COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary

Catalytic dehydrogenation and hydrogenation of amines and alcohols are important in the synthesis of fine chemicals. Despite several efficient homogeneous catalysts having been identified, highly active heterogeneous catalysts remain elusive, although they would meet an unmet need. Here, we show that bimetallic Pd-Au nanoparticles with Pd-to-Au molar ratios of 3:1 immobilized on multiwall carbon nanotubes

When a medium is rapidly heated and cooled, heat transfers to its surroundings as sound. A controllable source of this sound is realized through joule heating of thin, conductive films by an alternating current. Here, we show that arrays of these sources generate sound unique to this mechanism. From the sound alone, we spatially resolve current flow by varying the film geometry and electrical phase

Bright, iridescent colors observed in nature are often caused by light interference within nanoscale periodic lattices, inspiring numerous strategies for coloration devoid of inorganic pigments. Here, we describe and characterize the septum of the Lunaria annua plant that generates large (multicentimeter), freestanding iridescent sheets, with distinctive silvery-white reflective appearance. This originates

How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically

Repeated concussion represents a serious health problem as it can result in various brain pathologies, ranging from minor focal tissue injury to severe chronic traumatic encephalopathy. The calcium-dependent protease, calpain, participates in the development of neurodegeneration following concussion, but there is no information regarding the relative contribution of calpain-1 and calpain-2, the major

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed

When we make economic choices, the brain first evaluates available options and then decides whether to choose them. Midbrain dopamine neurons are known to reinforce economic choices through their signal evoked by outcomes after decisions are made. However, although critical internal processing is executed while decisions are being made, little is known about the role of dopamine neurons during this

Chronic inflammatory gastric reflux alters the esophageal microenvironment and induces metaplastic transformation of the epithelium, a precancerous condition termed Barrett’s esophagus (BE). The microenvironmental niche, which includes the extracellular matrix (ECM), substantially influences cell phenotype. ECM harvested from normal porcine esophageal mucosa (eECM) was formulated as a mucoadhesive

Plant economics run on carbon and nutrients instead of money. Leaf strategies aboveground span an economic spectrum from “live fast and die young” to “slow and steady,” but the economy defined by root strategies belowground remains unclear. Here, we take a holistic view of the belowground economy and show that root-mycorrhizal collaboration can short circuit a one-dimensional economic spectrum, providing

Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the Ser/Thr phosphatase calcineurin (CN). It has been shown that excessive inhibition of CN is a critical factor for Down syndrome and Alzheimer’s disease. Here, we determined RCAN1’s mode of action. Using a combination of structural, biophysical, and biochemical studies, we show that RCAN1 inhibits CN via multiple routes: first, by blocking

Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA’s short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single

Cell lines are commonly used as cancer models. The tissue of origin provides context for understanding biological mechanisms and predicting therapy response. We therefore systematically examined whether cancer cell lines exhibit features matching the presumed cancer type of origin. Gene expression and DNA methylation classifiers trained on ~9000 tumors identified 35 (of 614 examined) cell lines that

Increased appreciation of 5-hydroxymethylcytosine (5hmC) as a stable epigenetic mark, which defines cell identity and disease progress, has engendered a need for cost-effective, but high-resolution, 5hmC mapping technology. Current enrichment-based technologies provide cheap but low-resolution and relative enrichment of 5hmC levels, while single-base resolution methods can be prohibitively expensive

Kv2.1 channels mediate cell death–enabling loss of cytosolic potassium in neurons following plasma membrane insertion at somatodendritic clusters. Overexpression of the carboxyl terminus (CT) of the cognate channel Kv2.2 is neuroprotective by disrupting Kv2.1 surface clusters. Here, we define a seven–amino acid declustering domain within Kv2.2 CT (DP-2) and demonstrate its neuroprotective efficacy

Slow earthquakes, like regular earthquakes, result from unstable frictional slip. They produce little slip and can therefore repeat frequently. We assess their predictability using the slip history of the Cascadia subduction between 2007 and 2017, during which slow earthquakes have repeatedly ruptured multiple segments. We characterize the system dynamics using embedding theory and extreme value theory

In thermal and nuclear power plants, 70% of the generated thermal energy is lost as waste heat. The temperature of the waste heat is below the boiling temperature of water. Here, we show a long-term heat-storage material that absorbs heat energy at warm temperatures from 38°C (311 K) to 67°C (340 K). This unique series of material is composed of scandium-substituted lambda-trititanium-pentoxide (λ-ScxTi3−xO5)

Chromatin conformation regulates gene expression and thus, constant remodeling of chromatin structure is essential to guarantee proper cell function. To gain insight into the spatiotemporal organization of the genome, we use high-density photoactivated localization microscopy and deep learning to obtain temporally resolved super-resolution images of chromatin in living cells. In combination with high-resolution

Many cancer patients not responding to current immunotherapies fail to produce tumor-specific T cells for various reasons, such as a lack of recognition of cancer cells as foreign. Here, we suggest a previously unidentified method for xenogenizing (turning self to non-self) tumors by using fusogenic exosomes to introduce fusogenic viral antigens (VSV-G) onto the tumor cell surface. We found that xenogenized

Every day, we do things that cause effects in the outside world with little doubt about who caused what. To some, this sense of agency derives from a post hoc reconstruction of a likely causal relationship between an event and our preceding movements; others propose that the sense of agency originates from prospective comparisons of motor programs and their effects. Using functional magnetic resonance

Most systems have more than two stable crystalline states in the phase diagram, which is known as polymorphism. Crystallization in such a system is often under strong influence of competing orderings linked to those crystals. However, how such competition affects crystal nucleation and ordering toward the final crystalline state is largely unknown. This is primarily because the competition takes place

Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein

Rigid electromagnetic actuators serve our society in a myriad of ways for more than 200 years. However, their bulky nature restricts close collaboration with humans. Here, we introduce soft electromagnetic actuators (SEMAs) by replacing solid metal coils with liquid-metal channels embedded in elastomeric shells. We demonstrate human-friendly, simple, stretchable, fast, durable, and programmable centimeter-scale

A major critical issue in systemically administered nanomedicines is nonspecific clearance by the liver sinusoidal endothelium, causing a substantial decrease in the delivery efficiency of nanomedicines into the target tissues. Here, we addressed this issue by in situ stealth coating of liver sinusoids using linear or two-armed poly(ethylene glycol) (PEG)–conjugated oligo(l-lysine) (OligoLys). PEG-OligoLys

Many countries are formalizing customary land rights systems with the aim of improving agricultural productivity and facilitating community forest management. This paper evaluates the impact on tree cover loss of the first randomized control trial of such a program. Around 70,000 landholdings were demarcated and registered in randomly chosen villages in Benin, a country with a high rate of deforestation

Brain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain based purely on the unbiased identification of spatially defining features by employing whole-brain spatial transcriptomics. We found that the molecular information was sufficient to deduce the complex

Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)–driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens), to integrate the immunological

Mimicking the comprehensive functions of human sensing via electronic skins (e-skins) is highly interesting for the development of human-machine interactions and artificial intelligences. Some e-skins with high sensitivity and stability were developed; however, little attention is paid to their comfortability, environmental friendliness, and antibacterial activity. Here, we report a breathable, biodegradable

Electrode-polymer interfaces dictate many of the properties of thin films such as capacitance, the electric field experienced by polymers, and charge transport. However, structure and dynamics of charged polymers near electrodes remain poorly understood, especially in the high concentration limit representative of the melts. To develop an understanding of electric field–induced transformations of electrode-polymer

In efforts to promote equality and combat gender bias, traditionally male-occupied professions are investing resources into hiring more women. Looking forward, if women do become well represented in a profession, does this mean equality has been achieved? Are issues of bias resolved? Two studies including a randomized double-blind experiment demonstrate that biases persist even when women become well

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1

Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution

Mid-oceanic ridge basalts (MORBs) are depleted in incompatible elements, but ridge segments far from mantle plumes frequently erupt chemically enriched MORBs (E-MORBs). Two major explanations of E-MORBs are that these basalts are generated by the melting of entrained recycled crust (pyroxenite) beneath ridges or by the melting of refertilized peridotites. These two hypotheses can be discriminated with

Recent work has highlighted the fact that lysosomes are a critical signaling hub of metabolic processes, providing fundamental building blocks crucial for anabolic functions. How lysosomal functions affect other cellular compartments is not fully understood. Here, we find that lysosomal recycling of the amino acids lysine and arginine is essential for proper ER quality control through the UPRER. Specifically

Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm

While the Atlantic Meridional Overturning Circulation (AMOC) is projected to slow down under anthropogenic warming, the exact role of the AMOC in future climate change has not been fully quantified. Here, we present a method to stabilize the AMOC intensity in anthropogenic warming experiments by removing fresh water from the subpolar North Atlantic. This method enables us to isolate the AMOC climatic

DNA demethylation is important for the erasure of DNA methylation. The role of DNA demethylation in plant development remains poorly understood. Here, we found extensive DNA demethylation in the CHH context around pericentromeric regions and DNA demethylation in the CG, CHG, and CHH contexts at discrete genomic regions during ectopic xylem tracheary element (TE) differentiation. While loss of pericentromeric

The question of what computational capacities, if any, differ between humans and nonhuman animals has been at the core of foundational debates in cognitive psychology, anthropology, linguistics, and animal behavior. The capacity to form nested hierarchical representations is hypothesized to be essential to uniquely human thought, but its origins in evolution, development, and culture are controversial

Lake evaporation can influence basin-wide hydrological cycles and is an important factor in loss of water resources in endorheic lakes of the Tibetan Plateau. Because of the scarcity of data, published lake evaporation values are inconsistent, and their spatial distribution has never been reported. Presenting a plausible hypothesis of energy balance during the ice-free seasons, we explored the multiyear

There has been considerable progress in engineering cardiac scaffolds for the treatment of myocardial infarction (MI). However, it is still challenging to replicate the structural specificity and variability of cardiac tissues using traditional bioengineering approaches. In this study, a four-dimensional (4D) cardiac patch with physiological adaptability has been printed by beam-scanning stereolithography

Transplanting beneficial bacteria to the gut microbiome can positively modulate the bacterial composition and remains of great interest in prevention and treatment. However, environmental assaults and rapid transit times in the gastrointestinal (GI) tract result in low oral bioavailability and limited intestinal colonization. Here, we describe a bioinspired strategy of self-coating with biofilms that

Ice-nucleating particles (INPs) have the potential to remove much of the liquid water in climatically important mid- to high-latitude shallow supercooled clouds, markedly reducing their albedo. The INP sources at these latitudes are very poorly defined, but it is known that there are substantial dust sources across the high latitudes, such as Iceland. Here, we show that Icelandic dust emissions are

Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full knockout for SCAF1, or the wild-type version of the protein and

Early processing of visual information takes place in the human retina. Mimicking neurobiological structures and functionalities of the retina provides a promising pathway to achieving vision sensor with highly efficient image processing. Here, we demonstrate a prototype vision sensor that operates via the gate-tunable positive and negative photoresponses of the van der Waals (vdW) vertical heterostructures

Borocarbonitrides (BCNs) have emerged as highly selective catalysts for the oxidative dehydrogenation (ODH) reaction. However, there is a lack of in-depth understanding of the catalytic mechanism over BCN catalysts due to the complexity of the surface oxygen functional groups. Here, BCN nanotubes with multiple active sites are synthesized for oxygen-assisted methanol conversion reaction. The catalyst

Population trends and breeding success variability of Adélie penguins, a bioindicator of Antarctic environments, have been attributed to changing sea-ice extents; however, causative mechanisms remain unclear. By electronically tagging 175 penguins in four seasons with contrasting sea-ice conditions, we show that ice-free environments enhance, not deteriorate, foraging efficiencies and breeding success

The realization of the quantum spin Hall effect in HgTe quantum wells has led to the development of topological materials, which, in combination with magnetism and superconductivity, are predicted to host chiral Majorana fermions. However, the large magnetization in conventional quantum anomalous Hall systems makes it challenging to induce superconductivity. Here, we report two different emergent quantum

Campylobacter coli and Campylobacter jejuni are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. Despite its global importance, Campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring

It is challenging to design effective drug delivery systems (DDS) that target metastatic breast cancers (MBC) because of lack of competent imaging and image analysis protocols that suitably capture the interactions between DDS and metastatic lesions. Here, we integrate high temporal resolution of in vivo whole-body PET-CT, ex vivo whole-organ optical imaging, high spatial resolution of confocal microscopy

Drugs of abuse elevate dopamine levels in the nucleus accumbens (NAc) and alter transcriptional programs believed to promote long-lasting synaptic and behavioral adaptations. Here, we leveraged single-nucleus RNA-sequencing to generate a comprehensive molecular atlas of cell subtypes in the NAc, defining both sex-specific and cell type–specific responses to acute cocaine experience in a rat model system

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype

Living single yeast cells show a specific cellular motion at the nanometer scale with a magnitude that is proportional to the cellular activity of the cell. We characterized this cellular nanomotion pattern of nonattached single yeast cells using classical optical microscopy. The distribution of the cellular displacements over a short time period is distinct from random motion. The range and shape

For the current generation of earth system models participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6), the range of equilibrium climate sensitivity (ECS, a hypothetical value of global warming at equilibrium for a doubling of CO2) is 1.8°C to 5.6°C, the largest of any generation of models dating to the 1990s. Meanwhile, the range of transient climate response (TCR, the surface

Already moderate alcohol consumption has detrimental long-term effects on brain function. However, how alcohol produces its potent addictive effects despite being a weak reinforcer is a poorly understood conundrum that likely hampers the development of successful interventions to limit heavy drinking. In this translational study, we demonstrate widespread increased mean diffusivity in the brain gray

Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics are regulated by bioscavengers that are selected in the course of evolution. Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. A new subfamily of AmiN-like kinases, isolated from the Siberian bear microbiome,

Messenger RNA (mRNA) represents an attractive therapeutic modality for potentially a wide range of clinical indications but requires uridine chemistry modification and/or tuning of the production process to prevent activation of cellular innate immune sensors and a concomitant reduction in protein expression. To decipher the relative contributions of these factors on immune activation, here, we compared

Set1A and Set1B, two members of the COMPASS family of methyltransferases that methylate the histone H3 lysine 4 (H3K4) residue, have been accredited as primary depositors of global H3K4 trimethylation (H3K4me3) in mammalian cells. Our previous studies in mouse embryonic stem cells (ESCs) demonstrated that deleting the enzymatic SET domain of Set1A does not perturb bulk H3K4me3, indicating possible

Posttranscriptional gene silencing (PTGS) is a powerful tool to understand and control plant metabolic pathways, which is central to plant biotechnology. PTGS is commonly accomplished through delivery of small interfering RNA (siRNA) into cells. Standard plant siRNA delivery methods (Agrobacterium and viruses) involve coding siRNA into DNA vectors and are only tractable for certain plant species. Here

Cells respond to oxidative stress by inducing intracellular signaling, including stress-activated p38 and JNK MAPK (SAPK) pathways, but the underlying mechanisms remain unclear. Here, we report that the MAP three kinase 1 (MTK1) SAPK kinase kinase (SAPKKK) functions as an oxidative-stress sensor that perceives the cellular redox state and transduces it into SAPK signaling. Following oxidative stress

Ceramic aerogels are promising lightweight and high-efficient thermal insulators for applications in buildings, industry, and aerospace vehicles but are usually limited by their brittleness and structural collapse at high temperatures. In recent years, fabricating nanostructure-based ultralight materials has been proved to be an effective way to realize the resilience of ceramic aerogels. However,