Residues at the tip of the pore loop of NR3B-containing NMDA receptors determine Ca<Superscript>2+</Superscript> permeability and Mg<Superscript>2+</Superscript>block

Background  

Members of the complex N-methyl-D-aspartate receptor (NMDAR) subfamily of ionotropic glutamate receptors (iGluRs) conventionally assemble from NR1 and NR2 subunits, the composition of which determines receptor properties. Hallmark features of conventional NMDARs include the requirement for a coagonist, voltage-dependent block by Mg²⁺, and high permeability for Ca²⁺. Both Mg²⁺ sensitivity and Ca²⁺ permeability are critically dependent on the amino acids at the N and N+1 positions of NR1 and NR2. The recently discovered NR3 subunits feature an unprecedented glycine-arginine combination at those critical sites within the pore. Diheteromers assembled from NR1 and NR3 are not blocked by Mg²⁺ and are not permeable for Ca²⁺.     

Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus)

Background  

Metabotropic glutamate receptors (mGluRs) regulate neuronal excitability and synaptic strength. The group I mGluRs, mGluR1 and 5, are widespread in the brain and localize to post-synaptic sites. The Homer protein family regulates group I mGluR function and distribution. Constitutively expressed 'long' Homer proteins (Homer 1b, 1c, 2 and 3) induce dendritic localization of group I mGluRs and receptor clustering, either internally or on the plasma membrane. Short Homer proteins (Homer 1a, Ania-3) exhibit regulated expression and act as dominant negatives, producing effects on mGluR distribution and function that oppose those of the long Homer proteins.     

Effects of the group I metabotropic glutamate receptor agonist,DHPG, and injection stress on striatal cell signaling in food-restricted and ad libitum fed rats

Background  

Chronic food restriction augments the rewarding effect of centrally administered psychostimulant drugs and this effect may involve a previously documented upregulation of D-1 dopamine receptor-mediated MAP kinase signaling in nucleus accumbens (NAc) and caudate-putamen (CPu). Psychostimulants are known to induce striatal glutamate release, and group I metabotropic glutamate receptors (mGluR) have been implicated in the cellular and behavioral responses to amphetamine. The purpose of the present study was to evaluate whether chronic food restriction increases striatal MAP kinase signaling in response to the group I mGluR agonist, DHPG.     

Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity

Background  

The involvement of different NMDA receptor (NMDAR) subunits has been implicated in several forms of synaptic plasticity. However, it is still controversial to what extent the involvement is specific, and little is known about the role of NMDAR subunits in certain "non-conventional" forms of plasticity. In this study we used subunit-specific blockers to test the roles of NR2A- and NR2B-containing NMDARs in a type of chemical long-term depression (LTD) induced by brief bath application of the NMDAR agonist NMDA to hippocampal slices from 12–18 days old rats. For comparison, we also examined other forms of plasticity, including a "slow LTD" induced by 0.1 Hz stimulation under low Mg²⁺ conditions as well as long-term potentiation (LTP).     

Effects of NR1 splicing on NR1/NR3B-type excitatory glycine receptors

Background  

N-methyl-D-aspartate receptors (NMDARs) are the most complex of ionotropic glutamate receptors (iGluRs). Subunits of this subfamily assemble into heteromers, which – depending on the subunit combination – may display very different pharmacological and electrophysiological properties. The least studied members of the NMDAR family, the NR3 subunits, have been reported to assemble with NR1 to form excitatory glycine receptors in heterologous expression systems. The heterogeneity of NMDARs in vivo is in part conferred to the receptors by splicing of the NR1 subunit, especially with regard to proton sensitivity.     

Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines

Background  

Homer is a postsynaptic scaffold protein that links various synaptic signaling proteins, including the type I metabotropic glutamate receptor subunits 1α and 5, the inositol 1,4,5-trisphosphate receptor, Shank and Cdc42 small GTPase. Overexpression of Homer induces changes in dendritic spine morphology in cultured hippocampal neurons. However, the molecular basis underpinning Homer-mediated spine morphogenesis remains unclear. In this study, we aimed to elucidate the structural and functional properties of the interaction between Cupidin/Homer2 and two actin-cytoskeletal regulators, Cdc42 small GTPase and Drebrin.     

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

Background  

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸ or 1 × 10⁹ genomic copies of AAV1-GFP and 1 × 10⁵ transducing units of LV-dsRed.     

Interactions between β-carboline alkaloids and bovine serum albumin: Investigation by spectroscopic approach

β-Carboline alkaloids are present in medicinal plants such as Peganum harmala L. that have been used as folk medicine in anticancer therapy. BSA¹ is the major soluble protein constituent of the circulatory system, and has many physiological functions including the transport of a variety of compounds. This study is the first attempt to investigate the binding of β-carboline alkaloids to BSA by using a constant protein concentration and varying drug concentrations at pH 7.2. FTIR² and UV–Vis³ spectroscopic methods were used to analyze the binding modes of β-carboline alkaloids, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that β-carboline alkaloids bind BSA via hydrophobic interaction and van der Waals contacts along with H-bonding with the –NH groups, with overall binding constants of K_{harmine–BSA}=2.04×10⁴ M^?1, K_{tryptoline–BSA}=1.2×10⁴ M^?1, K_{harmaline–BSA}=5.04×10³ M^?1, K_{harmane–BSA}=1.41×10³ M^?1 and K_{harmalol–BSA}=1.01×10³ M^?1, assuming that there is one drug molecule per protein. The BSA secondary structure was altered with a major decrease of α-helix from 64% (free protein) to 59% (BSA–harmane), 56% (BSA–harmaline and BSA–harmine), 55% (BSA–tryptoline), 54% (BSA–harmalol) and β-sheet from 15% (free protein) to 6–8% upon β-carboline alkaloids complexation, inducing a partial protein destabilization.     

A Highly Fluorescent Pyrene-Based Sensor for Selective Detection Of Fe3+ Ion in Aqueous Medium: Computational Investigations

In this work, we introduce a highly selective and sensitive fluorescent sensor based on pyrene derivative for Fe(III) ion sensing in DMSO/water media. 2-(pyrene-2-yl)-1-(pyrene-2-ylmethyl)-1H-benzo[d]imidazole (PEBD) receptor was synthesized via simple condensation reaction and confirmed by spectroscopic techniques. The receptor exhibits fluorescence quenching in the presence of Fe(III) ions at 440 nm. ESI–MS and Job’s method were used to confirm the 1:1 molar binding ratio of the receptor PEBD to Fe(III) ions. Using the Benesi-Hildebrand equation the binding constant value was determined as 8.485?×?10³ M^?1. Furthermore, the limit of detection (LOD, 3σ/K) value was found to be 1.81 µM in DMSO/water (95/5, v/v) media. According to the Environmental Protection Agency (EPA) of the United States, it is lower than the acceptable value of Fe³⁺ in drinking water (0.3 mg/L). The presence of 14 other metal ions such Co²⁺, Cr³⁺, Cu²⁺, Fe²⁺, Hg²⁺, Pb²⁺, K⁺, Ni²⁺, Mg²⁺, Cd²⁺, Ca²⁺, Mn²⁺, Al³⁺, and Zn²⁺ did not interfere with the detection of Fe(III) ions. The fluorescence life-time of the receptor PEBD with and without Fe³⁺ ion was found to be 1.097?×?10^?9 s and 0.9202?×?10^?9 s respectively. Similarly, the quantum yield of the receptor PEBD with Fe³⁺ and without Fe³⁺ ion was calculated, and found as 0.05 and 0.25 respectively. Computational studies of the receptor PEBD were carried out with density functional theory (DFT) using B3LYP/ 6-311G (d, p), LANL2DZ level of theory.

Graphical Abstract

     

Molecular dynamics simulations on chitosan/graphene nanocomposites as anticancer drug delivery using systems

Several chitosan (CS) drug delivery systems (DDSs) were designed by molecular dynamics (MD) simulations. The systems were composed of pure graphene (G), P-doped (GP) or N-doped (GN) graphene nanosheets for the anticancer drug cyclophosphamide (CP) with the aim of discovering the most appropriate drug carrier. Furthermore, the temperature influence was investigated on the systems characteristics through performing the simulations at four different temperatures including 25, 35, 45 and 55 °C. The diffusion coefficients and mean square displacements (MSDs) were boosted with the temperature increase. At 55 °C, the CS-G-CP exhibited the greatest diffusion coefficient (0.0658 × 10^–5 cm²/s) but the CS-GN-CP had the smallest diffusion coefficient of 0.0553 × 10^–5 cm²/s and the CS-GP-CP illustrated a medium amount (0.0595 × 10^–5 cm²/s) indicating the most controlled/sustained drug diffusion could occur in the CS-GN-CP which could allow the most efficient drug delivery. Moreover, to evaluate the effects of PEG chains and VC molecule on the drug delivery capacity of the CS-GN-CP cell, they were added to the this system and the CS-GN-CP-PEG2-VC was nominated as the best DDS working at 35 °C (close to the human body temperature) due to it had a relatively high drug loading capacity as well as suitable CP diffusion coefficient and FV, FFV values.     

Magnetic resonance neurography of the lumbosacral plexus at 3 Tesla – CSF-suppressed imaging with submillimeter resolution by a three-dimensional turbo spin echo sequence

PurposeTo investigate magnetic resonance neurography (MRN) of the lumbosacral plexus (LSP) with cerebrospinal fluid (CSF) suppression by using submillimeter resolution for three-dimensional (3D) turbo spin echo (TSE) imaging.Materials and methodsUsing extended phase graph (EPG) analysis, the signal response of CSF was simulated considering dephasing from coherent motion for frequency-encoding voxel sizes ranging from 0.3 to 1.3 mm and for CSF velocities ranging from 0 to 4 cm/s. In-vivo MRN included 3D TSE data with frequency encoding parallel to the feet/head axis from 15 healthy adults (mean age: 28.5 ± 3.8 years, 5 females; acquisition voxel size: 2 × 2 × 2 mm³) and 16 pediatric patients (mean age: 6.7 ± 4.1 years, 7 females; acquisition voxel size: 0.7 × 0.7 × 1.4 mm³) acquired at 3 Tesla. Five of the adults were scanned repetitively with changing acquisition voxel sizes (1 × 2 × 2 mm³, 0.7 × 2× 2 mm³, and 0.5 × 2 × 2 mm³). Measurements of the bilateral ganglion of the L5 nerve root, averaged between sides, as well as the CSF in the thecal sac were obtained for all included subjects and compared between adults and pediatric patients and between voxel sizes, using a CSF-to-nerve signal ratio (CSFNR).ResultsAccording to simulations, the CSF signal is reduced along the echo train for moving spins. Specifically, it can be reduced by over 90% compared to the maximum simulated signal for flow velocities above 2 cm/s, and could be most effectively suppressed by considering a frequency-encoding voxel size of 0.8 mm or less. For in-vivo measurements, mean CSFNR was 1.52 ± 0.22 for adults and 0.10 ± 0.03 for pediatric patients (p < .0001). Differences in CSFNR were significant between measurements using a voxel size of 2 × 2 × 2 mm³ and measurements in data with reduced voxel sizes (p ≤ .0012), with submillimeter resolution (particularly 0.5 × 2 × 2 mm³) providing highest CSF suppression.ConclusionsApplying frequency-encoding voxel sizes in submillimeter range for 3D TSE imaging with frequency encoding parallel to the feet/head axis may considerably improve MRN of LSP pathology in adults in the future because of favorable CSF suppression.     

Photoluminescence properties of Er-doped β-FeSi2 grown by ion implantation

Photoluminescence (PL) properties of Er-doped β-FeSi₂ (β-FeSi₂:Er) and Er-doped Si (Si:Er) grown by ion implantation were investigated. In PL measurements at 4.2 K, the β-FeSi₂:Er showed the 1.54 μm PL due to the intra-4f shell transition of ⁴I_13/2→⁴I_15/2 in Er³⁺ ions without a defect-related PL observed in Si:Er. In the dependence of the PL intensity on excitation photon flux density, the obtained optical excitation cross-section σ in β-FeSi₂:Er (σ=7×10⁻¹⁷ cm²) is smaller than that in Si:Er (σ=1×10^-15 cm²). In the time-resolved PL and the temperature dependence of the PL intensity, the 1.54 μm PL in β-FeSi₂:Er showed a longer lifetime and larger activation energies for non-radiative recombination (NR) processes than Si:Er. These results revealed that NR centers induced by ion implantation damage were suppressed in β-FeSi₂:Er, but the energy back transfer from Er³⁺ to β-FeSi₂ was larger than Si:Er.     

Characterization of miniature RAD-HARD silicon diodes as dosimeters for small fields of photon beams used in radiotherapy

The dosimetric response characterization and beam data acquisition performance of a miniature Float Zone (FZ) silicon diode for photon beams was investigated using Novalis TX linear accelerator (Varian Medical Systems^®). In all measurements the unbiased diode operated in a short-circuit mode, connected to the input of a Keithley 6517B electrometer using a water phantom. For photon beams of the 6 and 15 MV the results presented good repeatability (coefficient of variation ≤1.6%), measured through switching on/off the photon beams. Moreover, the diode showed a quite linear response, given by the charge versus absorbed dose, with charge sensitivities higher than 6.9 nC/Gy. The output factor, percentage depth dose profile (PDD) and transversal dose profile (TDP) were also measured in a water phantom. For small field sizes, the output factor values using the FZ diode were compared with measurements obtained with a SFD (Stereotactic Field Diode) commercial diode and the differences were 5.4%, 2.5% and 1.3% for the field sizes of 1 × 1, 2 × 2 and 3 × 3 cm². For larger field sizes (≥4 × 4 cm²), the maximum difference found was 0.7% in comparison with values obtained with a CC13 ionization chamber. Thus, the result demonstrates that the unshielded FZ diode has the potential to be used for measuring of, as it performed acceptably well for both small and large field sizes. The TDP experimental results obtained with the FZ diode for field sizes of: 1 × 1 cm², 2 × 2 cm² and 4 × 4 cm² are in agreement with experimental results acquired with several commercial detectors. Through the TDP study, the comparison of the field penumbra size confirmed the excellent spatial resolution of the miniature diode. However, the PDD study, requires further investigation.     

Silica coating of Co–Pt alloy nanoparticles prepared in the presence of poly(vinylpyrrolidone)

This article describes a method for silica coating of Co–Pt alloy nanoparticles prepared in the presence of poly(vinylpyrrolidone) (PVP) as a stabilizer. The Co–Pt nanoparticles were prepared in an aqueous solution at 25–80 °C from CoCl₂ (3.0 × 10⁻⁴ M), H₂PtCl₆ (3.0 × 10⁻⁴ M), PVP (0–10 g/L), and NaBH₄ (4.8 × 10⁻³–2.4 × 10⁻² M). The silica coating was performed for the Co–Pt nanoparticle colloid containing the PVP ([Co] = [Pt] = 3.0 × 10⁻⁵ M) at 25 °C in (1/4) (v/v) water/ethanol solution with tetraethoxyorthosilicate (TEOS) (7.2 × 10⁻⁵–7.2 × 10⁻³ M) and ammonia (0.1–1.0 M). Silica particles, which had an average size of 43 nm and contained multiple cores of Co–Pt nanoparticles with a size of ca. 8 nm, were produced at 1.4 × 10⁻³ M TEOS and 0.5 M ammonia after the preparation of Co–Pt nanoparticles at 80 °C, 5 g/L PVP, and 2.4 × 10⁻² M NaBH₄. Their core particles were fcc Co–Pt alloy crystallites. Their saturation magnetization was 2.0-emu/g sample, and their coercive field was 12 Oe.     

Synergetic effects of ultrasound and sodium alginate coating on mass transfer and qualities of osmotic dehydrated pumpkin

This research studied the effects of combined ultrasound and 3% sodium alginate (SA) coating pretreatment (US + Coat) on mass transfer kinetics, quality aspects, and cell structure of osmotic dehydrated (OD) pumpkin. The results of the pretreatment were compared with the results of control (non-pretreated osmotic dehydration) and other three pretreatment methods, which were 1) ultrasound in distilled water for 10 min (USC), 2) ultrasound in 70% (w/w) sucrose solution (US) for 10, 20 and 30 min, and 3) coating with 1%, 2%, 3% (w/w) SA. The coating pretreatments with SA resulted in a higher water loss (WL) but lower water activity and solid gain (SG) than other treatments. US pretreatments resulted in the highest effective diffusion coefficients of water (D_w) and solid (D_s) but the cell structure of the product was deformed. The 3% SA coating treatment had the highest WL/SG (5.28) but with the longest OD time (12 h). Using the US + Coat pretreatment gave satisfactory high WL/SG (5.18), D_w (1.09 × 10⁻¹⁰ m²s⁻¹) and D_s (5.15 × 10⁻¹¹ m²s⁻¹), reduced the OD time to 9 h, and preserved the cell structure of the product. This research suggests that US + Coat pretreatment can be an effective processing step in the production of OD pumpkin.     

Determination of the OH radical in atmospheric pressure dielectric barrier discharge plasmas using near infrared cavity ring-down spectroscopy

The hydroxyl radical (OH) plays an important role in combustion systems, atmospheric chemistry and the removal of air pollutants by non-thermal plasmas. The present work reports the determination of the hydroxyl radicals in atmospheric dielectric barrier discharge plasmas via near infrared continuous wave cavity ring-down spectroscopy. The P-branches of OH X²Π_i (ν' = 2 ←ν^′′ = 0) bands were used for its number density measurements. The minimum measurable absorption coefficient is about 3 × 10^-8 cm^-1 in DBD plasmas. At certain experimental conditions (a.c. frequency of 70 kHz, 6700 ppm H₂O in He, 1 atm), when the peak-to-peak discharge voltage varied from 6 kV to 10.4 kV, the determined OH radical concentration increased from (2.1 ± 0.1) × 10¹³ molecules cm^-3 to (3.7 ± 0.1) × 10¹³ molecules cm^-3. The plasma gas temperature, derived from the Boltzmann plots of OH rotational population distributions, ranged from 312 ± 10 K to 363 ± 10 K when the discharge voltage was raised in the above range. The influences of O₂ and N₂ addition on the production of OH radicals have been also investigated.     

Low temperature oxidation of Fe2+ surface sites on the (2 × 1) reconstructed surface of α-Fe2O3(011­2)

Temperature programmed desorption (TPD), electron energy loss spectroscopy (ELS) and low energy electron diffraction (LEED) were used to study the interaction of molecular oxygen with the (2 × 1) reconstructed surface of hematite α-Fe₂O₃(011­2) under UHV conditions. The (2 × 1) surface is formed from vacuum annealing of the ‘ideal’ (1 × 1) surface and possesses Fe²⁺ surface sites based on ELS. While O₂ does not stick to the (1 × 1) surface at 120 K, the amount of O₂ that can be reversibly adsorbed at 120 K on the (2 × 1) surface was estimated to be ～ 0.5 ML (where 1 ML is defined as the Fe³⁺ surface coverage on the ideal (1 × 1) surface), with additional O₂ that is irreversibly adsorbed based on subsequent H₂O TPD. Molecularly and dissociatively adsorbed O₂ modifies the surface chemistry of H₂O both in terms of enhanced OH stability (relative to either the (1 × 1) or (2 × 1) surfaces) and in the blocking of H₂O adsorption sites. While O₂ adsorption at 120 to 300 K does not transform the (2 × 1) surface into the (1 × 1) surface, the influence of O₂ on the (2 × 1) surface involves both charge transfer from surface Fe²⁺ sites and formation of an ordered c(2 × 2) structure resulting from O₂ dissociation.     

Thermo,Iono and photoluminescence properties of 100 MeV Si7+ ions bombarded CaSiO3:Eu3+ nanophosphor

This paper reports on the thermo (TL), iono (IL) and photoluminescence (PL) properties of nanocrystalline CaSiO₃:Eu³⁺ (1–5 mol %) bombarded with 100 MeV Si⁷⁺ ions for the first time. The effect of different dopant concentrations and influence of ion fluence has been discussed. The characteristic emission peaks ⁵D₀→⁷F_J (J=0, 1, 2, 3, 4) of Eu³⁺ ions was recorded in both PL (1×10¹¹–1×10¹³ ions cm^?2) and IL (4.16×10¹²–6.77×10¹² ions cm^?2) spectra. It is observed that PL intensity increases with ion fluence, whereas in IL the peaks intensity increases up to fluence 5.20×10¹² ions cm^?2, then it decreases. A well resolved TL glow peak at ～304 °C was recorded in all the ion bombarded samples at a warming rate of 5 °C s^?1. The TL intensity is found to be maximum at 5 mol% Eu³⁺ concentration. Further, TL intensity increases sub linearly with shifting of glow peak towards lower temperature with ion fluence.     

Fluence dependant formation of <Emphasis Type="Italic">β</Emphasis>-SiC by ion implantation and thermal annealing

The β-SiC nanocrystals were synthesized by the implantation of carbon ions (C⁻) into silicon followed by high-temperature annealing. The carbon fluences of 1×10¹⁷, 2×10¹⁷, 5×10¹⁷, and 8×10¹⁷ atoms/cm² were implanted at an ion energy of 65 keV. It was observed that the average size of β-SiC crystals decreased and the amount of β-SiC crystals increased with the increase in the implanted fluences when the samples were annealed at 1100 °C for 1 h. However, it was observed that the amount of β-SiC linearly increased with the implanted fluences up to 5×10¹⁷ atoms/cm². Above this fluence the amount of β-SiC appears to saturate. The Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy, and X-ray diffraction (XRD) techniques were used to characterize the samples.