Browse Articles
Discover research articles across all indexed journals
Power quality optimization framework for three phase microgrids with grid tied solar PV and battery storage under nonlinear loads
Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily
Abstract The synaptic vesicle glycoprotein 2A (SV2A), a member of the major facilitator superfamily (MFS), is a key target for antiseizure medications and a biomarker for synaptic density imaging. Despite its clinical importance, the mechanisms underlying SV2A ligand binding and modulation remain poorly understood. Here, we report sub-3 Å resolution cryo-electron microscopy (cryo-EM) structures of human SV2A in its apo form and in complex with FDA-approved antiseizure medication levetiracetam; PET imaging tracer UCB-J; experimental antiseizure drug padsevonil; and allosteric modulator UCB1244283. We find that levetiracetam and UCB-J induce vestibule occlusion, a hallmark conformational transition of MFS transporters that had not been observed in previous SV2A structures. UCB1244283 binds to an allosteric site and enhances orthosteric ligand engagement by stabilizing the occluded state and slowing ligand dissociation. Notably, padsevonil occupies both orthosteric and allosteric sites, functionally precluding modulation. These findings uncover an allosteric mechanism of regulation and provide a structural framework for the development of modulators targeting SV2A and related MFS transporters.
Differential blood DNA methylation loci between Native Hawaiian and White women are associated with dietary patterns and metabolic biomarkers
Biodiversity benefits of China’s 20-year efforts in forest restoration
Revealing intracochlear microtrauma during cochlear implantation using optical coherence tomography and electrochemical sensing
The claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex
Abstract The claustrum is a densely interconnected structure involved in cognitive functions, but its influence on prefrontal circuits remains unclear. We conducted two-photon calcium imaging to assess mice dorsal prefrontal cortex (dPFC) cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons — sensory responsive, opto responsive, and opto-boosted cells—each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that claustrum stimulation increased single-cell variability while aligning average responses across neurons, thereby enhancing network homogeneity. During Pavlovian training, enhanced variability persisted, but homogeneity increased further, suggesting experience-dependent refinement. Finally, we performed claustrum axon silencing experiments which revealed that the claustrum may operate bidirectionally to maintain enhanced variability and homogeneity in the dPFC. These results highlight the crucial role of the claustrum in dynamically modulating dPFC activity, impacting both neuronal variability and network synchronization.
Stability analysis of reference genes in Maconellicoccus hirsutus across various conditions including dsRNA treatment
Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo
Abstract The selective autophagy receptor p62/SQSTM1 is known to form higher-order filaments in vitro and to undergo liquid-liquid phase separation when mixed with poly-ubiquitin. Here, we determine the full-length cryo-EM structure of p62 and elucidate a structured double helical filament scaffold composed of the PB1-domain associated with the flexible C-terminal part and the solvent-accessible major groove. At different pH values and upon binding to soluble LC3, LC3-conjugated membranes and poly-ubiquitin, we observe p62 filament re-arrangements in the form of structural unwinding, disassembly, lateral association and bundling, respectively. In the cellular environment, under conditions of ATG5 knockdown leading to stalled autophagy, we imaged high-contrast layers consisting of p62 oligomers enwrapping lipid droplets by cryogenic electron tomography in situ, which we identified as calcium as well as phosphorus by compositional spectroscopy analysis. Together, we visualize the cellular ultrastructure of p62 oligomers with high calcium content as a potential early stage of autophagy.
Co-incorporation of Chinese milk vetch and chemical fertilizers ameliorates chlorophyll content, nitrogen uptake and soil property favouring rice quality
Abiotic N2 reduction in submarine hydrothermal systems could quickly fertilize prebiotic oceans
Abstract NH 3 or NH 4 + is an essential component of the abiotic synthesis of organic compounds for the origin of life and an efficient greenhouse gas to address the faint young Sun paradox on the early Earth. Sustainable NH 3 or NH 4 + on the N 2 -dominated prebiotic Earth’s surface requires potent abiotic N 2 reduction (ANR) in hydrothermal systems, which has not been detected in the geological record despite numerous laboratory demonstrations. Here we report high concentrations and extreme 15 N depletions of NH 4 + in hydrothermal veins in oceanic crusts drilled from the South China Sea basin. Our data indicate that abundant 15 N-depleted NH 4 + was produced by ANR in deep fluid but progressively overprinted by 15 N-enriched biogenic NH 4 + toward the surface. Modeling suggests that ANR could supply up to 9.0 – 10.8×10 10 mol⋅year -1 NH 4 + to global oceans, which is minor to the large nitrogen inventory in modern oceans, but could quickly fertilize the oceans and supply NH 3 to the atmosphere in the prebiotic Earth.
Lineages to landscapes: mitogenomic insights and climate refugia informing proactive conservation of the endangered Tricarinate Hill Turtle (Melanochelys tricarinata) in the Indian subcontinent
Non-equilibrium plasma activated durable molybdenum oxycarbide electrocatalysts for acidic hydrogen evolution up to 10 A cm-2
Observation and prediction of bottom collapse and middle break phenomena in the blasting demolition of high chimneys
Visualizing intraorganellar ultrastructures, dynamics, and interactions with open-access background-free Lock-in-SIM
Abstract Structured illumination microscopy (SIM) is a powerful method for fast and gentle live-cell super-resolution imaging. However, its susceptibility to reconstruction artifacts from out-of-focus blur and background imposes substantial barriers to analyze the dynamics of densely packed volumetric intraorganellar ultrastructures that are typically in a size range of SIM’s spatial resolution. To address this limitation, we have developed Lock-in-SIM, an open-access two-dimensional SIM framework that eliminates background and maximizes the recovery of sub-diffraction information with the highest possible frequency extraction. By leveraging the intrinsic modulation differences of volumetric sample structures, Lock-in-SIM enables efficient optical sectioning, extends imaging depth, and improves data fidelity and quantifiability. We demonstrate the superiority of Lock-in-SIM by visualizing various challenging intraorganellar ultrastructures in live cells. Our investigations uncover mechanisms of mitochondrial fission and endoplasmic reticulum-lysosome interactions and provide insights into the intricate yet highly regulated structural remodeling of organelles.
Equitable colorectal cancer screening implementation framework via a modified Delphi Consensus for Romanian healthcare
Abstract Colorectal cancer (CRC) continues to be a predominant cause of cancer-related mortality on a global scale. Screening for early detection plays a crucial role in significantly reducing both incidence and mortality rates. However, screening uptake varies widely across regions due to disparities in healthcare resources and implementation of screening programs. The aim of this study was to evaluate various potential strategies for implementing an effective colorectal cancer screening program that enhances adherence. This program should be feasible and appropriate, considering the demographic characteristics, geographical distribution, and logistical factors, including human and material resources, of medical facilities at the national level in Romania. A multidisciplinary panel was convened using a modified Delphi process (two survey rounds and a consensus meeting in early 2022) to develop a harmonized CRC screening framework tailored to diverse healthcare settings. Clinicians and allied professionals from 19 countries (Europe, Asia, and Africa) contributed to the consensus recommendations for average-risk individuals. The panel advised that primary care physicians should play a central role in CRC risk assessment and patient engagement and endorsed initiating screening at age 45 and continuing to 75, with selective extension up to 85 for healthy, willing individuals. To improve participation, we recommended region-specific screening strategies that accommodate local resources and demographics and emphasized a patient-centered approach offering multiple modalities (colonoscopy, fecal immunochemical testing, CT colonography), emphasizing that the most effective test is one that patients are willing to complete. Finally, the study group deemed implementing a centralized system for screening invitations, result tracking, and patient recall essential. This consensus guideline provides a scalable model to enhance screening adherence and reduce CRC mortality through early detection and prevention. This framework is developed for the Romanian healthcare context, informed by international professional input but tailored to local healthcare infrastructure and estimated population needs.