Effect of Berberine Isolated from Barberry Species by Centrifugal Partition Chromatography on Memory and the Expression of Parvalbumin in the Mouse Hippocampus Proper

Neurodegenerative diseases associated with memory disturbances are important health issues occurring due to a prolonged life span. This article presents the results of a study targeting the emergence of a drug candidate with antiamnesic properties. The effect of berberine (BBR), an isoquinoline alkaloid isolated from the overground parts of Berberis sibirica Pall., on memory and expression of parvalbumin in the mouse hippocampus proper were determined. High-purity BBR was isolated by centrifugal partition chromatography from a methanolic extract from B. sibirica by using a methyl-tert-butyl ether and water (1:1 v/v) solvent system with 10 mmol/L of triethylamine and hydrochloric acid. In an in vivo study, we assessed the influence of the chronic administration of BBR on different stages of memory-related responses in mice. Our results indicated that the chronic administration of BBR in a higher dose (5 mg/kg) improves long-term memory acquisition in mice, as determined in the passive avoidance test. The hippocampal CA1–CA3 fields showed an increased number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers as compared to the control. No significant changes in the dentate gyrus were observed between the groups. The HPLC-ESI-QTOF-MS/MS analysis of the biological material revealed the content of BBR as 363.4 ± 15.0 ng (4.11% of RSD) per brain, 15.06 ± 0.89 ng (5.91% of RSD) per hippocampus, and 54.45 ± 1.40 (4.05% of RSD) ng in 100 µL plasma. The study showed that BBR could be a factor influencing the expression of PV in hippocampal neurons. We speculate that BBR may modulate the level of Ca²⁺ in neurons and thus potentially act as a neuroprotective factor against neuronal damages.     

Release of Soybean Isoflavones by Using a β-Glucosidase from Alicyclobacillus herbarius

β-Glucosidases are used in the food industry to hydrolyse glycosidic bonds in complex sugars, with enzymes sourced from extremophiles better able to tolerate the process conditions. In this work, a novel β-glycosidase from the acidophilic organism Alicyclobacillus herbarius was cloned and heterologously expressed in Escherichia coli BL21(DE3). AheGH1 was stable over a broad range of pH values (5–11) and temperatures (4–55 °C). The enzyme exhibited excellent tolerance to fructose and good tolerance to glucose, retaining 65 % activity in the presence of 10 % (w/v) glucose. It also tolerated organic solvents, some of which appeared to have a stimulating effect, in particular ethanol with a 1.7-fold increase in activity at 10 % (v/v). The enzyme was then applied for the cleavage of isoflavone from isoflavone glucosides in an ethanolic extract of soy flour, to produce soy isoflavones, which constitute a valuable food supplement, full conversion was achieved within 15 min at 30 °C.     

Early and Delayed Impact of Nanosilver on the Glutamatergic NMDA Receptor Complex in Immature Rat Brain

Silver nanoparticles (AgNPs) are the one of the most extensively used nanomaterials. The strong antimicrobial properties of AgNPs have led to their use in a wide range of medical and consumer products. Although the neurotoxicity of AgNPs has been confirmed, the molecular mechanisms have not been extensively studied, particularly in immature organisms. Based on information gained from previous in vitro studies, in the present work, we examine whether ionotropic NMDA glutamate receptors contribute to AgNP-induced neurotoxicity in an animal model of exposure. In brains of immature rats subjected to a low dose of AgNPs, we identified ultrastructural and molecular alterations in the postsynaptic region of synapses where NMDA receptors are localized as a multiprotein complex. We revealed decreased expression of several NMDA receptor complex-related proteins, such as GluN1 and GluN2B subunits, scaffolding proteins PSD95 and SynGAP, as well as neuronal nitric oxide synthase (nNOS). Elucidating the changes in NMDA receptor-mediated molecular mechanisms induced by AgNPs, we also identified downregulation of the GluN2B-PSD95-nNOS-cGMP signaling pathway which maintains LTP/LTD processes underlying learning and memory formation during development. This observation is accompanied by decreased density of NMDA receptors, as assessed by a radioligand binding assay. The observed effects are reversible over the post-exposure time. This investigation reveals that NMDA receptors in immature rats are a target of AgNPs, thereby indicating the potential health hazard for children and infants resulting from the extensive use of products containing AgNPs.     

AUTOMAT[R]IX: learning simple matrix pipelines

Machine Learning - Matrices are a very common way of representing and working with data in data science and artificial intelligence. Writing a small snippet of code to make a simple matrix...     

The effects of laser patterning 10CeTZP-Al2O3 nanocomposite disc surfaces: Osseous differentiation and cellular arrangement in vitro

Customized square grid arrangements of different groove depths (1.0, 1.5 and 3.0?µm) and separations (10 and 30?µm) were successfully laser patterned, using a nanosecond pulsed fibre laser, on the surface of 10?mol% ceria-stabilized zirconia and alumina (10CeTZP-Al₂O₃) nanocomposite discs (diameter: 10?mm; thickness: 1.5?mm). The patterned surfaces and the in vitro biological response of osteoblasts (SAOS-2) towards them were thoroughly analysed. In terms of composition, the laser treatment was found to cause superficial monoclinic-tetragonal zirconia phase transformation and alumina evaporation. In vitro, the most effective grid configuration for osseous differentiation was found to be 1.5?µm groove depth and 10?µm groove separation, and confocal microscopy revealed that the cells show a tendency to be sorted as groove depth increases. It is thought that custom-made patterns could be produced to guide cell attachment in vivo, which could favour implant integration and reduce healing time.     

Cationic curing of diglycidyl ether of bisphenol A and 2,2,5,5‐tetramethyl‐4,6‐dioxo‐1,3‐dioxane and degradation of the thermosets obtained

Ytterbium and lanthanum triflates were used as cationic initiators to cure mixtures of diglycidyl ether of bisphenol A and 2,2,5,5‐tetramethyl‐4,6‐dioxo‐1,3‐dioxane in several proportions. The evolution of the epoxy and lactone during curing and the linear ester groups in the final materials were evaluated with Fourier transform infrared in the attenuated total reflection mode. The shrinkage after curing and the thermal degradability of the materials with variations in the comonomer ratios and initiator used were evaluated and related to the chemical structure of the final network. The expandable character of 2,2,5,5‐tetramethyl‐4,6‐dioxo‐1,3‐dioxane was confirmed. The obtained materials were more degradable than conventional epoxy resins because of the tertiary ester groups incorporated into the network by copolymerization. The kinetic parameters of the curing and degradation processes were calculated with differential scanning calorimetry and thermogravimetric analysis, respectively, with isoconversional procedures applied in both cases. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes

We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pHi) and Na+ (Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+ probe), BCECF/AM (pHi probe) or SBFI/AM (Nai+ probe). Compared with hypothyroid animals, myocytes isolated from hyperthyroid rat hearts demonstrated a significant: (1) increase in extent of shortening; (2) decrease in the time to peak contraction; (3) increase in the peak amplitude of the fura-2 fluorescence ratio; (4) decrease in pHi (DeltapHi=0. 19+/-0.05); and (5) increase in Nai+ (DeltaNai+=2.88+/-0.55 mM). We have also compared pHi in Langendorff perfused hypo- and hyperthyroid rat hearts using NMR. We have found that hyperthyroid hearts are 0.15+/-0.03 pH units more acidic than hypothyroid hearts. Analysis of mRNA levels demonstrated that hyperthyroidism increased expression of both the Na+/Ca2+ exchanger and Na+/H+ antiporter, and decreased expression of Na+ channel mRNAs. These changes appear partially responsible for the observed changes in Nai+ and pHi. Our results provide the first evidence that changes in cardiac contractility associated with altered thyroid state not only involve effects on Ca2+, but may also involve changes in the response of the myofilaments to Cai2+mediated by altered pHi and Nai+.     

pH-responsive molecularly imprinted polymer for sorption and rapid desorption of dibutyl phthalate

The pH-responsive molecularly imprinted polymers (SR-MIPs) for the removal of dibutyl phthalate (DBP) were obtained. The polymers were synthesized using methyl methacrylate, methacrylic acid, divinylbenzene, and a template mixed at different ratios allowing to optimize the process. The so-prepared SR-MIPs were evaluated at various pH values in processes of DBP sorption. The studies covered evaluation of uptake capacity, sorption kinetics, selectivity, and elution. The imprinted samples are characterized by improved factors comparing to their non-imprinted analogues, revealing also pH-sensitivity. The highest removal of DBP (130 mg g^?1) was achieved at pH = 6, while pH-driven desorption (90%) was the most efficient at pH = 8.     

A multiagent player system composed by expert agents in specific game stages operating in high performance environment

This paper proposes a new approach for the non-supervised learning process of multiagent player systems operating in a high performance environment, being that the cooperative agents are trained so as to be expert in specific stages of a game. This proposal is implemented by means of the Checkers automatic player denominated D-MA-Draughts, which is composed of 26 agents. The first is specialized in initial and intermediary game stages, whereas the remaining are specialists in endgame stages (defined by board-games containing, at most, 12 pieces). Each of these agents consists of a Multilayer Neural Network, trained without human supervision through Temporal Difference Methods. The best move is determined by the distributed search algorithm known as Young Brothers Wait Concept. Each endgame agent is able to choose a move from a determined profile of endgame board. These profiles are defined by a clustering process performed by a Kohonen-SOM network from a database containing endgame boards retrieved from real matches. Once trained, the D-MA-Draughts agents can actuate in a match according to two distinct game dynamics. In fact, the D-MA-Draughts architecture corresponds to an extension of two preliminary versions: MP-Draughts, which is a multiagent system with a serial search algorithm, and D-VisionDraughts, which is a single agent with a distributed search algorithm. The D-MA-Draughts gains are estimated through several tournaments against these preliminary versions. The results show that D-MA-Draughts improves upon its predecessors by significantly reducing training time and the endgame loops, thus beating them in several tournaments.