Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.     

Comparison of dispersants performance on the suspension Lu2O3:Eu stability and high-density compacts on their basis

The conditions for obtaining a stable Lu₂O₃:Eu³⁺ suspension of spherical particles with a diameter of 100 nm using three dispersants possessing an electrosteric stabilizing effect (Dolapix CE 64, Darvan 821 A, Darvan C-N) have been studied. It has been shown that in colloidal processing of ceramics the packing density and microstructure of green bodies can be controlled by regulating the interactions between ceramic particles in the suspension. The influence of the molecular weight and concentration of the dispersant on the stability of Lu₂O₃:Eu³⁺ suspensions containing 5-10 vol.% of the solid loading has been considered. It has been determined that use of Dolapix CE 64 with a concentration of 1 mass.% in the alkaline pH range allows to obtain suspensions with high stability and low viscosity (∼1.7 сP). Such suspensions were used to produce compacts with a maximum relative density of ∼52% and uniform density distribution by the pressure slip casting method. The obtained compacts were densified into translucent Lu₂O₃:Eu³⁺ ceramics by the vacuum sintering method.     

Systematic study of back pressure and anode stoichiometry effects on spatial PEMFC performance distribution

A segmented cell system was applied to investigate the effects of the anode and cathode back pressure and hydrogen stoichiometry on fuel cell performance in terms of overpotential distributions along the flow field. The segmented cell system was designed with closed loop Hall sensors and a data acquisition system allowing simultaneous spatial electrochemical impedance spectra (EIS) measurements. It was determined that an increase in back pressure for the tested serpentine flow field design results in an improvement of the cell performance and uneven improvement of individual segments’ performance. In general, the performance and the overpotentials become more uniform downstream with an increase in the back pressure due to a decrease in activation and mass transfer losses. Spatial EIS data for the PEMFC operated at different back pressures support the overpotential analysis. Hydrogen stoichiometry variations do not affect the performance of the cell or the individual segments at low current density because there is no significant hydrogen concentration gradient in the flow field. However, at high current densities a reduction in hydrogen stoichiometry produces a slight decrease in performance for inlet segments while outlet segments showed a noticeable performance loss. The decrease in performance is attributed to an increase in mass transfer losses due to nitrogen diffusion from the cathode to the anode. This effect becomes more pronounced for the outlet segments due to a downstream nitrogen accumulation. Under high current density conditions, the cell is locally fuel starved even with a high fuel stoichiometry creating conditions leading to cell degradation by carbon corrosion. More importantly, this local degradation is masked by the overall cell performance which remains largely unaffected.     

Synergistic Effect in Selective Reduction of NO by Alkanes over Mechanically Mixed Oxide Catalysts

The process of selective catalytic reduction of nitrogen oxides by propane in the presence of O₂, as well as in the presence or absence of CO, was studied over series of commercial oxide catalysts used in petrochemical processes. For the first time synergistic effect was observed for catalytic systems consisting of mechanical mixtures of Cu–Zn–Ni–Al (catalyst I) + Fe–Cr (catalyst II) and Cu–Zn–Ni–Al (catalyst I) + Ni–Cr (catalyst III). The activity of these mixtures in nitrogen oxides reduction by propane was greater than that of individual components in each case. The worked-out catalytical systems showed high effectivity in the process of simultaneous removal of several toxic components: NO _x , CO, hydrocarbons – from model gas mixtures, as well as from real exhausts of automotive transport.     

Diaminofuroxan: Synthetic Approaches and Computer‐Aided Study of Thermodynamic Stability

Different approaches to synthesize diaminofuroxan are presented herein. Mathematical and quantum chemical methods were used to study the possible reasons for failures in the syntheses of diaminofuroxan. Additionally, structural isomers of this compound were generated. With the help of the results of quantum chemical calculations at levels of DFT B3LYP 6‐31G(d) and MP2 6‐31G(d), screening of the most stable isomeric forms in the gaseous phase and in water was performed. It was shown that diaminofuroxan is not the thermodynamically most stable isomer among its structural analogues.     

Tissue-Specific Ferritin- and GFP-Based Genetic Vectors Visualize Neurons by MRI in the Intact and Post-Ischemic Rat Brain

(1) Background: Neurogenesis is considered to be a potential brain repair mechanism and is enhanced in stroke. It is difficult to reconstruct the neurogenesis process only from the histological sections taken from different animals at different stages of brain damage and restoration. Study of neurogenesis would greatly benefit from development of tissue-specific visualization probes. (2) Purpose: The study aimed to explore if overexpression of ferritin, a nontoxic iron-binding protein, under a doublecortin promoter can be used for non-invasive visualization of neurogenesis using magnetic resonance imaging (MRI). (3) Methods: Ferritin heavy chain (FerrH) was expressed in the adeno-associated viral backbone (AAV) under the doublecortin promoter (pDCX), specific for young neurons, in the viral construct AAV-pDCX-FerrH. Expression of the enhanced green fluorescent protein (eGFP) was used as an expression control (AAV-pDCX-eGFP). The viral vectors or phosphate-buffered saline (PBS) were injected intracerebrally into 18 adult male Sprague–Dawley rats. Three days before injection, rats underwent transient middle-cerebral-artery occlusion or sham operation. Animals were subjected to In vivo MRI study before surgery and on days 7, 14, 21, and 28 days after injection using a Bruker BioSpec 11.7 T scanner. Brain sections obtained on day 28 after injection were immunostained for ferritin, young (DCX) and mature (NeuN) neurons, and activated microglia/macrophages (CD68). Additionally, RT-PCR was performed to confirm ferritin expression. (4) Results: T2* images in post-ischemic brains of animals injected with AAV-pDCX-FerrH showed two distinct zones of MRI signal hypointensity in the ipsilesioned hemisphere starting from 14 days after viral injection—in the ischemic lesion and near the lateral ventricle and subventricular zone (SVZ). In sham-operated animals, only one zone of hypointensity near the lateral ventricle and SVZ was revealed. Immunochemistry showed that ferritin-expressing cells in ischemic lesions were macrophages (88.1%), while ferritin-expressing cells near the lateral ventricle in animals both after ischemia and sham operation were mostly mature (55.7% and 61.8%, respectively) and young (30.6% and 7.1%, respectively) neurons. RT-PCR confirmed upregulated expression of ferritin in the caudoputamen and corpus callosum. Surprisingly, in animals injected with AAV-pDCX-eGFP we similarly observed two zones of hypointensity on T2* images. Cellular studies also showed the presence of mature (81.5%) and young neurons (6.1%) near the lateral ventricle in both postischemic and sham-operated animals, while macrophages in ischemic lesions were ferritin-positive (98.2%). (5) Conclusion: Ferritin overexpression induced by injection of AAV-pDCX-FerrH was detected by MRI using T2*-weighted images, which was confirmed by immunochemistry showing ferritin in young and mature neurons. Expression of eGFP also caused a comparable reduced MR signal intensity in T2*-weighted images. Additional studies are needed to investigate the potential and tissue-specific features of the use of eGFP and ferritin expression in MRI studies.     

CYP51: A Major Drug Target in the Cytochrome P450 Superfamily

The cytochrome P540 (CYP) superfamily currently includes about 9000 proteins forming more than 800 families. The enzymes catalyze monooxygenation of a vast array of compounds and play essentially two roles. They provide biodefense (detoxification of xenobiotics, antibiotic production) and participate in biosynthesis of important endogenous molecules, particularly steroids. Based on these two roles, sterol 14/*alpha*/-demethylases (CYP51) belong to the second group of P450s. The CYP51 family, however, is very special as its members preserve strict functional conservation in enzyme activity in all biological kingdoms. At amino acid identity across the kingdoms as low as 25-30%, they all catalyze essentially the same three-step reaction of oxidative removal of the 14/*alpha*/-methyl group from the lanostane frame. This reaction is the required step in sterol biosynthesis of pathogenic microbes. We have shown that specific inhibition of protozoan CYP51 can potentially provide treatment for human trypanosomiases. Three sets of CYP51 inhibitors tested in vitro and in trypanosomal cells in this study include azoles [best results being 50% cell growth inhibition at <1 and at 1.3 muM for Trypanosoma cruzi (TC) and Trypanosoma brucei (TB), respectively], non-azole compounds (50% TC cell growth inhibition at 5 microM) and substrate analogs of the 14/*alpha*/-demethylase reaction. 32-Methylene cyclopropyl lanost-7-enol exhibited selectivity toward TC with 50% cell growth inhibition at 3 microM.     

Yellow–green organic light-emitting diode based on tris(2-methyl-8-quinolinolate) scandium

Efficient yellow–green electroluminescence emission at λ_max = 530 nm with CIE coordinates x = 0.3913, y = 0.4947 was obtained with organic light-emitting devices based on tris(2-methyl-8-quinolinolate) scandium (1). The device with the configuration of indium tin oxide/N,N′-bis(3-methylphenyl)-N,N′-diphenylbenzidine/1/Yb exhibits current efficiency of 3.1 cd/A and power efficiency of 1.8 lm/W at a luminance of 100 cd/m². The DFT calculations demonstrate that structural changes of the scandium complex 1 influence the electroluminescence spectrum, the better agreement with experimental data being achieved when monodentate ligands are taken into consideration.     

Fatty Acid Biomarkers of Symbionts and Unusual Inhibition of Tetracosapolyenoic Acid Biosynthesis in Corals (Octocorallia)

Seven zooxanthellae-free species of octocorals (the genera Acanthogorgia, Acabaria, Chironephthya, Echinogorgia, Menella, Ellisella, and Bebryce) and two zooxanthellate octocorals (the genera Paralemnalia and Rumphella) were examined to elucidate their fatty acid (FA) composition. Arachidonic (about 40% of the total FA) and palmitic acids were predominant in all the species studied. Seven furan FA (F-acids) (up to 9.7%) were identified in the azooxanthellate octocorals. The main F-acids were 14,17-epoxy-15-methyldocosa-14,16-dienoic and 14,17-epoxy-15,16-dimethyldocosa-14,16-dienoic acids. In all specimens of Bebryce studeri, C_25–28 demospongic FA (about 20%) were identified. These FA reflect the presence of a symbiotic sponge in B. studeri and can be used as the specific markers for other corals. A significant difference (P < 0.01) between azooxanthellate and zooxanthellate corals was found for odd-chain and methyl-branched saturated FA, 18:1n-7, and 7-Me-16:1n-10; that indicated the presence of an advanced bacterial community in azooxanthellate corals. The zooxanthellate species were distinguished by significant amounts of 18:3n-6, 18:4n-3, and 16:2n-7 acids, which are proposed as the markers of zooxanthellae in soft corals. Contrary to the normal level of 24:5n-6 (9.4%) and 22:4n-6 (0.6%), unexpected low concentrations of 24:5n-6 (0.4%) accompanied by a high content of 22:4n-6 (up to 11.9%) were detected in some specimens. The presence of an unknown factor in octocorals, specific for n-6 PUFA, which inhibited elongation of 22:4n-6 to 24:4n-6, is conjectured.