Sleep drive is coupled to tissue damage via shedding of Caenorhabditis elegans EGFR ligand SISS-1.

The benefits of sleep extend beyond the nervous system. Peripheral tissues impact sleep regulation, and increased sleep is observed in response to damaging conditions, even those that selectively affect non-neuronal cells. However, the 'sleep need' signal released by stressed tissues is not known.

Characterizing mutation-treatment effects using clinico-genomics data of 78,287 patients with 20 types of cancers.

Evaluating the effectiveness of cancer treatments in relation to specific tumor mutations is essential for improving patient outcomes and advancing the field of precision medicine. Here we represent a comprehensive analysis of 78,287 U.S.

NaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.

The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).

Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release.

Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.

Infrared thermal modulation endoscopy for label-free tumor detection.

In optical imaging of solid tumors, signal contrasts derived from inherent tissue temperature differences have been employed to distinguish tumor masses from surrounding tissue. Moreover, with the advancement of active infrared imaging, dynamic thermal characteristics in response to exogenous thermal modulation (heating and cooling) have been proposed as novel measures of tumor assessment. Contrast factors such as the average rate of temperature changes and thermal recovery time constants have been investigated through an active thermal modulation imaging approach, yielding promising tumor characterization results in a xenograft mouse model.

Strongly coordinating mediator enables single-step resource recovery from heavy metal-organic complexes in wastewater.

Heavy metals complexed with organic ligands are among the most critical carcinogens threatening global water safety. The challenge of efficiently and cost-effectively removing and recovering these metals has long eluded existing technologies. Here, we show a strategy of coordinating mediator-based electro-reduction (CMBER) for the single-step recovery of heavy metals from wastewater contaminated with heavy metal-organic complexes.

The survival of B cells is compromised in kidney disease.

Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response.

Dynamic control of 2D non-Hermitian photonic corner skin modes in synthetic dimensions.

Non-Hermitian models describe the physics of ubiquitous open systems with gain and loss. One intriguing aspect of non-Hermitian models is their inherent topology that can produce intriguing boundary phenomena like resilient higher-order topological insulators (HOTIs) and non-Hermitian skin effects (NHSE). Recently, time-multiplexed lattices in synthetic dimensions have emerged as a versatile platform for the investigation of these effects free of geometric restrictions.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Strontium isoscape of sub-Saharan Africa allows tracing origins of victims of the transatlantic slave trade.

Strontium isotope (Sr/Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving Sr/Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the Sr/Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression.

Operando real-space imaging of a structural phase transformation in the high-voltage electrode LiNiMnO.

Discontinuous solid-solid phase transformations play a pivotal role in determining the properties of rechargeable battery electrodes. By leveraging operando Bragg Coherent Diffractive Imaging (BCDI), we investigate the discontinuous phase transformation in LiNiMnO within an operational Li metal coin cell. Throughout Li-intercalation, we directly observe the nucleation and growth of the Li-rich phase within the initially charged Li-poor phase in a 500 nm particle.

Functional anatomy of zinc finger antiviral protein complexes.

ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.

Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity.

The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances transcript elongation, and a UpxZ protein that inhibits noncognate UpxYs. This process, together with promoter inversions, ensures that a single CPS operon is transcribed in most cells.

Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.

The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.

MaizeCODE reveals bi-directionally expressed enhancers that harbor molecular signatures of maize domestication.

Modern maize (Zea mays ssp. mays) was domesticated from Teosinte parviglumis (Zea mays ssp. parviglumis), with subsequent introgressions from Teosinte mexicana (Zea mays ssp.

Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A receptor.

The structural basis of protective and nonprotective human monoclonal antibodies targeting the parainfluenza virus type 3 hemagglutinin-neuraminidase.

Parainfluenza virus 3 (PIV3) infection poses a substantial risk to vulnerable groups including infants, the elderly, and immunocompromised individuals, and lacks effective treatments or vaccines. This study focuses on targeting the hemagglutinin-neuraminidase (HN) protein, a structural glycoprotein of PIV3 critical for viral infection and egress. With the objective of targeting these activities of HN, we identified eight neutralizing human monoclonal antibodies (mAbs) with potent effects on viral neutralization, cell-cell fusion inhibition, and complement deposition.

Strained two-dimensional tungsten diselenide for mechanically tunable exciton transport.

Tightly bound electron-hole pairs (excitons) hosted in atomically-thin semiconductors have emerged as prospective elements in optoelectronic devices for ultrafast and secured information transfer. The controlled exciton transport in such excitonic devices requires manipulating potential energy gradient of charge-neutral excitons, while electrical gating or nanoscale straining have shown limited efficiency of exciton transport at room temperature. Here, we report strain gradient induced exciton transport in monolayer tungsten diselenide (WSe) across microns at room temperature via steady-state pump-probe measurement.

Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.

SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection.

Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure.

Small-angle scattering interferometry with neutron orbital angular momentum states.

Methods to prepare and characterize neutron helical waves carrying orbital angular momentum (OAM) were recently demonstrated at small-angle neutron scattering (SANS) facilities. These methods enable access to the neutron orbital degree of freedom which provides new avenues of exploration in fundamental science experiments as well as in material characterization applications. However, it remains a challenge to recover phase profiles from SANS measurements.

Topological transformation of microbial proteins into iron single-atom sites for selective hydrogen peroxide electrosynthesis.

The emergence of single-atom catalysts offers exciting prospects for the green production of hydrogen peroxide; however, their optimal local structure and the underlying structure-activity relationships remain unclear. Here we show trace Fe, up to 278 mg/kg and derived from microbial protein, serve as precursors to synthesize a variety of Fe single-atom catalysts containing FeNO (1 ≤ x ≤ 4) moieties through controlled pyrolysis. These moieties resemble the structural features of nonheme Fe-dependent enzymes while being effectively confined on a microbe-derived, electrically conductive carbon support, enabling high-current density electrolysis.

Recycling e-waste into gold-loaded covalent organic framework catalysts for terminal alkyne carboxylation.

The rising demand for gold requires innovative methods for its recovery from e-waste. Here we present the synthesis of two tetrazine-based vinyl-linked covalent organic frameworks: TTF-COF and TPE-COF that adsorb gold ions and nanoparticles and catalyze the carboxylation of terminal alkynes. These covalent organic frameworks have low band gaps and high photocurrent responses.

Electrochemically synthesized HO at industrial-level current densities enabled by in situ fabricated few-layer boron nanosheets.

Carbon nanomaterials show outstanding promise as electrocatalysts for hydrogen peroxide (HO) synthesis via the two-electron oxygen reduction reaction. However, carbon-based electrocatalysts that are capable of generating HO at industrial-level current densities (>300 mA cm) with high selectivity and long-term stability remain to be discovered. Herein, few-layer boron nanosheets are in-situ introduced into a porous carbon matrix, creating a metal-free electrocatalyst (B-C) with HO production rates of industrial relevance in neutral or alkaline media.

In vivo imaging of glycogen in human muscle.

Probing regional glycogen metabolism in humans non-invasively has been challenging due to a lack of sensitive approaches. Here we studied human muscle glycogen dynamics post-exercise with a spatial resolution of millimeters and temporal resolution of minutes, using relayed nuclear Overhauser effect (glycoNOE) MRI. Data at 5T showed a homogeneous distribution of glycogen in resting muscle, with an average concentration of 99 ± 13 mM.