More than two decades ago, my coauthors, Raymond Bradley and Malcolm Hughes, and I published the now iconic “hockey stick” curve. It was a simple graph, derived from large-scale networks of diverse climate proxy (“multiproxy”) data such as tree rings, ice cores, corals, and lake sediments, that captured the unprecedented nature of the warming taking place today. It became a focal point in the debate

Bacterial suspensions show turbulence-like spatiotemporal dynamics and vortices moving irregularly inside the suspensions. Understanding these ordered vortices is an ongoing challenge in active matter physics, and their application to the control of autonomous material transport will provide significant development in microfluidics. Despite the extensive studies, one of the key aspects of bacterial

The COVID-19 pandemic has led to numerous mathematical models for the spread of infection, the majority of which are large compartmental models that implicitly constrain the generation-time distribution. On the other hand, the continuous-time Kermack–McKendrick epidemic model of 1927 (KM27) allows an arbitrary generation-time distribution, but it suffers from the drawback that its numerical implementation

The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast

Endoplasmic reticulum (ER) stress and Unfolded Protein Response (UPR) signaling promote the pathology of many human diseases. Loss-of-function variants of the UPR regulator Activating Transcription Factor 6 (ATF6) cause severe congenital vision loss diseases such as achromatopsia by unclear pathomechanisms. To investigate this, we generated retinal organoids from achromatopsia patient induced pluripotent

Plant innate immunity is activated upon perception of invasion pattern molecules by plant cell-surface immune receptors. Several bacteria of the genera Pseudomonas and Burkholderia produce rhamnolipids (RLs) from l-rhamnose and (R)-3-hydroxyalkanoate precursors (HAAs). RL and HAA secretion is required to modulate bacterial surface motility, biofilm development, and thus successful colonization of hosts

We examine how bottom-up (or stimulus-driven) and top-down (or goal-driven) processes govern the distribution of attention in risky choice. In three experiments, participants chose between a certain payoff and the chance of receiving a payoff drawn randomly from an array of eight numbers. We tested the hypothesis that initial attention is driven by perceptual properties of the stimulus (e.g., font

Extensive classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations are used to establish the structural features of the O state in bacteriorhodopsin (bR) and its conversion back to the bR ground state. The computed free energy surface is consistent with available experimental data for the kinetics and thermodynamics of the O to bR transition. The simulation results

Nervous system malignancies are characterized by rapid progression and poor survival rates. These clinical observations underscore the need for novel therapeutic insights and pharmacological targets. To this end, here, we identify the orphan nuclear receptor NR5A2/LRH1 as a negative regulator of cancer cell proliferation and promising pharmacological target for nervous system–related tumors. In particular

d-amino acids are increasingly recognized as important signaling molecules in the mammalian central nervous system. However, the d-stereoisomer of the amino acid with the fastest spontaneous racemization ratein vitro in vitro, cysteine, has not been examined in mammals. Using chiral high-performance liquid chromatography and a stereospecific luciferase assay, we identify endogenous d-cysteine in the

Names for colors vary widely across languages, but color categories are remarkably consistent. Shared mechanisms of color perception help explain consistent partitions of visible light into discrete color vocabularies. But the mappings from colors to words are not identical across languages, which may reflect communicative needs—how often speakers must refer to objects of different color. Here we quantify

Fertilization is the fundamental process that initiates the development of a new individual in all sexually reproducing species. Despite its importance, our understanding of the molecular players that govern mammalian sperm–egg interaction is incomplete, partly because many of the essential factors found in nonmammalian species do not have obvious mammalian homologs. We have recently identified the

Few questions in science are as controversial as human nature. At stake is whether our basic concepts and emotions are all learned from experience, or whether some are innate. Here, I demonstrate that reasoning about innateness is biased by the basic workings of the human mind. Psychological science suggests that newborns possess core concepts of “object” and “number.” Laypeople, however, believe that

Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 μm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides

Dislocations in metals affect their properties on the macro- and the microscales. For example, they increase a metal’s hardness and strength. Dislocation outcrops exist on the surfaces of such metals, and atoms in the proximity of these outcrops are more loosely bonded, facilitating local chemical corrosion and reactivity. In this study, we present a unique autocatalytic mechanism by which a system

Hundreds of millions of smallholders in emerging countries substantially overuse nitrogen (N) fertilizers, driving local environmental pollution and global climate change. Despite local demonstration-scale successes, widespread mobilization of smallholders to adopt precise N management practices remains a challenge, largely due to associated high costs and complicated sampling and calculations. Here

Existing tactile stimulation technologies powered by small actuators offer low-resolution stimuli compared to the enormous mechanoreceptor density of human skin. Arrays of soft pneumatic actuators initially show promise as small-resolution (1- to 3-mm diameter), highly conformable tactile display strategies yet ultimately fail because of their need for valves bulkier than the actuators themselves.

Many sensory systems utilize parallel ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways consist of ensembles or grids of ON and OFF detectors spanning sensory space. Yet, encoding by opponent pathways raises a question: How should grids of ON and OFF detectors be arranged to optimally encode natural stimuli? We investigated this question using a model

Light provides the primary signal for entraining circadian rhythms to the day/night cycle. In addition to rods and cones, the retina contains a small population of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). Concerns have been raised that exposure to dim artificial lighting in the evening (DLE) may perturb circadian rhythms and sleep patterns, and OPN4

When the motion of a motile cell is observed closely, it appears erratic, and yet the combination of nonequilibrium forces and surfaces can produce striking examples of organization in microbial systems. While most of our current understanding is based on bulk systems or idealized geometries, it remains elusive how and at which length scale self-organization emerges in complex geometries. Here, using

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, is one of the biggest threats to public health. However, the dynamic of SARS-CoV-2 infection remains poorly understood. Replication-competent recombinant viruses expressing reporter genes provide valuable tools to investigate viral infection. Low levels of reporter gene expressed from

Plague is a deadly zoonosis caused by the gram-negative bacteria Yersinia pestis, and the clinical aspect of the disease partially depends on the way of transmission. While primary bubonic and septicemic plagues chiefly result from an ectoparasite bite or contact with an animal’s carcass, primary pneumonic plague is caused by the inhalation of infected droplets (1). Paleogenomics data indicate that

As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins. However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of

Reduced succinate dehydrogenase (SDH) activity resulting in adverse succinate accumulation was previously considered relevant only in 0.05 to 0.5% of kidney cancers associated with germline SDH mutations. Here, we sought to examine a broader role for SDH loss in kidney cancer pathogenesis/progression. We report that underexpression of SDH subunits resulting in accumulation of oncogenic succinate is

Human metapneumovirus (HMPV) is a major cause of respiratory disease worldwide, particularly among children and the elderly. Although there is no licensed HMPV vaccine, promising candidates have been identified for related pneumoviruses based on the structure-based stabilization of the fusion (F) glycoprotein trimer, with prefusion-stabilized F glycoprotein trimers eliciting significantly higher neutralizing

Globalization is routinely blamed for various ills, including fueling conflict in strategic locations. To investigate whether these accusations are well founded, we have built a database to assess any given location’s strategic importance. Consistent with our game-theoretic model of strategic interaction, we find that overall fighting is more frequent in strategic locations close to maritime choke

Bushcrickets (katydids) rely on only 20 to 120 sensory units located in their forelegs to sense sound. Situated in tiny hearing organs less than 1 mm long (40× shorter than the human cochlea), they cover a wide frequency range from 1 kHz up to ultrasounds, in tonotopic order. The underlying mechanisms of this miniaturized frequency-place map are unknown. Sensory dendrites in the hearing organ (crista

T cells play an important role in adaptive immunity. An enormous clonal diversity of T cells with a different specificity, encoded by the T cell receptor (TCR), protect the body against infection. Most TCRβ chains are generated from a V, D, and J segment during recombination in the thymus. Although complete absence of the D segment is not easily detectable from sequencing data, we find convincing evidence

Vaccination is an essential public health measure for infectious disease prevention. The exposure of the immune system to vaccine formulations with the appropriate kinetics is critical for inducing protective immunity. In this work, faceted microneedle arrays were designed and fabricated utilizing a three-dimensional (3D)-printing technique called continuous liquid interface production (CLIP). The

Dense assemblies of self-propelled particles that can form solid-like states also known as active or living glasses are abundant around us, covering a broad range of length scales and timescales: from the cytoplasm to tissues, from bacterial biofilms to vehicular traffic jams, and from Janus colloids to animal herds. Being structurally disordered as well as strongly out of equilibrium, these systems

Suberin is a hydrophobic biopolymer that can be deposited at the periphery of cells, forming protective barriers against biotic and abiotic stress. In roots, suberin forms lamellae at the periphery of endodermal cells where it plays crucial roles in the control of water and mineral transport. Suberin formation is highly regulated by developmental and environmental cues. However, the mechanisms controlling

MICROBIOLOGY Koala mother and joey. Image credit: Michael Pyne (Currumbin Wildlife Hospital, Currumbin, Australia). Transmission dynamics of koala retrovirus The rapid decline of koala populations in Australia has been tied to koala retrovirus (KoRV), an endogenous retrovirus found in wild and captive koalas that can cause cancer. However, nonhereditary transmission...

Animals interact with microbes that affect their performance and fitness, including endosymbionts that reside inside their cells. Maternally transmitted Wolbachia bacteria are the most common known endosymbionts, in large part because of their manipulation of host reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) that reduces host embryonic viability when Wolbachia-modified

Homozygous mutation of the RNA kinase CLP1 (cleavage factor polyribonucleotide kinase subunit 1) causes pontocerebellar hypoplasia type 10 (PCH10), a pediatric neurodegenerative disease. CLP1 is associated with the transfer RNA (tRNA) splicing endonuclease complex and the cleavage and polyadenylation machinery, but its function remains unclear. We generated two mouse models of PCH10: one homozygous

Many biological functions are leaky, and organisms that perform them contribute some of their products to a community “marketplace” in which nonperforming individuals may compete for them. Leaky functions are partitioned unequally in microbial communities, and the evolutionary forces determining which species perform them and which become beneficiaries are poorly understood. Here, we demonstrate that

The timing of reproduction is an adaptive trait in many organisms. In plants, the timing, duration, and intensity of flowering differ between annual and perennial species. To identify interspecies variation in these traits, we studied introgression lines derived from hybridization of annual and perennial species, Arabis montbretiana and Arabis alpina, respectively. Recombination mapping identified

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field

Combining mass spectrometry–based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes of oxidative phosphorylation and found that dimeric apoptosis-inducing factor 1 (AIFM1) forms a defined complex with ∼10% of monomeric cytochrome c oxidase (COX) but hardly interacts with respiratory chain supercomplexes. Multiple AIFM1 intercross-links

Skeletal ciliopathies (e.g., Jeune syndrome, short rib polydactyly syndrome, and Sensenbrenner syndrome) are frequently associated with nephronophthisis-like cystic kidney disease and other organ manifestations. Despite recent progress in genetic mapping of causative loci, a common molecular mechanism of cartilage defects and cystic kidneys has remained elusive. Targeting two ciliary chondrodysplasia

Enzymes possessing the nickel-pincer nucleotide (NPN) cofactor catalyze C2 racemization or epimerization reactions of α-hydroxyacid substrates. LarB initiates synthesis of the NPN cofactor from nicotinic acid adenine dinucleotide (NaAD) by performing dual reactions: pyridinium ring C5 carboxylation and phosphoanhydride hydrolysis. Here, we show that LarB uses carbon dioxide, not bicarbonate, as the

Elevated levels of MUC5AC, one of the major gel-forming mucins in the lungs, are closely associated with chronic obstructive lung diseases such as chronic bronchitis and asthma. It is not known, however, how the structure and/or gel-making properties of MUC5AC contribute to innate lung defense in health and drive the formation of stagnant mucus in disease. To understand this, here we studied the biophysical

Extracellular adenosine triphosphate (ATP) released by mucosal immune cells and by microbiota in the intestinal lumen elicits diverse immune responses that mediate the intestinal homeostasis via P2 purinergic receptors, while overactivation of ATP signaling leads to mucosal immune system disruption, which leads to pathogenesis of intestinal inflammation. In the small intestine, hydrolysis of luminal

Microorganisms have coevolved diverse mechanisms to impair host defenses. A major one, superantigens, can result in devastating effects on the immune system. While all known superantigens induce vast immune cell proliferation and come from opportunistic pathogens, recently, proteins with similar broad specificity to antibody variable (V) domain families were identified in a commensal microbiota. These

Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute

For most life on Earth, the rising and setting of the sun coincides with daily patterns of activity. However, biological organisms have internal clocks that orchestrate their daily rhythms even in the absence of sunlight. These circadian rhythms, which set the schedule for the sleep–wake cycle, are the reason people feel jetlag when crossing time zones. On a cellular level, circadian rhythms control

APPLIED BIOLOGICAL SCIENCES Correction for “Ranking the risk of animal-to-human spillover for newly discovered viruses,” by Zoë L. Grange, Tracey Goldstein, Christine K. Johnson, Simon Anthony, Kirsten …

CELL BIOLOGY Correction for “Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence,” by Ben Sang, Yuan Yuan Zhang, Su Tang Guo, Ling Fei Kong, Qiong Cheng, Guang Zhi Liu, Rick F. Thorne, Xu Dong Zhang, Lei Jin, and Mian Wu, which was first published November 26, 2018; 10.1073/pnas.1805950115 (Proc. Natl. Acad. Sci. U.S.A. 115, E11661–E11670)

DEVELOPMENTAL BIOLOGY Correction for “CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation,” by Jingmei Hsu, Hsuan-Ting Huang, Chung-Tsai Lee, Avik Choudhuri, Nicola K. Wilson, Brian J. Abraham, Victoria Moignard, Iwo Kucinski, Shuqian Yu, R. Katherine Hyde, Joanna Tober, Xiongwei Cai, Yan Li, Yalin Guo, Song Yang, Michael Superdock, Eirini Trompouki, Fernando J

Imai et al. (1) have characterized yet another variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, this one originating in Brazil. The good news is that it appears that vaccines currently available are still expected to provide protection against this variant. However, what about the next variant, one we have not seen yet? Will we still be protected

How homologous DNA duplexes in chromosomes are checked for correct alignment prior to exchange of genetic information during meiosis in Eukaryotes is a longstanding puzzle (1), a gap in our knowledge of the molecular processes essential for evolution in the more complex cellular organisms that include fungi, plants, and primates. A mechanism to check correct alignment of homologous DNA duplexes prior

The core message of our recent report (1) is that nanomolar concentrations of cyanide increase O2 consumption rate (OCR) and Complex IV (CcOX) activity and elevate adenosine triphosphate (ATP) levels in intact human cells (1). This effect—directionally opposite of the well-known inhibitory effect that cyanide exerts at higher concentrations—was demonstrated using several independent methods, including

Randi et al. (1) claim that vanishingly small concentrations of cyanide added to human cell lines 1) increases cell proliferation, 2) reduces the basal glutathionylation of bovine cytochrome c oxidase (CcO), 3) increases the steady-state activity of CcO, and 4) produces spectral changes of purified CcO.

Necroptosis is a form of regulated necrosis mediated by the formation of the necrosome, composed of the RIPK1/RIPK3/MLKL complex. Here, we developed a proximity ligation assay (PLA) that allows in situ visualization of necrosomes in necroptotic cells and in vivo. Using PLA assay, we show that necrosomes can be found in close proximity to the endoplasmic reticulum (ER). Furthermore, we show that necroptosis

Aspergillus fumigatus is a human opportunistic pathogen showing emerging resistance against a limited repertoire of antifungal agents available. The GTPase Rho1 has been identified as an important regulator of the cell wall integrity signaling pathway that regulates the composition of the cell wall, a structure that is unique to fungi and serves as a target for antifungal compounds. Rom2, the guanine

On May 25, 2020, George Floyd, an unarmed Black American male, was killed by a White police officer. Footage of the murder was widely shared. We examined the psychological impact of Floyd’s death using two population surveys that collected data before and after his death; one from Gallup (117,568 responses from n = 47,355) and one from the US Census (409,652 responses from n = 319,471). According to

By 2 y of age, children possess expectations about several different moral principles. Building on these results, we asked whether children who observed a wrongdoer violate a principle would draw negative inferences from this violation about how the wrongdoer was likely to behave in other contexts. In four experiments, 25-mo-old toddlers (n = 152) first saw a wrongdoer harm a protagonist. When toddlers

The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis

The bZIP transcription factor ATF6α is a master regulator of endoplasmic reticulum (ER) stress response genes. In this report, we identify the multifunctional RNA polymerase II transcription factor Elongin as a cofactor for ATF6α-dependent transcription activation. Biochemical studies reveal that Elongin functions at least in part by facilitating ATF6α-dependent loading of Mediator at the promoters

Molecular and structural facets of cell–cell adhesion have been extensively studied in monolayered epithelia. Here, we perform a comprehensive analysis of cell–cell contacts in a series of multilayered tissues in the Xenopus gastrula model. We show that intercellular contact distances range from 10 to 1,000 nm. The contact width frequencies define tissue-specific contact spectra, and knockdown of adhesion