We introduce a method to draw causal inferences—inferences immune to all possible confounding—from genetic data that include parents and offspring. Causal conclusions are possible with these data because the natural randomness in meiosis can be viewed as a high-dimensional randomized experiment. We make this observation actionable by developing a conditional independence test that identifies regions

Peptidomimetic macrocycles have the potential to regulate challenging therapeutic targets. Structures of this type having precise shapes and drug-like character are particularly coveted, but are relatively difficult to synthesize. Our laboratory has developed robust methods that integrate small-peptide units into designed scaffolds. These methods create macrocycles and embed condensed heterocycles

Surveying a campus community about sexual harassment can be a daunting task during normal times. It’s especially daunting during a pandemic. Institutional leaders may balk at committing scarce resources to survey efforts. Some may wonder how to interpret results that look dramatically different from prior assessments. Also, they may worry about adding to the burdens of already stressed staff, faculty

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs

The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types

Hebbian plasticity is a key mechanism for higher brain functions, such as learning and memory. This form of synaptic plasticity primarily involves the regulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) abundance and properties, whereby AMPARs are inserted into synapses during long-term potentiation (LTP) or removed during long-term depression (LTD). The molecular

In their Letter, Ng et al. (1) state that our (2) comparison of the coronavirus disease 2019 (COVID-19) to Hurricane Katrina is “slightly contrived.” We appreciate the opportunity for discussion. However, we maintain that there is much to be learned from prior disasters, including Hurricane Katrina, for anticipating and mitigating the indirect health consequences of the COVID-19 pandemic.

In a recent Brief Report by Raker et al. (1), the investigators analyze data from a prospective study of young, low-income mothers who survived Hurricane Katrina and apply this to the ongoing coronavirus disease 2019 (COVID-19) pandemic to discuss strategies to mitigate the pandemic’s indirect effects on survivors. We appreciate the comparison made, but it is slightly contrived for several reasons

We commend Malisch et al. on their Opinion (1) on immediate solutions to ensure gender equity during the COVID-19 pandemic given the disproportionate burden placed on women due to childcare and household responsibilities. Given early reports showing fewer women are submitting academic papers during the pandemic (2), we encourage institutions to immediately examine how to improve gender equity in the

As increasing evidence emerges concerning the disproportionate impact of COVID-19 on women academics (1, 2), we hope our work continues to prompt institutions and departments to advance gender equity in tenure and promotion (3). For example, Arora et al. (4) have developed a department-specific rubric to assess COVID-19’s impact on a case-by-case basis. This rubric is in the form of a curriculum vitae

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls

Mechanistic studies of anaerobic gut bacteria have been hindered by the lack of a fluorescent protein system to track and visualize proteins and dynamic cellular processes in actively growing bacteria. Although underappreciated, many gut “anaerobes” are able to respire using oxygen as the terminal electron acceptor. The oxygen continually released from gut epithelial cells creates an oxygen gradient

Integrating a long-established soil erosion model with Intergovernmental Panel on Climate Change (IPCC) scenarios, Borrelli et al. (1) set out to meet the needs of policymakers and earth-system modelers to better understand the future of soil erosion this century. Policymakers need this insight because of the constraints erosion places on achievement of multiple sustainable development goals including

Edilson Consuelo de Oliveira has regained his sense of taste and smell, so he has finally been able to enjoy a plate of pirapitinga, his favorite fish in all the Amazon. Before contracting coronavirus disease 2019 (COVID-19), Edilson had been in lockdown on a small farm outside of Rio Branco, the capital of Acre state in Brazil, but in early June a nephew came to visit from the city, bringing a dry

Grain growth under shear annealing is crucial for controlling the properties of polycrystalline materials. However, their microscopic kinetics are not well understood because individual atomic trajectories are difficult to track. Here, we study grain growth with single-particle kinetics in colloidal polycrystals using video microscopy. Rich grain-growth phenomena are revealed in three shear regimes

In the real world, complex dynamic scenes often arise from the composition of simpler parts. The visual system exploits this structure by hierarchically decomposing dynamic scenes: When we see a person walking on a train or an animal running in a herd, we recognize the individual’s movement as nested within a reference frame that is, itself, moving. Despite its ubiquity, surprisingly little is understood

The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed

MICROBIOLOGY Correction to Supporting Information for “Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection,” by Honglei Sun, Yihong Xiao, Jiyu Liu, Dayan Wang, Fangtao Li, …

APPLIED BIOLOGICAL SCIENCES Correction to Supporting Information for “Inducers of the endothelial cell barrier identified through chemogenomic screening in genome-edited hPSC-endothelial cells,” by Filip Roudnicky, Jitao David …

GENETICS Correction for “Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia,” by Bing Chen, Lu Jiang, Meng-Ling Zhong, Jian-Feng Li, Ben-Shang Li, …

CELL BIOLOGY Correction for “Endocytosis is required for E-cadherin redistribution at mature adherens junctions,” by Simon de Beco, Charles Gueudry, François Amblard, and Sylvie Coscoy, which was first published April 28, 2009; 10.1073/pnas.0811253106 (Proc. Natl. Acad. Sci. U.S.A. 106, 7010–7015).

Enzyme turnover numbers (kcats) are essential for a quantitative understanding of cells. Because kcats are traditionally measured in low-throughput assays, they can be inconsistent, labor-intensive to obtain, and can miss in vivo effects. We use a data-driven approach to estimate in vivo kcats using metabolic specialist Escherichia coli strains that resulted from gene knockouts in central metabolism

The United States Environmental Protection Agency (EPA) Science Advisory Board (SAB) provides expert advice to inform agency decision-making. Recent regulations have decreased the representation of academic scientists on the EPA SAB and increased the representation of industry scientists. In an experiment, we asked how the US public views the goals and legitimacy of the board as a function of its composition

Terrorist attacks often fuel online hate and increase the expression of xenophobic and antiminority messages. Previous research has focused on the impact of terrorist attacks on prejudiced attitudes toward groups linked to the perpetrators as the cause of this increase. We argue that social norms can contain the expression of prejudice after the attacks. We report the results of a combination of a

Resource sharing has always been a central component of human sociality. Children require heavy investments in human capital; during working years, help is needed due to illness, disability, or bad luck. While hunter-gatherer elders assisted their descendants, more recently, elderly withdraw from work and require assistance as well. Willingness to share has been critically important for our past evolutionary

Programs seeking to transform undergraduate science, technology, engineering, and mathematics courses often strive for participating faculty to share their knowledge of innovative teaching practices with other faculty in their home departments. Here, we provide interview, survey, and social network analyses revealing that faculty who use innovative teaching practices preferentially talk to each other

Sexual harassment abounds in academia. We know this from a 2018 report published by the National Academies of Sciences, Engineering, and Medicine (1). As members of the committee who authored that report,* we have presented its findings to colleges and universities around the country. It has been deeply gratifying to see so many leaders want to address sexual harassment in their institutions. But according

Does being disagreeable—that is, behaving in aggressive, selfish, and manipulative ways—help people attain power? This question has long captivated philosophers, scholars, and laypeople alike, and yet prior empirical findings have been inconclusive. In the current research, we conducted two preregistered prospective longitudinal studies in which we measured participants’ disagreeableness prior to entering

Exposure to even subtle forms of misleading information can significantly alter memory for past events. Memory distortion due to misinformation has been linked to faulty reconstructive processes during memory retrieval and the reactivation of brain regions involved in the initial encoding of misleading details (cortical reinstatement). The current study investigated whether warning participants about

Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale

Most Republicans in a January 2020 survey agreed that “the traditional American way of life is disappearing so fast that we may have to use force to save it.” More than 40% agreed that “a time will come when patriotic Americans have to take the law into their own hands.” (In both cases, most of the rest said they were unsure; only one in four or five disagreed.) I use 127 survey items to measure six

To engineer Mo-dependent nitrogenase function in plants, expression of the structural proteins NifD and NifK will be an absolute requirement. Although mitochondria have been established as a suitable eukaryotic environment for biosynthesis of oxygen-sensitive enzymes such as NifH, expression of NifD in this organelle has proven difficult due to cryptic NifD degradation. Here, we describe a solution

The recently discovered, chlorophyll-f-containing, far-red photosystem II (FR-PSII) supports far-red light photosynthesis. Participation and kinetics of spectrally shifted far-red pigments are directly observable and separated from that of bulk chlorophyll-a. We present an ultrafast transient absorption study of FR-PSII, investigating energy transfer and charge separation processes. Results show a

Heterostyly represents a fascinating adaptation to promote outbreeding in plants that evolved multiple times independently. While l-morph individuals form flowers with long styles, short anthers, and small pollen grains, S-morph individuals have flowers with short styles, long anthers, and large pollen grains. The difference between the morphs is controlled by an S-locus “supergene” consisting of several

In higher plants, molecular responses to exogenous hypoxia are driven by group VII ethylene response factors (ERF-VIIs). These transcriptional regulators accumulate in the nucleus under hypoxia to activate anaerobic genes but are destabilized in normoxic conditions through the action of oxygen-sensing plant cysteine oxidases (PCOs). The PCOs catalyze the reaction of oxygen with the conserved N-terminal

Lipid droplets (LDs) are intracellular organelles found in a wide range of organisms and play important roles in stress tolerance. During nitrogen (N) starvation, Chlamydomonas reinhardtii stores large amounts of triacylglycerols (TAGs) inside LDs. When N is resupplied, the LDs disappear and the TAGs are degraded, presumably providing carbon and energy for regrowth. The mechanism by which cells degrade

Many plants use environmental cues, including seasonal changes of day length (photoperiod), to control their flowering time. Under inductive conditions, FLOWERING LOCUS T (FT) protein is synthesized in leaves, and FT protein is a mobile signal, which is able to travel to the shoot apex to induce flowering. Dodders (Cuscuta, Convolvulaceae) are root- and leafless plants that parasitize a large number

Currently there is an unmet need for treatments that can prevent hypertrophic cardiomyopathy (HCM). Using a murine model we previously identified that HCM causing cardiac troponin I mutation Gly203Ser (cTnI-G203S) is associated with increased mitochondrial metabolic activity, consistent with the human condition. These alterations precede development of the cardiomyopathy. Here we examine the efficacy

Thalidomide exerts its teratogenic and immunomodulatory effects by binding to cereblon (CRBN) and thereby inhibiting/modifying the CRBN-mediated ubiquitination pathway consisting of the Cullin4-DDB1-ROC1 E3 ligase complex. The mechanism of thalidomide’s classical hypnotic effect remains largely unexplored, however. Here we examined whether CRBN is involved in the hypnotic effect of thalidomide by generating

The β2-adrenergic receptor (β2AR) is a prototypical G protein-coupled receptor (GPCR) that preferentially couples to the stimulatory G protein Gs and stimulates cAMP formation. Functional studies have shown that the β2AR also couples to inhibitory G protein Gi, activation of which inhibits cAMP formation [R. P. Xiao, Sci. STKE 2001, re15 (2001)]. A crystal structure of the β2AR-Gs complex revealed

Animals use active sensing to respond to sensory inputs and guide future motor decisions. In flight, flies generate a pattern of head and body movements to stabilize gaze. How the brain relays visual information to control head and body movements and how active head movements influence downstream motor control remains elusive. Using a control theoretic framework, we studied the optomotor gaze stabilization

The small GTPase ARL4C participates in the regulation of cell migration, cytoskeletal rearrangements, and vesicular trafficking in epithelial cells. The ARL4C signaling cascade starts by the recruitment of the ARF–GEF cytohesins to the plasma membrane, which, in turn, bind and activate the small GTPase ARF6. However, the role of ARL4C–cytohesin–ARF6 signaling during hippocampal development remains

Humans have an extraordinary ability to interact and cooperate with others. Despite the social and evolutionary significance of collaboration, research on finding its neural correlates has been limited partly due to restrictions on the simultaneous neuroimaging of more than one participant (also known as hyperscanning). Several studies have used dyadic fMRI hyperscanning to examine the interaction

The 100-y-old neuron doctrine from Ramón y Cajal states that neurons are individual cells, rejecting the process of cell−cell fusion in the normal development and function of the nervous system. However, fusogens—specialized molecules essential and sufficient for the fusion of cells—are expressed in the nervous system of different species under conditions of viral infection, stress, or disease. Despite

Visual motion detection is one of the most important computations performed by visual circuits. Yet, we perceive vivid illusory motion in stationary, periodic luminance gradients that contain no true motion. This illusion is shared by diverse vertebrate species, but theories proposed to explain this illusion have remained difficult to test. Here, we demonstrate that in the fruit fly Drosophila, the

Numerous rhodopsin mutations have been implicated in night blindness and retinal degeneration, often with unclear etiology. D190N-rhodopsin (D190N-Rho) is a well-known inherited human mutation causing retinitis pigmentosa. Both higher-than-normal spontaneous-isomerization activity and misfolding/mistargeting of the mutant protein have been proposed as causes of the disease, but neither explanation

Our decisions often depend on multiple sensory experiences separated by time delays. The brain can remember these experiences and, simultaneously, estimate the timing between events. To understand the mechanisms underlying working memory and time encoding, we analyze neural activity recorded during delays in four experiments on nonhuman primates. To disambiguate potential mechanisms, we propose two

The fusiform face area responds selectively to faces and is causally involved in face perception. How does face-selectivity in the fusiform arise in development, and why does it develop so systematically in the same location across individuals? Preferential cortical responses to faces develop early in infancy, yet evidence is conflicting on the central question of whether visual experience with faces

Memory is typically thought of as enabling reminiscence about past experiences. However, memory also informs and guides processing of future experiences. These two functions of memory are often at odds: Remembering specific experiences from the past requires storing idiosyncratic properties that define particular moments in space and time, but by definition such properties will not be shared with similar

The unique extracellular electron transfer (EET) ability has positioned electroactive bacteria (EAB) as a major class of cellular chassis for genetic engineering aimed at favorable environmental, energy, and geoscience applications. However, previous efforts to genetically enhance EET ability have often impaired the basal metabolism and cellular growth due to the competition for the limited cellular

Antibodies may bind to bacterial pathogens or their toxins to control infections, and their effector activity is mediated through the recruitment of complement component C1q or the engagement with Fcγ receptors (FcγRs). For bacterial pathogens that rely on a single toxin to cause disease, immunity correlates with toxin neutralization. Most other bacterial pathogens, including Staphylococcus aureus

Immune evasion through membrane remodeling is a hallmark of Yersinia pestis pathogenesis. Yersinia remodels its membrane during its life cycle as it alternates between mammalian hosts (37 °C) and ambient (21 °C to 26 °C) temperatures of the arthropod transmission vector or external environment. This shift in growth temperature induces changes in number and length of acyl groups on the lipid A portion

Medium-chain fatty alcohols (MCFOHs, C6 to C12) are potential substitutes for fossil fuels, such as diesel and jet fuels, and have wide applications in various manufacturing processes. While today MCFOHs are mainly sourced from petrochemicals or plant oils, microbial biosynthesis represents a scalable, reliable, and sustainable alternative. Here, we aim to establish a Saccharomyces cerevisiae platform

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection

Many countries have passed their first COVID-19 epidemic peak. Traditional epidemiological models describe this as a result of nonpharmaceutical interventions pushing the growth rate below the recovery rate. In this phase of the pandemic many countries showed an almost linear growth of confirmed cases for extended time periods. This new containment regime is hard to explain by traditional models where

Sometime next year, managers at the US Department of Energy’s (DOE) Argonne National Laboratory in Lemont, IL, will power up a calculating machine the size of 10 tennis courts and vault the country into a new age of computing. The $500-million mainframe, called Aurora, could become the world’s first “exascale” supercomputer, running an astounding 1018, or 1 quintillion, operations per second.

The DNA-dependent protein kinase (DNA-PK), which is composed of the KU heterodimer and the large catalytic subunit (DNA-PKcs), is a classical nonhomologous end-joining (cNHEJ) factor. Naïve B cells undergo class switch recombination (CSR) to generate antibodies with different isotypes by joining two DNA double-strand breaks at different switching regions via the cNHEJ pathway. DNA-PK and the cNHEJ