Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na⁺,K⁺-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na⁺,K⁺-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.     

Non-Singular Stresses in Gradient Elasticity at Bi-Material Interface with Transverse Crack

Bi-material interfaces are studied with cracks that end perpendicular to the interface. As is well-known, singularities in the stresses appear when classical elasticity is used. Moreover, the nature of the singularity depends on the difference in elastic constants of the two materials. In this paper, the gradient elasticity theory of Aifantis is used to remove these singularities. This is demonstrated for a range of ratios between the two Young’s moduli.     

Identification and Characterization of Δ12, Δ6, and Δ5 Desaturases from the Green Microalga <Emphasis Type="Italic">Parietochloris incisa</Emphasis>

The freshwater microalga Parietochloris incisa accumulates, under nitrogen starvation, large amounts of triacylglycerols containing approximately 60% of the ω6 very long-chain polyunsaturated fatty acid (VLC-PUFA), arachidonic acid. Based on sequence homology, we isolated three cDNA sequences from P. incisa, designated PiDesD12, PiDesD6, PiDesD5. The deduced amino acid sequences of the three genes contained three conserved histidine motifs; the front-end desaturases, PiDes6 and PiDes5, contained a fused N-terminal cytochrome b5 domain. By functional characterization in the yeast Saccharomyces cerevisiae, we confirmed that PiDesD6, PiDesD5 cDNA encode membrane bound desaturases with Δ6, and Δ5 activity, respectively. Both PiDes6 and PiDes5 can indiscriminately desaturate both ω6 and ω3 substrates. A phylogenetic analysis showed that the three genes were homologous to the corresponding desaturases from green microalgae and lower plants that were functionally characterized. Quantitative real-time PCR revealed the concerted expression pattern of all three genes in P. incisa cells subjected to nitrogen starvation, featuring maximum expression level on day 3 of starvation, corresponding to the sharpest increase in the share of arachidonic acid.     

High-Temperature Chemistry and Oxidation of ZrB2 Ceramics Containing SiC, Si3N4, Ta5Si3, and TaSi2

The effect of Si₃N₄, Ta₅Si₃, and TaSi₂ additions on the oxidation behavior of ZrB₂ was characterized at 1200°–1500°C and compared with both ZrB₂ and ZrB₂/SiC. Significantly improved oxidation resistance of all Si-containing compositions relative to ZrB₂ was a result of the formation of a protective layer of borosilicate glass during exposure to the oxidizing environment. Oxidation resistance of the Si₃N₄-modified ceramics increased with increasing Si₃N₄ content and was further improved by the addition of Cr and Ta diborides. Chromium and tantalum oxides induced phase separation in the borosilicate glass, which lead to an increase in liquidus temperature and viscosity and to a decrease in oxygen diffusivity and of boria evaporation from the glass. All tantalum silicide-containing compositions demonstrated phase separation in the borosilicate glass and higher oxidation resistance than pure ZrB₂, with the effect increasing with temperature. The most oxidation-resistant ceramics contained 15 vol% Ta₅Si₃, 30 vol% TaSi₂, 35 vol% Si₃N₄, or 20 vol% Si₃N₄ with 10 mol% CrB₂. These materials exceeded the oxidation resistance of the ZrB₂/SiC ceramics below 1300°–1400°C. However, the ZrB₂/SiC ceramics showed slightly superior oxidation resistance at 1500°C.     

Possible Role of Crystal-Bearing Cells in Tomato Fertility and Formation of Seedless Fruits

Crystal-bearing cells or idioblasts, which deposit calcium oxalate, are located in various tissues and organs of many plant species. The functional significance of their formation is currently unclear. Idioblasts in the leaf parenchyma and the development of crystal-bearing cells in the anther tissues of transgenic tomato plants (Solanum lycopersicon L.), expressing the heterologous FeSOD gene and which showed a decrease in fertility, were studied by transmission and scanning electron microscopy. The amount of calcium oxalate crystals was found to increase significantly in the transgenic plants compared to the wild type (WT) ones in idioblasts and crystal-bearing cells of the upper part of the anther. At the same time, changes in the size and shape of the crystals and their location in anther organs were noted. It seems that the interruption in the break of the anther stomium in transgenic plants was associated with the formation and cell death regulation of a specialized group of crystal-bearing cells. This disturbance caused an increase in the pool of these cells and their localization in the upper part of the anther, where rupture is initiated. Perturbations were also noted in the lower part of the anther in transgenic plants, where the amount of calcium oxalate crystals in crystal-bearing cells was reduced that was accompanied by disturbances in the morphology of pollen grains. Thus, the induction of the formation of crystal-bearing cells and calcium oxalate crystals can have multidirectional effects, contributing to the regulation of oxalate metabolism in the generative and vegetative organs and preventing fertility when the ROS balance changes, in particular, during oxidative stresses accompanying most abiotic and biotic environmental factors.     

Functional Roles of PARP2 in Assembling Protein–Protein Complexes Involved in Base Excision DNA Repair

Poly(ADP-ribose) polymerase 2 (PARP2) participates in base excision repair (BER) alongside PARP1, but its functions are still under study. Here, we characterize binding affinities of PARP2 for other BER proteins (PARP1, APE1, Polβ, and XRCC1) and oligomerization states of the homo- and hetero-associated complexes using fluorescence-based and light scattering techniques. To compare PARP2 and PARP1 in the efficiency of PAR synthesis, in the absence and presence of protein partners, the size of PARP2 PARylated in various reaction conditions was measured. Unlike PARP1, PARP2 forms more dynamic complexes with common protein partners, and their stability is effectively modulated by DNA intermediates. Apparent binding affinity constants determined for homo- and hetero-oligomerized PARP1 and PARP2 provide evidence that the major form of PARP2 at excessive PARP1 level is their heterocomplex. Autoregulation of PAR elongation at high PARP and NAD⁺ concentrations is stronger for PARP2 than for PARP1, and the activity of PARP2 is more effectively inhibited by XRCC1. Moreover, the activity of both PARP1 and PARP2 is suppressed upon their heteroPARylation. Taken together, our findings suggest that PARP2 can function differently in BER, promoting XRCC1-dependent repair (similarly to PARP1) or an alternative XRCC1-independent mechanism via hetero-oligomerization with PARP1.     

Phase evolution and microstructure analysis of CaZrTi2O7 zirconolite in glass

The internal crystallization of CaZrTi₂O₇ zirconolite in a sodium alumino-borosilicate glass has been investigated with powder X-ray diffraction (XRD), scanning electron microscopy and energy dispersion spectroscopy (SEM-EDS), transmission electron microscopy (TEM) and selected area electron diffraction (SAED) techniques. The samples have been prepared using a soft chemistry route and ceramic phase evolution has been observed with sintering time. Zirconolite as the dominant phase at 1 h sintering gradually changes to baddeleyite structured materials for longer sintering times. XRD shows that one dominant phase belongs to zirconolite at 3 h sintering, however, SEM-EDS reveals that the dominant ceramic phase is actually baddeleyite phase, which is enclosed by zirconolite phase. TEM and SAED patterns also confirm the crystallization of zirconolite phase in glass. The addition of CaO enhances the formation of zirconolite (i.e. impedes baddeleyite phase) with CaO to glass weight ratio ≤ 35:100.     

The effect of crystal polymorphism of ferroelectric copolymer vinylidene fluoride-hexafluoropropylene on its high-voltage polarization

Dielectric response of vinylidene fluoride-hexafluoropropylene copolymer, crystallized in different polymorph modifications, to a high-voltage electric field was studied. Polarization switching at high electric fields below coercive was detected. It was found that crystallization of the copolymer predominantly in nonpolar α-phase is accompanied by more intensive growth of electric displacement at polarization. For the sample with higher content of polar γ-phase, the value of high-voltage conductivity “anomalously” decreased with increasing field at fields above coercive. The data on the field dependences of the remnant polarization showed that this should be attributed to an increase of the effective capture cross section of deep traps of γ-phase polar planes for impurity and injected carriers. X-ray diffraction has revealed the field-induced transition of a part of the chains of the amorphous phase to the crystal.     

Maternal Melatonin Deficiency Leads to Endocrine Pathologies in Children in Early Ontogenesis

The review summarizes the results of experimental and clinical studies aimed at elucidating the causes and pathophysiological mechanisms of the development of endocrine pathology in children. The modern data on the role of epigenetic influences in the early ontogenesis of unfavorable factors that violate the patterns of the formation of regulatory mechanisms during periods of critical development of fetal organs and systems and contribute to the delayed development of pathological conditions are considered. The mechanisms of the participation of melatonin in the regulation of metabolic processes and the key role of maternal melatonin in the formation of the circadian system of regulation in the fetus and in the protection of the genetic program of its morphofunctional development during pregnancy complications are presented. Melatonin, by controlling DNA methylation and histone modification, prevents changes in gene expression that are directly related to the programming of endocrine pathology in offspring. Deficiency and absence of the circadian rhythm of maternal melatonin underlies violations of the genetic program for the development of hormonal and metabolic regulatory mechanisms of the functional systems of the child, which determines the programming and implementation of endocrine pathology in early ontogenesis, contributing to its development in later life. The significance of this factor in the pathophysiological mechanisms of endocrine disorders determines a new approach to risk assessment and timely prevention of offspring diseases even at the stage of family planning.