblad equation, we obtain th
Polyethylene (PE) accounts for more than a quarter of all plastic produced, owing to its exceptional material properties and scalable production. 1 However, pristine PE lacks critical properties, such as adhesion, that are needed for many additional commercial applications. 2 Selective post-polymerization functionalization of PE can impart properties that are absent in the pristine polymer, but global functionalization in a uniform medium perturbs bulk properties. 3-5 Here, we demonstrate cataly
Modern slavery remains pervasive across many economic sectors. Progress toward eradicating it has been partially hindered by a lack of tested, comprehensive policy responses. Using data on millions of cattle transactions in Brazil, we evaluated how ranchers changed their selling behavior after being added to the “Dirty List,” a public registry that names and shames employers found to use modern slavery. Dirty Listed ranchers significantly reduced direct sales to slaughterhouses that signed susta
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection 1 . However, the functions and mechanisms of many DRTs remain unknown 2 . Here we identify a new antiviral defense system, DRT10, that associates with a noncoding RNA (ncRNA) to catalyze processive, protein-primed synthesis of tandem-repeat DNA. Reverse transcription is templated by a defined ncRNA region with a characteristic sequence pattern a
Simulations of the ocean wave climate are critical for assessment of coastal processes and hazards in observation sparse regions such as the Arctic. While the multidecade wind and ice datasets necessary for driving long-term wave simulations have proven reliable for such efforts, the presence of landfast ice along shorelines at scales not represented by these data has been a persistent uncertainty impeding accurate analysis of impacts to Arctic coasts. Here, we explore this uncertainty by produc
Informal settlements are widespread and rapidly growing, often associated with high vulnerabilities. However, global-scale understanding on their spatial distribution and complexity of vulnerability is limited. Here, we delineate the informal settlements across a sample of 1,914 cities of the Global South by integrating Sentinel-2 imagery with deep learning models, and we explore the heterogeneity of vulnerability using Urban Informal Settlement Vulnerability Index that encompasses living condit
Abstract Nanocrystalline metal halide perovskites are promising light emitters for light-emitting diodes (PeLEDs) because they suppress the intrinsic problem of exciton dissociation through charge confinement within nanocrystalline domains. Although these nanostructures have enabled high-emission efficiencies, such confinement strategies typically result in significantly reduced charge transport. This limitation is attributed to numerous grain boundaries, which induce severe charge carrier scatt
Abstract Hetero-cycloaddition reactions are powerful, atom-economical strategies for the rapid construction of heterocyclic frameworks from readily available building blocks. Over the past two decades, advances in photochemistry, photocatalysis, and modern excitation strategies have driven remarkable developments in the field. By accessing electronically excited states, light enables cycloaddition pathways inaccessible under classical thermal conditions, providing access to reactive radical, ion
Systemic therapy for breast cancer has evolved rapidly since 2020, driven by the expansion of targeted therapies, antibody-drug conjugates, and immunotherapy across biologic subtypes. The integration of tumor molecular profiling and germline testing has enabled increasingly personalized, biomarker-guided treatment strategies. In hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, cyclin-dependent kinase 4 and 6 inhibitors remain foundational, whereas phos
Fast radio bursts (FRBs) are millisecond-duration radio transients from extragalactic sources. Their frequency and polarization properties are affected by plasma and magnetic fields along the line of sight to Earth. We report radio observations of FRB 20240304B and near-infrared follow-up to identify its host galaxy. The host is a low-mass, clumpy, star-forming galaxy at redshift 2.148 ± 0.0013, corresponding to 3 billion years after the Big Bang. This FRB occurred during the peak of cosmic
The generation and manipulation of entanglement with low error are essential in quantum information systems. In practice, two-qubit entangling gates constitute a dominant error source, limiting circuit depths and performance in fault-tolerant architectures. Using a neutral-atom quantum processor, we realized entangling controlled- Z gates with a high-Rabi-frequency smooth-amplitude pulse, employing state-selective readout and qubit reuse for fast calibration, and achieved a fidelity of 99.854(4)
Low-symmetry materials unlock rich Berry curvature physics and anomalous transport phenomena that are forbidden in high-symmetry quantum systems through rigorous crystalline symmetry constraints. Current approaches rely on external fields or complex heterogeneous stacking to break crystalline symmetries, which hinders scalable device integration. In this work, we demonstrate surface premelting engineering to create wafer-scale low-symmetry graphene on germanium-110 [Ge(110)]. Controlled premelti
Lupins ( Lupinus spp.) are promising protein crops that accumulate bitter and toxic quinolizidine alkaloids (QAs). The effective removal of QAs through new breeding technologies is hampered by a poor understanding of their biosynthesis. In this study, we used pathway reconstruction and mutant analysis to elucidate the full QA pathway in L. angustifolius [narrow-leafed lupin (NLL)] comprising 15 enzymatic steps. Major latex protein–like proteins play a prominent role in the pathway by acceleratin
The origin of Bronze Age tin is one of the most compelling mysteries in global archaeology. A number of studies were carried out to identify fingerprints to determine tin sources, but all failed to suit the contexts of Bronze Age China. This study provides the first comprehensive provenance analysis of the tin ore utilized during the Shang dynasty of China. Using U-Pb dating analysis on cassiterite grains surviving in various contexts including primary smelting site, metal resource hoard, and br
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that detects aberrant DNA and activates the STING-dependent innate immune response. Although cGAS is predominantly localized in the nucleus under physiological conditions, its nuclear function remains incompletely understood. Here, we identify nuclear cGAS as a transcriptional repressor that restrains inflammatory gene expression independently of STING signaling. Using macrophages challenged with lipopolysaccharide (LPS), we found that cGA
Post-transcriptional transfer RNA (tRNA) modifications dynamically regulate translational capacity, yet whether the tRNA epitranscriptome is temporally coordinated with gene expression programs during bacterial growth remains unknown. Here, we combine time-resolved nanopore tRNA sequencing, liquid chromatography-tandem mass spectrometry modification profiling, transcriptomics, and proteomics across the Pseudomonas aeruginosa PA14 growth cycle to show that tRNA-modifying enzymes, the correspondin
Giredestrant and everolimus target the estrogen receptor (ER) pathway and the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, respectively, which are implicated in endocrine-therapy resistance. In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease progression or recurrence after receipt of a
Menopause is an important biological transition with up to 72 symptoms that shapes aging trajectories across organs and encompasses ~40% of the female lifespan. Although menopause awareness is increasing, research on strategies for menopause symptom management and optimizing health in the postmenopausal period is lacking. This Review highlights that menopause characteristics, such as type, timing, and symptom burden, influence health outcomes and later-life disease risk. Similarly, menopause hor
Stationary entanglement between the motion of macroscopic objects and light is a long-standing goal of quantum optomechanics, with implications for both fundamental tests of quantum physics and emerging quantum technologies. We report the generation of quantum entanglement between the center-of-mass motion of a nanosphere levitated in an optical tweezer inside an optical cavity and the electromagnetic field. Using heterodyne detection, we reconstructed the full set of optomechanical correlations
Enhancing toughness in nanocomposites often involves viscoelastic organic phases, but this typically reduces stiffness. We describe a high-modulus toughening mechanism in mature Cristaria plicata nacre arising from a crystalline organic-inorganic framework composed of aragonite nanorods alternately integrated with intratabular biomolecular crystallites. Due to the critical slip-length effect, these crystalline units approach the theoretical limits of modulus and strength. The nanoconfined biomol
Optical frequency combs (OFCs) are frequency rulers essential for precision metrology, next-generation navigation and testing of fundamental physics 1 . Despite intense efforts, chip-integrated OFCs remain laboratory-bound, unable to fulfil their promise of compact and cost-effective deployment. Although improvements in fabrication and integration are important, a conceptual limitation has stymied progress: on-chip OFC architectures have aimed to miniaturize their table-top counterparts and reli
Abstract The dazzling stripes found on zebras and snakes have long been thought to interfere with predator motion perception 1,2 , but this hypothesis has received little empirical support so far 3 . Butterflies show enormously diverse and high-contrast wing patterns, the function of which has inspired intense theoretical debate and research 4 . Here we suggest that butterfly wing patterns work in tandem with flight dynamics to create visual illusions that confuse predators. We use multiple line
Insecticide resistance poses a major challenge to global pest management, yet its cascading effects on ecological networks remain poorly understood. Here, we show that target-site-resistant herbivorous insects can accumulate unmetabolized insecticides and inadvertently function as "toxic prey," impairing the fitness of their natural enemies. Using neonicotinoid- and spinosyn-resistant Myzus persicae and genetically modified Drosophila melanogaster , we demonstrate that resistant hosts surviving
Humans collaborating with AI hold the promise of achieving superior outcomes compared to either acting alone (i.e., human-AI synergy). However, the conditions that facilitate such synergy when humans are advised by AI are not well understood. A recent meta-analysis showed that, on average, human-AI combinations do not outperform the better individual agent. We argue that this pessimistic conclusion arises from insufficient attention to human learning in experimental designs. To substantiate this
In congenital handlessness, where individuals rely on their feet for compensatory manual functions, reorganization in the primary somatosensory cortex (SI) appears to be limited to local shifts by adjacent body parts. It remains unclear how congenital handlessness and lifelong compensatory foot use shape the sensorimotor system beyond SI, and whether compensatory abilities can drive broader functional reorganization. Here, we used task-based and resting-state functional MRI (fMRI) to investigate
The cGAS (cyclic GMP-AMP synthase)-STING (Stimulator of interferon genes) pathway plays a central role in antiviral innate immunity in vertebrates. Recent studies have shown that invertebrates possess a related cGLR (cGAS-like receptor)-STING pathway. However, due to the lack of direct evidence demonstrating viral evasion of cGLR-STING-mediated immunity, the functional importance of cGLR-STING pathway in antiviral responses remains uncertain in invertebrates. Here, we show that an insect picorna
Tony Leggett (1938-2026) was one of the great theoretical physicists of his generation, specializing in the quantum mechanics of fluids and solids. Rightly recognized by the 2003 Nobel Prize in Physics for his explanation of the experiments discovering the superfluidity of helium-3, he will be remembered equally for his pioneering inquiries into the transition from the quantum to the classical world and the extent to which we can observe quantum phenomena on macroscopic scales.
Mg 3 (Sb, Bi) 2 has emerged as a promising material due to its favorable combination of high thermoelectric performance and ductility. However, a key question remains regarding how plastic deformation affects its thermoelectric properties. Here we investigate the evolution of deformation-induced defects and their influence on the transport and mechanical properties of Mg 3 (Sb, Bi) 2 . Compressive deformation introduces high densities of dislocations and deformation twins, accompanied by a prono
Retatrutide is a triple-receptor agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks. Primary outcomes (evaluated in the 9-mg and 12-mg groups each vs. placebo) were the percent change in body weight and the change in the WOM
Wavelike bosonic particles can accumulate in a single mode characterized by a particular wavelength, and such condensates are at the heart of phenomena such as superconductivity and superfluidity where usually a single complex number describes their state. If there are several flavors of excitations or particles, a vector containing several complex numbers can characterize multicomponent condensation, thus opening new possibilities for textures, dynamics, and devices. Thus far, multicomponent co
People often cooperate out of concern for their reputation. The corresponding theory of indirect reciprocity predicts that such cooperation can only evolve if people's opinions of each other are sufficiently correlated. This correlation, however, can be difficult to achieve when individuals form their opinions independently from one another, as in private assessment models. In that case, errors can generate disagreements that propagate throughout a population. Here, we identify a simple mechanis
Shoot branching patterns and their diversity arise from variable activities of axillary meristems (AMs). A common feature of flowering plants is delayed AM initiation and growth during the vegetative phase, followed by a sudden and rapid acceleration of apical AM initiation during the reproductive phase. The mechanisms underlying this pronounced developmental shift are poorly understood. During tomato floral transition, the primary shoot meristem (PSM) terminates in a flower after producing two
David Botstein, who died on February 27, 2026, was a towering figure in the field of modern molecular genetics. His research career was largely focused on the development of methods to better understand biological systems, beginning with his early work on Salmonella phage P22 and yeast, where he exploited the use of conditional lethal mutations as suppressors to identify genes with common functions and to order them in a pathway. He is best remembered for developing restriction fragment length p
We pioneered a strategy based on low-frequency vibronic coupling to design narrowband room-temperature phosphorescent (RTP) materials. Here we select coronene derivative (CoDe) system and report that attaching aroyl group to the coronene core disrupts its intrinsic symmetry and introduces abundant low-frequency vibrational modes, thereby affording efficient room-temperature phosphorescence with a full width at half maximum (FWHM) of approximately 25 nm or narrower. In CoDe systems functionalized
DNA methyltransferase DNMT3A-mediated de novo DNA methylation is important for proper regulation of gene expression and genomic stability in development. The DNMT3A R882H (DNMT3A R882H ) mutation, a hot-spot mutation in acute myeloid leukemia and developmental disorders, exerts a dominant-negative effect in DNMT3A-mediated DNA methylation through promoting high-order protein assembly. However, due to the lack of structural knowledge on DNMT3A homo-oligomers, the mechanism behind wild-type DNMT3A
Twenty-five years after the draft of the human genome sequence, genomics has revolutionized many areas of biology, the diagnosis of familial and early-onset diseases, and the development of targeted therapies, particularly in oncology. Genomic knowledge has had little effect on the diagnosis and treatment of most common adult-onset conditions. Genomewide association studies have revealed that for these conditions, thousands of genetic variants of small effect underpin the polygenic nature of ris
