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Electrostatically driven pattern formation in mixed charged–neutral multicomponent elastic membranes
Multicomponent crystalline and amorphous elastic shells exhibit heterogeneous surface patterns that provide distinctive functionalities in cellular environments. Such patterning typically arises from the competition between short-range attractive and long-range repulsive interactions in membranes. Here, we demonstrate that the intrinsic competition between electrostatic repulsion and elastic deformation is sufficient to drive spontaneous surface patterning in elastic shells, requiring no additional attractive interactions. Using numerical simulations, we demonstrate pattern formation in mechanically homogeneous membranes with heterogeneous surface charge composition across different topologies, including spheres, discs, and flat periodic membranes. We also examine patterns in crystalline and amorphous shells of coassembled charged and neutral components with different bending rigidities. At low charge fraction, discrete charged surface domains form. At intermediate charge fraction, the competition between electrostatics and elasticity leads to elongated domains (rods) of the charged component, which results in lamellar patterns at nearly equal fraction of the charged and neutral components. At high charge fraction, nanodomains of the neutral component form. Amorphous shells exhibit similar progressions but with disordered structures rather than ordered lamellar patterns. These pattern morphologies are observed in both the closed shells and flat membranes. As salt concentration increases, all patterns coarsen due to the screening of electrostatic interactions.
Quantum-enhanced privacy aggregation for healthcare monitoring in wireless body area networks
Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors
Abstract For all drugs, effective target engagement requires sufficient intracellular concentrations of drug to be reached, but whether tumour heterogeneity impacts drug distribution and efficacy is poorly studied. Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed treatment opportunities for women with high-grade serous ovarian carcinoma, but resistance remains a clinical hurdle in this highly heterogeneous tumour type. Here, we present a patient-derived explant multi-modal imaging pipeline, which demonstrates that cell-intrinsic PARP inhibitor accumulation is highly variable, both between patients and within tumours. Spatial transcriptomics reveals enrichment of apoptotic and lysosomal signatures in high-drug regions. Rucaparib, an intrinsically fluorescent PARP inhibitor, accumulates heterogeneously at the single-cell level, with rucaparib-high cells demonstrating increased drug response relative to rucaparib-low. Mechanistically, lysosomal sequestration creates a rucaparib reservoir that determines drug levels in the nucleus. Perturbation of lysosomal content alters intracellular levels of weak base PARP inhibitors rucaparib and niraparib, but not olaparib. Together these data suggest that lysosomes act as a reservoir for a subset of PARP inhibitor drugs to improve drug response.
Immune cells employ intermittent integrin-mediated traction forces for 3D migration
To reach targets outside the bloodstream, immune cells can extravasate and migrate through connective tissue. During tissue infiltration, immune cells migrate in an amoeboid fashion, characterized by weak matrix adhesions and low traction forces, that allows them to achieve high migration speeds of up to 10 µm/min. How immune cells reconcile amoeboid migration with the need to overcome steric hindrance in dense matrices is currently not understood. Here we show that NK92 (natural killer) cells can switch from their default amoeboid migration mode to a contractile, mesenchymal-like migration mode when moving through fibrous human amniotic membrane (HAM) tissue. We subsequently study immune cell migration in reconstituted 3D collagen networks with known mechanical properties and pore sizes and apply time-lapse confocal reflection microscopy to obtain simultaneous measurements of migration speed, directional persistence, and cell contractility. We find that NK92 cells exert substantial acto-myosin driven, integrin-mediated contractile forces of up to 100 nN on the extracellular matrix during short contractile phases. This burst-like contractile behavior is also found in primary B, T, NK cells, neutrophils, and monocytes, and is tightly related to the fraction of cells that become stuck in narrow pores of the surrounding matrix. Our results demonstrate that steric hindrance guides the rapid regulation of integrin-mediated adhesion to the ECM in a large number of immune cell subtypes.
Effect of optimized germination on nutritional functional and phytochemical characteristics of green gram
Abstract Germination is an effective bioprocessing strategy for enhancing the nutritional quality and functional potential of legumes. This study systematically evaluated the effects of controlled germination on the nutritional, functional, phytochemical, antioxidant, and sensory characteristics of ten elite green gram ( Vigna radiata L.) cultures, with the objective of identifying genotypes suitable for sprout-based functional food applications. Germination was conducted for 8, 12, 16, and 20 h, and optimization was achieved based on overall sensory acceptability (OSA) score using a nine-point hedonic scale. The highest sensory acceptability scores, ranging from 6.01 to 8.60, were observed at 8 - 12 h of germination, whereas extended germination significantly reduced acceptability due to the development of bitterness. Compared with non-germinated samples, optimally germinated green gram cultures exhibited significant improvements in nutritional composition, including increased crude protein content from 17.38 – 24.81 to 20.12 - 26.32 g 100 g⁻ 1 and crude fiber from 9.86 - 13.82 to 11.36 - 16.42 g 100 g⁻ 1 . Ash content also increased marginally following germination. Vitamin C, which was absent in raw grains, was synthesized during germination and reached levels of approximately 55.04 to 85.48 mg 100 g⁻ 1 . In contrast, anti-nutritional factors were substantially reduced, with tannin content decreasing from 320 - 458 to 65 - 97 mg tannic acid equivalent 100 g⁻ 1 and phytic acid from about 754 - 906 to 102 - 175 mg 100 g⁻ 1 . Germination significantly enhanced phytochemical composition and antioxidant capacity, as evidenced by increased total phenolic and flavonoid contents and higher DPPH radical scavenging activity, which increased from 23.78 - 32.41% in raw grains to 35.47 - 40.59% in germinated samples. Functional properties, including water and oil absorption capacities, were also significantly improved following germination. Overall, this study presents a novel comparative screening of elite green gram cultures and establishes optimized germination as a practical and scalable approach for developing green gram sprouts in both fresh and dry forms in salads, weaning/supplementary foods, nutrient-dense convenience foods, etc., for improved nutrition.
Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex
Predicting individual incubation of opioid craving by whole-brain functional connectivity
A high risk of relapse triggered by craving during abstinence remains a main challenge in opioid addiction treatment. Multiple brain regions have been implicated in opioid craving, but the brain-wide neural mechanisms underlying this process remain poorly understood. Using resting-state fMRI and connectome-based predictive modeling, we identified a whole-brain connectome that predicted the time-dependent increases (incubation) in oxycodone craving in individual rats after voluntary abstinence induced by exposure to an electric barrier. Incubation of oxycodone craving was operationally defined as the increase in nonreinforced lever pressing during relapse tests from early (day 1) to late (day 15) abstinence (incubation score). We found that changes in whole-brain functional connectivity during abstinence, but not during oxycodone self-administration, predicted the incubation score. Greater decreases in functional connectivity were associated with higher incubation scores. The predictive connectome involved complex interactions across multiple brain systems, including frontal-striatal, frontal-insula, insula-striatal, and hippocampal and sensorimotor circuits. To test causality of the predictive connectome, we examined the effect of pharmacological inactivation of dorsomedial striatum (DMS), which significantly decreased oxycodone seeking after electric barrier-induced abstinence. DMS inactivation increased connectivity strength within the predictive connectome, supporting a causal role of this connectome in incubation of oxycodone craving. The predictive connectome did not predict food-reward seeking after electric barrier-induced abstinence, indicating specificity to oxycodone craving. Our findings identify a brain-wide connectome marker that predicts individual differences in the incubation of opioid craving and provide potential targets for developing personalized interventions and monitoring therapeutic outcomes in opioid addiction treatment.
Genomic identification and complete mitochondrial recovery of a Late Holocene porcupine (Erethizon dorsatum) mummy from Yukon permafrost
Abstract We identified a 3000-year-old specimen from the Traditional Territory of the Tr’ondëk Hwëch’in in central Yukon Territory, Canada as the first known mummified remains of an ancient North American porcupine (Erethizon dorsatum) , known as “Ts’ey” in the Hän language, using genetic analysis and metagenomic validation. Our analysis of the sample yielded the first-ever complete ancient mitochondrial genome for (E. dorsatum) and only the second full mitogenome for the species. Its Holocene age is considerably younger than the Pleistocene megafauna typically recovered in the Yukon permafrost, demonstrating the potential for these deposits to preserve specimens from interglacial periods. Crucially, this finding confirms the presence of porcupines in the region 3000 years ago, in line with the hypothesis that this species only dispersed into Yukon and Alaska following the establishment of boreal forests after the Last Glacial Period.
Oligomerization-competent PIF4 drives thermomorphogenesis through functional redundancy in transactivation and DNA binding
Coexpression among eastern oyster host and microbiome genes suggests coordinated regulation of calcifying fluid chemistry
Marine animals that build shells, such as oysters, carefully regulate the chemistry of their internal calcifying fluids, but the molecular mechanisms behind this control, as well as whether microbes play a role in calcification, are poorly understood. To better understand oysters’ molecular mechanisms and the role of their calcifying-fluid microbes, we conducted experiments that simulated a tidal cycle, measured calcifying fluid pH and total dissolved inorganic carbon, and characterized host and microbial gene expression via transcriptomics. These experiments showed that calcifying fluid pH remained relatively stable throughout tidal pH fluctuations, with corresponding increases in oyster transcripts for ion transport and acid–base regulation. These data provide direct evidence that tidal fluctuations drive rapid changes in oyster calcifying fluid chemistry. Most surprisingly, increases in microbial transcripts related to nitrogen and sulfur cycling correlated to higher calcifying fluid DIC, and coexpression network analysis revealed patterns of gene expression that linked oyster immune and neural pathways to microbial redox processes, providing molecular evidence of potential host modulation of microbial metabolism. Together, these results reveal that oysters actively regulate their calcifying fluid pH over short timescales, and the endemic microbiome metabolic responses can yield metabolites that influence calcifying fluid pH, alkalinity, and ultimately calcification. These data offer a perspective on oyster physiological capacity and, most importantly, the potential role of microbes in oyster calcification. In light of ongoing changes in ocean pH and temperature, oysters provide a model for studying animal–microbial responses to environmental acidification and how their interactions may shape biomineralization.
Modular 4WD agricultural robot for cutting, collection, and precision seeding: design and simulation-based evaluation
Abstract This paper presents a four-wheel differential-drive (4WD) autonomous platform that consolidates grass cutting, collection, leaf crushing, and precision seeding through modular, quick-release toolheads. A vertically stacked two-unit architecture separates the drive/blower subsystem in a steel-framed base from a high-capacity collection chamber; transparent panels aid inspection and service. System specifications are formalized, and operating energy budgets are modelled to predict runtimes across cutting (≈ 1.2 h), crushing (≈ 2.0 h), and seeding (≈ 8.0 h) modes. Coverage-path algorithms (zigzag, spiral, concentric) are simulated, with results confirming that the boustrophedon pattern achieves complete rectangular coverage with minimal redundancy. Robustness simulations quantify debris deflection (> 95% rejection), slope climb limits (≈ 25° at < 20% slip), and stone-ingestion probability (≈ 10%), validating operational resilience. Finite-element analysis of the steel and aluminum chassis demonstrates high safety factors (> 15) with negligible stress or deformation under representative static loads. Beyond robotic functions, composting pathways for collected biomass are outlined to close the loop on sustainability. While dynamic load events and hardware validation are deferred to future work, the results indicate that the proposed modular 4WD platform integrates cutting, collection, and seed delivery with serviceability, structural robustness, and environmental benefit, making it a promising candidate for campus and small-scale agricultural automation.
Visualizing the breakdown of the quantum anomalous Hall effect
The creation of topologically nontrivial matter across electronic, mechanical, cold-atom, and photonic platforms is advancing rapidly, yet understanding the breakdown of topological protection remains a major challenge. In this work, we use magnetic imaging combined with global electrical transport measurements to visualize the current-induced breakdown of the quantum anomalous Hall effect (QAHE) in a magnetically doped topological insulator. We find that dissipation emerges at localized hot spots near electrical contacts, where an abrupt change in Hall angle leads to significant distortions of the current density. Using changes in the local magnetization as a proxy for electron temperature, we directly observe that the electrons are driven out of equilibrium with the lattice at the hot spots and throughout the device in the breakdown regime. By characterizing energy relaxation processes in our device, we show that the breakdown of quantization is governed entirely by electron heating, and that a vanishing thermal relaxation strength at millikelvin temperatures limits the robustness of the QAHE. Our findings provide a framework for diagnosing energy relaxation in topological materials and will guide realizing robust topological protection in magnetic topological insulators.
Deterministic statistical patterns preceding ice shocks revealed by ice deformation measurements
A synthetic ERFVII-dependent circuit in yeast sheds light on the regulation of early hypoxic responses of plants
Plants face hypoxic conditions either chronically, as particular tissues are characterized by fluctuating or stable low oxygen levels, or acutely, when flooded. In vascular plants, transcriptional adaptive responses to hypoxia are rapidly mounted by Ethylene Response Factors VII (ERFVIIs), regulated by Plant Cysteine Oxidases (PCOs) through the cysteine branch of the N-degron pathway (Cys-NDP) for oxygen sensing. However, this relatively simple regulatory circuit, consisting of both constitutively expressed as well as hypoxia-inducible ERFVIIs and PCOs, interacts with diverse signaling cues and pathways invoked by hypoxia. To understand the share of the PCO-mediated oxygen sensing mechanism in the production of hypoxia responses, we insulated the PCO/ERFVII circuit from Arabidopsis thaliana and adapted it to Saccharomyces cerevisiae . Using a reporter gene to monitor the output of the circuit allowed us to compare the speed and amplitude of response to hypoxia in the engineered yeast and the source organism. Hypoxia triggered ERFVII stabilization both in Arabidopsis and yeast, leading to a similarly fast transcriptional response that was however larger in plants. A simple hypoxia-inducible feedback loop improved the amplitude of response in yeast, demonstrating the importance of this regulation in the endogenous PCO/ERFVII circuit. Finally, computational modeling of the yeast circuit enabled us to identify promoter competition and presence of hypoxia-inducible PCOs as key parameters that shape early hypoxia responses in plant cells.
Multi-dimensional deep learning–based segmentation and volumetric assessment of sphenoid sinus fluid on postmortem CT in drowning cases
Macrophage–glia interactions regulate immune damage to enteric neurons during West Nile virus infection
Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we defined such neuron–glia–macrophage interactions after West Nile virus (WNV) infection; this model neurotropic virus causes GI tract dysmotility in mice via injury of enteric neurons through a T cell–mediated cytolytic mechanism. In response to WNV infection, RNA sequencing analysis showed that resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. Whereas pharmacological depletion of resident macrophages did not affect the viral burden in the GI tract, it instead reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. The amplified recruitment of these immune cell types worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.
Exogenous estradiol does not regulate daily metabolic rhythms underlying diet-induced obesity in male mice
Male mice fed high-fat diet become obese, but female mice are resistant to diet-induced weight gain. We previously found that circulating estradiol in females protects their daily rhythms from disruption by high-fat feeding to prevent diet-induced obesity. The goal of this study was to determine the effects of estradiol on daily metabolic rhythms in male mice. Male C57BL/6J mice were treated with estradiol and fed high-fat diet for 2 weeks. We measured the effects of high-fat diet feeding on daily rhythms of eating behavior and locomotor activity, and on the phases, or timing, of circadian rhythms in central and peripheral tissues. We found that males treated with estradiol had lower blood glucose when fed high-fat diet than males treated with vehicle even though there were no effects of estradiol treatment on body weight and adiposity. There was no effect of estradiol on the daily rhythm of eating behavior as it was low-amplitude or arrhythmic during high-fat diet feeding in both vehicle- and estradiol-treated males. Locomotor activity rhythms were also unaffected by estradiol treatment. Likewise, the phases of circadian rhythms in the suprachiasmatic nucleus (SCN), liver, muscle, and other peripheral tissues were not altered by estradiol treatment. Thus, treatment of male mice with estradiol did not protect daily rhythms from disruption by high-fat diet, as it does in females. Together these data suggest that the mechanisms underlying sex differences in daily metabolic rhythms are complex and may require both developmental and adult exposure to hormones.
Regulating female ear morphogenesis in maize by uniconazole and 5-aminolevulinic acid for yield improvement
Expert evaluation of LLM world models: A high-T <sub> <i>c</i> </sub> superconductivity case study
Large Language Models (LLMs) show great promise as a powerful tool for scientific literature exploration. However, their effectiveness in providing scientifically accurate and comprehensive answers to complex questions within specialized domains remains an active area of research. Using the field of high-temperature cuprates as an exemplar, we evaluate the ability of LLM systems to understand the literature at the level of an expert. We construct an expert-curated database of 1,726 scientific papers that covers the history of the field, and a set of 67 expert-formulated questions that probe deep understanding of the literature. We then evaluate six different LLM-based systems for answering these questions, including both commercially available closed models and a custom retrieval-augmented generation (RAG) system capable of retrieving images alongside text. Experts then evaluate the answers of these systems against a rubric that assesses balanced perspectives, factual comprehensiveness, succinctness, and evidentiary support. Among the six systems, two using RAG on curated literature outperformed existing closed models across key metrics, particularly in providing comprehensive and well-supported answers. We discuss promising aspects of LLM performances as well as critical short-comings of all the models. The set of expert-formulated questions and the rubric will be valuable for assessing expert level performance of LLM based reasoning systems.
Silence in physician clinical practice: a scoping review protocol
Objective The objective of this review is to map, describe and conceptualize how silence is discussed within literature on interactions between physicians and patients, in clinical settings. Methods We will use the methodological framework of Arksey & O’Malley, adapted by Levac et al and Joanna Briggs Institute. Empirical studies including quantitative, qualitative, mixed methods, observational studies and reviews will be included. Commentaries, editorials, and grey literature will also be examined. The databases MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Scopus and Web of Science will be searched. A two-part study selection strategy will be applied. First, reviewers will follow inclusion and exclusion criteria based on ‘Population-Concept-Context’ framework to independently screen titles and abstracts. Next, full texts will be screened. Data will be extracted, collated, and charted to summarize methods, outcomes and key findings from the articles included. Findings will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews. (PRISMA-ScR). Expected results and implications This scoping review will provide an extensive description of how physicians engage with silence in clinical settings. Findings will identify how silence is perceived in physician patient interactions, the roles it plays, what factors influence use of silence and guide development of educational initiatives on use of silence in clinical settings.