Search Results (542)

One major challenge in cellular neuroscience is to elucidate how the accurate alignment of presynaptic release sites with postsynaptic densely clustered ligand-gated ion channels at chemical synapses is achieved upon synapse assembly. The clustering of neurotransmitter receptors at postsynaptic sites is a key moment of synaptogenesis and determinant for effective synaptic transmission. The number of the ionotropic neurotransmitter receptors at these postsynaptic sites of both excitatory and inhibitory synapses is variable and is regulated by different mechanisms, thus allowing the modulation of synaptic strength, which is essential to tune neuronal network activity. Several well-regulated processes seem to be involved, including lateral diffusion within the plasma membrane and local anchoring as well as receptor endocytosis and recycling. The molecular mechanisms implicated are numerous and were reviewed recently in great detail. The role of pre-synaptically released neurotransmitters within the complex regulatory apparatus organizing the postsynaptic site underneath presynaptic terminals is not completely understood, even less for inhibitory synapses. In this mini review article, we focus on this aspect of synapse formation, summarizing and contrasting findings on the functional role of the neurotransmitters glycine and γ-aminobutyric acid (GABA) for initiation of postsynaptic receptor clustering and regulation of Cl⁻ channel receptor numbers at inhibitory synapses gathered over the last two decades. Full article

Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article

Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, receptor subtype, and species selectivity. Here, we systematically analyzed over 700 amino acid sequences of three-finger neurotoxins that interact with nicotinic acetylcholine receptors. Based on the amino acid residue substitutions in the functional sites and structural features of various classes of neurotoxins, we have classified them into over 150 distinct subgroups. Currently, only a small number of typical examples representing these subgroups have been studied for their structure, function, and subtype selectivity. The functional site residues responsible for their interaction with specific receptor subtypes of several toxins are yet to be identified. The molecular details of each subgroup representative toxin with its target receptor will contribute towards the understanding of subtype- and/or interface-selectivity. Thus, this review will provide new impetus in the toxin research and pave the way for the design of potent, selective ligands for nicotinic acetylcholine receptors. Full article

Mechanosensitive ion channels such as OSCA1.2 enable cells to sense and respond to mechanical forces by translating membrane tension into ionic flux. While lipid rearrangement in the inter-subunit cleft has been proposed as a key activation mechanism, the contributions of other domains to OSCA gating remain unresolved. Here, we combined the genetic encoding of the photoactivatable crosslinker p-benzoyl-L-phenylalanine (BzF) with functional Ca²⁺ imaging and molecular dynamics simulations to dissect the roles of specific residues in OSCA1.2 gating. Targeted UV-induced crosslinking at positions F22, H236, and R343 locked the channel in a non-conducting state, indicating their functional relevance. Structural analysis revealed that these residues are strategically positioned: F22 interacts with lipids near the activation gate, H236 lines the lipid-filled cavity, and R343 forms cross-subunit contacts. Together, these results support a model in which mechanical gating involves a distributed network of residues across multiple channel regions, allosterically converging on the activation gate. This study expands our understanding of mechanotransduction by revealing how distant structural elements contribute to force sensing in OSCA channels. Full article

Organic nonvolatile transistor memories (ONVMs) using a hybrid spiro [fluorene-9,7′-dibenzo [c, h] acridine]-5′-one (SFDBAO)/polystyrene (PS) film as bulk-heterojunction-like tunneling and trapping elements were fabricated. From the characterization of the 10% SFDBAO/PS based on ONVM, a sterically hindered small-molecule SFDBAO with rigid orthogonal configuration and a donor–acceptor (D-A) structure as a molecular-scale charge storage element demonstrated significantly higher charge trapping ability than other small-molecule materials such as C₆₀ and Alq₃. The ONVM based on 10% SFDBAO/PS presents ambipolar memory behaviors with a wide memory window (146 V), a fast-switching speed (20 ms), an excellent retention time (over 5 × 10⁴ s), and stable reversibility (36 cycles without any noticeable decay). By applying different gate voltages, the above ONVM shows reliable four-level data storage characteristics. The investigation demonstrates that the strategical bulk-heterojunction-like tunneling and trapping elements composed of small-molecule materials and polymers exhibit promising potential for high-performance ambipolar ONVMs. Full article

Saxitoxin (STX) is a potent toxin produced by marine dinoflagellates and freshwater or brackish water cyanobacteria, and is a member of the paralytic shellfish toxins (PSTs). As a highly specific blocker of voltage-gated sodium channels (NaVs), STX blocks sodium ion influx, thereby inhibiting nerve impulse transmission and leading to systemic physiological dysfunctions in the nervous, respiratory, cardiovascular, and digestive systems. Severe exposure can lead to paralysis, respiratory failure, and mortality. STX primarily enters the human body through the consumption of contaminated shellfish, posing a significant public health risk as the causative agent of paralytic shellfish poisoning (PSP). Beyond its acute toxicity, STX exerts cascading impacts on food safety, marine ecosystem integrity, and economic stability, particularly in regions affected by harmful algal blooms (HABs). Moreover, the complex molecular structure of STX—tricyclic skeleton and biguanide group—and its diverse analogs (more than 50 derivatives) have made it the focus of research on natural toxins. In this review, we traced the discovery history, chemical structure, molecular biosynthesis, biological enrichment mechanisms, and toxicological actions of STX. Moreover, we highlighted recent advancements in the potential for detection and treatment strategies of STX. By integrating multidisciplinary insights, this review aims to provide a holistic understanding of STX and to guide future research directions for its prevention, management, and potential applications. Full article

Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. Methods: Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein–protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). Results: Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. Conclusions: The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women. Full article

Polymers have a wide range of applications in materials science, chemistry, and biomedical domains. Conventional design methods for polymers are mostly event-oriented, directed by intuition, experience, and abstract insights. Nevertheless, they have been effectively utilized to determine several essential materials; these techniques are facing important challenges owing to the great requirement of original materials and the huge design area of organic polymers and molecules. Enhanced and inverse materials design is the best solution to these challenges. With developments in high-performing calculations, artificial intelligence (AI) (particularly Deep learning (DL) and Machine learning (ML))-aided materials design is developing as a promising tool to show development in various domains of materials science and engineering. Several ML and DL methods are established to perform well for polymer classification and detection presently. In this paper, we design and develop a Simplified Molecular Input Line Entry System Based Polymer Property Detection and Classification Using Pareto Optimization Algorithm (SMILES-PPDCPOA) model. This study presents a novel deep learning framework tailored for polymer property classification using SMILES input. By integrating a one-dimensional convolutional neural network (1DCNN) with a gated recurrent unit (GRU) and optimizing the model via Pareto Optimization, the SMILES-PPDCPOA model demonstrates superior classification accuracy and generalization. Unlike existing methods, our model is designed to capture both local substructures and long-range chemical dependencies, offering a scalable and domain-specific solution for polymer informatics. Furthermore, the proposed SMILES-PPDCPOA model executes a one-dimensional convolutional neural network and gated recurrent unit (1DCNN-GRU) technique for the classification process. Finally, the Pareto optimization algorithm (POA) adjusts the hyperparameter values of the 1DCNN-GRU algorithm optimally and results in greater classification performance. Results on a benchmark dataset show that SMILES-PPDCPOA achieves an average classification accuracy of 98.66% (70% Training, 30% Testing) across eight polymer property classes, with high precision and recall metrics. Additionally, it demonstrates superior computational efficiency, completing tasks in 4.97 s, outperforming other established methods such as GCN-LR and ECFP-NN. The experimental validation highlights the potential of SMILES-PPDCPOA in polymer property classification, making it a promising approach for materials science and engineering. The simulation result highlighted the improvement of the SMILES-PPDCPOA system when compared to other existing techniques. Full article

We present a scalable and resource-aware framework for the quantum simulation of large proteins, grounded in systematic molecular fragmentation, analytical Toffoli gate modeling, and empirical validation. The ground-state energy of a target biomolecule is reconstructed from capped amino acid fragments, with fixed corrections to account for artificial boundaries. Analytical cost estimates—derived from reduced Hamiltonians—are benchmarked against empirical Toffoli counts using PennyLane’s resource estimation module. Our model maintains predictive accuracy across biologically relevant systems of up to 1852 electrons, capturing consistent patterns across diverse fragments. This framework enables early-stage feasibility assessments for achieving quantum advantage in biochemical simulation pipelines. Full article

TRPA1 (Transient Receptor Potential Ankyrin 1), a cation channel predominantly expressed in sensory neurons, plays a critical role in detecting noxious stimuli and mediating pain signal transmission. As a key player in nociceptive signaling pathways, TRPA1 has emerged as a promising therapeutic target for the development of novel analgesics. Crotalphine (CRP), a 14-amino acid peptide, has been demonstrated to specifically activate TRPA1 and elicit potent analgesic effects. Previous cryo-EM (cryo-electron microscopy) studies have elucidated the structural mechanisms of TRPA1 activation by small-molecule agonists, such as iodoacetamide (IA), through covalent modification of N-terminal cysteine residues. However, the molecular interactions between TRPA1 and peptide ligands, including crotalphine, remain unclear. Here, we present the cryo-EM structure of ligand-free human TRPA1 consistent with the literature, as well as TRPA1 complexed with crotalphine, with resolutions of 3.1 Å and 3.8 Å, respectively. Through a combination of single-particle cryo-EM studies, patch-clamp electrophysiology, and microscale thermophoresis (MST), we have identified the cysteine residue at position 621 (Cys621) within the TRPA1 ion channel as the primary binding site for crotalphine. Upon binding to the reactive pocket containing C621, crotalphine induces rotational and translational movements of the transmembrane domain. This allosteric modulation coordinately dilates both the upper and lower gates, facilitating ion permeation. Full article

The axon initial segment (AIS) is a specialized subcellular domain that plays an essential role in action potential initiation and the diffusion barrier. A key organizer of the AIS is Ankyrin-G, a scaffolding protein responsible for clustering voltage-gated ion channels, cell adhesion molecules (CAMs), and cytoskeletal components at this critical neuronal domain. Recent proteomic analyses have revealed a complex network of proteins in the AIS, emphasizing Ankyrin-G’s central role in its molecular architecture. This review discusses new findings in the study of AIS-associated proteins. It explains how Ankyrin-G and its binding partners (such as ion channels, CAMs, spectrins, actin, and microtubule-associated proteins including end-binding protein 3, tripartite motif-containing protein 46, and calmodulin-regulated spectrin-associated protein 2) organize their structure. Understanding the dynamic regulation and molecular interactions within the AIS offers insights into neuronal excitability and reveals potential therapeutic targets for axonal dysfunction–related diseases. Through these dynamic interactions, Ankyrin-G ensures the proper alignment and dense clustering of key channel complexes, thereby maintaining the AIS’s distinctive molecular and functional identity. By further unraveling the complexity of Ankyrin-G’s interactome, our understanding of AIS formation, maintenance, and plasticity will be considerably enhanced, contributing to the elucidation of the pathogenesis of neurological and neuropsychiatric disorders. Full article

Anesthesia is a cornerstone of modern medicine, enabling surgery, pain management, and critical care. Despite its widespread use, the precise molecular mechanisms of anesthetic action remain incompletely understood. Recent advancements in structural biology, including cryo-electron microscopy (Cryo-EM), X-ray crystallography, and computational modeling, have provided high-resolution insights into anesthetic–target interactions. This review examines key molecular targets, including GABA_A receptors, NMDA receptors, two-pore-domain potassium (K2P) channels (e.g., TREK-1), and voltage-gated sodium (Nav) channels. General anesthetics modulate GABA_A and NMDA receptors, affecting inhibitory and excitatory neurotransmission, while local anesthetics primarily block Nav channels, preventing action potential propagation. Structural studies have elucidated anesthetic binding sites and gating mechanisms, providing a foundation for drug optimization. Advances in computational drug design and AI-assisted modeling have accelerated the development of safer, more selective anesthetics, paving the way for precision anesthesia. Future research aims to develop receptor-subtype-specific anesthetics, Nav1.7-selective local anesthetics, and investigate the neural mechanisms of anesthesia-induced unconsciousness and postoperative cognitive dysfunction (POCD). By integrating structural biology, AI-driven drug discovery, and neuroscience, anesthesia research is evolving toward safer, more effective, and personalized strategies, enhancing clinical outcomes and patient safety. Full article

Neuropathic pain is a chronic and debilitating disorder of the somatosensory system that affects a significant proportion of the population and is characterized by abnormal responses such as hyperalgesia and allodynia. Voltage-gated ion channels, including sodium (Na_V), calcium (Ca_V), and potassium (K_V) channels, play a pivotal role in modulating neuronal excitability and pain signal transmission following nerve injury. This review intends to provide a comprehensive analysis of the molecular and cellular mechanisms by which dysregulation in the expression, localization, and function of specific Na_V channel subtypes (mainly Na_V1.7 and Na_V1.8) and their auxiliary subunits contributes to aberrant neuronal activation, the generation of ectopic discharges, and sensitization in neuropathic pain. Likewise, special emphasis is placed on the crucial role of Ca_V channels, particularly Ca_V2.2 and the auxiliary subunit Ca_Vα₂δ, whose overexpression increases calcium influx, neurotransmitter release, and neuronal hyperexcitability, thus maintaining persistent pain states. Furthermore, K_V channels (particularly K_V7 channels) function as brakes on neuronal excitability, and their dysregulation facilitates the development and maintenance of neuropathic pain. Therefore, targeting specific K_V channel subtypes to restore their function is also a promising therapeutic strategy for alleviating neuropathic pain symptoms. On the other hand, recent advances in the development of small molecules as selective modulators or inhibitors targeting voltage-gated ion channels are also discussed. These agents have improved efficacy and safety profiles in preclinical and clinical studies by attenuating pathophysiological channel activity and restoring neuronal function. This review seeks to contribute to guiding future research and drug development toward more effective mechanism-based treatments by discussing the molecular mechanisms underlying neuropathic pain and highlighting translational therapeutic opportunities. Full article

Our first-principles calculations have unveiled a profound influence of varied external charges on the energy levels and spin distributions of zero-, one-, and two-dimensional carbon nanomaterials. By leveraging the Fermi distribution formula, we systematically analyze the temperature-dependent electron occupancy probabilities of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Notably, configurations with specific additional electron loads exhibit a stable total occupancy of HOMO + LUMO equal to 1 across a wide temperature range, forming a robust basis for orbital qubits. This stability persists even under Fermi energy corrections, demonstrating minimal temperature sensitivity up to 300 K. Furthermore, we identify a universal criterion—E_HOMO + E_LUMO = 2E_Fermi—that governs qubit feasibility across diverse carbon nanostructures, independent of dimensionality or atom count. Experimental validation via charge injection methods (e.g., gate modulation or electron beam irradiation) is supported by existing precedents in carbon-based quantum devices. Our findings establish low-dimensional carbon nanomaterials as versatile, scalable platforms for quantum computing, combining thermal stability and dimensional adaptability, thus bridging theoretical insights with practical quantum engineering. Full article

Desulfovibrio vulgaris is an anaerobic microorganism belonging to the group of sulphate-reducing bacteria (SRB). SRB form biofilms on metal surfaces in water supply networks, producing a microbiologically influenced corrosion (MIC). This process produces the deterioration of metal surfaces, leading to high economic costs and different environmental safety and health problems related to its chemical treatment. For that reason, rapid and accurate detection methods of SRB are needed. In this work, a new detection system for Desulfovibrio has been developed using gated nanoporous materials. The probe is based on hybrid nanoporous alumina films encapsulating a fluorescent molecule (rhodamine B), whose release is controlled by an oligonucleotide gate. Upon exposure to Desulfovibrio’s genomic material, a movement of the oligonucleotide gatekeeper happens, resulting in the selective delivery of the entrapped rhodamine B. The developed material shows high selectivity and sensitivity for detecting Desulfovibrio DNA in aqueous buffer and biological media. The implementation of this technology for the detection of Desulfovibrio as a tool for monitoring water supply networks is innovative and allows real-time in situ monitoring, making it possible to detect the growth of Desulfovibrio inside of pipes at an early stage and perform timely interventions to reverse it. Full article