Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography–computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic

Microbial communities are essential to fundamental processes on Earth. Underlying the compositions and functions of these communities are nutritional interdependencies among individual species. One class of nutrients, cobamides (the family of enzyme cofactors that includes vitamin B12), is widely used for a variety of microbial metabolic functions, but these structurally diverse cofactors are synthesized

During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects

Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the

Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community. Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically required to enable C(sp3)–H bond cleavage, barring potential applications in synthetic organic chemistry. Here, we report a general and mild strategy to activate C(sp3)–H bonds in methane, ethane, propane, and

The role of reduced dimensionality in high-temperature superconductors is still under debate. Recently, ultracold atoms have emerged as an ideal model system to study such strongly correlated two-dimensional (2D) systems. Here, we report on the realization of a Josephson junction in an ultracold 2D Fermi gas. We measure the frequency of Josephson oscillations as a function of the phase difference across

The direct-current (dc) Josephson effect provides a phase-sensitive tool for investigating superfluid order parameters. We report on the observation of dc Josephson supercurrents in strongly interacting fermionic superfluids across a tunneling barrier in the absence of any applied potential difference. For sufficiently strong barriers, we observed a sinusoidal current-phase relation, in agreement with

Dielectric capacitors can store and release electric energy at ultrafast rates and are extensively studied for applications in electronics and electric power systems. Among various candidates, thin films based on relaxor ferroelectrics, a special kind of ferroelectric with nanometer-sized domains, have attracted special attention because of their high energy densities and efficiencies. We show that

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2–specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a

Bacterial biofilms represent a basic form of multicellular organization that confers survival advantages to constituent cells. The sequential stages of cell ordering during biofilm development have been studied in the pathogen and model biofilm-former Vibrio cholerae. It is unknown how spatial trajectories of individual cells and the collective motions of many cells drive biofilm expansion. We developed

Species’ vulnerability to climate change depends on the most temperature-sensitive life stages, but for major animal groups such as fish, life cycle bottlenecks are often not clearly defined. We used observational, experimental, and phylogenetic data to assess stage-specific thermal tolerance metrics for 694 marine and freshwater fish species from all climate zones. Our analysis shows that spawning

Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase

The CRISPR RNA (crRNA)–guided nuclease Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. However, how viruses can counteract this immunity is not known. We describe a listeriaphage (ϕLS46) encoding an anti-CRISPR protein (AcrVIA1) that inactivates the type VI-A CRISPR system of Listeria seeligeri

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is highly

Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical in advancing nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined flat bands exist and induce robust yet independently switchable dipoles exhibiting a unique ferroelectricity in HfO2. Flat polar phonon

Versatile chemical transformations of surface functional groups in 2D transition-metal carbides (MXenes) open up a new design space for this broad class of functional materials. We introduce a general strategy to install and remove surface groups by performing substitution and elimination reactions in molten inorganic salts. Successful synthesis of MXenes with O, NH, S, Cl, Se, Br, and Te surface terminations

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly

Catalyzing water dissociation (WD) into protons and hydroxide ions is important both for fabricating bipolar membranes (BPMs) that can couple different pH environments into a single electrochemical device, and for accelerating electrocatalytic reactions that consume protons in neutral-to-alkaline media. We designed a BPM electrolyzer to quantitatively measure WD kinetics and show that, for metal nanoparticles

Uromodulin is the most abundant protein in human urine and forms filaments that antagonize the adhesion of uropathogens; however, filament structure and mechanism of protection remain poorly understood. We used cryo-electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that

Whole-genome duplication has played a central role in the genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated, and factors that influence the retention of persisting duplicates remain poorly understood. We describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping of digenic

Decision-making in complex environments relies on flexibly using prior experience. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe, but it remains unknown how these structures implement selective memory retrieval. We recorded single neurons in the MFC, amygdala, and hippocampus while human subjects switched between making recognition memory–based and categorization-based

Neuronal circuits damaged or lost after injury can be regenerated in some adult organisms, but the mechanisms enabling this process are largely unknown. We used the planarian Schmidtea mediterranea to study visual system regeneration after injury. We identify a rare population of muscle cells tightly associated with photoreceptor axons at stereotyped positions in both uninjured and regenerating animals

The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo–electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution

Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old

Photosynthesis achieves near unity light-harvesting quantum efficiency yet it remains unknown whether there exists a fundamental organizing principle giving rise to robust light harvesting in the presence of dynamic light conditions and noisy physiological environments. Here, we present a noise-canceling network model that relates noisy physiological conditions, power conversion efficiency, and the

The development of two-dimensional metasurfaces has shown great potential in quantum-optical technologies because of the excellent flexibility in light-field manipulation. By integrating a metalens array with a nonlinear crystal, we demonstrate a 100-path spontaneous parametric down-conversion photon-pair source in a 10 × 10 array, which shows promise for high-dimensional entanglement and multiphoton-state

Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature

Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical patterns that direct seeded growth into NPs with pronounced morphological and optical

The Sun’s magnetic field is generated by subsurface motions of the convecting plasma. The latitude at which the magnetic field emerges through the solar surface (as sunspots) drifts toward the equator over the course of the 11-year solar cycle. We use helioseismology to infer the meridional flow (in the latitudinal and radial directions) over two solar cycles covering 1996–2019. Two data sources are

DNA and proteins are chiral: Their three-dimensional structures cannot be superimposed with their mirror images. Circular dichroism spectroscopy is widely used to characterize chiral compounds, but data interpretation is difficult in the case of mixtures. We recorded the electronic circular dichroism spectra of DNA helices separated in a mass spectrometer. We studied guanine-rich strands having various

Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo–electron microscopy at two preferred

As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. How cohesin executes these fundamental DNA transactions is not understood. Using cryo–electron microscopy (cryo-EM), we determined the structure of human cohesin bound to its loader NIPBL and DNA at medium

Gene regulation is chiefly determined at the level of individual linear chromatin molecules, yet our current understanding of cis-regulatory architectures derives from fragmented sampling of large numbers of disparate molecules. We developed an approach for precisely stenciling the structure of individual chromatin fibers onto their composite DNA templates using nonspecific DNA N6-adenine methyltransferases

Atomically precise graphene nanoribbons (GNRs) attract great interest because of their highly tunable electronic, optical, and transport properties. However, on-surface synthesis of GNRs is typically based on metal-surface assisted chemical reactions, where metallic substrates strongly screen their designer electronic properties and limit further applications. Here, we present an on-surface synthesis

Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in pre-ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves tRNA-like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo-EM structures of Saccharomyces cerevisiae

France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those <20 years of age (ya) to 10.1% in those >80ya. Across all ages, men are more likely

Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups

Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits

Forests have considerable potential to help mitigate human-caused climate change and provide society with many cobenefits. However, climate-driven risks may fundamentally compromise forest carbon sinks in the 21st century. Here, we synthesize the current understanding of climate-driven risks to forest stability from fire, drought, biotic agents, and other disturbances. We review how efforts to use

Meissner corpuscles are mechanosensory end organs that densely occupy mammalian glabrous skin. We generated mice that selectively lacked Meissner corpuscles and found them to be deficient in both perceiving the gentlest detectable forces acting on glabrous skin and fine sensorimotor control. We found that Meissner corpuscles are innervated by two mechanoreceptor subtypes that exhibit distinct responses

Although perovskite solar cells have produced remarkable energy conversion efficiencies, they cannot become commercially viable without improvements in durability. We used gas chromatography–mass spectrometry (GC-MS) to reveal signature volatile products of the decomposition of organic hybrid perovskites under thermal stress. In addition, we were able to use GC-MS to confirm that a low-cost polymer/glass

How does neural activity generate perception? Finding the combinations of spatial or temporal activity features (such as neuron identity or latency) that are consequential for perception remains challenging. We trained mice to recognize synthetic odors constructed from parametrically defined patterns of optogenetic activation, then measured perceptual changes during extensive and controlled perturbations

The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this

The enzyme nitrogenase uses a suite of complex metallocofactors to reduce dinitrogen (N2) to ammonia. Mechanistic details of this reaction remain sparse. We report a 1.83-angstrom crystal structure of the nitrogenase molybdenum-iron (MoFe) protein captured under physiological N2 turnover conditions. This structure reveals asymmetric displacements of the cofactor belt sulfurs (S2B or S3A and S5A) with

Plants emit an extraordinary diversity of chemicals that provide information about their identity and mediate their interactions with insects. However, most studies of this have focused on a few model species in controlled environments, limiting our capacity to understand plant-insect chemical communication in ecological communities. Here, by integrating information theory with ecological and evolutionary

The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result

Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence

The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop

The vibrant evolutionary patterns made by earthquake swarms are incompatible with standard, effectively two-dimensional (2D) models for general fault architecture. We leverage advances in earthquake monitoring with a deep-learning algorithm to image a fault zone hosting a 4-year-long swarm in southern California. We infer that fluids are naturally injected into the fault zone from below and diffuse

Electrochemistry offers opportunities to promote single-electron transfer (SET) redox-neutral chemistries similar to those recently discovered using visible-light photocatalysis but without the use of an expensive photocatalyst. Herein, we introduce a microfluidic redox-neutral electrochemistry (μRN-eChem) platform that has broad applicability to SET chemistry, including radical-radical cross-coupling

Developing ultrahigh-strength steels that are ductile, fracture resistant, and cost effective would be attractive for a variety of structural applications. We show that improved fracture resistance in a steel with an ultrahigh yield strength of nearly 2 gigapascals can be achieved by activating delamination toughening coupled with transformation-induced plasticity. Delamination toughening associated

Global biodiversity assessments have highlighted land-use change as a key driver of biodiversity change. However, there is little empirical evidence of how habitat transformations such as forest loss and gain are reshaping biodiversity over time. We quantified how change in forest cover has influenced temporal shifts in populations and ecological assemblages from 6090 globally distributed time series

The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory

The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common

Many classical and emerging methodologies in organic chemistry rely on CO2 extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates, have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic acids and malonate

Scalable, coherent many-body systems can enable the realization of previously unexplored quantum phases and have a potential to exponentially speed up information processing. Here we report the cooling of a quantum simulator with ten thousand atoms and mass production of high-fidelity entangled pairs. In a two-dimensional plane, we cool Mott-insulator samples by immersing them into removable superfluid

The absence of motor vehicle traffic and suspended manufacturing during the COVID-19 pandemic in China produced a unique experiment to assess the efficiency of air pollution mitigation. Up to 90% reduction of certain emissions during the city-lockdown period can be identified from satellite and ground-based observations. Unexpectedly, extreme particulate matter levels simultaneously occurred in northern

The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3