Nuclear factor κB (NF-κB) is an important transcriptional regulator that is involved in numerous cellular processes, including cell proliferation, immune response, cell survival, and malignant transformation. It relies on the ubiquitin–proteasome system (UPS) for several of the steps in the concerted cascade of its activation. Previously, we showed that the ubiquitin (Ub) ligase KPC1 is involved in

Flaviviruses such as Zika virus and West Nile virus have the potential to cause severe neuropathology if they invade the central nervous system. The type I interferon response is well characterized as contributing to control of flavivirus-induced neuropathogenesis. However, the interferon-stimulated gene (ISG) effectors that confer these neuroprotective effects are less well studied. Here, we used

Understanding how rivers adjust to the sediment load they carry is critical to predicting the evolution of landscapes. Presently, however, no physically based model reliably captures the dependence of basic river properties, such as its shape or slope, on the discharge of sediment, even in the simple case of laboratory rivers. Here, we show how the balance between fluid stress and gravity acting on

Information derived from metagenome sequences through deep-learning techniques has significantly improved the accuracy of template free protein structure modeling. However, most of the deep learning–based modeling studies are based on blind sequence database searches and suffer from low efficiency in computational resource utilization and model construction, especially when the sequence library becomes

The relationship between sample thickness and quality of data obtained is investigated by microcrystal electron diffraction (MicroED). Several electron microscopy (EM) grids containing proteinase K microcrystals of similar sizes from the same crystallization batch were prepared. Each grid was transferred into a focused ion beam and a scanning electron microscope in which the crystals were then systematically

We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from

Protein homeostasis is constantly being challenged with protein misfolding that leads to aggregation. Hsp70 is one of the versatile chaperones that interact with misfolded proteins and actively support their folding. Multifunctional Hsp70s are harnessed to specific roles by J-domain proteins (JDPs, also known as Hsp40s). Interaction with the J-domain of these cochaperones stimulates ATP hydrolysis

During the last glacial interval, marine sediments recorded reduced current ventilation within the ocean interior below water depths of approximately >1,500 m [B. A. Hoogakker et al., Nat. Geosci. 8, 40–43 (2015)]. The degree of the associated oxygen depletion in the different ocean basins, however, is still poorly constrained. Here, we present sedimentary records of redox-sensitive metals from the

Preclinical models have been the workhorse of cancer research, producing massive amounts of drug response data. Unfortunately, translating response biomarkers derived from these datasets to human tumors has proven to be particularly challenging. To address this challenge, we developed TRANSACT, a computational framework that builds a consensus space to capture biological processes common to preclinical

Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial

RNA velocity is a promising technique for quantifying cellular transitions from single-cell transcriptome experiments and revealing transient cellular dynamics among a heterogeneous cell population. However, the cell transitions estimated from high-dimensional RNA velocity are often unstable or inaccurate, partly due to the high technical noise and less informative projection. Here, we present Velocity

The term Fermi liquid is almost synonymous with the metallic state. The association is known to break down at quantum critical points (QCPs), but these require precise values of tuning parameters, such as pressure and applied magnetic field, to exactly suppress a continuous phase transition temperature to the absolute zero. Three-dimensional non-Fermi liquid states, apart from superconductivity, that

Despite the complexity of human memory, paradigms like free recall have revealed robust qualitative and quantitative characteristics, such as power laws governing recall capacity. Although abstract random matrix models could explain such laws, the possibility of their implementation in large networks of interacting neurons has so far remained underexplored. We study an attractor network model of long-term

Functionalist accounts of language suggest that forms are paired with meanings in ways that support efficient communication. Previous work on grammatical marking suggests that word forms have lengths that enable efficient production, and work on the semantic typology of the lexicon suggests that word meanings represent efficient partitions of semantic space. Here we establish a theoretical link between

Transporters cycle through large structural changes to translocate molecules across biological membranes. The temporal relationships between these changes and function, and the molecular properties setting their rates, determine transport efficiency—yet remain mostly unknown. Using single-molecule fluorescence microscopy, we compare the timing of conformational transitions and substrate uptake in the

Near the 100th anniversary of the discovery of ferroelectricity, so-called sliding ferroelectricity has been proposed and confirmed recently in a series of experiments that have stimulated remarkable interest. Such ferroelectricity exists widely and exists only in two-dimensional (2D) van der Waals stacked layers, where the vertical electric polarization is switched by in-plane interlayer sliding.

The term “core microbiome” has become widely used in microbial ecology over the last decade. Broadly, the core microbiome refers to any set of microbial taxa, or the genomic and functional attributes associated with those taxa, that are characteristic of a host or environment of interest. Most commonly, core microbiomes are measured as the microbial taxa shared among two or more samples from a particular

In less than 25 y, the field of animal genome science has transformed from a discipline seeking its first glimpses into genome sequences across the Tree of Life to a global enterprise with ambitions to sequence genomes for all of Earth’s eukaryotic diversity [H. A. Lewin et al., Proc. Natl. Acad. Sci. U.S.A. 115, 4325–4333 (2018)]. As the field rapidly moves forward, it is important to take stock of

A series of sodium phosphorothioate complexes are shown to have electrochemical properties attractive for sodium-sulfur battery applications across a wide operating temperature range. As cathode materials, they resolve a long-standing issue of cyclic liquid–solid phase transition that causes sluggish reaction kinetics and poor cycling stability in conventional, room-temperature sodium-sulfur batteries

Water-assisted proton transport through confined spaces influences many phenomena in biomolecular and nanomaterial systems. In such cases, the water molecules that fluctuate in the confined pathways provide the environment and the medium for the hydrated excess proton migration via Grotthuss shuttling. However, a definitive collective variable (CV) that accurately couples the hydration and the connectivity

Gene silencing in budding yeast is mediated by Sir protein binding to unacetylated nucleosomes to form a chromatin structure that inhibits transcription. Transcriptional silencing is characterized by the high-fidelity transmission of the silent state. Despite its relative stability, the constituent parts of the silent state are in constant flux, giving rise to a model that silent loci can tolerate

The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person’s infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop viral dynamic models of SARS-CoV-2 infection and fit them to data to estimate key within-host parameters such as the infected cell half-life and the within-host reproductive

There is ample evidence that masking and social distancing are effective in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, due to the complexity of airborne disease transmission, it is difficult to quantify their effectiveness, especially in the case of one-to-one exposure. Here, we introduce the concept of an upper bound for one-to-one exposure to infectious

Across the tree of life, organisms modify their local environment, rendering it more or less hospitable for other species. Despite the ubiquity of these processes, simple models that can be used to develop intuitions about the consequences of widespread habitat modification are lacking. Here, we extend the classic Levins metapopulation model to a setting where each of n species can colonize patches

Reading and writing DNA were once the rate-limiting step in synthetic biology workflows. This has been replaced by the search for the optimal target sequences to produce systems with desired properties. Directed evolution and screening mutant libraries are proven technologies for isolating strains with enhanced performance whenever specialized assays are available for rapidly detecting a phenotype

Nitrogen-fixing organisms perform dinitrogen reduction to ammonia at an Fe-M (M = Mo, Fe, or V) cofactor (FeMco) of nitrogenase. FeMco displays eight metal centers bridged by sulfides and a carbide having the MFe7S8C cluster composition. The role of the carbide ligand, a unique motif in protein active sites, remains poorly understood. Toward addressing how the carbon bridge affects the physical and

Humans efficiently estimate the grip force necessary to lift a variety of objects, including slippery ones. The regulation of grip force starts with the initial contact and takes into account the surface properties, such as friction. This estimation of the frictional strength has been shown to depend critically on cutaneous information. However, the physical and perceptual mechanism that provides such

Competition among animals for resources, notably food, territories, and mates, is ubiquitous at all scales of life. This competition is often resolved through contests among individuals, which are commonly understood according to their outcomes and in particular, how these outcomes depend on decision-making by the contestants. Because they are restricted to end-point predictions, these approaches cannot

G protein–coupled receptors display multifunctional signaling, offering the potential for agonist structures to promote conformational selectivity for biased outputs. For β2-adrenergic receptors (β2AR), unbiased agonists stabilize conformation(s) that evoke coupling to Gαs (cyclic adenosine monophosphate [cAMP] production/human airway smooth muscle [HASM] cell relaxation) and β-arrestin engagement

Syntaxin helps in catalyzing membrane fusion during exocytosis. It also forms clusters in the plasma membrane, where both its transmembrane and SNARE domains are thought to homo-oligomerize. To study syntaxin clustering in live PC12 cells, we labeled granules with neuropeptide-Y-mCherry and syntaxin clusters with syntaxin-1a green fluorescent protein (GFP). Abundant clusters appeared under total internal

ENVIRONMENTAL SCIENCES, PSYCHOLOGICAL AND COGNITIVE SCIENCES Correction for “The concurrent decline of soil lead and children’s blood lead in New Orleans,” by Howard W. Mielke, Christopher R. Gonzales, Eric T. Powell, Mark A. S. Laidlaw, Kenneth J. Berry, Paul W. Mielke Jr., and Sara Perl Egendorf, which was first published October 14, 2019; 10.1073/pnas.1906092116 (Proc. …

SOCIAL SCIENCES Correction for “Measuring the predictability of life outcomes with a scientific mass collaboration,” by Matthew J. Salganik, Ian Lundberg, Alexander T. Kindel, Caitlin E. Ahearn, Khaled Al-Ghoneim, Abdullah Almaatouq, Drew M. Altschul, Jennie E. Brand, Nicole Bohme Carnegie, Ryan James Compton, Debanjan Datta, Thomas Davidson, Anna Filippova, Connor Gilroy, Brian J. Goode, Eaman Jahani

Curbing climate change goes hand-in-hand with decarbonizing energy production. But how can communities continue to meet the global demand for electricity without releasing more CO2? A cadre of chemists says one solution may be hiding in an unlikely source: ammonia—the pungent, clear, nitrogen-rich gas, or liquid, that’s most often used as an agricultural fertilizer. Most of the ammonia produced in

Body and canine size dimorphism in fossils inform sociobehavioral hypotheses on human evolution and have been of interest since Darwin’s famous reflections on the subject. Here, we assemble a large dataset of fossil canines of the human clade, including all available Ardipithecus ramidus fossils recovered from the Middle Awash and Gona research areas in Ethiopia, and systematically examine canine dimorphism

Tactile nerve fibers fall into a few classes that can be readily distinguished based on their spatiotemporal response properties. Because nerve fibers reflect local skin deformations, they individually carry ambiguous signals about object features. In contrast, cortical neurons exhibit heterogeneous response properties that reflect computations applied to convergent input from multiple classes of afferents

CRISPR-Cas12a, an RNA-guided DNA targeting endonuclease, has been widely used for genome editing and nucleic acid detection. As part of the essential processes for both of these applications, the two strands of double-stranded DNA are sequentially cleaved by a single catalytic site of Cas12a, but the mechanistic details that govern the generation of complete breaks in double-stranded DNA remain to

Fishes exhibit an astounding diversity of locomotor behaviors from classic swimming with their body and fins to jumping, flying, walking, and burrowing. Fishes that use their body and caudal fin (BCF) during undulatory swimming have been traditionally divided into modes based on the length of the propulsive body wave and the ratio of head:tail oscillation amplitude: anguilliform, subcarangiform, carangiform

In nature, roots of healthy plants are colonized by multikingdom microbial communities that include bacteria, fungi, and oomycetes. A key question is how plants control the assembly of these diverse microbes in roots to maintain host–microbe homeostasis and health. Using microbiota reconstitution experiments with a set of immunocompromised Arabidopsis thaliana mutants and a multikingdom synthetic microbial

The quest for how to collectively self-organize in order to maximize the survival chances of the members of a social group requires finding an optimal compromise between maximizing the well-being of an individual and that of the group. Here we develop a minimal model describing active individuals which consume or produce, and respond to a shared resource—such as the oxygen concentration for aerotactic

Microbes typically secrete a plethora of molecules to promote niche colonization. Soil-dwelling microbes are well-known producers of antimicrobials that are exploited to outcompete microbial coinhabitants. Also, plant pathogenic microbes secrete a diversity of molecules into their environment for niche establishment. Upon plant colonization, microbial pathogens secrete so-called effector proteins that

Liquid crystals (LCs) form an extremely rich range of self-assembled topological structures with artificially or naturally created topological defects. Some of the main applications of LCs are various optical and photonic devices, where compared to their solid-state counterparts, soft photonic systems are fundamentally different in terms of unique properties such as self-assembly, self-healing, large

Biomolecular folding involves searching among myriad possibilities for the native conformation, but the elementary steps expected from theory for this search have never been detected directly. We probed the dynamics of folding at high resolution using optical tweezers, measuring individual trajectories as nucleic acid hairpins passed through the high-energy transition states that dominate kinetics

ANTHROPOLOGY Aerial view of the mound of Los Morteros; the Pacific Ocean is in the background. Origin of adobe bricks Clay adobe bricks are often used in traditional earthen architecture in the Andes. The pre-Hispanic Andean origin and technological evolution of adobe bricks are unclear. Ana Cecilia Mauricio et al....

In natural environments, bacteria are frequently subject to conditions of nutrient scarcity, upon which they cease to grow (1). Nongrowing bacterial cells are faced with a multitude of stresses, including nutrient depletion, alterations in cellular pH, and protein damage. While such cells mount a general stress response that renders them resistant to a variety of environmental insults (1, 2), they

Despite having similar structures, each member of the heteromeric amino acid transporter (HAT) family shows exquisite preference for the exchange of certain amino acids. Substrate specificity determines the physiological function of each HAT and their role in human diseases. However, HAT transport preference for some amino acids over others is not yet fully understood. Using cryo–electron microscopy

Refining a theorem of Zarhin, we prove that, given a g-dimensional abelian variety X and an endomorphism u of X, there exists a matrix A∈M2g(ℤ) such that each Tate module TℓX has a ℤℓ-basis on which the action of u is given by A, and similarly for the covariant Dieudonné module if over a perfect field of characteristic p.

Double-network gels are a class of tough soft materials comprising two elastic networks with contrasting structures. The formation of a large internal damage zone ahead of the crack tip by the rupturing of the brittle network accounts for the large crack resistance of the materials. Understanding what determines the damage zone is the central question of the fracture mechanics of double-network gels

Auditory transduction is mediated by chordotonal (Cho) neurons in Drosophila larvae, but the molecular identity of the mechanotransduction (MET) channel is elusive. Here, we established a whole-cell recording system of Cho neurons and showed that two transient receptor potential vanilloid (TRPV) channels, Nanchung (NAN) and Inactive (IAV), are essential for MET currents in Cho neurons. NAN and IAV

The fragility index is a clinically meaningful metric based on modifying patient outcomes that is increasingly used to interpret the robustness of clinical trial results. The fragility index relies on a concept that explores alternative realizations of the same clinical trial by modifying patient measurements. In this article, we propose to generalize the fragility index to a family of fragility indices

A basic principle of perception is that as objects increase in distance from an observer, they also become logarithmically compressed in perception (i.e., not differentiated from one another), making them hard to distinguish. Could this basic principle apply to perhaps our most meaningful mental representation: our own sense of self? Here, we report four studies that suggest selves are increasingly

Antigen-specific peripheral tolerance is crucial to prevent the development of organ-specific autoimmunity. However, its function decoupled from thymic tolerance remains unclear. We used desmoglein 3 (Dsg3), a pemphigus antigen expressed in keratinocytes, to analyze peripheral tolerance under physiological antigen-expression conditions. Dsg3-deficient thymi were transplanted into athymic mice to create

Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used whole-genome sequences from 57 tigers to estimate individual inbreeding and

Normally, dendritic size is established prior to adolescence and then remains relatively constant into adulthood due to a homeostatic balance between growth and retraction pathways. However, schizophrenia is characterized by accelerated reductions of cerebral cortex gray matter volume and onset of clinical symptoms during adolescence, with reductions in layer 3 pyramidal neuron dendritic length, complexity

IMMUNOLOGY AND INFLAMMATION Correction for “Dual oxidase 1 promotes antiviral innate immunity,” by Demba Sarr, Aaron D. Gingerich, Nuha Milad Asthiwi, Faris Almutairi, Giuseppe A. Sautto, Jeffrey Ecker, Tamás Nagy, Matthew B. Kilgore, Joshua D. Chandler, Ted M. Ross, Ralph A. Tripp, and Balázs Rada, which published June 24, 2021; 10.1073/pnas.2017130118 (Proc. Natl. Acad. Sci. U.S.A. 118, e2017130118)

ENVIRONMENTAL SCIENCES, EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Correction for “Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean,” by Mario Lebrato, Dieter Garbe-Schönberg, Marius N. Müller, Sonia Blanco-Ameijeiras, Richard A. Feely, Laura Lorenzoni, Juan-Carlos Molinero, Karen Bremer, Daniel O. B. Jones, Debora Iglesias-Rodriguez, Dana Greeley, Miles D. Lamare, Aurelien

George F. Vande Woude Jr., a pioneer in retrovirology and molecular oncology, a tremendous scientific mentor, and an all-around versatile, exuberant human being, passed away on April 13, 2021. George was one of the first scientists to consider the molecular basis of cancer. He determined that long-terminal repeat segments linked to oncogenes could transform mammalian cells, and his laboratory defined

Hothouse Earth is endangering the stability of planetary ecosystems at an unprecedented level; consequently, an immediate phase-out of anthropogenic greenhouse gases is required to restabilize global ecosystems (1). Approximately 84% of global CO2 emissions are anthropogenic, relating to the energy system and industrial activities (2). The leading economies of the world must, therefore, assume a role

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; >5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic

We appreciate the interest Putnam-Hornstein et al. (1) have shown in our work (2) in their letter, “Contact with the child protection system is pervasive, but are recent estimates correct?”

Brown adipose tissue has been extensively studied in the last decade for its potential to counteract the obesity pandemic. However, the paracrine regulation within brown tissue is largely unknown. Here, we show that local acetate directly inhibits brown fat thermogenesis, without changing acetate levels in the circulation. We demonstrate that modulating acetate within brown tissue at physiological