Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton

We discuss the current state of knowledge of stable homotopy groups of spheres. We describe a computational method using motivic homotopy theory, viewed as a deformation of classical homotopy theory. This yields a streamlined computation of the first 61 stable homotopy groups and gives information about the stable homotopy groups in dimensions 62 through 90. As an application, we determine the groups

Modern practice for training classification deepnets involves a terminal phase of training (TPT), which begins at the epoch where training error first vanishes. During TPT, the training error stays effectively zero, while training loss is pushed toward zero. Direct measurements of TPT, for three prototypical deepnet architectures and across seven canonical classification datasets, expose a pervasive

The deep structure of the continental collision between India and Asia and whether India’s lower crust is underplated beneath Tibet or subducted into the mantle remain controversial. It is also unknown whether the active normal faults that facilitate orogen-parallel extension of Tibetan upper crust continue into the lower crust and upper mantle. Our receiver-function images collected parallel to the

Scientists worldwide are racing to develop effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic. An important and perhaps underappreciated aspect of this endeavor is ensuring that the vaccines being developed confer immunity to all viral lineages in the global population. Toward this end, a seminal study published in PNAS

The failure of polypeptides to achieve conformational maturation following biosynthesis can result in the formation of protein aggregates capable of disrupting essential cellular functions. In the secretory pathway, misfolded asparagine (N)-linked glycoproteins are selectively sorted for endoplasmic reticulum-associated degradation (ERAD) in response to the catalytic removal of terminal alpha-linked

The tropical Andes are an important natural laboratory to understand speciation in many taxa. Here we examined the evolutionary history of parasites of the Leishmania braziliensis species complex based on whole-genome sequencing of 67 isolates from 47 localities in Peru. We first show the origin of Andean Leishmania as a clade of near-clonal lineages that diverged from admixed Amazonian ancestors,

Major depressive disorder emerges from the complex interactions of biological systems that span genes and molecules through cells, networks, and behavior. Establishing how neurobiological processes coalesce to contribute to depression requires a multiscale approach, encompassing measures of brain structure and function as well as genetic and cell-specific transcriptional data. Here, we examine anatomical

Targeted treatments for advanced gastric cancer (GC) are needed, particularly for HER2-negative GC, which represents the majority of cases (80 to 88%). In this study, in silico analyses of the lysine histone demethylases (KDMs) involved in diverse biological processes and diseases revealed that PHD finger protein 8 (PHF8, KDM7B) was significantly associated with poor clinical outcome in HER2-negative

Human decisions can be biased by irrelevant information. For example, choices between two preferred alternatives can be swayed by a third option that is inferior or unavailable. Previous work has identified three classic biases, known as the attraction, similarity, and compromise effects, which arise during choices between economic alternatives defined by two attributes. However, the reliability, interrelationship

While near-cognate codons are frequently used for translation initiation in eukaryotes, their efficiencies are usually low (<10% compared to an AUG in optimal context). Here, we describe a rare case of highly efficient near-cognate initiation. A CUG triplet located in the 5′ leader of POLG messenger RNA (mRNA) initiates almost as efficiently (∼60 to 70%) as an AUG in optimal context. This CUG directs

Whereas the gill chambers of jawless vertebrates open directly into the environment, jawed vertebrates evolved skeletal appendages that drive oxygenated water unidirectionally over the gills. A major anatomical difference between the two jawed vertebrate lineages is the presence of a single large gill cover in bony fishes versus separate covers for each gill chamber in cartilaginous fishes. Here, we

In the high spin–orbit-coupled Sr2IrO4, the high sensitivity of the ground state to the details of the local lattice structure shows a large potential for the manipulation of the functional properties by inducing local lattice distortions. We use epitaxial strain to modify the Ir–O bond geometry in Sr2IrO4 and perform momentum-dependent resonant inelastic X-ray scattering (RIXS) at the metal and at

Midlatitude Asia (MLA), strongly influenced by westerlies-controlled climate, is a key source of global atmospheric dust, and plays a significant role in Earth’s climate system . However, it remains unclear how the westerlies, MLA aridity, and dust flux from this region evolved over time. Here, we report a unique high-resolution eolian dust record covering the past 3.6 Ma, retrieved from the thickest

There is an expectation that, on average, pain will increase with age, through accumulated injury, physical wear and tear, and an increasing burden of disease. Consistent with that expectation, pain rises with age into old age in other wealthy countries. However, in America today, the elderly report less pain than those in midlife. This is the mystery of American pain. Using multiple datasets and definitions

The oligoadenylate synthetase (OAS)–RNase L system is an IFN-inducible antiviral pathway activated by viral infection. Viral double-stranded (ds) RNA activates OAS isoforms that synthesize the second messenger 2-5A, which binds and activates the pseudokinase-endoribonuclease RNase L. In cells, OAS activation is tamped down by ADAR1, an adenosine deaminase that destabilizes dsRNA. Mutation of ADAR1

Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory

Drought alters carbon (C) allocation within trees, thereby impairing tree growth. Recovery of root and leaf functioning and prioritized C supply to sink tissues after drought may compensate for drought-induced reduction of assimilation and growth. It remains unclear if C allocation to sink tissues during and following drought is controlled by altered sink metabolic activities or by the availability

It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice

Fishers with individual catch quota, but limited control over the mix of species caught, depend on trade and catch–quota balancing allowances to fully utilize their quota without discarding. However, these allowances can theoretically lead to overfishing if total allowable catches (TACs) are consistently exceeded. This study investigates usage of balancing allowances by the Icelandic demersal fleet

Size is a key to locomotion. In insects, miniaturization leads to fundamental changes in wing structure and kinematics, making the study of flight in the smallest species important for basic biology and physics, and, potentially, for applied disciplines. However, the flight efficiency of miniature insects has never been studied, and their speed and maneuverability have remained unknown. We report a

Domesticated dogs show unparalleled diversity in body size across breeds, but within breeds variation is limited by selective breeding. Many heritable diseases of dogs are found among breeds of similar sizes, suggesting that as in humans, alleles governing growth have pleiotropic effects. Here, we conducted independent genome-wide association studies in the small Shetland Sheepdog breed and discovered

Asymptomatic carriers of Plasmodium parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density infections (<100 parasites per microliter blood) that work in resource-limited settings (RLS). Sensitive point-of-care diagnostics are also lacking for nonfalciparum malaria, which is characterized by lower density infections

Controlling autonomous propulsion of microswimmers is essential for targeted drug delivery and applications of micro/nanomachines in environmental remediation and beyond. Herein, we report two-dimensional (2D) carbon nitride-based Janus particles as highly efficient, light-driven microswimmers in aqueous media. Due to the superior photocatalytic properties of poly(heptazine imide) (PHI), the microswimmers

Investigations on the chronic health effects of fine particulate matter (PM2.5) exposure in China are limited due to the lack of long-term exposure data. Using satellite-driven models to generate spatiotemporally resolved PM2.5 levels, we aimed to estimate high-resolution, long-term PM2.5 and associated mortality burden in China. The multiangle implementation of atmospheric correction (MAIAC) aerosol

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on

Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these

Maintaining the fidelity of nascent peptide chain (NP) synthesis is essential for proteome integrity and cellular health. Ribosome-associated quality control (RQC) serves to resolve stalled translation, during which untemplated Ala/Thr residues are added C terminally to stalled peptide, as shown during C-terminal Ala and Thr addition (CAT-tailing) in yeast. The mechanism and biological effects of CAT-tailing–like

Several initiatives have been proposed to mitigate forest loss and climate change through tree planting as well as maintaining and restoring forest ecosystems. These initiatives have both inspired and been inspired by global assessments of tree and forest attributes and their contributions to offset carbon dioxide (CO2) emissions. Here we use data from more than 130,000 national forest inventory plots

Methane clathrates are widespread on the ocean floor of the Earth. A better understanding of methane clathrate formation has important implications for natural-gas exploitation, storage, and transportation. A key step toward understanding clathrate formation is hydrate nucleation, which has been suggested to involve multiple evolution pathways. Herein, a unique nucleation/growth pathway for methane

The loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common inherited intellectual disability. How the loss of FMRP alters protein expression and astroglial functions remains essentially unknown. Here we showed that selective loss of astroglial FMRP in vivo up-regulates a brain-enriched miRNA, miR-128-3p, in mouse and human FMRP-deficient astroglia, which

Many mental health disorders first manifest in adolescence, and early treatment may affect the course of the disease. Using a large national database of insurance claims, this study focuses on variations in the type of care that adolescent patients receive when they are treated for an initial episode of mental illness. We found large variations in the probability that children receive follow-up care

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed

Many diseases have no visual cues in the early stages, eluding image-based detection. Today, osteoarthritis (OA) is detected after bone damage has occurred, at an irreversible stage of the disease. Currently no reliable method exists for OA detection at a reversible stage. We present an approach that enables sensitive OA detection in presymptomatic individuals. Our approach combines optimal mass transport

Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal

In humans and other long-lived species, harsh conditions in early life often lead to profound differences in adult life expectancy. In response, natural selection is expected to accelerate the timing and pace of reproduction in individuals who experience some forms of early-life adversity. However, the adaptive benefits of reproductive acceleration following early adversity remain untested. Here, we

Many mental illnesses arise in adolescence, and a study of national insurance claims in the United States finds a large variance in how adolescent patients are treated even within the same zip code. The findings, reported in Janet Currie’s Inaugural Article (IA) (1), reveal that 45% of adolescents receive first-line treatments that are not approved by the US Food and Drug Administration (FDA) (1).

The structure of lincomycin A consists of the unusual eight-carbon thiosugar core methyllincosamide (MTL) decorated with a pendent N-methylprolinyl moiety. Previous studies on MTL biosynthesis have suggested GDP-ᴅ-erythro-α-ᴅ-gluco-octose and GDP-ᴅ-α-ᴅ-lincosamide as key intermediates in the pathway. However, the enzyme-catalyzed reactions resulting in the conversion of GDP-ᴅ-erythro-α-ᴅ-gluco-octose

Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11-cis-retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11-cis- to all-trans-retinal configuration. Continued light sensitivity necessitates the regeneration of 11-cis-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B2 synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled

Australian funnel-web spiders are infamous for causing human fatalities, which are induced by venom peptides known as δ-hexatoxins (δ-HXTXs). Humans and other primates did not feature in the prey or predator spectrum during evolution of these spiders, and consequently the primate lethality of δ-HXTXs remains enigmatic. Funnel-web envenomations are mostly inflicted by male spiders that wander from their

Our study reveals a hitherto overlooked ecological threat of climate change. Studies of warming events in the ocean have typically focused on the events’ maximum temperature and duration as the cause of devastating disturbances in coral reefs, kelp forests, and rocky shores. In this study, however, we found that the rate of onset (Ronset), rather than the peak, was the likely trigger of mass mortality

CELL BIOLOGY Correction for “β-Arrestin2 is a critical component of the GPCR–eNOS signalosome,” by Songling Liu, Louis M. Luttrell, Richard T. …

DEVELOPMENTAL BIOLOGY Correction for “Acrosin is essential for sperm penetration through the zona pellucida in hamsters,” by Michiko Hirose, Arata …

BIOCHEMISTRY, CHEMISTRY Correction for “Genomic analysis of siderophore β-hydroxylases reveals divergent stereocontrol and expands …

APPLIED PHYSICAL SCIENCES Correction for “Dimple drainage before the coalescence of a droplet deposited on a smooth substrate,” by Laurent Duchemin and Christophe Josserand, which was first published August 11, 2020; …

GENETICS Correction for “Natural cryptic variation in epigenetic modulation of an embryonic gene regulatory network,” by Chee Kiang Ewe, Yamila N. Torres Cleuren, Sagen E. Flowers, Geneva Alok, Russell G. Snell, and Joel H. Rothman, which was first published June 1, 2020; 10.1073/pnas.1920343117 (Proc. Natl. Acad. Sci. U.S.A. 117, 13637–13646).

MEDICAL SCIENCES Correction for “Regulation of T cell activation, anxiety, and male aggression by RGS2,” by Antonio J. Oliveira-dos-Santos, Goichi Matsumoto, Bryan E. Snow, Donglin Bai, Frank P. Houston, Ian Q. Whishaw, Sanjeev Mariathasan, Takehiko Sasaki, Andrew Wakeham, Pamela S. Ohashi, John C. Roder, …

MICROBIOLOGY Correction for “Using synthetic biology to overcome barriers to stable expression of nitrogenase …

We introduce a method to draw causal inferences—inferences immune to all possible confounding—from genetic data that include parents and offspring. Causal conclusions are possible with these data because the natural randomness in meiosis can be viewed as a high-dimensional randomized experiment. We make this observation actionable by developing a conditional independence test that identifies regions

Peptidomimetic macrocycles have the potential to regulate challenging therapeutic targets. Structures of this type having precise shapes and drug-like character are particularly coveted, but are relatively difficult to synthesize. Our laboratory has developed robust methods that integrate small-peptide units into designed scaffolds. These methods create macrocycles and embed condensed heterocycles

Surveying a campus community about sexual harassment can be a daunting task during normal times. It’s especially daunting during a pandemic. Institutional leaders may balk at committing scarce resources to survey efforts. Some may wonder how to interpret results that look dramatically different from prior assessments. Also, they may worry about adding to the burdens of already stressed staff, faculty

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs

The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types

Hebbian plasticity is a key mechanism for higher brain functions, such as learning and memory. This form of synaptic plasticity primarily involves the regulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) abundance and properties, whereby AMPARs are inserted into synapses during long-term potentiation (LTP) or removed during long-term depression (LTD). The molecular

In their Letter, Ng et al. (1) state that our (2) comparison of the coronavirus disease 2019 (COVID-19) to Hurricane Katrina is “slightly contrived.” We appreciate the opportunity for discussion. However, we maintain that there is much to be learned from prior disasters, including Hurricane Katrina, for anticipating and mitigating the indirect health consequences of the COVID-19 pandemic.

In a recent Brief Report by Raker et al. (1), the investigators analyze data from a prospective study of young, low-income mothers who survived Hurricane Katrina and apply this to the ongoing coronavirus disease 2019 (COVID-19) pandemic to discuss strategies to mitigate the pandemic’s indirect effects on survivors. We appreciate the comparison made, but it is slightly contrived for several reasons

We commend Malisch et al. on their Opinion (1) on immediate solutions to ensure gender equity during the COVID-19 pandemic given the disproportionate burden placed on women due to childcare and household responsibilities. Given early reports showing fewer women are submitting academic papers during the pandemic (2), we encourage institutions to immediately examine how to improve gender equity in the

As increasing evidence emerges concerning the disproportionate impact of COVID-19 on women academics (1, 2), we hope our work continues to prompt institutions and departments to advance gender equity in tenure and promotion (3). For example, Arora et al. (4) have developed a department-specific rubric to assess COVID-19’s impact on a case-by-case basis. This rubric is in the form of a curriculum vitae