Most transposable elements (TEs) in the mouse genome are heavily modified by DNA methylation and repressive histone modifications. However, a subset of TEs exhibit variable methylation levels in genetically identical individuals, and this is associated with epigenetically conferred phenotypic differences, environmental adaptability, and transgenerational epigenetic inheritance. The evolutionary origins

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication

Therapeutic approaches for the induction of immune tolerance remain an unmet clinical need for the treatment of autoimmune diseases, including multiple sclerosis (MS). Based on its role in the control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is a candidate target for novel immunotherapies. Here, we report the development of AhR-activating nanoliposomes

In untreated HIV-1 infection, rapid viral evolution allows escape from immune responses. Viral replication can be blocked by antiretroviral therapy. However, HIV-1 persists in a latent reservoir in resting CD4+ T cells, and rebound viremia occurs following treatment interruption. The reservoir, which is maintained in part by clonal expansion, can be measured using quantitative viral outgrowth assays

Processing and presentation of self-antigens and foreign antigens and their loading into class I and class II molecules of the major histocompatibility complex (MHC) constitute a major feature of the cellular immune response and induce CD8 and CD4 T cell immune responses (1, 2), respectively. The MHC complex, in human, called human leukocyte antigen complex (HLA), is the most polymorphic locus of the

Diverse efforts in protein engineering are beginning to produce novel kinds of symmetric self-assembling architectures, from protein cages to extended two-dimensional (2D) and three-dimensional (3D) crystalline arrays. Partial theoretical frameworks for creating symmetric protein materials have been introduced, but no complete system has been articulated. Only a minute fraction of the possible design

Engineered cytokines are gaining importance in cancer therapy, but these products are often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as a target for therapeutic strategies with agonistic antibodies or using its cognate cytokine ligand, 4-1BBL. Here we describe

McConnell et al. (1) suggest that the eruption of Alaska’s Okmok volcano in 43 BCE strongly affected historical events in the late Roman Republic and the Ptolemaic Kingdom.

We report (1) ice core evidence that unambiguously identifies massive sulfur fallout over much of the Arctic, attributed using tephra geochemistry to eruption of Alaska’s Okmok volcano, with climate model simulations indicating 2 y of extreme temperatures and precipitation throughout the Northern Hemisphere starting in early 43 BCE. This climate event occurred in the waning years of the Roman Republic

Kalokerinos et al. (1) demonstrate that emotional variability, as assessed via the SD, is not significantly associated with neuroticism once the confound with mean negative emotion is controlled for, r = 0.05. To control for this confound, the authors use the relative SD (RSD), which mathematically corrects for the nonlinear dependency between the SD and the mean (2). The authors prefer the RSD over

Wenzel and Kubiak (1) reanalyze our data (2) and conclude that 1) there is overlap between the relative SD (RSD) (3) and mean of negative emotion and 2) after controlling for this overlap, the RSD weakly but significantly predicts neuroticism. We question both points and note that these findings leave our conclusions unchanged.

Choi and Kim (1) used the alignment-free feature frequency profile (FFP) method to reconstruct a broad sketch of the tree of life (ToL). The FFP tree reports many relationships that strongly contradict the current consensus view of the ToL, including sister group relationships for plants + animals, Bacteria + Archaea, and Mollusca (incorrectly referred to as cnidarians) + deuterostomes. The FFP tree

SOCIAL SCIENCES Correction for “Demographic perspectives on the mortality of COVID-19 and other epidemics,” by Joshua R. Goldstein and Ronald D. Lee, which was first published August 20, 2020; 10.1073/pnas.2006392117 (Proc. Natl. Acad. Sci. U.S.A. …

EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Correction for “Global increase in major tropical cyclone exceedance probability over the past four decades,” by James P. Kossin, Kenneth R. Knapp, Timothy L. Olander, and Christopher S. Velden, which was first published May 18, 2020; 10.1073/pnas.1920849117 (Proc. Natl. Acad. Sci. U.S.A. 117, 11975–11980).

BIOPHYSICS AND COMPUTATIONAL BIOLOGY, MICROBIOLOGY Correction for “Mechanism of water extraction from gypsum rock by desert colonizing microorganisms,” by Wei Huang, Emine Ertekin, Taifeng Wang, Luz …

Colloquium Correction for “Humoral immune response to native eukaryotic prion protein correlates with anti-prion protection,” by Magdalini Polymenidou, Frank L. Heppner, Erica C. Pellicioli, Eduard Urich, Gino Miele, Nathalie Braun, Franziska Wopfner, Hermann M. Schätzl, Burkhard Becher, and Adriano Aguzzi, which was first published August 3, 2004; 10.1073/pnas.0404772101 (Proc. Natl. Acad. Sci. …

The justification and targeting of conservation policy rests on reliable measures of public and private benefits from competing land uses. Advances in Earth system observation and modeling permit the mapping of public ecosystem services at unprecedented scales and resolutions, prompting new proposals for land protection policies and priorities. Data on private benefits from land use are not available

Nuclear war, beyond its devastating direct impacts, is expected to cause global climatic perturbations through injections of soot into the upper atmosphere. Reduced temperature and sunlight could drive unprecedented reductions in agricultural production, endangering global food security. However, the effects of nuclear war on marine wild-capture fisheries, which significantly contribute to the global

Many animals, and an increasing number of artificial agents, display sophisticated capabilities to perceive and manipulate objects. But human beings remain distinctive in their capacity for flexible, creative tool use—using objects in new ways to act on the world, achieve a goal, or solve a problem. To study this type of general physical problem solving, we introduce the Virtual Tools game. In this

Space-related processing recruits a network of brain regions separate from those recruited in object processing. This dissociation has largely been explored by contrasting views of navigable-scale spaces to views of close-up, isolated objects. However, in naturalistic visual experience, we encounter spaces intermediate to these extremes, like the tops of desks and kitchen counters, which are not navigable

Distinct scientific theories can make similar predictions. To adjudicate between theories, we must design experiments for which the theories make distinct predictions. Here we consider the problem of comparing deep neural networks as models of human visual recognition. To efficiently compare models’ ability to predict human responses, we synthesize controversial stimuli: images for which different

A fundamental natural visual task is the identification of specific target objects in the environments that surround us. It has long been known that some properties of the background have strong effects on target visibility. The most well-known properties are the luminance, contrast, and similarity of the background to the target. In previous studies, we found that these properties have highly lawful

When encountering unexpected event changes, memories of relevant past experiences must be updated to form new representations. Current models of memory updating propose that people must first generate memory-based predictions to detect and register that features of the environment have changed, then encode the new event features and integrate them with relevant memories of past experiences to form

Understanding how the brain works requires interpreting neural activity. The behaviorist tradition aims to understand the brain as a black box solely from its inputs and outputs. Modern neuroscience has been able to gain major insights by looking inside the black box, but still largely relates measurements of neural activity to the brain’s inputs and outputs. While this is the basis of both sensory

Production and expression of RNA requires the action of multiple RNA-binding proteins (RBPs). New RBPs are most often created by novel combinations of dedicated RNA-binding modules. However, recruiting existing genes to create new RBPs is also an important evolutionary strategy. In this report, we analyzed the eight-member uL18 ribosomal protein family in Arabidopsis. uL18 proteins share a short structurally

Potassium channels can become nonconducting via inactivation at a gate inside the highly conserved selectivity filter (SF) region near the extracellular side of the membrane. In certain ligand-gated channels, such as BK channels and MthK, a Ca2+-activated K+ channel from Methanobacterium thermoautotrophicum, the SF has been proposed to play a role in opening and closing rather than inactivation, although

Topological edge modes are excitations that are localized at the materials’ edges and yet are characterized by a topological invariant defined in the bulk. Such bulk–edge correspondence has enabled the creation of robust electronic, electromagnetic, and mechanical transport properties across a wide range of systems, from cold atoms to metamaterials, active matter, and geophysical flows. Recently, the

The exotic properties of quantum spin liquids (QSLs) have continually been of interest since Anderson’s 1973 ground-breaking idea. Geometrical frustration, quantum fluctuations, and low dimensionality are the most often evoked material’s characteristics that favor the long-range fluctuating spin state without freezing into an ordered magnet or a spin glass at low temperatures. Among the few known QSL

Recent experiments on twisted bilayer graphene have shown a high-temperature parent state with massless Dirac fermions and broken electronic flavor symmetry; superconductivity and correlated insulators emerge from this parent state at lower temperatures. We propose that the superconducting and correlated insulating orders are connected by Wess–Zumino–Witten terms, so that defects of one order contain

Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970

Sequential activity has been observed in multiple neuronal circuits across species, neural structures, and behaviors. It has been hypothesized that sequences could arise from learning processes. However, it is still unclear whether biologically plausible synaptic plasticity rules can organize neuronal activity to form sequences whose statistics match experimental observations. Here, we investigate

Analysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca2+ in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation

Object-based attention describes the brain’s capacity to prioritize one set of stimuli while ignoring others. Human research suggests that the binding of diverse stimuli into one attended percept requires phase-locked oscillatory activity in the brain. Even insects display oscillatory brain activity during visual attention tasks, but it is unclear if neural oscillations in insects are selectively correlated

Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca2+. However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca2+ channels (CaChs) and excitation–contraction coupling in vertebrate skeletal muscles. There

Food is a powerful entrainment cue for circadian clocks in peripheral tissues, and changes in the composition of nutrients have been demonstrated to metabolically reprogram peripheral clocks. However, how food challenges may influence circadian metabolism of the master clock in the suprachiasmatic nucleus (SCN) or in other brain areas is poorly understood. Using high-throughput metabolomics, we studied

Transmembrane channel-like protein 1 (TMC1) and lipoma HMGIC fusion partner-like 5 (LHFPL5) are recognized as two critical components of the mechanotransduction complex in inner-ear hair cells. However, the physical and functional interactions of TMC1 and LHFPL5 remain largely unexplored. We examined the interaction between TMC1 and LHFPL5 by using multiple approaches, including our recently developed

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory

The prefrontal cortex encodes and stores numerous, often disparate, schemas and flexibly switches between them. Recent research on artificial neural networks trained by reinforcement learning has made it possible to model fundamental processes underlying schema encoding and storage. Yet how the brain is able to create new schemas while preserving and utilizing old schemas remains unclear. Here we propose

The link between mind, brain, and behavior has mystified philosophers and scientists for millennia. Recent progress has been made by forming statistical associations between manifest variables of the brain (e.g., electroencephalogram [EEG], functional MRI [fMRI]) and manifest variables of behavior (e.g., response times, accuracy) through hierarchical latent variable models. Within this framework, one

Humans have the fascinating ability to achieve goals in a complex and constantly changing world, still surpassing modern machine-learning algorithms in terms of flexibility and learning speed. It is generally accepted that a crucial factor for this ability is the use of abstract, hierarchical representations, which employ structure in the environment to guide learning and decision making. Nevertheless

Humans readily form social impressions, such as attractiveness and trustworthiness, from a stranger’s facial features. Understanding the provenance of these impressions has clear scientific importance and societal implications. Motivated by the efficient coding hypothesis of brain representation, as well as Claude Shannon’s theoretical result that maximally efficient representational systems assign

Prior work has shown that the brain represents memories within a cognitive map that supports inference about connections between individual related events. Real-world adaptive behavior is also supported by recognizing common structure among numerous distinct contexts; for example, based on prior experience with restaurants, when visiting a new restaurant one can expect to first get a table, then order

Neuronal population responses to sensory stimuli are remarkably flexible. The responses of neurons in visual cortex have heterogeneous dependence on stimulus properties (e.g., contrast), processes that affect all stages of visual processing (e.g., adaptation), and cognitive processes (e.g., attention or task switching). Understanding whether these processes affect similar neuronal populations and whether

Organelle remodeling is critical for cellular homeostasis, but host factors that control organelle function during microbial infection remain largely uncharacterized. Here, a genome-scale CRISPR/Cas9 screen in intestinal epithelial cells with the prototypical intracellular bacterial pathogen Salmonella led us to discover that type I IFN (IFN-I) remodels lysosomes. Even in the absence of infection,

Kinetoplastids are unicellular eukaryotic parasites responsible for such human pathologies as Chagas disease, sleeping sickness, and leishmaniasis. They have a single large mitochondrion, essential for the parasite survival. In kinetoplastid mitochondria, most of the molecular machineries and gene expression processes have significantly diverged and specialized, with an extreme example being their

Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant pathogens for which new treatments are desperately needed. Carbapenemases and other types of antibiotic resistance genes are carried almost exclusively on large, low-copy-number plasmids (pCRE). Accordingly, small molecules that efficiently evict pCRE plasmids should restore much-needed treatment options. We therefore designed a

Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1,

Nuclear factor–ĸB (NF-ĸB) transcription factor is a family of essential regulators of the immune response and cell proliferation and transformation. A typical factor is a heterodimer made of either p50 or p52, which are limited processing products of either p105 or p100, respectively, and a member of the Rel family of proteins, typically p65. The transcriptional program of NF-ĸB is tightly regulated

We find ourselves ten months into one of the most catastrophic global health events of our lifetime and, disturbingly, we still do not know how it began. What’s even more troubling is that despite the critical importance of this question, efforts to investigate the origins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and of the associated disease, coronavirus disease 2019

Inflammasomes have been implicated in the detection and clearance of a variety of bacterial pathogens, but little is known about whether this innate sensing mechanism has any regulatory effect on the expression of stimulatory ligands by the pathogen. During infection with Salmonella and many other pathogens, flagellin is a major activator of NLRC4 inflammasome-mediated macrophage pyroptosis and pathogen

In the brain, compact clusters of neuron cell bodies, termed nuclei, are essential for maintaining parameters of host physiology within a narrow range optimal for health. Neurons residing in the brainstem dorsal motor nucleus (DMN) project in the vagus nerve to communicate with the lungs, liver, gastrointestinal tract, and other organs. Vagus nerve-mediated reflexes also control immune system responses

Meningococcal meningitis remains a substantial cause of mortality and morbidity worldwide. Until recently, countries in the African meningitis belt were susceptible to devastating outbreaks, largely attributed to serogroup A Neisseria meningitidis (MenA). Vaccination with glycoconjugates of MenA capsular polysaccharide led to an almost complete elimination of MenA clinical cases. To understand the

Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails

Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild

Climate change affects organisms worldwide with profound ecological and evolutionary consequences, often increasing population extinction risk. Climatic factors can increase the strength, variability, or direction of natural selection on phenotypic traits, potentially driving adaptive evolution. Phenotypic plasticity in relation to temperature can allow organisms to maintain fitness in response to

Collective conflicts among humans are widespread, although often highly destructive. A classic explanation for the prevalence of such warfare in some human societies is leadership by self-serving individuals that reap the benefits of conflict while other members of society pay the costs. Here, we show that leadership of this kind can also explain the evolution of collective violence in certain animal

The COVID-19 pandemic has led to environmental recovery in some ecosystems from a global “anthropause,” yet such evidence for natural resources with extraction or production value (e.g., fisheries) is limited. This brief report provides a data-driven global snapshot of expert-perceived impacts of COVID-19 on inland fisheries. We distributed an online survey assessing perceptions of inland fishery pressures

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The “Beautiful China” strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 μg/m3 or below for annual mean concentration of PM2.5 (particulate matter with aerodynamic diameter less than 2.5 μm) by 2035. Meanwhile, China adopts a portfolio of low-carbon

The rapid spread of COVID-19 across the world has revealed major gaps in our ability to respond to new virulent pathogens. Rapid, accurate, and easily configurable molecular diagnostic tests are imperative to prevent global spread of new diseases. CRISPR-based diagnostic approaches are proving to be useful as field-deployable solutions. In one basic form of this assay, the CRISPR–Cas12 enzyme complexes

Virus–microbe interactions have been studied in great molecular details for many years in cultured model systems, yielding a plethora of knowledge on how viruses use and manipulate host machinery. Since the advent of molecular techniques and high-throughput sequencing, methods such as cooccurrence, nucleotide composition, and other statistical frameworks have been widely used to infer virus–microbe