Physiological and Pathological Remodeling of Cerebral Microvessels

There is growing evidence that the remodeling of cerebral microvessels plays an important role in plastic changes in the brain associated with development, experience, learning, and memory consolidation. At the same time, abnormal neoangiogenesis, and deregulated regulation of microvascular regression, or pruning, could contribute to the pathogenesis of neurodevelopmental diseases, stroke, and neurodegeneration. Aberrant remodeling of microvesselsis associated with blood–brain barrier breakdown, development of neuroinflammation, inadequate microcirculation in active brain regions, and leads to the dysfunction of the neurovascular unit and progressive neurological deficits. In this review, we summarize current data on the mechanisms of blood vessel regression and pruning in brain plasticity and in Alzheimer’s-type neurodegeneration. We discuss some novel approaches to modulating cerebral remodeling and preventing degeneration-coupled aberrant microvascular activity in chronic neurodegeneration.     

A Role of DNA Methylation within the CYP17A1 Gene in the Association of Genetic and Environmental Risk Factors with Stress-Related Manifestations of Schizophrenia

As genetic and environmental influences on schizophrenia might converge on DNA methylation (DNAm) within loci which are both associated with the disease and implicated in response to environmental stress, we examined whether DNAm within CYP17A1, a hypothalamus–pituitary–adrenal axis gene which is situated within the schizophrenia risk locus 10q24.32, would mediate genetic and environmental effects on stress-related schizophrenia symptoms. DNAm within an exonic–intronic fragment of CYP17A1 was assessed in the blood of 66 schizophrenia patients and 63 controls using single-molecule real-time bisulfite sequencing. Additionally, the VNTR polymorphism of the AS3MT gene, a plausible causal variant within the 10q24.32 locus, was genotyped in extended patient and control samples (n = 700). The effects of local haplotype, VNTR and a polyenviromic risk score (PERS) on DNAm, episodic verbal memory, executive functions, depression, and suicidality of patients were assessed. Haplotype and PERS differentially influenced DNAm at four variably methylated sites identified within the fragment, with stochastic, additive, and allele-specific effects being found. An allele-specific DNAm at CpG-SNP rs3781286 mediated the relationship between the local haplotype and verbal fluency. Our findings do not confirm that the interrogated DNA fragment is a place where genetic and environmental risk factors converge to influence schizophrenia symptoms through DNAm.     

Planar defect of the nano-structured zinc oxide as the site for stabilization of the copper active species in Cu/ZnO catalysts

The catalytic activity of CuZn catalysts in the synthesis of methanol is related to those reduced Cu species, which originate from the Cu_xZn_1−xO solid solution of wurtzite-like structure. Copper cations in the Cu_xZn_1−xO solid solution are localized in the extended stacking faults of the ZnO lattice. Copper sites could be supposedly described as the product of introducing (OH)Cu(OH) to the planar defects of zinc oxide structure. Hydroxyl groups stabilize the planar defects of ZnO. The process of the samples reduction leads to the formation of flat Cu⁰ particles over the surface of zinc oxide. The planar defects of ZnO structure are preserved in the reduced state. During the reoxidation, copper atoms return back to the extended stacking faults of ZnO as the tape-like clusters of flat-square coordinated copper cations.     

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.     

Novel Antitumor L‐Arabinose Derivative of Indolocarbazole with High Affinity to DNA

Novel indolocarbazole derivative 12‐(α‐L ‐arabinopyranosyl)indolo[2,3‐α]pyrrolo[3,4‐c]carbazole‐5,7‐dione (AIC) demonstrated high potency (at submicromolar concentrations) against the NCI panel of human tumor cell lines and transplanted tumors in vivo. In search of tentative targets for AIC, we found that the drug formed high affinity intercalative complexes with d(AT)₂₀, d(GC)₂₀ and calf thymus DNA (binding constants (1.6×10⁶) M ^?1≤K_a≤(3.3×10⁶) M ^?1). The drug intercalated preferentially into GC pairs of the duplex. Importantly, the concentrations at which AIC formed the intercalative complexes with DNA (C≤1 μM ) were identical to the concentrations that triggered p53‐dependent gene reporter transactivation, the replication block, the inhibition of topoisomerase I‐mediated DNA relaxation and death of HCT116 human colon carcinoma cells. We conclude that the formation of high affinity intercalative complexes with DNA is an important factor for anticancer efficacy of AIC.     

New water-soluble copolymers of 2-methacryloyloxyethyl phosphorylcholine for surface modification

New copolymers of 2-methacryloyloxyethyl phosphorylcholine with 2-Deoxy-2-methacrylamido-D-glucose, N-vinylpyrrolidone, and N-vinyl-N-methylacetamide were synthesized and characterized; the obtained copolymers contained 10–50 mol% of phosphorylcholine moieties, and their molecular masses ranged from 1.05 × 10⁵ to 4.40 × 10⁵. Reactivity ratios of the monomers were estimated. Conformational states of the copolymers in aqueous solutions were studied. The synthesized copolymer was grafted onto the surface of carbon fiber biosorbent using γ-radiation.     

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.     

Development of vibration damping materials based on butyl rubber: A study of the phase equilibrium,rheological, and dynamic properties of compositions

A detailed study of butyl rubber-based vibration damping formulations linking their composition, morphology, phase structure, viscosity, mechanical loss factor, and other characteristics is presented for the first time. High performance of the compositions including aromatic petroleum oil is explained by limited solubility of the plasticizer that leads to the formation of a highly-viscous emulsion (η_20°C ≈ 1000 Pa·s) consisting of a swollen butyl rubber matrix and dispersed oil droplets in the broad composition range. Chalk is found to be the best inorganic filler as its spherical particles provide strong adhesion to the reinforcing layer of aluminum foil. Aiming to eliminate ecologically unfriendly aromatic compounds, a new low-cost binding agent formulation based on butyl rubber mixed with polyisobutylene and highly refined mineral oil is suggested. Being environmentally safe, it possesses high viscosity of 1000–3000 Pa·s, cohesion strength of 3.5–5.0 N/cm, penetration of 4.5–6.0 mm, and mechanical loss factor up to 0.34 at room temperature, which are as good as, or even better than, the properties of currently produced vibration damping materials containing aromatic compounds. New materials can be used in car and aircraft parts for effective vibration isolation.