Search Results (69)

B-raf (rapidly accelerated fibrosarcoma) is a crucial player within the ERK/MAPK signaling pathway. In the CNS, B-raf has been implicated in neuronal differentiation, long-term memory, and major depression. Mice with forebrain neuron-specific B-raf knockout show behavioral deficits in spatial learning tasks and impaired hippocampal long-term potentiation (LTP). To elucidate the mechanism(s) underlying diminished synaptic plasticity in B-raf-deficient mice, we performed whole-cell recordings from CA1 pyramidal cells in hippocampal slices of control and B-raf mutant mice. We found that the NMDA/AMPA ratio of excitatory postsynaptic currents (EPSCs) at the Schaffer collateral—CA1 pyramidal cell synapses was significantly reduced in B-raf mutants, which would at least partially account for their impaired LTP. Interestingly, the reduced NMDA component of field postsynaptic potentials in mutant preparations was partially reinstated by blocking the apamin-sensitive small-conductance Ca²⁺-activated K⁺ (SK) channels, which have also been reported to modulate hippocampal LTP and learning tasks. To determine the impact of B-raf-dependent signaling on SK current, we isolated the apamin-sensitive tail current after a strong depolarizing event and found indeed a significantly bigger SK current in B-raf-deficient cells compared to controls, which is consistent with the reduced action potential firing and the stronger facilitating effect of apamin on CA1 somatic excitability in B-raf-mutant hippocampus. Our data suggest that B-raf signaling readjusts the delicate balance between NMDA receptors and SK channels to promote synaptic plasticity and facilitate hippocampal learning and memory. Full article

This study describes a quite special and interesting atmospheric event characterized by the simultaneous presence of fresh and aged smoke layers. These peculiar conditions occurred on 16 July 2024 at the CNR-IMAA atmospheric observatory (CIAO) in Potenza (Italy), and represent an ideal case for the evaluation of the impact of aging and transport mechanisms on both the optical and microphysical properties of biomass burning aerosol. The fresh smoke was originated by a local wildfire about 2 km from the measurement site and observed about one hour after its ignition. The other smoke layer was due to a wide wildfire occurring in Canada that, according to backward trajectory analysis, traveled for about 5–6 days before reaching the observatory. Synergetic use of lidar, ceilometer, radar, and microwave radiometer measurements revealed that particles from the local wildfire, located at about 3 km a.s.l., acted as condensation nuclei for cloud formation as a result of high humidity concentrations at this altitude range. Optical characterization of the fresh smoke layer based on Raman lidar measurements provided lidar ratio (LR) values of 46 ± 4 sr and 34 ± 3 sr, at 355 and 532 nm, respectively. The particle linear depolarization ratio (PLDR) at 532 nm was 0.067 ± 0.002, while backscatter-related Ångström exponent (AEβ) values were 1.21 ± 0.03, 1.23 ± 0.03, and 1.22 ± 0.04 in the spectral ranges of 355–532 nm, 355–1064 nm and 532–1064 nm, respectively. Microphysical inversion caused by these intensive optical parameters indicates a low contribution of black carbon (BC) and, despite their small size, particles remained outside the ultrafine range. Moreover, a combined use of CIAO remote sensing and in situ instrumentation shows that the particle properties are affected by humidity variations, thus suggesting a marked particle hygroscopic behavior. In contrast, the smoke plume from the Canadian wildfire traveled at altitudes between 6 and 8 km a.s.l., remaining unaffected by local humidity. Absorption in this case was higher, and, as observed in other aged wildfires, the LR at 532 nm was larger than that at 355 nm. Specifically, the LR at 355 nm was 55 ± 2 sr, while at 532 nm it was 82 ± 3 sr. The AEβ values were 1.77 ± 0.13 and 1.41 ± 0.07 at 355–532 nm and 532–1064 nm, respectively and the PLDR at 532 nm was 0.040 ± 0.003. Microphysical analysis suggests the presence of larger, yet much more absorbent particles. This analysis indicates that both optical and microphysical properties of smoke can vary significantly depending on its origin, persistence, and transport in the atmosphere. These factors that must be carefully incorporated into future climate models, especially considering the frequent occurrences of fire events worldwide. Full article

Aceclofenac (ACF), a non-steroidal anti-inflammatory drug, was obtained in its amorphous state by cooling from melt. The glass transition was investigated using dielectric and calorimetric techniques, namely, dielectric relaxation spectroscopy (DRS), thermally stimulated depolarization currents (TSDC), and conventional and temperature-modulated differential scanning calorimetry (DSC and TM-DSC). The dynamic behavior in both the glassy and supercooled liquid states revealed multiple relaxation processes. Well below the glass transition, DRS was able to resolve two secondary relaxations, γ and β, the latter of which was also detectable by TSDC. The kinetic parameters indicated that both processes are associated with localized motions within the molecule. The main (α) relaxation was clearly observed by DRS and TSDC, and results from both techniques confirmed a non-Arrhenian temperature dependence of the relaxation times. However, the glass transition temperature (T_g) extrapolated from DRS data significantly differed from that obtained via TSDC, which in turn showed reasonable agreement with the calorimetric T_g (T_g-DSC = 9.2 °C). The values of the fragility index calculated by the three experimental techniques converged in attributing the character of a moderately fragile glass former to ACF. Above the α relaxation, TSDC showed a well-defined peak. In DRS, after “removing” the high-conductivity contribution using ε’ derivative analysis, a peak with shape parameters α_HN = β_HN = 1 was also detected. The origin of these peaks, found in the full supercooled liquid state, has been discussed in the context of structural and dynamic heterogeneity. This is supported by significant differences observed between the FTIR spectra of the amorphous and crystalline samples, which are likely related to aggregation differences resulting from variations in the hydrogen bonds between the two phases. Additionally, the pronounced decoupling between translational and relaxational motions, as deduced from the low value of the fractional exponent x = 0.72, derived from the fractional Debye–Stokes–Einstein (FDSE) relationship, further supports this interpretation. Full article

Ba_0.75Ca_0.25TiO₃ ceramics were successfully synthesized by a simple solid-state reaction method. This study examined the influence of sintering temperature on the structure, microstructure, dielectric properties and electrical behavior of the material. The XRD analysis reveals that the tetragonal phase (P4mm) is dominant in all the synthesized materials, with those sintered at T = 1400 °C and T = 1450 °C being single-phase, while others exhibit a minor orthorhombic phase (Pbnm). Higher sintering temperatures promoted better grain boundary formation and larger grain sizes. The electric permittivity increased with temperature up to T = 1400 °C, followed by a sharp decline at T = 1450 °C. Additionally, the Curie temperature decreased with increasing sintering temperature, indicating changes in phase transition characteristics. Thermal analysis showed that higher sintering temperatures led to sharper heat capacity peaks, while pyroelectric and thermally stimulated depolarization currents were maximized at T = 1400 °C due to oxygen vacancies. These findings highlight the significant impact of sintering temperature on the material’s structural and functional properties. Full article

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC₅₀ = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior. Full article

We consider a two-group social conflict under the corporates’ research and development (R&D) business processes. Conflict participants are divided into two groups depending on their attitude to new ideas, technologies, and behavioral style for R&D creative problems—innovators and adapters. We reveal the contradiction that arises between the need to include both types of employees in one project team and their objectively antagonistic positions regarding the methods and approaches to R&D processes. The proposed research methodology is based on a modern post-non-classical paradigm formed on the principles of coherence, interdisciplinarity, openness, and nonlinearity, as well as a sociophysical approach to the social conflicts modeling. We use the general theories of magnetism, paramagnetism, and functions of P. Langevin and L. Brillouin to describe the dynamics of group participants’ preferences regarding the style of conflict behavior. The analogy of paramagnetism, consisting in the orienting effect of the magnetic field, is used to describe social groups interactions that have not only their own interests, but are also influenced by the opinions of opposite social groups. A two-dimensional, four-parameter map represents the dynamics of group conflict. Modeling results show that regardless of the initial states and with certain parameters of intra-group and intergroup interactions, the trajectories eventually converge to an attractor (limit cycle) in a two-dimensional space. No non-periodic or chaotic modes are identified in the two-group conflict, which determines the controllability of the described conflict. The results of the simulation experiments are used as decision support and contradictions resolution aimed at forming the required modes of the corporates’ research and development business processes and ensuring the group participants’ cohesion and depolarization. The results of testing the model at an industrial enterprise are presented. 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 strength of inhibitory neurotransmission depends on intracellular neuronal chloride concentration, primarily regulated by the activity of cation–chloride cotransporters NKCC1 (Sodium–Potassium–Chloride Cotransporter 1) and KCC2 (Potassium–Chloride Cotransporter 2). Brain-derived neurotrophic factor (BDNF) influences the functioning of these co-transporters. BDNF is synthesized from precursor proteins (proBDNF), which undergo proteolytic cleavage to yield mature BDNF (mBDNF). While previous studies have indicated the involvement of BDNF signaling in the activity of KCC2, its specific mechanisms are unclear. We investigated the interplay between both forms of BDNF and chloride homeostasis in rat hippocampal neurons and in utero electroporated cortices of rat pups, spanning the behavioral, cellular, and molecular levels. We found that both pro- and mBDNF play a comparable role in immature neurons by inhibiting the capacity of neurons to extrude chloride. Additionally, proBDNF increases the endocytosis of KCC2 while maintaining a depolarizing shift of E_GABA in maturing neurons. Behaviorally, proBDNF-electroporated rat pups in the somatosensory cortex exhibit sensory deficits, delayed huddling, and cliff avoidance. These findings emphasize the role of BDNF signaling in regulating chloride transport through the modulation of KCC2. In summary, this study provides valuable insights into the intricate interplay between BDNF, chloride homeostasis, and inhibitory synaptic transmission, shedding light on the underlying cellular mechanisms involved. Full article

The beneficial effects of lanthanide incorporation into 0.94Na_0.5Bi_0.5TiO₃-0.06BaTiO₃ (BNT-BT) matrix on its functional properties were investigated. The conventional solid-state method was used for synthesizing samples. The structural refinement revealed that all samples crystallized in R3c rhombohedral symmetry. Raman spectroscopy study was carried out using green laser excitation and revealed that no clear perceptible variation in frequency is observed. Dielectric measurements unveiled that the introduction of rare earth obstructed the depolarization temperature promoted in BNT-BT, the diffusive phase transition decreasing with increasing lanthanide size. Only dysprosium addition showed comparable diffusion constant and dielectric behavior as the unmodified composition. Further, the comparison of the obtained ferroelectric hysteresis and strain-electric field loops revealed that only Dy-phase exhibited interesting properties comparing parent composition. In addition, the incorporation of lanthanides Ln³⁺ into the BNT-BT matrix led to the development of luminescence characteristics in the visible and near infrared regions, depending on the excitation wavelengths. The simultaneous occurrence of photoluminescence and ferroelectric/piezoelectric properties opens up possibilities for BNT-BT-Ln to exhibit multifunctionality in a wide range of applications. Full article

The matrix material used in this paper was low-density polyethene (LDPE), and the added particles selected were silicon oxide (SiO₂) particles and montmorillonite (MMT) particles. The sizes of the SiO₂ particles were 1 µm, 30 nm, and 100 nm, respectively; three kinds of SiO₂/MMT/LDPE multi-component composites were prepared based on MMT/LDPE composites doped with MMT particles. The effect of the SiO₂ particle size on the crystallization behavior and space charge properties of SiO₂/MMT/LDPE composites was studied. The crystalline behaviors and crystallinity of the materials were analyzed. At the same time, the changes in the relative dielectric constant ε_r and loss factor tanδ for each material with the influence of frequency were studied, and the space charge accumulation, residual characteristics, and apparent charge mobility of each material were explored. The results show that the smaller the size of the added particles, the smaller the grain size and the clearer the grain outline for the multi-composite material. After adding 30 nm SiO₂ particles, the crystallinity of the material increases significantly. The microstructure formed by the addition of 100 nm SiO₂ particles effectively restricts molecular chain movement and makes it difficult to establish the polarization of the composite. The incorporation of large-size particles can reduce the proportion of the crystalline structure for the material as a whole, resulting in the formation of a new structure to promote charge transfer. Among the three kinds of SiO₂ particles, the addition of 30 nm SiO₂ particles can effectively suppress the space charge, and the composite material has the lowest residual space charge after depolarization. The addition of 100 nm SiO₂ particles can cause the accumulation of many homopolar charges near the anode. Full article

PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts. Full article

Oxytocin (OT) is a neuropeptide that modulates social-related behavior and cognition in the central nervous system of mammals. In the CA1 area of the hippocampus, the indirect effects of the OT on the pyramidal neurons and their role in information processing have been elucidated. However, limited data are available concerning the direct modulation exerted by OT on the CA1 interneurons (INs) expressing the oxytocin receptor (OTR). Here, we demonstrated that TGOT (Thr4,Gly7-oxytocin), a selective OTR agonist, affects not only the membrane potential and the firing frequency but also the neuronal excitability and the shape of the action potentials (APs) of these INs in mice. Furthermore, we constructed linear mixed-effects models (LMMs) to unravel the dependencies between the AP parameters and the firing frequency, also considering how TGOT can interact with them to strengthen or weaken these influences. Our analyses indicate that OT regulates the functionality of the CA1 GABAergic INs through different and independent mechanisms. Specifically, the increase in neuronal firing rate can be attributed to the depolarizing effect on the membrane potential and the related enhancement in cellular excitability by the peptide. In contrast, the significant changes in the AP shape are directly linked to oxytocinergic modulation. Importantly, these alterations in AP shape are not associated with the TGOT-induced increase in neuronal firing rate, being themselves critical for signal processing. Full article

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABA_A channels are permeable to anions, the reversal potential of GABA_A is very close to that of Cl⁻, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl⁻, respectively. Due to the closeness between GABA_A reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABA_A a uniquely flexible signaling system. In most neurons of the adult brain, the GABA_A reversal potential is slightly more negative than the resting membrane potential, which makes GABA_A hyperpolarizing. Alterations in GABA_A reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer’s disease, schizophrenia, and Down’s syndrome), GABA_A becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABA_A reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation. Full article

The electrochemical behavior of dysprosium ions, as well as dysprosium and nickel ion co-reduction, on inert tungsten electrodes and active nickel electrodes were studied in the eutectic KCl-NaCl-CsCl melt at a temperature of 823 K using the methods of cyclic and square-wave voltammetry and open circuit chronopotentiometry. The process of Dy³⁺ ions electroreduction was found to be reversible and to proceed within a single three-electron stage up to the polarization rate of 0.1 V/s. The increase in the polarization rate indicates a slower rate of the charge transfer, which causes the quasi-reversible character of the charge transfer. It is shown that when the KCl-NaCl-CsCl eutectic melt contains both nickel and dysprosium ions, the voltammetry curves at 823 K have a wave of nickel ion reduction at the potentials of −(0.22–0.28) V and a dysprosium ion reduction at the potentials of −(2.175–2.250) V relative to a chlorine-silver reference electrode. Apart from these waves, the voltammograms have two reduction waves at the potentials of −(1.9–1.95) V and −(2.05–2.1) V. These waves are associated with the reduction of dysprosium ions and their depolarization on metallic nickel, which was preliminary deposited on the tungsten electrode, as well as the formation of the intermetallic phases of dysprosium and nickel of various Dy_xNi_y compositions. The (E-t) dependencies of the open circuit chronopotentiometry elucidate plateaus of the potential delay, which correspond to the dissolution of separate dysprosium and nickel intermetallic phases. Based on the results of the voltammetry changes and the chronopotentiometry of the open circuit, a series of electrochemical syntheses were performed in the potentiostatic regime at the potentials of −(1.7–2.1) V. The intermetallic phases of DyNi₅, DyNi₃ and DyNi₂ were obtained at a definite ratio of the dysprosium and nickel chloride concentrations in the KCl-NaCl-CsCl eutectic melt and at a temperature of 823 K. The synthesized intermetallic samples were characterized by X-ray diffraction and scanning electron microscopy. Full article

The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting single-step conformational changes and transitions to stable closed or sub-conducting states. However, the influence on voltage regulation of Cu²⁺ ions, capable of completely closing the lysenin channels in a two-step process, was not sufficiently addressed. In this respect, we employed electrophysiology approaches to investigate the response of lysenin channels to variable voltage stimuli in the presence of small concentrations of Cu²⁺ ions. Our experimental results showed that the hysteretic behavior, recorded in response to variable voltage ramps, is accentuated in the presence of Cu²⁺ ions. Using simultaneous AC/DC stimulation, we were able to determine that Cu²⁺ prevents the reopening of channels previously closed by depolarizing potentials and the channels remain in the closed state even in the absence of a transmembrane voltage. In addition, we showed that Cu²⁺ addition reinstates the voltage gating and hysteretic behavior of lysenin channels reconstituted in neutral lipid membranes in which lysenin channels lose their voltage-regulating properties. In the presence of Cu²⁺ ions, lysenin not only regained the voltage gating but also behaved like a long-term molecular memory controlled by electrical potentials. Full article