Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage–myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a)

RNA abasic sites and the mechanisms involved in their regulation are mostly unknown; in contrast, DNA abasic sites are well-studied. We found surprisingly that, in yeast and human cells, RNA abasic sites are prevalent. When a base is lost from RNA, the remaining ribose is found as a closed-ring or an open-ring sugar with a reactive C1′ aldehyde group. Using primary amine-based reagents that react with

Exploiting earth-abundant iron-based metal complexes as high-performance photosensitizers demands long-lived electronically excited metal-to-ligand charge-transfer (MLCT) states, but these species suffer typically from femtosecond timescale charge-transfer (CT)-state quenching by low-lying nonreactive metal-centered (MC) states. Here, we engineer supermolecular Fe(II) chromophores based on the bis

The mitochondrial contact site and cristae organizing system (MICOS) is a multisubunit protein complex that is essential for the proper architecture of the mitochondrial inner membrane. MICOS plays a key role in establishing and maintaining crista junctions, tubular or slit-like structures that connect the cristae membrane with the inner boundary membrane, thereby ensuring a contiguous inner membrane

In 2005, we reported evidence indicating that upcoming phonological word forms—e.g., kite vs. airplane—were predicted during reading. We recorded brainwaves (electroencephalograms [EEGs]) as people read word-by-word and then correlated the predictability in context of indefinite articles that preceded nouns (a kite vs. an airplane) with the average event-related brain potentials (ERPs) they elicited

Organic frameworks (OFs) offer a novel strategy for assembling organic semiconductors into robust networks that facilitate transport, especially the covalent organic frameworks (COFs). However, poor electrical conductivity through covalent bonds and insolubility of COFs limit their practical applications in organic electronics. It is known that the two-dimensional intralayer π∙∙∙π transfer dominates

Recombinases polymerize along single-stranded DNA (ssDNA) at the end of a broken DNA to form a helical nucleofilament with a periodicity of ∼18 bases. The filament catalyzes the search and checking for homologous sequences and promotes strand exchange with a donor duplex during homologous recombination (HR), the mechanism of which has remained mysterious since its discovery. Here, by inserting mismatched

We analyze the adoption of nonpharmaceutical interventions in the Organisation for Economic Co-operation and Development (OECD) countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. Given the complexity associated with pandemic decisions, governments are faced with the dilemma of how to act quickly when their core decision-making processes are based on deliberations

The role of obesity and overweight in occurrence of COVID-19 is unknown. We conducted a large-scale general population study using data from a community-dwelling sample in England (n = 334,329; 56.4 ±8.1 y; 54.5% women) with prospective linkage to national registry on hospitalization for COVID-19. Body mass index (BMI, from measured height and weight) was used as an indicator of overall obesity, and

The voltage-gated proton channel Hv1 is a member of the voltage-gated ion channel superfamily, which stands out in design: It is a dimer of two voltage-sensing domains (VSDs), each containing a pore pathway, a voltage sensor (S4), and a gate (S1) and forming its own ion channel. Opening of the two channels in the dimer is cooperative. Part of the cooperativity is due to association between coiled-coil

Examining linkages among multiple sustainable development outcomes is key for understanding sustainability transitions. Yet rigorous evidence on social and environmental outcomes of sustainable development policies remains scarce. We conduct a national-level analysis of Brazil’s flagship social protection program, Zero Hunger (ZH), which aims to reduce food insecurity and poverty. Using data from rural

Temperate bacteriophages can enter one of two life cycles following infection of a sensitive host: the lysogenic or the lytic life cycle. The choice between the two alternative life cycles is dependent upon a tight regulation of promoters and their cognate regulatory proteins within the phage genome. We investigated the genetic switch of TP901-1, a bacteriophage of Lactococcus lactis, controlled by

Platelets are the second most abundant cell type in blood and play an essential role in the immune response by orchestrating blood coagulation during wound healing (1). Because of their short life span of under 10 d, it is critical for the body to be able to constantly replenish platelets in the blood stream, and low platelet counts are indeed associated with a slew of pathologies with major health

Profilin2 (PFN2) is a target of the embryonic stem cell (ESC)-enriched miR-290 family of microRNAs (miRNAs) and an actin/dynamin-binding protein implicated in endocytosis. Here we show that the miR-290-PFN2 pathway regulates many aspects of ESC biology. In the absence of miRNAs, PFN2 is up-regulated in ESCs, with a resulting decrease in endocytosis. Reintroduction of miR-290, knockout of Pfn2, or disruption

Bacterial flagella differ in their number and spatial arrangement. In many species, the MinD-type ATPase FlhG (also YlxH/FleN) is central to the numerical control of bacterial flagella, and its deletion in polarly flagellated bacteria typically leads to hyperflagellation. The molecular mechanism underlying this numerical control, however, remains enigmatic. Using the model species Shewanella putrefaciens

Transcription factor fusions (TFFs) are present in ∼30% of soft-tissue sarcomas. TFFs are not readily “druggable” in a direct pharmacologic manner and thus have proven difficult to target in the clinic. A prime example is the CIC-DUX4 oncoprotein, which fuses Capicua (CIC) to the double homeobox 4 gene, DUX4. CIC-DUX4 sarcoma is a highly aggressive and lethal subtype of small round cell sarcoma found

The complexity of the cellular medium can affect proteins’ properties, and, therefore, in-cell characterization of proteins is essential. We explored the stability and conformation of the first baculoviral IAP repeat (BIR) domain of X chromosome-linked inhibitor of apoptosis (XIAP), BIR1, as a model for a homodimer protein in human HeLa cells. We employed double electron–electron resonance (DEER) spectroscopy

Research into human working memory limits has been shaped by the competition between different formal models, with a central point of contention being whether internal representations are continuous or discrete. Here we describe a sampling approach derived from principles of neural coding as a framework to understand working memory limits. Reconceptualizing existing models in these terms reveals strong

The placenta is an organ of fetal origin that develops at the interface with the maternal uterus (1). It performs numerous and diverse functions fundamental for the proper growth and development of the semiallogeneic fetus, including gas, nutrient, and waste exchange; production of hormones; and modulation of maternal immune response. Placental development begins, following implantation of the blastocyst-stage

In plants, environmental stressors trigger plasma membrane depolarizations. Being electrically interconnected via plasmodesmata, proper functional dissection of electrical signaling by electrophysiology is basically impossible. The green alga Chlamydomonas reinhardtii evolved blue light-excited channelrhodopsins (ChR1, 2) to navigate. When expressed in excitable nerve and muscle cells, ChRs can be

The major histocompatibility complex class-I (MHC-I) peptide-loading complex (PLC) is a cornerstone of the human adaptive immune system, being responsible for processing antigens that allow killer T cells to distinguish between healthy and compromised cells. Based on a recent low-resolution cryo-electron microscopy (cryo-EM) structure of this large membrane-bound protein complex, we report an atomistic

In this paper, we draw on common-pool resource theory to argue that indigenous territories, when granted full property rights, will be effective at curbing deforestation. Using satellite data, we test the effect of property rights on deforestation between 1982 and 2016. In order to identify causal effects, we combine a regression discontinuity design with the orthogonal timing of homologation. We find

Quantifying evolutionary dynamics of cancer initiation and progression can provide insights into more effective strategies of early detection and treatment. Here we develop a mathematical model of colorectal cancer initiation through inactivation of two tumor suppressor genes and activation of one oncogene, accounting for the well-known path to colorectal cancer through loss of tumor suppressors APC

Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified

Thin liquid or gas films are everywhere in nature, from foams to submillimetric bubbles at a free surface, and their rupture leaves a collection of small drops and bubbles. However, the mechanisms at play responsible for the bursting of these films is still in debate. The present study thus aims at understanding the drainage dynamics of the thin air film squeezed by gravity between a millimetric droplet

Language processing involves the ability to store and integrate pieces of information in working memory over short periods of time. According to the dominant view, information is maintained through sustained, elevated neural activity. Other work has argued that short-term synaptic facilitation can serve as a substrate of memory. Here we propose an account where memory is supported by intrinsic plasticity

Tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) levels are frequently found reduced in human cancers, but how PTEN is down-regulated is not fully understood. In addition, although a compelling connection exists between PRL (phosphatase of regenerating liver) 2 and cancer, how this phosphatase induces oncogenesis has been an enigma. Here, we discovered that PRL2 ablation

Motivated by recent experiments on magnetically frustrated heavy fermion metals, we theoretically study the phase diagram of the Kondo lattice model with a nonmagnetic valence bond solid ground state on a ladder. A similar physical setting may be naturally occurring in YbAl3C3, CeAgBi2, and TmB4 compounds. In the insulating limit, the application of a magnetic field drives a quantum phase transition

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that latently infects hematopoietic cells and has the ability to reactivate when triggered by immunological stress. This reactivation causes significant morbidity and mortality in immune-deficient patients, who are unable to control viral dissemination. While a competent immune system helps prevent clinically detectable viremia, a portrait of the

NEUROSCIENCE Correction for “Single-nucleus RNA sequencing of mouse auditory cortex reveals critical period triggers and brakes,” by Brian T. Kalish, Tania R. Barkat, Erin E. Diel, Elizabeth J. Zhang, Michael E. Greenberg, and Takao …

IMMUNOLOGY AND INFLAMMATION Correction for “Cytomegalovirus inhibition of extrinsic apoptosis determines fitness and resistance to cytotoxic CD8 T cells,” by M. …

CELL BIOLOGY, CHEMISTRY Correction for “Contact-ID, a tool for profiling organelle contact sites, reveals regulatory proteins of mitochondrial-associated membrane formation,” by Chulhwan Kwak, Sanghee Shin, Jong-Seok Park, Minkyo Jung, Truong Thi My Nhung, Myeong-Gyun Kang, Chaiheon Lee, Tae-Hyuk Kwon, Sang Ki Park, Ji Young Mun, Jong-Seo Kim, and Hyun-Woo Rhee, which was first published May 15, 2020;

APPLIED PHYSICAL SCIENCES Correction for “Anisotropic spin-orbit torque generation in epitaxial SrIrO3 by symmetry design,” by T. Nan, T. J. Anderson, J. Gibbons, K. Hwang, N. Campbell, H. Zhou, Y. Q. Dong, G. Y. Kim, D. F. Shao, T. R. Paudel, N. Reynolds, X. J. Wang, N. X. Sun, E. Y. Tsymbal, S. …

Data analyses typically rely upon assumptions about the missingness mechanisms that lead to observed versus missing data, assumptions that are typically unassessable. We explore an approach where the joint distribution of observed data and missing data are specified in a nonstandard way. In this formulation, which traces back to a representation of the joint distribution of the data and missingness

Residential energy use accounts for roughly 20% of greenhouse gas (GHG) emissions in the United States. Using data on 93 million individual households, we estimate these GHGs across the contiguous United States and clarify the respective influence of climate, affluence, energy infrastructure, urban form, and building attributes (age, housing type, heating fuel) in driving these emissions. A ranking

Scaling current cereal production to a growing global population will be a challenge. Wheat supplies approximately one-fifth of the calories and protein for human diets. Vertical farming is a possible promising option for increasing future wheat production. Here we show that wheat grown on a single hectare of land in a 10-layer indoor vertical facility could produce from 700 ± 40 t/ha (measured) to

The severe acute respiratory syndrome coronavirus 2 originated in Wuhan, China at the end of 2019 and rapidly spread in more than 100 countries. Researchers in different fields have been working on finding explanations for the unequal impact of the virus and deaths from the associated coronavirus disease 2019 (COVID-19) across geographical areas. Demographers and other social scientists have hinted

The “income inequality hypothesis” holds that rising income inequality affects the distribution of a wide range of social and economic outcomes. Although it is often alleged that rising income inequality will increase the advantages of the well-off in the competition for college, some researchers have provided descriptive evidence at odds with the income inequality hypothesis. In this paper, we track

With multiple candidate vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entering efficacy testing, researchers and ethicists should come to grips with the distinctive medical ethics questions that could arise. An important one is determining the most ethical way to proceed when comparing a purportedly promising vaccine against a purportedly less-promising one. Imagine

This research presents a nudge-based approach to promoting honest behavior. Specifically, we introduce the moral barrier hypothesis, which posits that moral violations can be inhibited by the introduction of spatial boundaries, including ones that do not physically impede the act of transgressing. We found that, as compared to a no barrier condition, children cheated significantly less often when a

Developing expertise in any field usually requires acquisition of a wide range of skills. Most current studies on perceptual learning have focused on a single task and concluded that learning is quite specific to the trained task, and the ubiquitous individual differences reflect random fluctuations across subjects. Whether there exists a general learning ability that determines individual learning

Every day, we are faced with the conflict between the temptation to cheat for financial gains and maintaining a positive image of ourselves as being a “good person.” While it has been proposed that cognitive control is needed to mediate this conflict between reward and our moral self-image, the exact role of cognitive control in (dis)honesty remains elusive. Here we identify this role, by investigating

People may be sympathetic to violent extremism when it serves their own interests. Such support may manifest itself via biased recognition of hate crimes. Psychological surveys were conducted in the wakes of mass shootings in the United States, New Zealand, and the Netherlands (total n = 2,332), to test whether factors that typically predict endorsement of violent extremism also predict biased hate

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality

We resolve a controversy over two competing hypotheses about why people object to randomized experiments: 1) People unsurprisingly object to experiments only when they object to a policy or treatment the experiment contains, or 2) people can paradoxically object to experiments even when they approve of implementing either condition for everyone. Using multiple measures of preference and test criteria

Whose voices are most likely to receive news coverage in the US debate about climate change? Elite cues embedded in mainstream media can influence public opinion on climate change, so it is important to understand whose perspectives are most likely to be represented. Here, I use plagiarism-detection software to analyze the media coverage of a large random sample of business, government, and social

We have used recent measurements of mammalian cone light responses and voltage-gated currents to calculate cone ATP utilization and compare it to that of rods. The largest expenditure of ATP results from ion transport, particularly from removal of Na+ entering outer segment light-dependent channels and inner segment hyperpolarization-activated cyclic nucleotide-gated channels, and from ATP-dependent

During rapid eye movement (REM) sleep, behavioral unresponsiveness contrasts strongly with intense brain-wide neural network dynamics. Yet, the physiological functions of this cellular activation remain unclear. Using in vivo calcium imaging in freely behaving mice, we found that inhibitory neurons in the lateral hypothalamus (LHvgat) show unique activity patterns during feeding that are reactivated

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis

The ventromedial hypothalamus (VMH) plays chief roles regulating energy and glucose homeostasis and is sexually dimorphic. We discovered that expression of metabotropic glutamate receptor subtype 5 (mGluR5) in the VMH is regulated by caloric status in normal mice and reduced in brain-derived neurotrophic factor (BDNF) mutants, which are severely obese and have diminished glucose balance control. These

Opioid addiction is a chronic, relapsing disorder associated with persistent changes in brain plasticity. Reconfiguration of neuronal connectivity may explain heightened abuse liability in individuals with a history of chronic drug exposure. To characterize network-level changes in neuronal activity induced by chronic opiate exposure, we compared FOS expression in mice that are morphine-naïve, morphine-dependent

Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. However, the underlying mechanisms have remained elusive. Here, we identify a gene regulatory and character identity network defining the deutocerebral–tritocerebral boundary (DTB) in Drosophila. This network comprises genes homologous to those directing

Zinc starvation in mycobacteria leads to remodeling of ribosomes, in which multiple ribosomal (r-) proteins containing the zinc-binding CXXC motif are replaced by their motif-free paralogues, collectively called C− r-proteins. We previously reported that the 70S C− ribosome is exclusively targeted for hibernation by mycobacterial-specific protein Y (Mpy), which binds to the decoding center and stabilizes

Oxidative damage to DNA is a threat to the genomic integrity and coding accuracy of the chromosomes of all living organisms. Guanine is particularly susceptible to oxidation, and 8-oxo-dG (OG), when produced in situ or incorporated by DNA polymerases, is highly mutagenic due to mispairing with adenine. In many bacteria, defense against OG depends on MutT enzymes, which sanitize OG in the nucleotide

Previous analysis of postentry events revealed that human cytomegalovirus (HCMV) displays a unique, extended nuclear translocation pattern in monocytes. We determined that c-Src signaling through pentamer engagement of integrins is required upon HCMV entry to avoid sorting of the virus into late endosomes and subsequent degradation. To follow up on this previous study, we designed experiments to investigate

Understanding the genetics of susceptibility to infectious agents is of great importance to our ability to combat disease. Here, we show that voltage-gated calcium channels (VGCCs) are critical for cellular binding and entry of the New World arenaviruses Junín and Tacaribe virus, suggesting that zoonosis via these receptors could occur. Moreover, we demonstrate that α1s haploinsufficiency renders cells

Alternative ribosome subunit proteins are prevalent in the genomes of diverse bacterial species, but their functional significance is controversial. Attempts to study microbial ribosomal heterogeneity have mostly relied on comparing wild-type strains with mutants in which subunits have been deleted, but this approach does not allow direct comparison of alternate ribosome isoforms isolated from identical

The DNA sensor cGAS catalyzes the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses. We addressed the functionality of cGAS-mediated DNA sensing in human and murine T cells. Activated primary CD4+ T cells expressed cGAS and responded to plasmid DNA by upregulation of ISGs and release of bioactive interferon. In mouse T cells, cGAS KO ablated sensing of plasmid DNA

Infection by malaria parasites triggers dynamic immune responses leading to diverse symptoms and pathologies; however, the molecular mechanisms responsible for these reactions are largely unknown. We performed Trans-species Expression Quantitative Trait Locus analysis to identify a large number of host genes that respond to malaria parasite infections. Here we functionally characterize one of the host

A better understanding of how antibiotic exposure impacts the evolution of resistance in bacterial populations is crucial for designing more sustainable treatment strategies. The conventional approach to this question is to measure the range of concentrations over which resistant strain(s) are selectively favored over a sensitive strain. Here, we instead investigate how antibiotic concentration impacts