Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional

The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic “megamitochondria” with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown

Precise three-dimensional (3D) atomic structure determination of individual nanocrystals is a prerequisite for understanding and predicting their physical properties. Nanocrystals from the same synthesis batch display what are often presumed to be small but possibly important differences in size, lattice distortions, and defects, which can only be understood by structural characterization with high

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2’s Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera

A defining feature of emergent phenomena in complex oxides is the competition and cooperation between ground states. In manganites, the balance between metallic and insulating phases can be tuned by the lattice; extending the range of lattice control would enhance the ability to access other phases. We stabilized uniform extreme tensile strain in nanoscale La0.7Ca0.3MnO3 membranes, exceeding 8% uniaxially

Slip of marine-terminating ice streams over beds of deformable till is responsible for most of the contribution of the West Antarctic Ice Sheet to sea level rise. Flow models of the ice sheet and till-bedded glaciers elsewhere require a law that relates slip resistance, slip velocity, and water pressure at the bed. We present results of experiments in which pressurized ice at its melting temperature

The design of modular protein logic for regulating protein function at the posttranscriptional level is a challenge for synthetic biology. Here, we describe the design of two-input AND, OR, NAND, NOR, XNOR, and NOT gates built from de novo–designed proteins. These gates regulate the association of arbitrary protein units ranging from split enzymes to transcriptional machinery in vitro, in yeast and

Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid reactive oxygen species (ROS). Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. In this work, we show that the import of oxidized cysteine (cystine) via system xC– is a critical dependency of pancreatic ductal

Understanding the neurobiological underpinnings of emotion relies on objective readouts of the emotional state of an individual, which remains a major challenge especially in animal models. We found that mice exhibit stereotyped facial expressions in response to emotionally salient events, as well as upon targeted manipulations in emotion-relevant neuronal circuits. Facial expressions were classified

As primary producers, plants rely on a large aboveground surface area to collect carbon dioxide and sunlight and a large underground surface area to collect the water and mineral nutrients needed to support their growth and development. Accessibility of the essential nutrients nitrogen (N) and phosphorus (P) in the soil is affected by many factors that create a variable spatiotemporal landscape of

The success of poly(ADP-ribose) polymerase–1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. Although different forms of PARPi all target the catalytic center of the enzyme, they have variable abilities to trap PARP-1. We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break. Other inhibitors

Understanding the extinction of Australopithecus and origins of Paranthropus and Homo in South Africa has been hampered by the perceived complex geological context of hominin fossils, poor chronological resolution, and a lack of well-preserved early Homo specimens. We describe, date, and contextualize the discovery of two hominin crania from Drimolen Main Quarry in South Africa. At ~2.04 million to

Multi-cellular organisms use mitogens to regulate cell proliferation, yet how fluctuating mitogenic signals are converted into proliferation-quiescence decisions is poorly understood. Here we combine live-cell imaging with temporally controlled perturbations to determine the timescale and mechanisms underlying the system. Contrary to the textbook model that cells only sense mitogen availability in

While there have been no cases of type-2 wild poliovirus for over 20 years, transmission of type-2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the type-2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all poliovirus type 2. Globally

The newly emergent human virus SARS-CoV-2 is resulting in high fatality rates and incapacitated health systems. Preventing further transmission is a priority. We analyzed key parameters of epidemic spread to estimate the contribution of different transmission routes and determine requirements for case isolation and contact-tracing needed to stop the epidemic. We conclude that viral spread is too fast

Responding to an outbreak of a novel coronavirus (agent of COVID-19) in December 2019, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. We investigated the spread and control of COVID-19 using a unique data set including case reports, human movement and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor

Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection

Spin-orbit coupling has proven indispensable in realizing topological materials and more recently Ising pairing in two-dimensional superconductors. This pairing mechanism relies on inversion symmetry breaking and sustains anomalously large in-plane polarizing magnetic fields whose upper limit is predicted to diverge at low temperatures. Here we show that the recently discovered superconductor few-layer

Spectroscopy is a powerful tool for studying molecules and is commonly performed on large thermal molecular ensembles that are perturbed by motional shifts and interactions with the environment and one another, resulting in convoluted spectra and limited resolution. Here, we use quantum-logic techniques to prepare a trapped molecular ion in a single quantum state, drive terahertz rotational transitions

The wave function of a Tonks-Girardeau (T-G) gas of strongly interacting bosons in one dimension maps onto the absolute value of the wave function of a noninteracting Fermi gas. Although this fermionization makes many aspects of the two gases identical, their equilibrium momentum distributions are quite different. We observed dynamical fermionization, where the momentum distribution of a T-G gas evolves

Observations of nearby galaxies and galaxy clusters have reported an unexpected x-ray emission line around 3.5 kilo–electron volts (keV). Proposals to explain this line include decaying dark matter—in particular, that the decay of sterile neutrinos with a mass around 7 keV could match the available data. If this interpretation is correct, the 3.5-keV line should also be emitted by dark matter in the

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in breast cancer patient-derived CTCs to identify genes that promote their distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression

The structure of melt-quenched zeolitic imidazole framework (ZIF) glasses can provide insights into their glass-formation mechanism. We directly detected short-range disorder in ZIF glasses using ultrahigh-field zinc-67 solid-state nuclear magnetic resonance spectroscopy. Two distinct Zn sites characteristic of the parent crystals transformed upon melting into a single tetrahedral site with a broad

The El Niño–Southern Oscillation (ENSO) shapes global climate patterns yet its sensitivity to external climate forcing remains uncertain. Modeling studies suggest that ENSO is sensitive to sulfate aerosol forcing associated with explosive volcanism but observational support for this effect remains ambiguous. Here, we used absolutely dated fossil corals from the central tropical Pacific to gauge ENSO’s

The premature abscission of flowers and fruits limits crop yield under environmental stress. Drought-induced flower drop in tomato plants was found to be regulated by phytosulfokine (PSK), a peptide hormone previously known for its growth-promoting and immune-modulating activities. PSK formation in response to drought stress depends on phytaspase 2, a subtilisin-like protease of the phytaspase subtype

Disrupting North Atlantic Deep Water (NADW) ventilation is a key concern in climate projections. We use (sub)centennially resolved bottom water δ13C records that span the interglacials of the last 0.5 million years to assess the frequency of and the climatic backgrounds capable of triggering large NADW reductions. Episodes of reduced NADW in the deep Atlantic, similar in magnitude to glacial events

Hybrid semiconductor-superconductor nanowires have emerged as a promising platform for realizing topological superconductivity (TSC). Here, we present a route to TSC using magnetic flux applied to a full superconducting shell surrounding a semiconducting nanowire core. Tunneling into the core reveals a hard induced gap near zero applied flux, corresponding to zero phase winding, and a gapped region

Marine food–reliant subsistence systems such as those in the African Middle Stone Age (MSA) were not thought to exist in Europe until the much later Mesolithic. Whether this apparent lag reflects taphonomic biases or behavioral distinctions between archaic and modern humans remains much debated. Figueira Brava cave, in the Arrábida range (Portugal), provides an exceptionally well preserved record of

This article reviews an emerging area of research within economics that seeks to better understand contemporary economic outcomes by taking a historical perspective. The field has established that many of the contemporary differences in comparative economic development have their roots in the distant past. The insights gained from this literature are not only of academic importance but also useful

Dissipation is a general feature of non-Hermitian systems. But rather than being an unavoidable nuisance, non-Hermiticity can be precisely controlled and, hence, used for sophisticated applications such as optical sensors with enhanced sensitivity. In our work, we implement a non-Hermitian photonic mesh lattice by tailoring the anisotropy of the inter-site coupling. The appearance of an interface results

Transcription polymerases can exhibit an unusual mode of regenerating certain RNA templates from RNA, yielding systems that can replicate and evolve with RNA as information carrier. Two classes of pathogenic RNAs (Hepatitis delta virus in animals and viroids in plants) are copied by host transcription polymerases. Using in vitro RNA replication by the transcription polymerase of T7 bacteriophage as

Manipulation of DNA by CRISPR-Cas enzymes requires the recognition of a protospacer adjacent motif (PAM), limiting target site recognition to a subset of sequences. To remove this constraint, we engineered variants of Streptococcus pyogenes Cas9 (SpCas9) to eliminate the NGG PAM requirement. We developed a variant named SpG capable of targeting an expanded set of NGN PAMs, and further optimized this

Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs this process involves a long-range radical transfer between two subunits, α and β. Due

Maximizing the power conversion efficiency (PCE) of perovskite-silicon tandem solar cells that can exceed the Shockley-Queisser single-cell limit requires a high performing, stable perovskite top cell with a wide band gap. We developed a stable perovskite solar cell with a band gap of ~1.7 electron volt that retained over 80% of its initial PCE of 20.7% after 1000 hours of continuous illumination.

The ongoing COVID-19 outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions have been undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We use real-time mobility data

Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics

The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, 3CLpro), due to its essential role in processing the polyproteins that are translated from the viral RNA. We report the X-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed

Antarctica contains most of Earth’s fresh water stored in two large ice sheets. The more stable East Antarctic Ice Sheet is larger and older, rests on higher topography, and hides entire mountain ranges and ancient lakes. The less stable West Antarctic Ice Sheet is smaller and younger and was formed on what was once a shallow sea. Recent observations made with several independent satellite measurements

The Southern Ocean exerts a major influence on the mass balance of the Antarctic Ice Sheet, either indirectly, by its influence on air temperatures and winds, or directly, mostly through its effects on ice shelves. How much melting the ocean causes depends on the temperature of the water, which in turn is controlled by the combination of the thermal structure of the surrounding ocean and local ocean

The Antarctic Ice Sheet is losing mass at an accelerating pace, and ice loss will likely continue over the coming decades and centuries. Some regions of the ice sheet may reach a tipping point, potentially leading to rates of sea level rise at least an order of magnitude larger than those observed now, owing to strong positive feedbacks in the ice-climate system. How fast and how much Antarctica will

Moderate-temperature thermal sources (100-400°C) that radiate waste heat are often the by-product of mechanical work, chemical or nuclear reactions, or information processing. We demonstrate conversion of thermal radiation into electrical power using a bipolar grating-coupled complimentary metal-oxide-silicon (CMOS) tunnel diode. A two-step photon-assisted tunneling charge pumping mechanism results

Class B G protein–coupled receptors, an important class of therapeutic targets, signal mainly through the Gs class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo–electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, Gs or Gi1. These two structures

We report the profiling of spatial and energetic distributions of trap states in metal halide perovskite single-crystalline and polycrystalline solar cells. The trap densities in single crystals varied by five orders of magnitude, with a lowest value of 2 × 1011 per cubic centimeter and most of the deep traps located at crystal surfaces. The charge trap densities of all depths of the interfaces of

Vegetation influences erosion by stabilizing hillslopes and accelerating weathering, thereby providing a link between the biosphere and Earth’s surface. Previous studies investigating vegetation effects on erosion have proved challenging owing to poorly understood interactions between vegetation and other factors, such as precipitation and surface processes. We address these complexities along 3500

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a

Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate [PI(4)P] on trans-Golgi network

The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating

Hybridization—interbreeding between species—is generally thought to occur randomly between members of two species. Contrary to expectation, female plains spadefoot toads (Spea bombifrons) can increase their evolutionary fitness by preferentially mating with high-quality males of another species, the Mexican spadefoot toad (Spea multiplicata). Aspects of Mexican spadefoot males’ mating calls predict

Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 and caspase-11–mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1β secretion. In vitro, however, murine macrophages require a second “danger signal” for the inflammasome-driven maturation of

Profitability and sustainability of future biorefineries are dependent on efficient feedstock utilization. It is essential to valorize lignin when using wood. We have developed an integrated biorefinery that converts 78 wt.% of birch into xylochemicals. Reductive catalytic fractionation of wood gives a carbohydrate pulp amenable to bioethanol production and a lignin oil. After extraction of lignin

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole

The two tandem bromodomains of the BET proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that

Trapped atoms and ions, which are among the best-controlled quantum systems, find widespread applications in quantum science. For molecules, a similar degree of control is currently lacking owing to their complex energy-level structure. Quantum-logic protocols in which atomic ions serve as probes for molecular ions are a promising route for achieving this level of control, especially for homonuclear

Spin ices are exotic phases of matter characterized by frustrated spins obeying local "ice rules," in analogy with the electric dipoles in water ice. In two dimensions, one can similarly define ice rules for in-plane Ising-like spins arranged on a kagome lattice. These ice rules require each triangle plaquette to have a single monopole and can lead to different types of orders and excitations. Using

Cluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune disorders, but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX,

How long-lived memories withstand molecular turnover is a fundamental question. Aggregates of a prion-like RNA-binding protein, cytoplasmic polyadenylation element-binding (CPEB) protein, is a putative substrate of long-lasting memories. We isolated aggregated Drosophila CPEB, Orb2, from adult heads and determined its activity and atomic structure, at 2.6-angstrom resolution, using cryo-electron microscopy

Radiometric dating of glacial terminations over the past 640,000 years suggests pacing by Earth's climatic precession, with each glacial-interglacial period spanning four or five cycles of ~20,000 years. However, the lack of firm age estimates for older Pleistocene terminations confounds attempts to test the persistence of precession forcing. We combine an Italian speleothem record anchored by a uranium-lead

In neurons, the loading of neurotransmitters into synaptic vesicles uses energy from proton-pumping vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases). These membrane protein complexes possess numerous subunit isoforms, which complicates their analysis. We isolated homogeneous rat brain V-ATPase through its interaction with SidK, a Legionella pneumophila effector protein. Cryo-electron