Topological transport is determined by global properties of physical media where it occurs and is characterized by quantized amounts of adiabatically transported quantities. Discovered for periodic potential, it was also explored in disordered and discrete quasiperiodic systems. Here, we report on experimental observation of pumping of a light beam in a genuinely continuous incommensurate photorefractive

How do people search for information when they are given the opportunity to freely explore their options? Previous research has suggested that people focus on reducing uncertainty before making a decision, but it remains unclear how exactly they do so and whether they do so consistently. We present an analysis of over 1,000,000 information-search decisions made by over 2,500 individuals in a decis

Spin and orbital degrees of freedom are crucial in not only fundamental particles but also classical waves such as optical systems, wherein the spin–orbit interaction (SOI) of light provides new perspectives for manipulating electromagnetic waves. Elastic waves possess similar spin angular momentum (SAM) and orbital angular momentum (OAM). However, the elastic counterpart of SOI remains unexplored

Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (ADP-ribose) (PAR) from PARylated proteins. Loss or inhibition of PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents. PARG inhibitors are now undergoing clinical development for patients having tumors with homologous recombination deficiency (HRD), such as

We develop a game-theoretic model of strategic interdependence and tipping in public policy choices and show that the model can be estimated by probit and logit estimators. We test its validity and applicability by using daily data on state-level COVID-19 responses in the United States. Social distancing via shelter-in-place (SIP) strategies and wearing masks emerged as the most effective nonpharmaceutical

Hepatitis E virus (HEV) infections are one of the most common causes of acute viral hepatitis, annually causing over 3 million symptomatic cases and 70,000 deaths worldwide. Historically, HEV was described as a hepatotropic virus, but has recently been associated with various extrahepatic manifestations including neurological disorders such as Guillain–Barré syndrome and neuralgic amyotrophy. However

Plants use seasonal cold to time the transition to reproductive development. Short- and long-term cold exposure is registered via parallel transcriptional shutdown and Polycomb-dependent epigenetic silencing of the Arabidopsis thaliana major flowering repressor locus FLOWERING LOCUS C ( FLC ). The cold-induced antisense transcripts ( COOLAIR ) determine the dynamics of FLC transcriptional shutdown

Plasticity, a key hallmark of cancer, enables cells to transition into different states, driving tumor heterogeneity. This cellular plasticity is associated with cancer progression, treatment resistance, and relapse. Cancer stem cells (CSCs) play a central role in this process, yet the molecular factors underlying cancer cell stemness remain poorly understood. In this study, we explored the role of

Photosynthetic algae play a significant role in oceanic carbon capture. However, their performance is constantly challenged by fluctuations in environmental light conditions. While phototaxis is a common strategy to cope with such fluctuations, nonmotile species must adopt alternative mechanisms to avoid light-induced damage. Here, we show that the nonmotile, single-celled marine dinoflagellate Pyrocystis

Mercury (Hg) is a heavy metal that exhibits high biological toxicity. Monomethylmercury and dimethylmercury are neurotoxins and a significant environmental concern as they bioaccumulate and biomagnify within the aquatic food web. Microbial Hg methylation involves two proteins, HgcA and HgcB. Here, we show that HgcA and HgcB can be heterologously coexpressed, and the HgcAB complex can be purified. We

Accurate estimation of the dispersal velocity or speed of evolving organisms is no mean feat. In fact, existing probabilistic models in phylogeography or spatial population genetics generally do not provide an adequate framework to define velocity in a relevant manner. For instance, the very concept of instantaneous speed simply does not exist under one of the most popular approaches that models the

The distinctive characteristics of water, evident in its thermodynamic anomalies, have implications across disciplines from biology to geophysics. Considered a valid hypothesis to rationalize its unique properties, a liquid–liquid phase transition in water below the freezing point, in the so-called supercooled regime, has nowadays been observed in several molecular dynamics simulations and is being

RIG-I-like receptors (RLRs)-mitochondrial antiviral signaling protein (MAVS) are crucial for type I interferon (IFN) signaling pathway and innate immune responses triggered by RNA viruses. However, the regulatory molecular mechanisms underlying RNA virus-activated type I IFN signaling pathway remain incompletely understood. Here, we found that protein arginine methyltransferase 7 (PRMT7) serves as

To tackle significant environmental and energy challenges from increased greenhouse gas emissions in the atmosphere, we propose a method that synergistically combines cost-efficient integrated systems with parallel catalysis to produce high-value chemicals from CO 2 , NO, and other gases. We employed asymmetrically stretched InO 5 S with symmetry-breaking indium sites as a highly efficient trifunctional

The gut microbiota produces high concentrations of antimicrobial short-chain fatty acids (SCFAs) that restrict the growth of invading microorganisms. The enteric pathogen Salmonella enterica serovar ( S. ) Typhimurium triggers inflammation in the large intestine to ultimately reduce microbiota density and bloom, but it is unclear how the pathogen gains a foothold in the homeostatic gut when SCFA-producing

Animals chain movements into long-lived motor strategies, exhibiting variability across scales that reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build Markov models of movement sequences that bridge across timescales and enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish responding

Human hearing is robust to noise, but the basis of this robustness is poorly understood. Several lines of evidence are consistent with the idea that the auditory system adapts to sound components that are stable over time, potentially achieving noise robustness by suppressing noise-like signals. Yet background noise often provides behaviorally relevant information about the environment and thus seems

The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There are indications that both receptors interact functionally and physically, but the precise role of this interdependence is poorly understood. Here, we analyzed the impact of GR coexpression on MR genome-wide transcriptional responses and chromatin

Dopaminergic (DA) neurons exhibit significant diversity characterized by differences in morphology, anatomical location, axonal projection pattern, and selective vulnerability to disease. More recently, scRNAseq has been used to map DA neuron diversity at the level of gene expression. These studies have revealed a higher than expected molecular diversity in both mouse and human DA neurons. However

Current evidence suggests that ontogeny may account for the functional heterogeneity of some tissue macrophages, but not others. Here, we asked whether developmental origin drives different functions of skin Langerhans cells (LCs), an embryo-derived mononuclear phagocyte with features of both tissue macrophages and dendritic cells. Using time-course analyses, bone marrow chimeras, and fate tracing

Microscale objects responding to chemical gradients by migrating toward or away from a preferred species is a simple yet constitutive mechanism by which transport occurs in biological organisms. Synthetic chemotaxis provides key physical descriptions of simplified systems that can be used in biological models, or in the creation of advanced responsive material systems. In this article, we provide a

Imaging methods that span both functional measures in living tissue and anatomical measures in fixed tissue have played critical roles in advancing our understanding of the brain. However, making direct comparisons between different imaging modalities, particularly spanning living and fixed tissue, has remained challenging. For example, comparing brain-wide neural dynamics across experiments and aligning

The importance of CD4 + T cells in cancer immunotherapy has gained increasing recognition. Particularly, a specific subset of CD4 + T cells coexpressing the T helper type 1 (Th1) and Th17 markers has demonstrated remarkable antitumor potential. However, the underlying mechanisms governing the differentiation of these cells and their subsequent antitumor responses remain incompletely understood. Single-cell

To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambient incubator oxygen level at 21%, which is higher than

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva

Electrooxidation of renewable and CO 2 -neutral biomass for low-cost hydrogen production is a promising and green technology. Various biomass platform molecules (BPMs) oxidation assisted hydrogen production technologies have obtained noticeable progress. However, BPMs anodic oxidation is highly dependent on electrocatalysts, and the oxidation mechanism is ambiguous. Meanwhile, the complexity and insolubility

Fracture networks are preferential flow paths playing a critical role in a wide range of environmental and industrial problems. Their complex multiscale structure leads to broad distributions of fluid travel times, affecting many biogeochemical processes. Yet, the relationship between the fracture network structures, their hydrodynamic properties, and the resulting anomalous transport dynamics remains

Early embryos undergo profound changes in their genomic architecture to establish the totipotent state, enabling pioneer factors to access chromatin and drive zygotic genome activation (ZGA). However, the mechanisms by which the totipotent state is established and properly interpreted by pioneer factors to allow orderly ZGA remain unknown. Here, we identify the H3.3-specific chaperone HIRA as a factor

Triple-negative breast cancers (TNBC) are treated primarily by chemotherapy and lack clinically validated therapeutic targets. In particular, inhibitors of the PI3K/AKT/mTOR pathway, abnormally activated in many breast cancers, failed to achieve clinical efficacy in TNBC due to the development of adaptive drug resistance, which is largely driven by the transcriptomic plasticity of TNBC. Expression

Cancer cells often display errors in chromosome segregation, some of which result from improper chromosome alignment at the spindle midplane. Chromosome alignment is facilitated by different rates of microtubule poleward flux between sister kinetochore fibers. However, the role of the poleward flux in supporting mitotic fidelity remains unknown. Here, we introduce the hypothesis that the finely tuned

Axonemal dynein, the macromolecular machine that powers ciliary motility, assembles in the cytosol with the help of dynein axonemal assembly factors (DNAAFs). These DNAAFs localize in cytosolic foci thought to form via liquid–liquid phase separation. However, the functional significance of DNAAF foci formation and how the production and assembly of multiple components are so efficiently coordinated

Cooperative spin crossover (SCO) compounds are one of the most promising molecular bistable solids due to their intriguing thermal hysteresis phenomena around room temperature. It is well known that hysteresis is an essential kinetic effect, however, accurate assessment of the spin transition kinetics of SCO nanomaterials remains scarce. Herein, we developed a thermal-optical methodology to image the

Sliding electrical contacts are commonly applied in electrical connectors, such as conductive slip rings, pantographs, switches, and commutators. However, they suffer from several unavoidable problems caused by friction and wear, including high energy consumption, intermittent failures, limited life, and even failure disasters. In this study, we realized an ultralow-friction and long-distance wear-free

Tyrosine phosphorylation of metabolic enzymes is an evolutionarily conserved posttranslational modification that facilitates rapid and reversible modulation of enzyme activity, localization, or function. Despite the high abundance of tyrosine phosphorylation events detected on metabolic enzymes in high-throughput mass spectrometry-based studies, functional characterization of tyrosine phosphorylation

Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated the impact of G1 phase extension on resource allocation, metabolic functions, and the unfolded protein response (UPR) in yeast, along with the potential for enhancing the production of lipophilic compounds. In brief, the regulation of

Sugar is the largest agricultural crop by mass and has seen a rapid increase in consumption around the world. There are widespread public health efforts to curb sugar intake through targeted policies given its association with noncommunicable diseases. Although curbing sugar intake aligns with sustainable diets that meet essential environmental and health targets, such a shift may be challenging from

Reactive inhibitory control is crucial for survival. Traditionally, this control in mammals was attributed solely to the hyperdirect pathway, with cortical control signals flowing unidirectionally from the subthalamic nucleus (STN) to basal ganglia output regions. Yet recent findings have put this model into question, suggesting that the STN is assisted in stopping actions through ascending control

Electrical motor cortex stimulation can produce corticospinal system plasticity and enhance motor function after injury. We investigate molecular mechanisms of structural and physiological plasticity following electrical neuromodulation, focusing on identifying molecular predictors, or biomarkers, for durable plasticity. We used two neuromodulation protocols, repetitive multipulse stimulation (rMPS)

While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation

Land use change is crucial to addressing the existential threats of climate change and biodiversity loss while enhancing food security [M. Zurek et al. , Science 376 , 1416–1421 (2022)]. The interconnected and spatially varying nature of the impacts of land use change means that these challenges must be addressed simultaneously [H.-O. Pörtner et al. , Science 380 , eabl4881 (2023)]. However, governments

Primary osteoporosis, manifesting as decreased bone mass and increased bone fragility, is a “silent disease” that is often ignored until a bone breaks. Accordingly, it is urgent to develop reliable biomarkers and novel therapeutic strategies for osteoporosis treatment. Here, we identified REGγ as a potential biomarker of osteoporotic populations through proteomics analysis. Next, we demonstrated that

Microorganisms have evolved sophisticated sensor-actuator circuits to perform taxis in response to various environmental stimuli. How any given circuit can select between different taxis responses in noisy vs. saturated stimuli conditions is unclear. Here, we investigate how Euglena gracilis can select between positive vs. negative phototaxis under low vs. high light intensities, respectively. We propose

Porphyromonas gingivalis is a gram-negative anaerobic bacterium linked to periodontal disease. Remarkably, P. gingivalis thrives in an inflamed environment rich in activated neutrophils. Toll-like receptor 2 (TLR2) recognition is required for P. gingivalis to evade innate immune killing; however, the mechanisms through which P. gingivalis uncouples host inflammation from bactericidal activity are only

In everyday tasks, our focus of attention shifts seamlessly between contents in the sensory environment and internal memory representations. Yet, research has mainly considered external and internal attention in isolation. We used magnetoencephalography to compare the neural dynamics of shifting attention to visual contents within vs. between the external and internal domains. Participants performed

The objective of this work was to develop a long-acting form of the lipidated peptide semaglutide that can be administered to humans once-monthly. Semaglutide was attached to hydrogel microspheres by a cleavable linker with an expected in vivo release half-life of about 1 mo. After a single subcutaneous dose, the pharmacokinetic parameters of released semaglutide and bodyweight loss were determined

Lipid bilayers, ubiquitous in living systems, form lubricious boundary layers in aqueous media, with broad relevance for biolubrication, especially in mechanically stressed environments such as articular cartilage in joints, as well as for modifying material interfacial properties. Model studies have revealed efficient lubricity by single-component lipid bilayers; synovial joints, however (e.g. hips

Animal behavior is organized into nested temporal patterns that span multiple timescales. This behavior hierarchy is believed to arise from a hierarchical neural architecture: Neurons near the top of the hierarchy are involved in planning, selecting, initiating, and maintaining motor programs, whereas those near the bottom of the hierarchy act in concert to produce fine spatiotemporal motor activity

The concept of targeted protein degradation is at the forefront of modern drug discovery, which aims to eliminate disease-causing proteins using specific molecules. In this paper, we explored the idea to design protein degraders based on the section of ligands that cause protein destabilization, hence that facilitate the cellular breakdown of the target. Our studies present covalent agents targeting

The Hedgehog (Hh) pathway plays diverse roles in cellular processes by activating the transcription factor Cubitus interruptus (Ci). Abnormal regulation of this pathway has been linked to various human diseases. While previous studies have focused on how Ci is regulated in the cytoplasm, the control of nuclear Ci remains poorly understood. In this study, we have found that the transcriptional cofactor

Nearly five billion people use and receive news through social media and there is widespread concern about the negative consequences of misinformation on social media (e.g., election interference, vaccine hesitancy). Despite a burgeoning body of research on misinformation, it remains largely unclear who is susceptible to misinformation and why. To address this, we conducted a systematic individual

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes

The role of transcription factors in photoreceptor gene regulation is fairly well understood, but knowledge of the cell-type-specific function of transcriptional cofactors remains incomplete. Here, we show that the transcriptional corepressor samd7 promotes rod differentiation and represses short-wavelength cone genes in long-wavelength cones in zebrafish. In samd7 −/− retinas, red cones are transformed

As a unique type of glycosylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) on Ser/Thr residues of proteins was discovered 40 y ago. O-GlcNAcylation is catalyzed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove O-GlcNAc, respectively. O-GlcNAcylation is an essential glycosylation that regulates the functions of many proteins in virtually

Sulfur is an essential element for life. Bacteria can obtain sulfur from inorganic sulfate; but in the sulfur starvation–induced response, Pseudomonads employ two-component flavin-dependent monooxygenases (TC-FMOs) from the msu and sfn operons to assimilate sulfur from environmental compounds including alkanesulfonates and dialkylsulfones. Here, we report binding studies of oxidized FMN to enzymes

We demonstrate an approach successfully measuring very small nuclear isomeric excitation cross sections (on the order of 10 to 100 picobarns) via laser–cluster interaction. The interaction between an intense laser pulse and Kr atomic clusters generates a high-temperature and high-density plasma ball in which nuclear excitations are facilitated by inelastic electron scattering. The electron temperature

The extraordinary chemistry of microdroplets has reshaped how we as a community think about reactivity near multiphase boundaries. Even though interesting physico-chemical properties of microdroplets have been reported, “sessile” droplets’ inherent mobility, which has been implicated as a driving force for curious chemistry, has not been well established. This paper seeks to answer the question: Can