Robert Kemp Adair, the Sterling Professor Emeritus of Physics at Yale University, passed away on September 28, 2020, in Hamden, Connecticut, at age 96. He was a distinguished, world-renowned pioneer in particle physics, but possibly even more remarkable as a warm all-round human being, a beloved and highly respected teacher, mentor, colleague, and supervisor. He had a delightful sense of humor, with

The relative role of genetic adaptation and phenotypic plasticity is of fundamental importance in evolutionary ecology [M. J. West-Eberhard, Proc. Natl. Acad. Sci. U.S.A. 102 (suppl. 1), 6543–6549 (2005)]. European eels have a complex life cycle, including transitions between life stages across ecological conditions in the Sargasso Sea, where spawning occurs, and those in brackish and freshwater bodies

The long-term fate of uranium-contaminated sediments, especially downstream former mining areas, is a widespread environmental challenge. Essential for their management is the proper understanding of uranium (U) immobilization mechanisms in reducing environments. In particular, the long-term behavior of noncrystalline U(IV) species and their possible evolution to more stable phases in subsurface conditions

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2. Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection

Runt domain-related (Runx) transcription factors are essential for early T cell development in mice from uncommitted to committed stages. Single and double Runx knockouts via Cas9 show that target genes responding to Runx activity are not solely controlled by the dominant factor, Runx1. Instead, Runx1 and Runx3 are coexpressed in single cells; bind to highly overlapping genomic sites; and have redundant

Photosystem II (PSII) is an intrinsic membrane protein complex that functions as a light-driven water:plastoquinone oxidoreductase in oxygenic photosynthesis. Electron transport in PSII is associated with formation of reactive oxygen species (ROS) responsible for oxidative modifications of PSII proteins. In this study, oxidative modifications of the D1 and D2 proteins by the superoxide anion (O2•−)

As the climate changes, human livelihoods will increasingly be threatened by extreme weather events. To provide adequate disaster relief, states extensively rely on multilateral institutions, in particular the United Nations (UN). However, the determinants of this multilateral disaster aid channeled through the UN are poorly understood. To fill this gap, we examine the determinants of UN disaster aid

In the open ocean, elevated carbon flux (ECF) events increase the delivery of particulate carbon from surface waters to the seafloor by severalfold compared to other times of year. Since microbes play central roles in primary production and sinking particle formation, they contribute greatly to carbon export to the deep sea. Few studies, however, have quantitatively linked ECF events with the specific

An evolutionarily stable strategy (ESS) is an evolutionary strategy that, if adapted by a population, cannot be invaded by any deviating (mutant) strategy. The concept of ESS has been extensively studied and widely applied in ecology and evolutionary biology [M. Smith, On Evolution (1972)] but typically on the assumption that the system is ecologically stable. With reference to a Rosenzweig–MacArthur

An influential reinforcement learning framework proposes that behavior is jointly governed by model-free (MF) and model-based (MB) controllers. The former learns the values of actions directly from past encounters, and the latter exploits a cognitive map of the task to calculate these prospectively. Considerable attention has been paid to how these systems interact during choice, but how and whether

The link between the biological clock and reproduction is evident in most metazoans. The fruit fly Drosophila melanogaster, a key model organism in the field of chronobiology because of its well-defined networks of molecular clock genes and pacemaker neurons in the brain, shows a pronounced diurnal rhythmicity in oogenesis. Still, it is unclear how the circadian clock generates this reproductive rhythm

An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features of in vivo stem cell-driven epithelial renewal, providing an excellent ex vivo platform for interrogation of key

We show that the Higgs mode of a superconductor, which is usually challenging to observe by far-field optics, can be made clearly visible using near-field optics by harnessing ultraconfined graphene plasmons. As near-field sources we investigate two examples: graphene plasmons and quantum emitters. In both cases the coupling to the Higgs mode is clearly visible. In the case of the graphene plasmons

Regulation of microtubule stability is crucial for the maintenance of cell structure and function. While the acetylation of α-tubulin lysine 40 by acetylase has been implicated in the regulation of microtubule stability, the in vivo functions of N-terminal acetyltransferases (NATs) involved in the acetylation of N-terminal amino acids are not well known. Here, we identify an N-terminal acetyltransferase

Reactive iodine plays a key role in determining the oxidation capacity, or cleansing capacity, of the atmosphere in addition to being implicated in the formation of new particles in the marine boundary layer. The postulation that heterogeneous cycling of reactive iodine on aerosols may significantly influence the lifetime of ozone in the troposphere not only remains poorly understood but also heretofore

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we

In PNAS, Zhang et al. (1) report the discovery of the insulator function of a cluster of CTCF-binding elements (CBEs) that defines the 3′-boundary of the immunoglobulin (Ig) heavy (H) chain locus and regulates IgH class switch recombination (CSR) (Fig. 1). This study not only resolves uncertainties surrounding the functional relevance of these CBEs in CSR (2, 3) but further strengthens a “cohesion-mediated

Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2–infected patients with moderate and severe COVID-19. We provide a deep and comprehensive

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-CoV that recently emerged as a human pathogen and is the causative agent of the COVID-19 pandemic. A molecular framework of how the virus manipulates host cellular machinery to facilitate infection remains unclear. Here, we focus on SARS-CoV-2 NSP1, which is proposed to be a virulence factor that inhibits protein synthesis by directly

Desperate phone calls made in the dead of night rarely convey good news, much less first word of a major scientific discovery. Alex Ji made such a call in 2015 from atop a mountain in Chile, where he was using one of the world’s largest telescopes. “This was actually the first time that I had taken data on a telescope ever,” says Ji, then a graduate student at the Massachusetts Institute of Technology

Liquid crystals are complex fluids that allow exquisite control of light propagation thanks to their orientational order and optical anisotropy. Inspired by recent advances in liquid-crystal photo-patterning technology, we propose a soft-matter platform for assembling topological photonic materials that holds promise for protected unidirectional waveguides, sensors, and lasers. Crucial to our approach

The monotopic phosphoglycosyl transferase (monoPGT) superfamily comprises over 38,000 nonredundant sequences represented in bacterial and archaeal domains of life. Members of the superfamily catalyze the first membrane-committed step in en bloc oligosaccharide biosynthetic pathways, transferring a phosphosugar from a soluble nucleoside diphosphosugar to a membrane-resident polyprenol phosphate. The

Strong correlations within a symmetry-unbroken ground-state wavefunction can show up in approximate density functional theory as symmetry-broken spin densities or total densities, which are sometimes observable. They can arise from soft modes of fluctuations (sometimes collective excitations) such as spin-density or charge-density waves at nonzero wavevector. In this sense, an approximate density functional

Hierarchically ordered oxides are of critical importance in material science and catalysis. Unfortunately, the design and synthesis of such systems remains a key challenge to realizing their potential. In this study, we demonstrate how the deposition of small oligomeric (MoO3)1–6 clusters—formed by the facile sublimation of MoO3 powders—leads to the self-assembly of locally ordered arrays of immobilized

A mathematical analysis of the evolution of a large population under the weak-mutation limit shows that such a population would spend most of the time in stasis in the vicinity of saddle points on the fitness landscape. The periods of stasis are punctuated by fast transitions, in lnNe/s time (Ne, effective population size; s, selection coefficient of a mutation), when a new beneficial mutation is fixed

Disordered nanostructures with correlations on the scale of visible wavelengths can show angle-independent structural colors. These materials could replace dyes in some applications because the color is tunable and resists photobleaching. However, designing nanostructures with a prescribed color is difficult, especially when the application—cosmetics or displays, for example—requires specific component

Policymaking during a pandemic can be extremely challenging. As COVID-19 is a new disease and its global impacts are unprecedented, decisions are taken in a highly uncertain, complex, and rapidly changing environment. In such a context, in which human lives and the economy are at stake, we argue that using ideas and constructs from modern decision theory, even informally, will make policymaking a more

RNA-dependent RNA polymerases (RdRps) of the Nidovirales (Coronaviridae, Arteriviridae, and 12 other families) are linked to an amino-terminal (N-terminal) domain, called NiRAN, in a nonstructural protein (nsp) that is released from polyprotein 1ab by the viral main protease (Mpro). Previously, self-GMPylation/UMPylation activities were reported for an arterivirus NiRAN-RdRp nsp and suggested to generate

The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with

ENVIRONMENTAL SCIENCES Plumbojarosite, an insoluble lead–iron hydroxysulfate mineral. Image credit: Wikimedia Commons/John Sobolewski (JSS), licensed under CC BY 3.0. Reducing lead bioavailability in soil Childhood exposure to lead can lead to long-term adverse health effects. A significant source of lead exposure in children is contaminated soil and dust. Because of...

We thank Stuchlík et al. for their comments (1) on our paper (2). First, for the sake of clarity, we note that Stuchlík et al. may have inadvertently stated “δ18O records in several ice cores from Greenland and Antarctica that were originally dated by the radiocarbon method.” This is obviously incorrect, as ice-core δ18O series are not radiocarbon-dated. We are also intrigued by their comment that

The two main blood flow patterns, namely, pulsatile shear (PS) prevalent in straight segments of arteries and oscillatory shear (OS) observed at branch points, are associated with atheroprotective (healthy) and atheroprone (unhealthy) vascular phenotypes, respectively. The effects of blood flow-induced shear stress on endothelial cells (ECs) and vascular health have generally been studied using human

Axon degeneration is an active program of self-destruction mediated by the protein SARM1. In healthy neurons, SARM1 is autoinhibited and, upon injury autoinhibition is relieved, activating the SARM1 enzyme to deplete NAD+ and induce axon degeneration. SARM1 forms a homomultimeric octamer with each monomer composed of an N-terminal autoinhibitory ARM domain, tandem SAM domains that mediate multimerization

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common blood disorder, presenting multiple symptoms, including hemolytic anemia. It affects 400 million people worldwide, with more than 160 single mutations reported in G6PD. The most severe mutations (about 70) are classified as class I, leading to more than 90% loss of activity of the wild-type G6PD. The crystal structure of G6PD reveals

Cheng et al. (1) provide data on oxygen-isotope δ18O in nine speleothems of Younger Dryas (YD) age from caves situated in several continents between 42°27′ N and 21°05′ S and dated by the U-Th method. They compare this data with δ18O records in several ice cores from Greenland and Antarctica that were originally dated by the radiocarbon method. While the presented YD records of δ18O and their bowl-shaped

Recent technological advances have expanded the annotated protein coding content of mammalian genomes, as hundreds of previously unidentified, short open reading frame (ORF)-encoded peptides (SEPs) have now been found to be translated. Although several studies have identified important physiological roles for this emerging protein class, a general method to define their interactomes is lacking. Here

DNA damage repair genes are modifiers of disease onset in Huntington’s disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We

The ability to cast a mail ballot can safeguard the franchise. However, because there are often additional procedural protections to ensure that a ballot cast in person counts, voting by mail can also jeopardize people’s ability to cast a recorded vote. An experiment carried out during the COVID-19 pandemic illustrates both forces. Philadelphia officials randomly sent 46,960 Philadelphia registrants

Foreign investors have acquired approximately 90 million hectares of land for agriculture over the past two decades. The effects of these investments on local food security remain unknown. While additional cropland and intensified agriculture could potentially increase crop production, preferential targeting of prime agricultural land and transitions toward export-bound crops might affect local access

The radial spoke (RS) heads of motile cilia and flagella contact projections of the central pair (CP) apparatus to coordinate motility, but the morphology is distinct for protozoa and metazoa. Here we show the murine RS head is compositionally distinct from that of Chlamydomonas. Our reconstituted murine RS head core complex consists of Rsph1, Rsph3b, Rsph4a, and Rsph9, lacking Rsph6a and Rsph10b,

Chemical modifications of histones, such as lysine acetylation and ubiquitination, play pivotal roles in epigenetic regulation of gene expression. Methods to alter the epigenome thus hold promise as tools for elucidating epigenetic mechanisms and as therapeutics. However, an entirely chemical method to introduce histone modifications in living cells without genetic manipulation is unprecedented. Here

Neurotransmitter release is governed by eight central proteins among other factors: the neuronal SNAREs syntaxin-1, synaptobrevin, and SNAP-25, which form a tight SNARE complex that brings the synaptic vesicle and plasma membranes together; NSF and SNAPs, which disassemble SNARE complexes; Munc18-1 and Munc13-1, which organize SNARE complex assembly; and the Ca2+ sensor synaptotagmin-1. Reconstitution

The intersection of expanding human development and wildland landscapes—the “wildland–urban interface” or WUI—is one of the most vexing contexts for fire management because it involves complex interacting systems of people and nature. Here, we document the dynamism and stability of an ancient WUI that was apparently sustainable for more than 500 y. We combine ethnography, archaeology, paleoecology

This work explores the concept that differential wave function overlap between excited states can be engineered within a molecular chromophore. The aim is to control excited state wave function symmetries, so that symmetry matches or mismatches result in differential orbital overlap and define low-energy trajectories or kinetic barriers within the excited state surface, that drive excited state population

Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts

Recurrent excitatory neural networks are unstable. In the hippocampus, excitatory mossy cells (MCs) receive strong excitatory inputs from dentate granule cells (GCs) and project back onto the proximal dendrites of GCs. By targeting the ipsi- and contralateral dentate gyrus (DG) along the dorsoventral axis of the hippocampus, MCs form an extensive recurrent excitatory circuit (GC-MC-GC) whose dysregulation

Bromodomains (BDs) are small protein modules that interact with acetylated marks in histones. These posttranslational modifications are pivotal to regulate gene expression, making BDs promising targets to treat several diseases. While the general structure of BDs is well known, their dynamical features and their interplay with other macromolecules are poorly understood, hampering the rational design

Atomically thin van der Waals materials stacked with an interlayer twist have proven to be an excellent platform toward achieving gate-tunable correlated phenomena linked to the formation of flat electronic bands. In this work we demonstrate the formation of emergent correlated phases in multilayer rhombohedral graphene––a simple material that also exhibits a flat electronic band edge but without the

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-fexpressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis

What is the relationship between money and well-being? Research distinguishes between two forms of well-being: people’s feelings during the moments of life (experienced well-being) and people’s evaluation of their lives when they pause and reflect (evaluative well-being). Drawing on 1,725,994 experience-sampling reports from 33,391 employed US adults, the present results show that both experienced

T cells detect with their T cell antigen receptors (TCRs) the presence of rare agonist peptide/MHC complexes (pMHCs) on the surface of antigen-presenting cells (APCs). How extracellular ligand binding triggers intracellular signaling is poorly understood, yet spatial antigen arrangement on the APC surface has been suggested to be a critical factor. To examine this, we engineered a biomimetic interface

Growth of plastic waste in the natural environment, and in particular in the oceans, has raised the accumulation of polystyrene and other polymeric species in eukyarotic cells to the level of a credible and systemic threat. Oligomers, the smallest products of polymer degradation or incomplete polymerization reactions, are the first species to leach out of macroscopic or nanoscopic plastic materials

Glacial landforms, including lobate debris aprons, are a global water ice reservoir on Mars preserving ice from past periods when high orbital obliquity permitted nonpolar ice accumulation. Numerous studies have noted morphological similarities between lobate debris aprons and terrestrial debris-covered glaciers, an interpretation supported by radar observations. On Earth and Mars, these landforms

In biosynthesis of the pancreatic cancer drug streptozotocin, the tridomain nonheme-iron oxygenase SznF hydroxylates Nδ and Nω′ of Nω-methyl-l-arginine before oxidatively rearranging the triply modified guanidine to the N-methyl-N-nitrosourea pharmacophore. A previously published structure visualized the monoiron cofactor in the enzyme’s C-terminal cupin domain, which promotes the final rearrangement

We analyze the zero-temperature phases of an array of neutral atoms on the kagome lattice, interacting via laser excitation to atomic Rydberg states. Density-matrix renormalization group calculations reveal the presence of a wide variety of complex solid phases with broken lattice symmetries. In addition, we identify a regime with dense Rydberg excitations that has a large entanglement entropy and

Variation in gene regulation is ubiquitous, yet identifying the mechanisms producing such variation, especially for complex traits, is challenging. Snake venoms provide a model system for studying the phenotypic impacts of regulatory variation in complex traits because of their genetic tractability. Here, we sequence the genome of the Tiger Rattlesnake, which possesses the simplest and most toxic venom

We have studied the role of protein dynamics in chemical catalysis in the enzyme dihydrofolate reductase (DHFR), using a pump–probe method that employs pulsed-laser photothermal heating of a gold nanoparticle (AuNP) to directly excite a local region of the protein structure and transient absorbance to probe the effect on enzyme activity. Enzyme activity is accelerated by pulsed-laser excitation when

Chromatin remodelers are ATP (adenosine triphosphate)-powered motors that reposition nucleosomes throughout eukaryotic chromosomes. Remodelers possess autoinhibitory elements that control the direction of nucleosome sliding, but underlying mechanisms of inhibition have been unclear. Here, we show that autoinhibitory elements of the yeast Chd1 remodeler block nucleosome sliding by preventing initiation

Hydrogel biomaterials derived from natural biopolymers (e.g., fibrin, collagen, decellularized extracellular matrix) are regularly utilized in three-dimensional (3D) cell culture and tissue engineering. In contrast to those based on synthetic polymers, natural materials permit enhanced cytocompatibility, matrix remodeling, and biological integration. Despite these advantages, natural protein-based

The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis. Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting