Browse Articles

A broad-spectrum inhibitor of copper-exporting P _1B -type ATPases

Copper (Cu) transporting ATPases represent a highly conserved subclass of P-type ATPases with critical roles in Cu export and metalloenzyme synthesis. Despite their important biological roles and association with a wide range of human diseases, no high-affinity small-molecule inhibitors have been described. Here, we identify MKV3 as a small molecule inhibitor of Cu-transporting P-type ATPases that targets a conserved Cu + entry site to the translocation pathway. In silico docking against the Xenopus ATP7B structure revealed a highly conserved pocket suitable for pharmacological inhibition. MKV3 bound human ATP7A and ATP7B with nanomolar affinity, competed with N-terminal metal-binding domains for access to the Cu + entry site, and selectively inhibited Escherichia coli CopA ATPase activity and Cu + transport. Mechanistically, MKV3 blocked chaperone-mediated Cu + delivery to the intramembranous CPC site of CopA that is essential for its transport function. We further identified a single charged P-domain residue that governed MKV3 affinity and potency across species. Functionally, MKV3 phenocopied the genetic loss of Cu + -ATPases in bacteria, fungi, plants, zebrafish, and mammals, impairing copper-dependent enzymes, transporter trafficking, and copper tolerance. These findings establish a conserved, druggable vulnerability in Cu + -ATPases and introduce MKV3 as a broadly active chemical tool to modulate copper homeostasis across biological kingdoms.

Transcriptomic changes in tomato brown rugose fruit virus-infected tomato in response to low-dose gamma irradiation

Ecological stability through nonlinear fluctuations and the portfolio effect

Much ecological theory has pursued understanding the mechanisms that stabilize communities, yet empirical analyses reveal deterministic nonlinear dynamics such as oscillations and chaos to be widespread in free-living populations. How then does stability emerge in ecosystems when the building blocks are unstable? We analyzed the extent to which deterministic nonlinear fluctuations produce the ecological stability gained via portfolio effects in globally important sockeye salmon ( Oncorhynchus nerka ) stock complexes from Bristol Bay and the Fraser River. Using empirical dynamic modeling of 27 populations spanning six decades, we show that stability emerges at the regional scale not despite, but specifically because constituent populations are highly nonlinear and orbit a shared attractor asynchronously. This asynchrony produced the uncorrelated fluctuations that underpin the portfolio effect and deterministic nonlinearity was the main source of variation, with attractor reconstruction accounting for 81 to 89% of the variance in annual sockeye recruitment in Bristol Bay and 61 to 78% in the Fraser River. Furthermore, local population dynamics were primarily chaotic, but when aggregated at the regional scale where commercial fisheries and some predators operate, the dynamics stabilized and interannual variability decreased by 47%. These results indicate that portfolio effects can transform locally unstable dynamics into stable outcomes at higher levels of aggregation, and that deterministic nonlinear dynamics rather than strong linear stochastic forcing produce the variation that portfolio effects act upon. Given the ubiquity of nonlinearity, the averaging of uncorrelated fluctuations produced by asynchronous nonlinear dynamics may be an underappreciated mechanism driving stability in ecosystems.

Viral pneumonia detection during the COVID-19 pandemic using deep learning and DCGAN-based data augmentation

NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is one of the most common cancers worldwide, representing 90% of malignant lymphomas. NHL is a diverse group of malignancies, and a subset of these lymphomas are caused by infection with the human gammaherpesvirus, Epstein–Barr virus (EBV). Many EBV-positive lymphomas are highly aggressive and rapidly develop resistance to treatment, leading to poor patient outcomes. Here, we identify the cellular kinase, NEK2, as a therapeutic target for EBV-positive NHL. We demonstrate NEK2 protein expression is increased in primary lymphocytes following EBV infection, and that the EBV latency proteins EBNA1, LMP1, and EBNA2 each independently drive NEK2 upregulation. We show NEK2 is necessary for the growth and survival of EBV-positive NHL, and that NEK2 inhibition selectively kills lymphoma cells but not normal lymphocytes. Inhibition of NEK2 resulted in EBV-specific inflammatory cell death characterized by reactive oxygen species accumulation and gasdermin D cleavage. Additionally, expression of the EBV oncoprotein, LMP1, and the cellular oncoprotein, c-myc, were decreased following NEK2 inhibition. Furthermore, we demonstrate multidrug resistance-associated protein 1 (MRP1) is the most active drug resistance transporter protein in EBV-positive NHL. NEK2 inhibition reduced the expression and activity of cellular drug resistance transporter proteins, including MRP1, leading to increased lymphoma cell chemosensitivity. Finally, using a humanized mouse model of EBV-driven lymphomagenesis, we demonstrate NEK2 inhibition significantly decreased tumor burden and tumor incidence while prolonging survival. Taken together, our data suggest NEK2 inhibition as a promising therapeutic strategy for EBV-positive NHL.

Expired fexofenadine hydrochloride acts as a high-performance sustainable corrosion inhibitor for copper in MSF desalination applications

The Antarctic Treaty System needs a disaster management authority to guard the continent against disasters

Loss masking-based gradient optimisation: A new approach for training supervised biomedical named entity recognition models using multi-dataset

Cross-individual translation of spontaneous zebrafish brain activity through a shared latent representation

Spontaneous activity is a hallmark of brain function, reflecting the underlying circuit organization. Identifying conserved structure across individuals in this self-sustained activity has remained a longstanding challenge, especially in vertebrates where one-to-one neuron correspondence is inaccessible. Here, we introduce latent-aligned Restricted Boltzmann Machines (LaRBMs), an unsupervised generative approach that uncovers a common representational space from cell-resolved whole-brain recordings in larval zebrafish. This latent space consists of spatially localized coactivation motifs, or cell assemblies, that generalize across animals and form interpretable building blocks of population-wide activity. LaRBMs enable bidirectional mapping of instantaneous whole-brain activity patterns between individuals: Activity patterns from one fish can be encoded into the latent space and decoded into another. The translated patterns are assigned high probability by the recipient model and retain the original spatial organization. These results show that spontaneous activity in the vertebrate brain is highly stereotyped at the level of functional cell assemblies and can be reliably captured through a common latent code. Because it provides an interpretable and quantitative framework for functional cross-individual alignment, LaRBM paves the way for comparative phenotyping of brain activity across developmental, genetic, and pathological variation.

Investigation of FGM patch repairs for cracked aluminum structures: J-integral analysis

Data-driven particle dynamics: Structure-preserving coarse-graining for emergent behavior in nonequilibrium systems

Multiscale systems are ubiquitous in science and technology, but are notoriously challenging to simulate as short spatiotemporal scales must be appropriately linked to emergent bulk physics. When expensive high-dimensional dynamical systems are coarse-grained into low-dimensional models, the entropic loss of information leads to emergent physics which are dissipative, history-dependent, and stochastic. To machine learn coarse-grained dynamics from time-series observations of particle trajectories, we propose a framework using the metriplectic bracket formalism that preserves these properties by construction; most notably, the framework guarantees discrete notions of the first and second laws of thermodynamics, conservation of momentum, and a discrete fluctuation–dissipation balance crucial for capturing nonequilibrium statistics. We introduce the mathematical framework abstractly before specializing to a particle discretization. As labels are generally unavailable for entropic state variables, we introduce a self-supervised learning strategy to identify emergent structural variables. We validate the method on benchmark systems and demonstrate its utility on two challenging examples: 1) coarse-graining star polymers at challenging levels of coarse-graining while preserving nonequilibrium statistics, and 2) learning models from high-speed video of colloidal suspensions that capture coupling between local rearrangement events and emergent stochastic dynamics. We provide open-source implementations in both PyTorch and LAMMPS, enabling large-scale inference and extensibility to diverse particle-based systems.

Study on the dynamic failure performance of bamboo fiber/high–density polyethylene composites with different fiber content using digital image correlation

Soft, skin-interfaced electronics enable cannula-free wireless monitoring of sleep respiration

Sleep-related breathing disorders are prevalent yet frequently underdiagnosed, in part due to limitations of conventional respiratory monitoring technologies. Standard nasal cannulas introduce airflow resistance, discomfort, and poor long-term adherence, constraining at-home and longitudinal assessment. Here, we report a soft, skin-interfaced nasal patch that enables cannula-free, wireless monitoring of respiratory activity during sleep. The device is constructed from ultrathin, elastomeric materials that conform to the nasal surface, coupling respiratory-induced tissue deformation to a strain-sensing element. The mechanics of the skin–device interface and the elastomeric response govern the sensitivity and linearity of signal transduction, enabling quantitative capture of breathing dynamics. An integrated wireless platform transmits deformation signals directly to mobile devices, eliminating the need for external tubing or tethered modules. Modular fabrication permits replacement of the strain sensor and skin-contact interface without compromising mechanical performance. Mechanical characterization under physiologically relevant deformation demonstrates high repeatability and low hysteresis, while in vivo studies confirm that the patch accurately reproduces respiratory waveforms and correlates closely with gold-standard nasal cannula measurements. By integrating soft materials mechanics, wearable strain sensing, and wireless electronics, this system provides a minimally obtrusive platform for continuous respiratory monitoring. The class of technologies presented in this work establishes design principles for skin-interfaced devices, in which elastomeric mechanics, strain transduction, and wireless integration combine to enable quantitative, unobtrusive physiological monitoring in clinical and home environments.

Spatial memory performance is associated with region-specific coordination of hippocampo-cortical sleep oscillations

<i>Wolbachia</i> -mediated viral transmission enhancement in insect vectors

The white-backed planthopper ( Sogatella furcifera ) serves as the vector for the southern rice black-streaked dwarf virus (SRBSDV), with varying transmission efficiencies across populations. This research identifies Wolbachia , a common insect symbiont, as a key facilitator in breaching the salivary gland barrier for SRBSDV, revealing a mechanism by which the virus exploits an insect symbiont for transmission. Through field and laboratory investigations, it was observed that high-transmission (HT) planthopper populations contained high levels of Wolbachia , while low-transmission (LT) populations had minimal titers. Experiments involving thoracic injections confirmed Wolbachia ’s specific role in infiltrating salivary glands, as SRBSDV was unable to colonize glands in Wolbachia -depleted insects despite being present systemically. Ultrastructural analysis showed Wolbachia enveloping SRBSDV particles within gland cells, further supported by molecular assays indicating a direct interaction between Wolbachia surface protein (WSP) and viral P8 capsid protein. Disruption of this interaction using anti-WSP antibodies reduced salivary gland viral load and transmission rates, underscoring its functional importance. These results contrast with Wolbachia ’s antiviral effects in mosquitoes, highlighting a context-dependent “hitchhiking” strategy for viral dissemination. The WSP–P8 interaction presents a specific target for inhibiting SRBSDV transmission without resorting to pesticides, proposing a symbiont-informed approach as a sustainable strategy against rice viral diseases.

Leveraging Leiden communities for enhanced collaborative filtering with matrix factorization techniques

Phospholipase D regulates on-membrane diffusivity of a myristoylated protein and defines the PIP3 patch territory

In living cells, the control of molecular diffusion is pivotal for highly fluidic membranes to serve as substrates for biochemical reactions and cytoskeletal assemblies. Lateral diffusion in membranes depends on a highly diverse and homeostatically controlled lipid composition. This complexity has limited our understanding of how diffusivity in biological membranes is regulated. In this study, we show that lipid diffusion in model membranes decreases markedly in the presence of cytosolic extracts. The reduction in lipid diffusivity can be pharmacologically inhibited by targeting phospholipase D (PLD). Conversely, lipid diffusivity was reduced when PLD alone was added to the membrane. Phosphatidic acid (PA), a direct product of PLD, diffuses slowly, and its presence reduces the diffusivity of surrounding lipids. Furthermore, we found that PLD controls the lateral diffusion of a myristoylated protein PKBR1 in Dictyostelium cells, possibly through auxiliary electrostatic interactions between cationic residues located near the lipidated tail and anionic phospholipids. In line with the role of PKBR1 in regulating phosphatidylinositol(3,4,5)-trisphosphates (PIP3), PLD overexpression suppressed the size and lifetime of PIP3 microdomains as well as the sensitivity of GPCR-mediated PIP3 elevation. Our results underscore the importance of PLD and its product PA as regulators of lipidated protein diffusivity, facilitating the dynamical lateral organization of phosphoinositides in the plasma membrane.

Data sharing and platform empowerment in vehicle–road–cloud integration: a prospect theory based evolutionary game analysis

QnAs with E. Dale Abel

Innovative silver-salicylic acid nanoparticle coatings based on CMC and chitosan for mango (Mangifera indica L. cv. “Fajri Klan”) fruit preservation

Abstract This research explores synthesis of silver-salicylic acid nanoparticles (AgNPs-SA) and their integration with carboxymethyl cellulose (CMC) to form CMC-AgNPs-SA and with chitosan to form Ch-AgNPs-SA. The effects of these composite materials were evaluated in terms of microbiological activity, storage performance, physicochemical attributes, and shelf-life extension of ‘Fajri Klan’ mangoes fruits at 13 °C. The synthesized AgNPs-SA was confirmed to be spherical, with sizes between 20.9 and 33.4 nm and a zeta potential of -20 mV. Additionally, CMC-AgNPs-SA, and Ch-AgNPs-SA demonstrated comparable antibacterial efficacy against Escherichia coli and Staphylococcus aureus . Over the storage period, cold-stored mangoes exhibited gradual increased in weight loss, respiration rate, and higher levels of total soluble solids (TSS), total sugars, and carotenoids. However, these changes were more pronounced in the uncoated samples (control). The application of CMC-AgNPs-SA and Ch-AgNPs-SA helped maintain fruit quality, suppressed decay, and extended shelf life. Although firmness and titratable acidity (TA) naturally declined with time, the coated mangoes retained these qualities better than the control group. Based on these findings, CMC-AgNPs-SA and Ch-AgNPs-SA show strong potential as effective coatings for preserving fruit quality and prolonging the storage duration of ‘Fajri Klan’ mangoes.