Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1, acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased

Brazil has been severely hit by COVID-19, with rapid spatial spread of both cases and deaths. We use daily data on reported cases and deaths to understand, measure, and compare the spatiotemporal pattern of the spread across municipalities. Indicators of clustering, trajectories, speed, and intensity of the movement of COVID-19 to interior areas, combined with indices of policy measures show that while

In the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to SARS-CoV-2. Two critical issues arise: how will the timing of delivery of the second dose affect both infection dynamics and prospects for the evolution of viral immune escape via a build-up of partially immune individuals. Both hinge on the robustness

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not

In most vertebrates, camera-style eyes contain retinal ganglion cell neurons that project to visual centers on both sides of the brain. However, in fish, ganglion cells were thought to innervate only the contralateral side, suggesting that bilateral visual projections appeared in tetrapods. Here we show that bilateral visual projections exist in non-teleost fishes and that the appearance of ipsilateral

Mutations in the BRCA1 or BRCA2 tumor suppressor genes predispose individuals to breast and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic nucleotide 5-hydroxymethyl-deoxyuridine (hmdU) monophosphate, potentiates the sensitivity of BRCA-deficient cells to PARP

The brains of modern humans differ from those of great apes in size, shape, and cortical organization, notably in frontal lobe areas involved in complex cognitive tasks, such as social cognition, tool use, and language. When these differences arose during human evolution is a question of ongoing debate. Here, we show that the brains of early Homo from Africa and Western Asia (Dmanisi) retained a primitive

Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in Arabidopsis, a stigmatic gatekeeper, the ANJEA–FERONIA (ANJ–FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production

Mild methods to cleave the carbon-oxygen (C−O) bond in alkyl ethers could simplify chemical syntheses through the elaboration of these robust, readily available precursors. Here we report that dibromoboranes react with alkyl ethers in the presence of a nickel catalyst and zinc reductant to insert boron into the C−O bond. Subsequent reactivity can effect oxygen-to-nitrogen substitution or one-carbon

Glass is one of the most relevant high-performance materials that has the benefit of a favorable environmental footprint compared with that of other commodity materials. Despite the advantageous properties of glasses, polymers are often favored because they can be processed using scalable industrial replication techniques like injection molding (IM). Glasses are generally processed through melting

Giant radio pulses (GRPs) are sporadic bursts emitted by some pulsars that last a few microseconds and are hundreds to thousands of times brighter than regular pulses from these sources. The only GRP-associated emission outside of radio wavelengths is from the Crab Pulsar, where optical emission is enhanced by a few percentage points during GRPs. We observed the Crab Pulsar simultaneously at x-ray

Bardeen-Cooper-Schrieffer (BCS) superfluidity and Bose-Einstein condensation (BEC) are the two extreme limits of the ground state of the paired fermion systems. We report crossover behavior from the BCS limit to the BEC limit realized by varying carrier density in a two-dimensional superconductor, electron-doped zirconium nitride chloride. The phase diagram, established by simultaneous measurements

The integration of two-dimensional (2D) van der Waals semiconductors into silicon electronics technology will require the production of large-scale, uniform, and highly crystalline films. We report a route for synthesizing wafer-scale single-crystalline 2H molybdenum ditelluride (MoTe2) semiconductors on an amorphous insulating substrate. In-plane 2D-epitaxy growth by tellurizing was triggered from

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration

DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants

During multicellular development, spatial position and lineage history play powerful roles in controlling cell fate decisions. Using a serine integrase–based recording system, we engineered cells to record lineage information in a format that can be read out in situ. The system, termed integrase-editable memory by engineered mutagenesis with optical in situ readout (intMEMOIR), allowed in situ reconstruction

Liquid biopsies that analyze cell-free DNA in blood plasma are used for noninvasive prenatal testing, oncology, and monitoring of organ transplant recipients. DNA molecules are released into the plasma from various bodily tissues. Physical and molecular features of cell-free DNA fragments and their distribution over the genome bear information about their tissues of origin. Moreover, patterns of DNA

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser

G protein–coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only a limited understanding of the behavior of GPCRs in the apo state and the conformational changes upon agonist binding that lead to G protein recruitment and activation. We expressed and purified unmodified apo and peptide-bound calcitonin gene–related peptide (CGRP)

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast

Eukaryotic transcription requires the assembly of a multisubunit preinitiation complex (PIC) composed of RNA polymerase II (Pol II) and the general transcription factors. The coactivator Mediator is recruited by transcription factors, facilitates the assembly of the PIC, and stimulates phosphorylation of the Pol II C-terminal domain (CTD) by the TFIIH subunit CDK7. Here, we present the cryo–electron

Geological evidence shows that ancient Mars had large volumes of liquid water. Models of past hydrogen escape to space, calibrated with observations of the current escape rate, cannot explain the present-day deuterium-to-hydrogen isotope ratio (D/H). We simulated volcanic degassing, atmospheric escape, and crustal hydration on Mars, incorporating observational constraints from spacecraft, rovers, and

The end-Cretaceous event was catastrophic for terrestrial communities worldwide, yet its long-lasting effect on tropical forests remains largely unknown. We quantified plant extinction and ecological change in tropical forests resulting from the end-Cretaceous event using fossil pollen (>50,000 occurrences) and leaves (>6000 specimens) from localities in Colombia. Late Cretaceous (Maastrichtian) rainforests

Van der Waals interfaces can be formed by layer stacking without regard to lattice constants or symmetries of individual building blocks. We engineered the symmetry of a van der Waals interface of tungsten selenide and black phosphorus and realized in-plane electronic polarization that led to the emergence of a spontaneous photovoltaic effect. Spontaneous photocurrent was observed along the polar direction

Topology, parity-time (PT) symmetry, and nonlinearity are at the origin of many fundamental phenomena in complex systems across the natural sciences, but their mutual interplay remains unexplored. We established a nonlinear non-Hermitian topological platform for active tuning of PT symmetry and topological states. We found that the loss in a topological defect potential in a non-Hermitian photonic

Oxidative dehydrogenation of propane (ODHP) is a key technology for producing propene from shale gas, but conventional metal oxide catalysts are prone to overoxidation to form valueless COx. Boron-based catalysts were recently found to be selective for this reaction, and B–O–B oligomers are generally regarded as active centers. We show here that the isolated boron in a zeolite framework without such

Pesticide impacts are usually discussed in the context of applied amounts while disregarding the large but environmentally relevant variations in substance-specific toxicity. Here, we systemically interpret changes in the use of 381 pesticides over 25 years by considering 1591 substance-specific acute toxicity threshold values for eight nontarget species groups. We find that the toxicity of applied

Human activities and climate change threaten marine biodiversity worldwide, though sensitivity to these stressors varies considerably by species and taxonomic group. Mapping the spatial distribution of 14 anthropogenic stressors from 2003 to 2013 onto the ranges of 1271 at-risk marine species sensitive to them, we found that, on average, species faced potential impacts across 57% of their ranges, that

Quantum gases of light, such as photon or polariton condensates in optical microcavities, are collective quantum systems enabling a tailoring of dissipation from, for example, cavity loss. This characteristic makes them a tool to study dissipative phases, an emerging subject in quantum many-body physics. We experimentally demonstrate a non-Hermitian phase transition of a photon Bose-Einstein condensate

Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life

T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)–T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of receptor signaling, or rest, on the development and maintenance of exhaustion. Induction

Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence

Culture can be defined as all that is learned from others and is repeatedly transmitted in this way, forming traditions that may be inherited by successive generations. This cultural form of inheritance was once thought specific to humans, but research over the past 70 years has instead revealed it to be widespread in nature, permeating the lives of a diversity of animals, including all major classes

Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase (Pol) II-mediated eukaryotic transcription. Here, we determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-DBE

Slovakia conducted multiple rounds of population-wide rapid antigen testing for SARS-CoV-2 in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% CI: 57-58%) within one week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic

Behavioral isolation can catalyze speciation and permit the slow accumulation of additional reproductive barriers between co-occurring organisms. We illustrate how this process occurs by examining the genomic and behavioral bases of pre-mating isolation between two bird species (Sporophila hypoxantha and the recently discovered S. iberaensis) that belong to the southern capuchino seedeaters, a recent

Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges

Changes in the concentration and isotopic composition of the major constituents in seawater reflect changes in their sources and sinks. Because many of the processes controlling these sources and sinks are tied to the cycling of carbon, such records can provide insights into what drives past changes in atmospheric carbon dioxide and climate. Here, we present a stable strontium (Sr) isotope record derived

Mitogens trigger cell division in animals. In plants, cytokinins, a group of phytohormones derived from adenine, stimulate cell proliferation. Cytokinin signaling is initiated by membrane-associated histidine kinase receptors and transduced through a phosphorelay system. We show that in the Arabidopsis shoot apical meristem (SAM), cytokinin regulates cell division by promoting nuclear shuttling of

The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on

The stabilization of black-phase formamidinium lead iodide (α-FAPbI3) perovskite under various environmental conditions is considered necessary for solar cells. However, challenges remain regarding the temperature sensitivity of α-FAPbI3 and the requirements for strict humidity control in its processing. Here we report the synthesis of stable α-FAPbI3, regardless of humidity and temperature, based

Surface phonon polaritons (SPhPs) are coupled photon-phonon excitations that emerge at the surfaces of nanostructured materials. Although they strongly influence the optical and thermal behavior of nanomaterials, no technique has been able to reveal the complete three-dimensional (3D) vectorial picture of their electromagnetic density of states. Using a highly monochromated electron beam in a scanning

Chiral assemblies of plasmonic nanoparticles are known for strong circular dichroism but not for high optical asymmetry, which is limited by the unfavorable combination of electrical and magnetic field components compounded by strong scattering. Here, we show that these limitations can be overcome by the long-range organization of nanoparticles in a manner similar to the liquid crystals and found in

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds

Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy

αβ and γδ T cell receptors (TCRs) are highly diverse antigen receptors that define two evolutionarily conserved T cell lineages. We describe a population of γμTCRs found exclusively in non-eutherian mammals that consist of a two-domain (Vγ-Cγ) γ-chain paired to a three-domain (Vμ-Vμj-Cμ) μ-chain. γμTCRs were characterized by restricted diversity in the Vγ and Vμj domains and a highly diverse unpaired

The pathways that lead to the development of tissue-resident lymphocytes, including liver type 1 innate lymphoid cells (ILC1s), remain unclear. We show here that the adult mouse liver contains Lin−Sca-1+Mac-1+ hematopoietic stem cells derived from the fetal liver. This population includes Lin−CD122+CD49a+ progenitors that can generate liver ILC1s but not conventional natural killer cells. Interferon-γ

Cytoskeletal regulatory protein dysfunction has been etiologically linked to inherited diseases associated with immunodeficiency and autoimmunity, but the mechanisms involved are incompletely understood. Here, we show that conditional Wave2 ablation in T cells causes severe autoimmunity associated with increased mammalian target of rapamycin (mTOR) activation and metabolic reprogramming that engender

Microbial roles in cancer formation, diagnosis, prognosis, and treatment have been disputed for centuries. Recent studies have provocatively claimed that bacteria, viruses, and/or fungi are pervasive among cancers, key actors in cancer immunotherapy, and engineerable to treat metastases. Despite these findings, the number of microbes known to directly cause carcinogenesis remains small. Critically

Cell-cell communication relies on the assembly of receptor-ligand complexes at the plasma membrane. The spatiotemporal receptor organization has a pivotal role in evoking cellular responses. We studied the clustering of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) and established a photoinstructive matrix with ultrasmall lock-and-key interaction pairs to control

After initial declines, in mid-2020 a resurgence in transmission of novel coronavirus disease (COVID-19) occurred in the United States and Europe. As efforts to control COVID-19 disease are reintensified, understanding the age demographics driving transmission and how these affect the loosening of interventions is crucial. We analyze aggregated, age-specific mobility trends from more than 10 million

Vacuolar myelinopathy is a fatal neurological disease that was initially discovered during a mysterious mass mortality of bald eagles in Arkansas in the United States. The cause of this wildlife disease has eluded scientists for decades while its occurrence has continued to spread throughout freshwater reservoirs in the southeastern United States. Recent studies have demonstrated that vacuolar myelinopathy

Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+ T cells recognizing epitopes presented by major histocompatibility complex (MHC)-II and MHC-E, not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular

Animals in the wild are able to subsist on pathogen-infected and poisonous food and show immunity to various diseases. These may be due to their microbiota, yet we have a poor understanding of animal microbial diversity and function. We used metagenomics to analyze the gut microbiota of over 180 species in the wild, covering diverse classes, feeding behaviors, geographies, and traits. Using de novo

The minor spliceosome mediates splicing of the rare but essential U12-type precursor messenger RNA. Here, we report the atomic features of the activated human minor spliceosome determined by cryo–electron microscopy at 2.9-angstrom resolution. The 5′ splice site and branch point sequence of the U12-type intron are recognized by the U6atac and U12 small nuclear RNAs (snRNAs), respectively. Five newly

Early life is thought to have required the self-replication of RNA by RNA replicases. However, how such replicases evolved and subsequently enabled gene expression remains largely unexplored. We engineered and selected a holopolymerase ribozyme that uses a sigma factor–like specificity primer to first recognize an RNA promoter sequence and then, in a second step, rearrange to a processive elongation