Search Results (1,186)

Many years ago, asbestos fibers were banned and replaced by synthetic vitreous fibers because of their carcinogenicity. However, the toxicity of the latter fibers is still under debate, especially when it concerns the early fiber interactions with biological cell membranes. Here, we aimed to investigate the effects of a synthetic vitreous fiber named FAV173 on the Xenopus laevis oocyte membrane, the cell model we have already used to characterize the effect of crocidolite asbestos fiber exposure. Using an electrophysiological approach, we found that, similarly to crocidolite asbestos, FAV173 was able to stimulate a chloride outward current evoked by step membrane depolarizations, that was blocked by the potent and specific TMEM16A channel antagonist Ani9. Exposure to FAV173 fibers also altered the oocyte cell membrane microvilli morphology similarly to crocidolite fibers, most likely as a consequence of the TMEM16A protein interaction with actin. However, FAV173 only partially mimicked the crocidolite fibers effects, even at higher fiber suspension concentrations. As expected, the crocidolite fibers’ effect was more similar to that induced by the co-treatment with (Fe³⁺ + H₂O₂), since the iron content of asbestos fibers is known to trigger reactive oxygen species (ROS) production. Taken together, our findings suggest that FAV173 may be less harmful that crocidolite but not ineffective in altering cell membrane properties. Full article

Transition metal dichalcogenide (TMD) monolayers exhibit unique valleytronics properties due to the dependency of the coupled valley and spin state at the hexagonal corner of the first Brillouin zone. Precisely controlling valley spin-polarization via manipulating the electron population enables its application in valley-based memory or quantum technologies. This study uncovered the uncompensated spins of the antiferromagnetic nickel oxide (NiO) serving as the ferromagnetic (FM) order to induce valley spin-polarization in molybdenum disulfide (MoS₂) monolayers via the magnetic proximity effect (MPE). Spin-resolved photoluminescence spectroscopy (SR-PL) was employed to observe MoS₂, where the spin-polarized trions appear to be responsible for the MPE, leading to a valley magnetism. Results indicate that local FM order from the uncompensated surface of NiO could successfully induce significant valley spin-polarization in MoS₂ with the depolarization temperature approximately at 100 K, which is relatively high compared to the related literature. This study reveals new perspectives in that the precise control over the surface orientation of AFMs serves as a crystallographic switch to activate the MPE and the magnetic sustainability of the trion state is responsible for the observed valley spin-polarization with the increasing temperature, which promotes the potential of AFM materials in the field of exchange-coupled Van der Waals heterostructures. Full article

Transcranial electrical brain stimulation techniques like transcranial direct current (tDCS) and transcranial alternating current (tACS) have emerged as potential tools for treating neurological diseases by modulating cortical excitability. These techniques deliver small electric currents to the brain non-invasively through electrodes on the scalp. tDCS uses constant direct current which weakly alters the membrane voltage of cortical neurons, while tACS utilizes alternating current to target and enhance cortical oscillations, though the underlying mechanisms are not fully understood more specifically. To elucidate how tACS perturbs endogenous network dynamics, we simulated spiking neuron network models. We identified distinct roles of the depolarizing and hyperpolarizing phases in driving network activity towards and away from the strong nonlinearity provided by pyramidal neurons. Exploring resonance effects, we found matching tACS frequency to the network’s endogenous resonance frequency creates greater entrainment. Based on this, we developed an algorithm to determine the network’s endogenous frequency, phase, and amplitude, then deliver optimized tACS to entrain network oscillations. Together, these computational results provide mechanistic insight into the effects of tACS on network dynamics and could inform future closed-loop tACS systems that dynamically tune stimulation parameters to ongoing brain activity. Full article

The closed-loop control of pathological brain activity is a challenging task. In this study, we investigated the sensitivity of continuous epileptiform short discharge generation to electrical stimulation applied at different phases between the discharges using an in vitro 4-AP-based model of epilepsy in rat hippocampal slices. As a measure of stimulation effectiveness, we introduced a sensitivity function, which we then measured in experiments and analyzed with different biophysical and abstract mathematical models, namely, (i) the two-order subsystem of our previous Epileptor-2 model, describing short discharge generation governed by synaptic resource dynamics; (ii) a similar model governed by shunting conductance dynamics (Epileptor-2B); (iii) the stochastic leaky integrate-and-fire (LIF)-like model applied for the network; (iv) the LIF model with potassium M-channels (LIF+KM), belonging to Class II of excitability; and (v) the Epileptor-2B model with after-spike depolarization. A semi-analytic method was proposed for calculating the interspike interval (ISI) distribution and the sensitivity function in LIF and LIF+KM models, which provided parametric analysis. Sensitivity was found to increase with phase for all models except the last one. The Epileptor-2B model is favored over other models for subthreshold oscillations in the presence of large noise, based on the comparison of ISI statistics and sensitivity functions with experimental data. This study also emphasizes the stochastic nature of epileptiform discharge generation and the greater effectiveness of closed-loop stimulation in later phases of ISIs. Full article

Here, we report for the first time on the mechanisms of action of the essential oil of Ruta graveolens (REO) against the plant pathogen Colletotrichum gloeosporioides. In particular, the presence of REO drastically affected the morphology of hyphae by inducing changes in the cytoplasmic membrane, such as depolarization and changes in the fatty acid profile where straight-chain fatty acids (SCFAs) increased by up to 92.1%. In addition, REO induced changes in fungal metabolism and triggered apoptosis-like responses to cell death, such as DNA fragmentation and the accumulation of reactive oxygen species (ROS). The production of essential enzymes involved in fungal metabolism, such as acid phosphatase, β-galactosidase, β-glucosidase, and N-acetyl-β-glucosaminidase, was significantly reduced in the presence of REO. In addition, C. gloeosporioides activated naphthol-As-BI phosphohydrolase as a mechanism of response to REO stress. The data obtained here have shown that the essential oil of Ruta graveolens has a strong antifungal effect on C. gloeosporioides. Therefore, it has the potential to be used as a surface disinfectant and as a viable replacement for fungicides commonly used to treat anthracnose in the postharvest testing phase. Full article

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 kinase pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce the FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on the FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (I_Na) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak I_Na density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitor’s opposite effects on I_Na. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine, and GSK3 inhibitor XIII was also observed in long-term inactivation and use dependency of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome. Full article

With the help of electrochemical methods, including CV and EIS, the influence of methimazole, carbimazole, and the concentration of the supporting electrolyte on the kinetics and mechanism of zinc electroreduction on a mercury electrode was compared and analyzed. Moreover, molecular dynamics simulations of zinc/carbimazole and zinc/methimazole solutions were carried out to determine the effect of drugs on the hydration sphere of Zn²⁺ ions. It was shown that the electroreduction of Zn²⁺ in the presence of methimazole and carbimazole occurs in two steps and the first one determines the kinetics of the entire process. The presence of both drugs in the solution and the increase in the concentration of the supporting electrolyte reduce the degree of hydration of the depolarizer ions and the hydration of the electrode surface, what is a factor favoring the rate of electroreduction. Based on theoretical studies, the formation of stable complexes between Zn²⁺ and the molecules of both drugs in a solution was considered unlikely. However, active complexes can be formed between depolarizer ions and molecules adsorbed at the electrode surface. They constitute a bridge facilitating charge exchange during the electrode reaction, revealing the catalytic abilities of methimazole and carbimazole. In the range of c_drug ≤ 1 × 10⁻³ mol dm⁻³, carbimazole is a better catalyst, whereas in the range of c_drug ≥ 5 × 10⁻³ mol dm⁻³, it is methimazole. The effectiveness of both compounds in catalyzing the first stage of the electrode reaction increases with the increase in the NaClO₄ concentration. Full article

Monitoring the processes inside crystalline materials under their operating conditions is of great interest in optoelectronics and scientific instrumentation. Early defect detection ensures the proper functioning of multiple crystal-based devices. In this study, a combination of acoustic emission (AE) sensing and cross-polarization imaging is proposed for the fast characterization of the crystal’s structure. For the experiments, tellurium dioxide (TeO₂) crystal was chosen due to its wide use in acousto-optics. Studies were performed under uniaxial compression loading with a simultaneous acquisition of AE signals and four polarized optical images. An analysis of the temporal dependencies of the AE data and two-dimensional maps of the light depolarization features was carried out in order to establish quantitative criteria for irreversible damage initiation and crack-like defect formation. The obtained results reveal the polarization image patterns and the AE pulse duration alteration specific to these processes, and they open up new possibilities for non-destructively monitoring in real-time the structure of optically transparent crystals under their operating conditions. Full article

Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future. Full article

Gastric cancer prognosis is still notably poor despite efforts made to improve diagnosis and treatment of the disease. Chemotherapy based on platinum agents is generally used, regardless of the fact that drug toxicity leads to limited clinical efficacy. In order to overcome these problems, our group has been working on the synthesis and study of trans platinum (II) complexes. Here, we explore the potential use of two phosphine-based agents with the general formula trans-[Pt(amine)Cl₂(PPh₃)], called P1 and P2 (with dimethylamine or isopropylamine, respectively). A cytotoxicity analysis showed that P1 and especially P2 decrease cell viability. Specifically, P2 exhibits higher activity than cisplatin in gastric cancer cells while its toxicity in healthy cells is slightly lower. Both complexes generate Reactive Oxygen Species, produce DNA damage and mitochondrial membrane depolarization, and finally lead to induced apoptosis. Thus, an intrinsic apoptotic pathway emerges as the main type of cell death through the activation of BAX/BAK and BIM and the degradation of MCL1. Additionally, we demonstrate here that P2 produces endoplasmic reticulum stress and activates the Unfolded Protein Response, which also relates to the impairment observed in autophagy markers such as p62 and LC3. Although further studies in other biological models are needed, these results report the biomolecular mechanism of action of these Pt(II)-phosphine prototypes, thus highlighting their potential as novel and effective therapies. Full article

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABA_A channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP. Full article

Under rainy conditions, atmospheric settling particles have significant depolarization effects on radar waves and thus affect the target detection performance. This paper establishes an extended target detection model for fully polarized radar under complex rainy conditions and proposes two polarization and waveform optimization methods by taking into account the transmission effect of rainfall. If the rainfall information is known, the polarization and waveform for transmitting and receiving are optimized by maximizing the system Signal-to-Clutter/Noise Ratio (SCNR). While the rainfall information is absent, the optimal transmitting polarization and waveform are obtained by directly compensating the transmission effect from non-rainfall optimization results using fully polarized radar observation parameters. Using measured data from the T-72 tank, The experimental results verify the effectiveness and robustness of the two methods in real scenarios and 4 dB on the improvement of SCNR can be achieved. Full article

Sleep deprivation (SD) is a recognized risk factor for atrial fibrillation (AF), yet the precise molecular and electrophysiological mechanisms behind SD-induced AF are unclear. This study explores the electrical and structural changes that contribute to AF in chronic partial SD. We induced chronic partial SD in Wistar rats using a modified multiple-platform method. Echocardiography demonstrated impaired systolic and diastolic function in the left ventricle (LV) of the SD rats. The SD rats exhibited an elevated heart rate and a higher low-frequency to high-frequency ratio in a heart-rate variability analysis. Rapid transesophageal atrial pacing led to a higher incidence of AF and longer mean AF durations in the SD rats. Conventional microelectrode recordings showed accelerated pulmonary vein (PV) spontaneous activity in SD rats, along with a heightened occurrence of delayed after-depolarizations in the PV and left atrium (LA) induced by tachypacing and isoproterenol. A Western blot analysis showed reduced expression of G protein-coupled receptor kinase 2 (GRK2) in the LA of the SD rats. Chronic partial SD impairs LV function, promotes AF genesis, and increases PV and LA arrhythmogenesis, potentially attributed to sympathetic overactivity and reduced GRK2 expression. Targeting GRK2 signaling may offer promising therapeutic avenues for managing chronic partial SD-induced AF. Future investigations are mandatory to investigate the dose–response relationship between SD and AF genesis. Full article

Leveraging weather radar technology for environmental monitoring, particularly the detection of biometeors like birds, bats, and insects, presents a significant challenge due to the dynamic nature of their behavior. Unlike hydrometeor targets, biometeor targets exhibit arbitrary changes in direction and position, which significantly alter radar wave polarization upon scattering. This study addresses this challenge by introducing a novel methodology utilizing Rwanda’s C-Band Polarization Radar. Our approach exploits the capabilities of dual-polarization radar by analyzing parameters such as differential reflectivity (ZDR) and correlation coefficient (RHOHV) to derive the Depolarization Ratio (DR). While existing radar metrics offer valuable insights, they have limitations in fully capturing depolarization effects. To address this, we propose an advanced fuzzy logic algorithm (FL_DR) integrating the DR parameter. The FL_DR’s performance was rigorously evaluated against a standard FL algorithm. Leveraging a substantial dataset comprising nocturnal clear air radar echoes collected during a Fall Armyworm (FAW) outbreak in maize fields from September 2020 to January 2021, the FL_DR demonstrated a notable improvement in accuracy compared to the existing FL algorithm. This improvement is evident in the Fraction of Echoes Correctly Identified (FEI), which increased from 98.42% to 98.93% for biological radar echoes and from 87.02% to 95.81% for meteorological radar echoes. This enhanced detection capability positions FL_DR as a valuable system for monitoring, identification, and warning of environmental phenomena in regions similar to tropical areas facing FAW outbreaks. Additionally, it could be tested and further refined for other migrating biological targets such as birds, insects, or bats. Full article

The oral detection of sugars relies on two types of receptor systems. The first is the G-protein-coupled receptor TAS1R2/TAS1R3. When activated, this receptor triggers a downstream signaling cascade involving gustducin, phospholipase Cβ2 (PLCβ2), and transient receptor potential channel M5 (TRPM5). The second type of receptor is the glucose transporter. When glucose enters the cell via this transporter, it is metabolized to produce ATP. This ATP inhibits the opening of K_ATP channels, leading to cell depolarization. Beside these receptor systems, sweet-sensitive taste cells have mechanisms to regulate their sensitivity to sweet substances based on internal and external states of the body. Sweet taste receptors are not limited to the oral cavity; they are also present in extraoral organs such as the gastrointestinal tract, pancreas, and brain. These extraoral sweet receptors are involved in various functions, including glucose absorption, insulin release, sugar preference, and food intake, contributing to the maintenance of energy homeostasis. Additionally, sweet receptors may have unique roles in certain organs like the trachea and bone. This review summarizes past and recent studies on sweet receptor systems, exploring the molecular mechanisms and physiological functions of sweet (sugar) detection in both oral and extraoral organs. Full article