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Exercise training and Silymarin consumption can ameliorate mitophagy signaling flux in hepatocytes of rats with dexamethasone-induced non-alcoholic fatty liver disease
Design, fabrication, and optical imaging performance comparison of precision microlens arrays for application in plenoptic microscopy systems
Global conformation of the Rag GTPase heterodimer governs eukaryotic amino acid sensing
The Rag GTPase heterodimer is a central mediator of amino acid sensing in eukaryotic cells. When amino acids are abundant, it binds to the mechanistic target of rapamycin complex 1 to activate cellular programs for growth and proliferation. In its functional cycle, besides local conformational changes near the nucleotides that are commonly observed in monomeric signaling GTPases, the relative positioning of the two Rag subunits, i.e., the global conformation, is unique due to the heterodimeric architecture. Although various global conformations have been captured in static structural models, dynamic transitions between these conformations and their biological relevance remain unclear. Here, we visualize the global conformation of the Rag GTPase heterodimer using single-molecule Förster resonance energy transfer. By tracking the movement of individual protein molecules, we found that the two subunits explore a wide conformational space, which is strictly dictated by the bound nucleotides, regulators, and mutations. Additionally, we demonstrate that proper modulation of the global conformation is crucial for correctly interpreting amino acid signals. Our results defined a checkpoint of amino acid sensing in eukaryotic cells.
Single-cell and bulk transcriptomics uncovers PRKD2-driven tumor stemness and progression in multiple myeloma
Evaluation of seven fermentation methods for enhancing the fertilizer potential of the liquid fraction of cow manure
Profile of Jean-Philippe Avouac
Jean-Philippe Avouac, elected to the National Academy of Sciences in 2025, explores deformations in Earth’s surface in an effort to understand the formation and behavior of earthquakes. Using geology, satellite data, radar imagery, and modeling, Avouac has characterized the strain along the Himalayan Arc and at other faults. In his Inaugural Article, Avouac characterizes the magnitude 7.7 earthquake along the Sagaing fault in Myanmar in 2025. The enormous 510 km rupture traversed a section of the fault assumed to be under strain since it had not erupted since 1839. However, the rupture also included sections of the fault that were not part of this seismic gap.
Cinnamaldehyde as a dietary modulator of gut microbiota and growth in broilers under low-protein feeding conditions
Exploring the antimicrobial potential from various parts of Ziziphus mauritiana Lam.
Correction for Bassiouni et al., Observed declines in leaf nitrogen explained by photosynthetic acclimation to CO <sub>2</sub>
Formation of few-electron triple quantum dots in ZnO heterostructures
Abstract In recent years, advancements in semiconductor manufacturing technology have enabled the formation of high-quality, high-mobility two-dimensional electron gases in zinc oxide (ZnO) heterostructures, making the electrostatic formation of quantum dots possible. ZnO, with its low natural abundance of isotopes possessing nuclear spin and its direct band gap, is considered a potentially suitable material for quantum bit applications. In this study, we achieve the formation of triple quantum dots and the realization of a few-electron state in ZnO heterostructure devices. We also confirm that by varying the gate voltage between the quantum dots, it is possible to control the interdot coupling. Additionally, we observe a tunneling phenomenon called a quantum cellular automata effect, where multiple electrons move simultaneously, which is not seen in single or double quantum dots, due to Coulomb interactions. Our results demonstrate that ZnO nanostructures have reached a level where they can function as controllable multiple quantum dot systems.
Synergistic effect of the next generation insecticide flupyradifurone with a fungal pathogen in the ant Lasius niger
Abstract Pesticides are important drivers of global insect declines, and their detrimental effects can be amplified by synergistic interactions with other stressors. While there is growing evidence of adverse impacts of the next-generation insecticide flupyradifurone (FPF) on pollinators, its effects on other insects and interactions with other stressors remain poorly understood. We investigated the effects of chronic exposure to a range of FPF concentrations, alone and in combination with the entomopathogenic fungus Metarhizium brunneum , in the non-target ant species Lasius niger . Twenty-day exposure to FPF concentrations ≥ 100 ppm significantly increased worker mortality, whereas lower concentrations (≤ 50 ppm) had no direct lethal effect. Furthermore, worker survival following acute exposure to M. brunneum was altered by prior pesticide exposure: compared to unexposed controls (0 ppm), workers exposed to sublethal FPF concentrations (5 and 50 ppm) for 10 days before fungal challenge were more susceptible to infection, with hazard ratios for fungal-induced mortality rising from 1.69 in controls to more than 3.5 in pesticide-exposed individuals. This demonstrates an indirect sublethal effect of FPF via synergy with the pathogen, raising further concerns about the environmental impact of novel pesticides and their implications for insect conservation.
Substrate-dependent activation of LONP1 informs on proteolytic regulation and ATPase motor function
AAA+ enzymes use energy from ATP hydrolysis to remodel diverse cellular targets. Structures of substrate-bound AAA+ complexes suggest that these enzymes employ a conserved hand-over-hand mechanism to thread substrates through their central pore. However, the fundamental aspects of the mechanisms governing motor function and substrate processing within specific AAA+ families remain unresolved. We used cryoelectron microscopy to structurally interrogate reaction intermediates from in vitro biochemical assays to inform the underlying regulatory mechanisms of the human mitochondrial AAA+ protease, LONP1. Our results demonstrate that substrate binding, rather than nucleotide binding, activates the assembly and allosterically regulates proteolytic activity. The N-terminal domain plays a critical role in this process and facilitates the initial stages of substrate selection and engagement. Moreover, structures of LONP1 actively degrading a substrate in the presence of ATP provide important context to the conventional understanding of the hand-over-hand translocation mechanism, suggesting that ATP hydrolysis is likely not limited to a single position in the right-handed spiral during the hand-over-hand translocation mechanism.
Safety evaluation of etrasimod for ulcerative colitis based on the FAERS database
In the wake of wildfires, toxic smoke is a lasting health concern
Enhancing the solubility of celecoxib via lyophilized solid dispersions using computational and experimental approaches
Correction for Bonetti et al., Decoding the elite soccer player’s psychological profile
Purification and biochemical characterization of l-glutaminase from Aspergillus oryzae with potential biotechnological applications in synthesis of l-theanine and as antitumor agent
Abstract Fungal glutaminase is of great importance in different industries fields. Thus, searching for a significantly catalytic l -glutaminase (Glut) with appraising its biochemical properties and biotechnological applications are the main purposes of this work. The Glut from Aspergillus oryzae was purified with a specific activity 258.33 (U/mg of protein), 215-fold and 36.47% yield. The molecular weight of the purified enzyme was 65 kDa. The purified enzyme exhibited remarkably improved resistance toward higher temperature in the presence of an exogenous trehalose. The enzyme had a greater affinity towards l -glutamine, l -cysteine, l -proline and l -lysine than l -valine, and l -glycine. The essentiality of arginine, tryptophan, histidine, and cysteine residues in the catalysis process of l -glutaminase was determined. The application of biocatalyst in the reaction mixture has not only remarkably increased l -theanine concentration but also has enhanced glutamic acid production in the presence of 10% compared with 15% NaCl. The deamidation of water insoluble Zea or rice glutelin was approximately 65% and 83% after 44 h by the enzymatic treatment. The purified Glut displayed remarkable antitumor activities against lung (A549), liver (HepG2) and human breast (MCF-7) carcinoma. Thus, l -Glut from A. oryzae has the potential to be used in food application and in treatment of various cancer cells.
Mitotic recombination events and single-base mutations induced by ultraviolet light in G1-arrested yeast cells
Ultraviolet light (UV) is a potent inducer of both single-base mutations and mitotic recombination. Although these genomic alterations are often attributed to the action of error-prone DNA polymerases on UV-induced DNA lesions during replicative DNA synthesis, UV damage can also result in mutagenic and recombinogenic DNA damage in nondividing cells. We examined the effects of UV on cells of the yeast Saccharomyces cerevisiae arrested in G 1 of the cell cycle. By mating an irradiated haploid with an unirradiated haploid, we found that recombination was initiated only on the irradiated chromosome. This result indicates that trans effects of UV on recombination (for example, induction of recombinogenic proteins stimulating DNA breaks on the unirradiated homolog) are small or negligible. In addition, we show that most of the UV-induced mutations produced in G 1 -irradiated cells result in mutations at identical positions in both strands of the duplex. As observed for recombination events, mutations are almost exclusively on the irradiated chromosome, indicating the near absence of a trans effect on mutations.
A mechatronic shirt kit to enhance psychomotor and life skills in autistic children: a pilot study
Abstract Training autistic children has become a global challenge, as the number of children diagnosed with it is increasing drastically. The conventional therapies to train autistic children have their own limitations. Technology-enabled training kits can be developed to help impart psychomotor skills to these children. Studies have reported that robot or robot-like features attract autistic children. Taking this as a leverage, in this work, a mechatronic kit has been developed to impart psychomotor and cognitive skills that are useful in day-to-day activities, especially when wearing a shirt. The psychomotor skills addressed are pincer grasp, elbow movement and hand-eye coordination, while the cognitive skills addressed are identification of shirt, colour identification and matching. Pilot trials have been conducted with seven autistic children to study how useful the kit is in imparting the targeted skills. The trials consisted of pre-assessment, training, and post-assessment sessions, having 15 tasks spanning over 7 sessions and 68 trials. After the training, from pre-assessment to post-assessment, an improvement of around 80% has been observed in the Daily Life Skills (DLS) of connecting the shirt with velcros and its associated psychomotor skills.