Stroke is a leading cause of death and disability. Recovery depends on a delicate balance between inflammatory responses and immune suppression, tipping the scale between brain protection and susceptibility to infection. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Here, we report…
Bacteria alternate between being free-swimming and existing as members of sessile multicellular communities called biofilms. The biofilm lifecycle occurs in three stages: cell attachment, biofilm maturation, and biofilm dispersal. Vibrio cholerae biofilms are hyperinfectious, and biofilm formation and dispersal are considered central to disease transmission. While biofilm formation is well…
Yellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of…
The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates…
Primate brains typically have regions within the ventral visual stream that are selectively responsive to faces. In macaques, these face patches are located in similar parts of inferotemporal cortex across individuals although correspondence with particular anatomical features has not been reported previously. Here, using high-resolution functional and anatomical imaging, we…
Intracerebral hemorrhage (ICH) is a devastating form of stroke affecting millions of people worldwide. Parenchymal hematoma triggers a series of reactions leading to primary and secondary brain injuries and permanent neurological deficits. Microglia and macrophages carry out hematoma clearance, thereby facilitating functional recovery after ICH. Here, we elucidate a pivotal…
Preclinical and clinical data support the use of focused ultrasound (FUS), in the presence of intravenously injected microbubbles, to safely and transiently increase the permeability of the blood–brain barrier (BBB). FUS-induced BBB permeability has been shown to enhance the bioavailability of administered intravenous therapeutics to the brain. Ideal therapeutics candidates…
α-Synuclein is expressed at high levels at presynaptic terminals, but defining its role in the regulation of neurotransmission under physiologically relevant conditions has proven elusive. We report that, in vivo, α-synuclein is responsible for the facilitation of dopamine release triggered by action potential bursts separated by short intervals (seconds) and…
CLC-2 is a voltage-gated chloride channel that is widely expressed in mammalian tissues. In the central nervous system, CLC-2 appears in neurons and glia. Studies to define how this channel contributes to normal and pathophysiological function in the central nervous system raise questions that remain unresolved, in part due to…
In photosynthetic eukaryotes, thousands of proteins are translated in the cytosol and imported into the chloroplast through the concerted action of two translocons—termed TOC and TIC—located in the outer and inner membranes of the chloroplast envelope, respectively. The degree to which the molecular composition of the TOC and TIC complexes…
Cell division is often regulated by extracellular signaling networks to ensure correct patterning during development. In Arabidopsis, the SHORT-ROOT (SHR)/SCARECROW (SCR) transcription factor dimer activates CYCLIND6;1 (CYCD6;1) to drive formative divisions during root ground tissue development. Here, we show plasma-membrane-localized BARELY ANY MERISTEM1/2 (BAM1/2) family receptor kinases are req
After eukaryotic fertilization, gamete nuclei migrate to fuse parental genomes in order to initiate development of the next generation. In most animals, microtubules control female and male pronuclear migration in the zygote. Flowering plants, on the other hand, have evolved actin filament (F-actin)-based sperm nuclear migration systems for karyogamy. Flowering…
The COVID-19 pandemic has caused more than 1,000,000 reported deaths globally, of which more than 200,000 have been reported in the United States as of October 1, 2020. Public health interventions have had significant impacts in reducing transmission and in averting even more deaths. Nonetheless, in many jurisdictions, the decline…
Population displacement may occur after natural disasters, permanently altering the demographic composition of the affected regions. Measuring this displacement is vital for both optimal postdisaster resource allocation and calculation of measures of public health interest such as mortality estimates. Here, we analyzed data generated by mobile phones and social media…
Understanding the processes underlying normal, impaired, and recovered language performance has been a long-standing goal for cognitive and clinical neuroscience. Many verbally described hypotheses about language lateralization and recovery have been generated. However, they have not been considered within a single, unified, and implemented computational framework, and the literatures on…
It is well established that speech perception is improved when we are able to see the speaker talking along with hearing their voice, especially when the speech is noisy. While we have a good understanding of where speech integration occurs in the brain, it is unclear how visual and auditory…
Recent estimates indicate that ∼70% of the world's seabird populations have declined since the 1950s due to human activities. However, for almost all bird populations, there is insufficient long-term monitoring to understand baseline (i.e., preindustrial) conditions, which are required to distinguish natural versus anthropogenically driven changes. Here, we address this…
Declining biodiversity and ecosystem functions put many of nature's contributions to people at risk. We review and synthesize the scientific literature to assess 50-y global trends across a broad range of nature's contributions. We distinguish among trends in potential and realized contributions of nature, as well as environmental conditions and…
The yeast Saccharomyces cerevisiae is a powerful model system for systems-wide biology screens and large-scale proteomics methods. Nearly complete proteomics coverage has been achieved owing to advances in mass spectrometry. However, it remains challenging to scale this technology for rapid and high-throughput analysis of the yeast proteome to investigate biological…
CHEMISTRY Correction for "In situ detection of live-to-dead bacteria ratio after inactivation by means of synchronous fluorescence and PCA," by Runze Li, Umang Goswami, Maria King, Jie Chen, Thomas C. Cesario, and Peter M. Rentzepis, which was first published January 8, 2018; 10.1073/pnas.1716514115 (Proc. Natl. Acad. Sci. U.S.A. 115, 668–673)….
MICROBIOLOGY Correction for "Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion in Yersinia pestis," by Courtney E. Chandler, Erin M. Harberts, Mark R. Pelletier, Iyarit Thaipisuttikul, Jace W. Jones, Adeline M. Hajjar, Jason W. Sahl, David R. Goodlett, Aaron C. Pride, David A….
Why giant pandas roll in manure A wild panda in Foping. Attraction to fecal matter among wild mammals is rare, but Qinling giant pandas have been observed to roll in horse manure. The behavior typically involves a panda sniffing the manure, rubbing against it with the cheek, rolling in the…
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. This interpretation is problematic, first because classical sources can plausibly be interpreted in completely different ways. The handling of natural disasters and…
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…
Leray et al. (1) reassuringly conclude that "GenBank is a reliable resource for 21st century biodiversity research" based on an important quantitative assessment of its taxonomic accuracy. However, their insightful analysis focuses only on taxonomic levels above species. GenBank (2) is the key reference database for the growing fields of…
Biodiversity studies increasingly rely on DNA sequences obtained from the environment (rather than individual organisms) for basic and applied research (1). Species-level assignment of sequences using genetic databases such as GenBank is often desirable (e.g., detecting invasive species, measuring range shifts, or interpreting interaction networks). Thus, Locatelli et al. (2)…
When geneticist Haig H. Kazazian Jr. was 16, he overheard a conversation between his father and a family friend. "What do you think? Is he going to be a doctor?" asked his father. "I think he'll be a scientist," replied the friend. Kazazian went on to become both. Trained in…
We are well into the 21st century and even the most fundamental aspects of protein biophysics continue to perplex us. For example, counter to any expectation, proteins are excellent conductors (1); globular proteins, the once hallowed paradigm of structural biology, are now believed to sample their unfolded ensemble multiple times…
Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease, and it is the most common form of muscular dystrophy caused by genetic mutations in the Dmd gene (1). The Dmd gene contains 79 exons, spans 2.4 Mb, and is the single largest gene in the human genome (2). This gene…
Myasthenia gravis (MG) is a disorder of the neuromuscular junction mediated by the actions of autoantibodies directed against one of several proteins expressed on the postjunction muscle membrane. For the large majority of MG patients the target for the autoantibodies is the acetylcholine receptor (AChR) (1) that interacts with acetylcholine,…
Research indicates that core dimensions of psychological well-being can be cultivated through intentional mental training. Despite growing research in this area and an increasing number of interventions designed to improve psychological well-being, the field lacks a unifying framework that clarifies the dimensions of human flourishing that can be cultivated. Here,…
We assess diet and economies of middle Holocene (∼7,500 to 4,000 calibrated [cal] B.P.) humans at coexisting mound sites (Huaca Prieta and Paredones) in north coastal Peru and document regular consumption of maize by ∼6,500 to 6,000 cal B.P. and its earliest use as a staple food in this area…
Cultural norms are key to cooperation in human societies. How they are regulated, maintained, and adapted to the change remains a matter of debate. Humans have dispositions for both retributive and restorative justice; recent focus has been on third-party punishment, punitive sanctions by those not directly harmed, as key for…
When a fluid interface is subjected to a strong viscous flow, it tends to develop near-conical ends with pointed tips so sharp that their radius of curvature is undetectable. In microfluidic applications, tips can be made to eject fine jets, from which micrometer-sized drops can be produced. Here we show…
What are the ground states of an interacting, low-density electron system? In the absence of disorder, it has long been expected that as the electron density is lowered, the exchange energy gained by aligning the electron spins should exceed the enhancement in the kinetic (Fermi) energy, leading to a (Bloch)…
The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of…
A structure of the murine voltage-dependent anion channel (VDAC) was determined by microcrystal electron diffraction (MicroED). Microcrystals of an essential mutant of VDAC grew in a viscous bicelle suspension, making it unsuitable for conventional X-ray crystallography. Thin, plate-like crystals were identified using scanning-electron microscopy (SEM). Crystals were milled into thin…
In translation elongation, two translational guanosine triphosphatase (trGTPase) factors EF1A and EF2 alternately bind to the ribosome and promote polypeptide elongation. The ribosomal stalk is a multimeric ribosomal protein complex which plays an essential role in the recruitment of EF1A and EF2 to the ribosome and their GTP hydrolysis for…
Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the…
The fundamental biological process of electron transfer (ET) takes place across proteins with common ET pathways of several nanometers. Recent discoveries push this limit and show long-range extracellular ET over several micrometers. Here, we aim in deciphering how protein-bound intramolecular cofactors can facilitate such long-range ET. In contrast to natural…
In eukaryotes, RNA polymerase II (RNApII) transcribes messenger RNA from template DNA. Decades of experiments have identified the proteins needed for transcription activation, initiation complex assembly, and productive elongation. However, the dynamics of recruitment of these proteins to transcription complexes, and of the transitions between these steps, are poorly understood….
Fluorescent molecules are like antennas: The rate at which they absorb light depends on their orientation with respect to the incoming light wave, and the apparent intensity of their emission depends on their orientation with respect to the observer. However, the directions along which the most important fluorescent molecules in…
Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been…
Integrin-dependent adhesions mediate reciprocal exchange of force and information between the cell and the extracellular matrix. These effects are attributed to the "focal adhesion clutch," in which moving actin filaments transmit force to integrins via dynamic protein interactions. To elucidate these processes, we measured force on talin together with actin…
Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We…
Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation…
Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form of this process (macrolipophagy) results in the engulfment of LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether this is an exclusive autophagic mechanism used by hepatocytes to catabolize LDs is unclear. It…
This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electrode takes place in different…
A hitherto unknown Neoproterozoic orogenic system, the Saharides, is described in North Africa. It formed during the 900–500-Ma interval. The Saharides involved large subduction accretion complexes occupying almost the entire Arabian Shield and much of Egypt and parts of the small Precambrian inliers in the Sahara including the Ahaggar mountains….
A gravity-driven droplet will rapidly flow down an inclined substrate, resisted only by stresses inside the liquid. If the substrate is compliant, with an elastic modulus G < 100 kPa, the droplet will markedly slow as a consequence of viscoelastic braking. This phenomenon arises due to deformations of the solid…
High-affinity iron (Fe) scavenging compounds, or siderophores, are widely employed by soil bacteria to survive scarcity in bioavailable Fe. Siderophore biosynthesis relies on cellular carbon metabolism, despite reported decrease in both carbon uptake and Fe-containing metabolic proteins in Fe-deficient cells. Given this paradox, the metabolic network required to sustain the…
Somatic LINE-1 (L1) retrotransposition has been detected in early embryos, adult brains, and the gastrointestinal (GI) tract, and many cancers, including epithelial GI tumors. We previously found numerous somatic L1 insertions in paired normal and GI cancerous tissues. Here, using a modified method of single-cell analysis for somatic L1 insertions,…
The plant growth hormone auxin controls cell identity, cell division, and expansion. In the primary root of Arabidopsis there is a robust auxin gradient with a peak concentration at the tip of the meristem and a significant decrease throughout the elongation zone. The molecular mechanisms of how such a steep…
Plant tropism refers to the directed movement of an organ or organism in response to external stimuli. Typically, these stimuli induce hormone transport that triggers cell growth or deformation. In turn, these local cellular changes create mechanical forces on the plant tissue that are balanced by an overall deformation of…
Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks…
We make use of uniquely comprehensive arrest data from the Texas Department of Public Safety to compare the criminality of undocumented immigrants to legal immigrants and native-born US citizens between 2012 and 2018. We find that undocumented immigrants have substantially lower crime rates than native-born citizens and legal immigrants across…
We use the synthetic control method to analyze the effect of face masks on the spread of COVID-19 in Germany. Our identification approach exploits regional variation in the point in time when wearing of face masks became mandatory in public transport and shops. Depending on the region we consider, we…
The depth at which groundwaters transition from fresh to more saline—the "base of fresh water"—is frequently used to determine the stringency and types of measures put in place to manage groundwater and protect it from contamination. Therefore, it is important to understand salinity distributions and compare defined bases of fresh…
We recently read, with great interest, the article by Kameda et al. (1). They conducted untargeted metabolomics analysis of whole blood samples of 19 older adults; identified 22 markers for frailty, cognition, and hypomobility; and find the following: 1) Metabolite profiles can efficiently distinguish frailty from nonfrailty; 2) antioxidant ergothioneine…
As frailty patients are vulnerable to stressors, due to declined physiological capacity of organs during aging, comprehensive frailty assessment efficiently predicts health risk of elderlies (1). First, Pan et al. raise concerns about the definition of frailty (2). Currently, there are three major approaches to defining "frailty": 1) the physical…
Using a global dataset of contemporary biological invasions, the recent paper by Liu et al. (1) presents a comprehensive test of the niche conservatism hypothesis. Specifically, Liu et al. demonstrate compelling support for climatic niche conservatism in most invasive species, even when accounting for differences in ecology and physiology (1)….
Islands have been widely recognized as natural laboratories in ecological and evolutionary studies (1, 2). Compared to mainland species, species endemic to islands (i.e., island endemics) may only occupy a small part of their fundamental niche due to dispersal limitation caused by surrounding water (3). When being introduced to new…
Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors…
Macroautophagy/autophagy is a highly conserved eukaryotic molecular process that facilitates the recycling of superfluous cytoplasmic materials, damaged organelles, and invading pathogens, resulting in proper cellular homeostasis and survival during stress conditions. Autophagy is stringently regulated at multiple stages, including control at transcriptional, translational, and posttranslational l
Inositol-1,4,5-triphosphate (IP3) kinase B (ITPKB) is a ubiquitously expressed lipid kinase that inactivates IP3, a secondary messenger that stimulates calcium release from the endoplasmic reticulum (ER). Genome-wide association studies have identified common variants in the ITPKB gene locus associated with reduced risk of sporadic Parkinson's disease (PD). Here, we investigate…
The sinus node (SAN) is the primary pacemaker of the human heart, and abnormalities in its structure or function cause sick sinus syndrome, the most common reason for electronic pacemaker implantation. Here we report that transcription factor GATA6, whose mutations in humans are linked to arrhythmia, is highly expressed in…
Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have…
Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in high-risk patients. Here we demonstrate the utility and potential for clinical translation of a fluorescently labeled cathepsin-activated chemical probe to highlight gastrointestinal lesions. This probe stay
RNA polymerase (RNAP) encounters various roadblocks during transcription. These obstacles can impede RNAP movement and influence transcription, ultimately necessitating the activity of RNAP-associated factors. One such factor is the bacterial protein Mfd, a highly conserved DNA translocase and evolvability factor that interacts with RNAP. Although Mfd is thought to function…
Randomized controlled trials (RCTs) enroll hundreds of millions of subjects and involve many human lives. To improve subjects' welfare, I propose a design of RCTs that I call Experiment-as-Market (EXAM). EXAM produces a welfare-maximizing allocation of treatment-assignment probabilities, is almost incentive-compatible for preference elicitation, and unbiasedly estimates any causal effect…
Identifying developmental explanations for the evolution of complex structures like mammalian molars is fundamental to studying phenotypic variation. Previous study showed that a "morphogenetic gradient" of molar proportions was explained by a balance between inhibiting/activating activity from earlier developing molars, termed the inhibitory cascade model (ICM). Although this model provides…
Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans….
The blood-clotting protein fibrinogen has been implicated in host defense following Staphylococcus aureus infection, but precise mechanisms of host protection and pathogen clearance remain undefined. Peritonitis caused by staphylococci species is a complication for patients with cirrhosis, indwelling catheters, or undergoing peritoneal dialysis. Here, we sought to characterize possible mechanisms.
Microbial activity in planktonic systems creates a dynamic and heterogeneous microscale seascape that harbors a diverse community of microorganisms and ecological interactions of global significance. In recent decades great effort has been put into understanding this complex system, particularly focusing on the role of chemical patchiness, while overlooking a physical…
Fertility relies upon pulsatile release of gonadotropin-releasing hormone (GnRH) that drives pulsatile luteinizing hormone secretion. Kisspeptin (KP) neurons in the arcuate nucleus are at the center of the GnRH pulse generation and the steroid feedback control of GnRH secretion. However, KP evokes a long-lasting response in GnRH neurons that is…
The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown….
We hereby show that root systems adapt to a spatially discontinuous pattern of water availability even when the gradients of water potential across them are vanishingly small. A paper microfluidic approach allowed us to expose the entire root system of Brassica rapa plants to a square array of water sources,…
Aerobic glycolysis (AG), that is, the nonoxidative metabolism of glucose, contributes significantly to anabolic pathways, rapid energy generation, task-induced activity, and neuroprotection; yet high AG is also associated with pathological hallmarks such as amyloid-β deposition. An important yet unresolved question is whether and how the metabolic benefits and risks of…
Coastal dunes protect beach communities and ecosystems from rising seas and storm flooding and influence the stability of barrier islands by preventing overwashes and limiting barrier migration. Therefore, the degree of dune recovery after a large storm provides a simple measure of the short-term resiliency (and potential long-term vulnerability) of…
Barrier islands are ubiquitous coastal features that create low-energy environments where salt marshes, oyster reefs, and mangroves can develop and survive external stresses. Barrier systems also protect interior coastal communities from storm surges and wave-driven erosion. These functions depend on the existence of a slowly migrating, vertically stable barrier, a…
Neurodegenerative disorders are frequently associated with β-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prio
Real-life decisions are often repeated. Whether considering taking a job in a new city, or doing something mundane like checking if the stove is off, decisions are frequently revisited even if no new information is available. This mode of behavior takes a particularly pathological form in obsessive–compulsive disorder (OCD), which…
The noble gas isotope systematics of ocean island basalts suggest the existence of primordial mantle signatures in the deep mantle. Yet, the isotopic compositions of lithophile elements (Sr, Nd, Hf) in these lavas require derivation from a mantle source that is geochemically depleted by melt extraction rather than primitive. Here,…
Primate offspring often depend on their mothers well beyond the age of weaning, and offspring that experience maternal death in early life can suffer substantial reductions in fitness across the life span. Here, we leverage data from eight wild primate populations (seven species) to examine two underappreciated pathways linking early…
The journey from plasma membrane to nuclear pore is a critical step in the lifecycle of DNA viruses, many of which must successfully deposit their genomes into the nucleus for replication. Viral capsids navigate this vast distance through the coordinated hijacking of a number of cellular host factors, many of…
The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyl-tRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an…
O antigens are important cell surface polysaccharides in gram-negative bacteria where they extend core lipopolysaccharides in the extracellular leaflet of the outer membrane. O antigen structures are serotype specific and form extended cell surface barriers endowing many pathogens with survival benefits. In the ABC transporter-dependent biosynthesis pathway, O antigens are…
Effective states govern by some combination of enforcement and voluntary compliance. To contain the COVID-19 pandemic, a critical decision is the extent to which policy makers rely on voluntary as opposed to enforced compliance, and nations vary along this dimension. While enforcement may secure higher compliance, there is experimental and…
Rivers carry the dissolved and solid products of silicate mineral weathering, a process that removes CO2 from the atmosphere and provides a key negative climate feedback over geological timescales. Here we show that, in some river systems, a reactive exchange pool on river suspended particulate matter, bonded weakly to mineral…
A pH-Low Insertion Peptide (pHLIP) is a pH-sensitive peptide that undergoes membrane insertion, resulting in transmembrane helix formation, on exposure to acidity at a tumor cell surface. As a result, pHLIPs preferentially accumulate within tumors and can be used for tumor-targeted imaging and drug delivery. Here we explore the determinants…
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using…
Type II tail-anchored (TA) membrane proteins are involved in diverse cellular processes, including protein translocation, vesicle trafficking, and apoptosis. They are characterized by a single C-terminal transmembrane domain that mediates posttranslational targeting and insertion into the endoplasmic reticulum (ER) via the Guided-Entry of TA proteins (GET) pathway. The GET system…
The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a…
Drosophila melanogaster females experience a large shift in energy homeostasis after mating to compensate for nutrient investment in egg production. To cope with this change in metabolism, mated females undergo widespread physiological and behavioral changes, including increased food intake and altered digestive processes. The mechanisms by which the female digestive…
The type 6 secretion system (T6SS) is a dynamic organelle encoded by many gram-negative bacteria that can be used to kill competing bacterial prey species in densely occupied niches. Some predatory species, such as Vibrio cholerae, use their T6SS in an untargeted fashion while in contrast, Pseudomonas aeruginosa assembles and…
Ordinary ice has a proton-disordered phase which is kinetically metastable, unable to reach, spontaneously, the ferroelectric (FE) ground state at low temperature where a residual Pauling entropy persists. Upon light doping with KOH at low temperature, the transition to FE ice takes place, but its microscopic mechanism still needs clarification….
Invasive organisms pose a global threat and are exceptionally difficult to eradicate after they become abundant in their new habitats. We report a successful multitactic strategy for combating the pink bollworm (Pectinophora gossypiella), one of the world's most invasive pests. A coordinated program in the southwestern United States and northern…
Diapause represents a major developmental switch in insects and is a seasonal adaptation that evolved as a specific subtype of dormancy in most insect species to ensure survival under unfavorable environmental conditions and synchronize populations. However, the hierarchical relationship of the molecular mechanisms involved in the perception of environmental signals…
The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and an attractive anticancer target that integrates diverse signals to control cell proliferation. Previous studies using mTOR inhibitors have shown that mTOR targeting suppresses gene expression and cell proliferation. To date, however, mTOR-targeted therapies in cancer have…
The regulatory mechanisms of circadian rhythms have been studied primarily at the level of the transcription–translation feedback loops of protein-coding genes. Regulatory modules involving noncoding RNAs are less thoroughly understood. In particular, emerging evidence has revealed the important role of microRNAs (miRNAs) in maintaining the robustness of the circadian system….
N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is…
Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7−/− mice to determine the role…
Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine…
Many materials, processes, and structures in science and engineering have important features at multiple scales of time and/or space; examples include biological tissues, active matter, oceans, networks, and images. Explicitly extracting, describing, and defining such features are difficult tasks, at least in part because each system has a unique set…
The tumor-suppressor p53 is a critical regulator of the cellular response to DNA damage and is tightly regulated by posttranslational modifications. Thr55 in the AD2 interaction motif of the N-terminal transactivation domain functions as a phosphorylation-dependent regulatory switch that modulates p53 activity. Thr55 is constitutively phosphorylated, becomes dephosphorylated upon DNA…
Tandem gene amplification is a frequent and dynamic source of antibiotic resistance in bacteria. Ongoing expansions and contractions of repeat arrays during population growth are expected to manifest as cell-to-cell differences in copy number (CN). As a result, a clonal bacterial culture could comprise subpopulations of cells with different levels…
Precise genome editing is a valuable tool to study gene function in model organisms. Prime editing, a precise editing system developed in mammalian cells, does not require double-strand breaks or donor DNA and has low off-target effects. Here, we applied prime editing for the model organism Drosophila melanogaster and developed…
Humans reached the Mariana Islands in the western Pacific by ∼3,500 y ago, contemporaneous with or even earlier than the initial peopling of Polynesia. They crossed more than 2,000 km of open ocean to get there, whereas voyages of similar length did not occur anywhere else until more than 2,000…
Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in…
Sugar transport across tonoplasts is essential for maintaining cellular sugar homeostasis and metabolic balance in plant cells. It remains unclear, however, how this process is regulated among different classes of sugar transporters. Here, we identified a tonoplast H+/glucose symporter, MdERDL6-1, from apples, which was highly expressed in fruits and exhibited…
Vaccination yields the direct individual benefit of protecting recipients from infectious diseases and also the indirect social benefit of reducing the transmission of infections to others, often referred to as herd immunity. This research examines how prosocial concern for vaccination, defined as people's preoccupation with infecting others if they do…
The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH]…
Hippocampal cells are central to spatial and predictive representations, and experience replays by place cells are crucial for learning and memory. Nonetheless, how hippocampal replay patterns dynamically change during the learning process remains to be elucidated. Here, we designed a spatial task in which rats learned a new behavioral trajectory…
Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact…
Knowledge of spatiotemporal distribution and likelihood of (re)occurrence of salt-affected soils is crucial to our understanding of land degradation and for planning effective remediation strategies in face of future climatic uncertainties. However, conventional methods used for tracking the variability of soil salinity/sodicity are extensively localized, making predictions on a global…
One of the greatest challenges to emerge from the COVID-19 pandemic is the need to develop new economic policies that steer nations safely between the Scylla of exponentially increasing infection rates and the Charybdis of a severe economic downturn. The obvious solution to curtail the rapidly increasing rate of COVID-19…
Fanconi anemia (FA) is caused by defects in cellular responses to DNA crosslinking damage and replication stress. Given the constant occurrence of endogenous DNA damage and replication fork stress, it is unclear why complete deletion of FA genes does not have a major impact on cell proliferation and germ-line FA…
Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the…
Ectodermal patterning is required for the establishment of multiple components of the vertebrate body plan. Previous studies have demonstrated that precise combinations of extracellular signals induce distinct ectodermal cell populations, such as the neural crest and the neural plate. Yet, we still lack understanding of how the response to inductive…
Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties…
Current proteomic studies clarified canonical synaptic proteins that are common to many types of synapses. However, proteins of diversified functions in a subset of synapses are largely hidden because of their low abundance or structural similarities to abundant proteins. To overcome this limitation, we have developed an "ultra-definition" (UD) subcellular…
How enzymes achieve their enormous rate enhancements remains a central question in biology, and our understanding to date has impacted drug development, influenced enzyme design, and deepened our appreciation of evolutionary processes. While enzymes position catalytic and reactant groups in active sites, physics requires that atoms undergo constant motion. Numerous…
Redox biochemistry plays a key role in the transduction of chemical energy in living systems. However, the compounds observed in metabolic redox reactions are a minuscule fraction of chemical space. It is not clear whether compounds that ended up being selected as metabolites display specific properties that distinguish them from…
Life in environments devoid of photosynthesis, such as on early Earth or in contemporary dark subsurface ecosystems, is supported by chemical energy. How, when, and where chemical nutrients released from the geosphere fuel chemosynthetic biospheres is fundamental to understanding the distribution and diversity of life, both today and in the…
The diverse composition of mammalian tissues poses challenges for understanding the cell–cell interactions required for organ homeostasis and how spatial relationships are perturbed during disease. Existing methods such as single-cell genomics, lacking a spatial context, and traditional immunofluorescence, capturing only two to six molecular features, cannot resolve these issues. Imaging…
Although the key role of long-distance trade in the transformation of cuisines worldwide has been well-documented since at least the Roman era, the prehistory of the Eurasian food trade is less visible. In order to shed light on the transformation of Eastern Mediterranean cuisines during the Bronze Age and Early…
Sustainable development (SD) policies targeting marine economic sectors, designed to alleviate poverty and conserve marine ecosystems, have proliferated in recent years. Many developing countries are providing poor fishing households with new fishing boats (fishing capital) that can be used further offshore as a means to improve incomes and relieve fishing…
ECOLOGY, EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Correction for "Biotic rescaling reveals importance of species interactions for variation in biodiversity responses to climate change," by Vigdis Vandvik, Olav Skarpaas, Kari Klanderud, Richard J. Telford, Aud H. Halbritter, and Deborah E. Goldberg, which was first published August 31, 2020; 10.1073/pnas.2003377117 (Proc. Natl….
Engineering neutron diffraction can nondestructively and noninvasively probe stress, strain, temperature, and phase evolutions deep within bulk materials. In this work, we demonstrate operando lattice strain measurement of internal combustion engine components by neutron diffraction. A modified commercial generator engine was mounted in the VULCAN diffractometer at the Spallation Neutron…
Does college change students' political preferences? While existing research has documented associations between college education and political views, it remains unclear whether these associations reflect a causal relationship. We address this gap in previous research by analyzing a quasi-experiment in which university students are assigned to live together as roommates….
Terrestrial ecosystems are increasingly enriched with resources such as atmospheric CO2 that limit ecosystem processes. The consequences for ecosystem carbon cycling depend on the feedbacks from other limiting resources and plant community change, which remain poorly understood for soil CO2 efflux, JCO2, a primary carbon flux from the biosphere…
Cytosine (DNA) methylation in plants regulates the expression of genes and transposons. While methylation in plant genomes occurs at CG, CHG, and CHH sequence contexts, the comparative roles of the individual methylation contexts remain elusive. Here, we present Physcomitrella patens as the second plant system, besides Arabidopsis thaliana, with viable…
Streptococcus pneumoniae is a leading cause of pneumonia and invasive disease, particularly, in the elderly. S. pneumoniae lung infection of aged mice is associated with high bacterial burdens and detrimental inflammatory responses. Macrophages can clear microorganisms and modulate inflammation through two distinct lysosomal trafficking pathways that involve 1A/1B-light chain 3…
François Nico Diederich, an iconic organic chemist who innovated and created in the fields of molecular recognition and host–guest chemistry, new allotropes of carbon and novel carbon-rich molecules, and drug activity and design, passed away on September 23, 2020 in Zurich, Switzerland at the age of 68, after battling an…
While forced labor in the world's fishing fleet has been widely documented, its extent remains unknown. No methods previously existed for remotely identifying individual fishing vessels potentially engaged in these abuses on a global scale. By combining expertise from human rights practitioners and satellite vessel monitoring data, we show that…
Exposure to lead (Pb) during early life has persistent adverse health effects. During childhood, ingestion of bioavailable Pb in contaminated soils can be a major route of Pb absorption. Remediation to alter physiochemical properties of soil-borne Pb can reduce Pb bioavailability. Our laboratory-based approach for soil Pb remediation uses addition…
INNER WORKINGS Correction for "Inner Workings: Physicists look to a new telescope to understand neutron stars and matter at the extremes," by Stephen Ornes, which was first published November 4, 2020; 10.1073/pnas.2021447117 (Proc. Natl. Acad. Sci. U.S.A. 117, 29249–29252). The editors note that ref. 5 appeared incorrectly. It should instead…
Single-cell quantification of RNAs is important for understanding cellular heterogeneity and gene regulation, yet current approaches suffer from low sensitivity for individual transcripts, limiting their utility for many applications. Here we present Hybridization of Probes to RNA for sequencing (HyPR-seq), a method to sensitively quantify the expression of hundreds of…
The formation and migration of disconnections (line defects constrained to the grain boundary [GB] plane with both dislocation and step character) control many of the kinetic and dynamical properties of GBs and the polycrystalline materials of which they are central constituents. We demonstrate that GBs undergo a finite-temperature topological phase…
Large-scale global forecasting and on-the-ground observations need to meld into one system to better predict and prevent wide-spread flooding disasters, according to an international research team who published a short view in Advances in Atmospheric Sciences on Dec. 23.
Research conducted in the Light-Matter Interactions for Quantum Technologies Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) has revealed the presence of small microplastics in the ocean surrounding Okinawa. The study was published in Science of the Total Environment.
A soil scientist from RUDN University studied the decomposition of organic matter in rice paddies—the sources of CO2 and methane emissions. Both gases add to the greenhouse effect and affect climate warming in subtropical regions. The emissions increase when the roots of plants influence microbial communities in the soil. This influence, in turn, depends on temperature changes. Therefore, climate
In the mountains across the world, different types of vegetation occur at different elevations creating distinct zones with well-defined borders between them. Each vegetation zone provides specific living conditions for animals. Therefore species that are adapted to habitats created in the specific zone occur only at the specific elevations and do not overlap with other species of similar ecology
With unexpectedly cold weather in the forecast and pandemic-related curfews in some places, Florida is about to have a Christmas unlike any other in recent memory, and it may involve falling iguanas.
In the mountains across the world, different types of vegetation occur at different elevations creating distinct zones with well-defined borders between them. Each vegetation zone provides specific living conditions for animals. Therefore species that are adapted to habitats created in the specific zone occur only at the specific elevations and do not overlap with other species of similar ecology
Editor's Note: The Atlantic is making vital coverage of the coronavirus available to all readers. Find the collection here . We'll begin with the good news: In every midwestern state—and in several others—COVID-19 cases and hospitalizations are declining. Elsewhere, however, the picture is mixed. In several large states, already large outbreaks appear to be rapidly worsening—and despite intense i
Do you find that you've been running on fumes lately? Well, you're not alone. This time of year is always a grind. The weather is getting colder. The daylight is getting shorter. And as fun and joyous as the holidays may be, getting ready for them is a lot of work. After a while all the hustle and bustle can start to take a serious toll, both physically and mentally. Of course, for a lot of peopl
As you set your New Year's resolutions for 2021, consider a resolution to help others, says an expert on motivation. Any motivational researcher would have "ambivalent feelings" about New Year's resolutions , says Richard Ryan , professor emeritus of psychology at the University of Rochester. "The evidence shows that most of the time people aren't successful at them." But don't throw in the towel
"Det är viktigt att ha mössa på sig för att vi tappar majoriteten av vår kroppsvärme genom huvudet." Detta är ett påstående som vi nästan alla någon gång fått höra. Men hur väl stämmer det?
A soil scientist from RUDN University studied the decomposition of organic matter in rice paddies–the sources of CO2 and methane emissions. Both gases add to the greenhouse effect and affect climate warming in subtropical regions. The emissions increase when the roots of plants influence microbial communities in the soil. This influence, in turn, depends on temperature changes. Therefore, climate
Using mathematical modeling, new interdisciplinary research from the lab of Arye Nehorai, the Eugene & Martha Lohman Professor of Electrical Engineering in the Preston M. Green Department of Electrical & Systems Engineering at Washington University in St. Louis, determines the best course of action when it comes to walking the line between economic stability and the best possible health outcomes.
The Lindbergh baby kidnapping case is the "perfect story," says Tom Doherty. "I'm a media person, and like most of America in the age of Netflix, I have an obsession with true crime," says Doherty , professor of American studies at Brandeis University. "The Lindbergh kidnapping case is right at the intersection—it's a crime story and a media story." There's a lot of writing about the kidnapping a
N o, of course the past few weeks—like the past few months, and the past few years—of Brexit drama have not made much sense. In economic terms, not a lot about Brexit ever has. Britain and the European Union have in recent days been locked in talks to conclude one of the most important trade agreements ever negotiated. As a New Year deadline approached, after which, absent a deal, the two sides w
Scientists initially estimated that 60 to 70 percent of the population needed to acquire resistance to the coronavirus to banish it. Now Dr. Anthony Fauci and others are quietly shifting that number upward.
The 1st Chinese carbon dioxide (CO2) monitoring satellite mission, TanSat, was launched in 2016. The 1st TanSat global map of CO2 dry-air mixing ratio (XCO2) measurements over land was released as version 1 data product with an accuracy of 2.11 ppmv (parts per million by volume) in 2017. A new (version 2) TanSat global XCO2 product is now released.
Tohoku University scientists have, for the first time, provided experimental evidence that cell stickiness helps them stay sorted within correct compartments during development. How tightly cells clump together, known as cell adhesion, appears to be enabled by a protein better known for its role in the immune system. The findings were detailed in the journal Nature Communications.
By transferring mouse aged hematopoietic stem cells (aged HSCs) to the environment of young mice (bone marrow niche), it was demonstrated that the pattern of stem cell gene expression was rejuvenated to that of young hematopoietic stem cells.
Electricity is a key ingredient in living bodies. We know that voltage differences are important in biological systems; they drive the beating of the heart and allow neurons to communicate with one another. But for decades, it wasn't possible to measure voltage differences between organelles—the membrane-wrapped structures inside the cell—and the rest of the cell.
A team of researchers affiliated with several institutions in Germany has developed new chemistry for improved control of the volume of liquid in volumetric additive manufacturing. In their paper published in the journal Nature, the group describes their process and how well it worked when tested.
Paleontologists have succeeded in reconstructing the chewing motion of an early mammal that lived almost 150 million years ago. This showed that its teeth worked extremely precisely and surprisingly efficiently.
They resemble small fragments of charcoal, but the soil samples collected from an asteroid and returned to Earth by a Japanese spacecraft were hardly disappointing.
Using the highest resolution satellite imagery currently available—Worldview 3—from Maxar Technologies and deep learning, (TensorFlow API, Google Brain) researchers at the University of Oxford Wildlife Conservation Research Unit and Machine Learning Research Group have detected elephants from space with comparable accuracy to human detection capabilities.
Using the highest resolution satellite imagery currently available—Worldview 3—from Maxar Technologies and deep learning, (TensorFlow API, Google Brain) researchers at the University of Oxford Wildlife Conservation Research Unit and Machine Learning Research Group have detected elephants from space with comparable accuracy to human detection capabilities.
A new device can continuously sense levels of virtually any protein or molecule in the blood, researchers report. They say it could be transformative for disease detection, patient monitoring, and biomedical research. "A blood test is great, but it can't tell you, for example, whether insulin or glucose levels are increasing or decreasing in a patient." For even the most routine of medical checku
This summer, when bars and restaurants and stores began to reopen across the United States, people headed out despite the continuing threat of COVID-19.
The gallium selenide monolayer has been recently discovered to have an alternative crystal structure and has diverse potential applications in electronics. Understanding its properties is crucial to understand its functions. Now, scientists from the Japan Advanced Institute of Science and Technology and the University of Tokyo have explored its structural stability, electronic states and transform
A multidisciplinary survey focusing on the role ecotourism has in sustainable development, led by the University of Tuscia (Viterbo, Italy) and published in Ecology and Society, reveals the great potential that hiking guides have in conveying principles of sustainability to tourists. The study highlights the main goals of sustainable development in four major national parks in the Apennines (Italy
As global temperatures rise, snowy winters could become a thing of the past in much of the UK, according to a recent Met Office analysis. Aside from depriving schoolchildren of the sheer fun of a snow day, climate change could lead the popular imaginary of British winters into uncharted territory.
The ultra-powerful James Webb Space Telescope will launch soon. Once it's deployed and in position at the Earth-Sun Lagrange Point 2, it'll begin work. One of its jobs is to examine the atmospheres of exoplanets and look for biosignatures. It should be simple, right? Just scan the atmosphere until you find oxygen, then close your laptop and head to the pub: Fanfare, confetti, Nobel prize.
When thinking of fierce predators of the past, it's difficult not to imagine dinosaurs, considering theropods are well known for having blade-like teeth with serrated cutting edges used for biting and ripping their prey.
The gallium selenide monolayer has been recently discovered to have an alternative crystal structure and has diverse potential applications in electronics. Understanding its properties is crucial to understand its functions. Now, scientists from the Japan Advanced Institute of Science and Technology and the University of Tokyo have explored its structural stability, electronic states, and transfor
In the mountains of world, species adapt to habitats in specific elevation zones that do not overlap with other species' elevation zones. Polish ornithologists, following the old traditions of Polish ornithology in South America, discovered that two Andean warbler species that typically occur at different elevations and hunt by tricking insects to escape can co-occur at the same elevation due to f
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