Vol 52, No 6 (2016)

Gene therapy can offer a new approach to arthritis treatment which acts at an inflammation site. Numerous studies show high efficacy of gene therapy in different models of arthritis in humans. Even a single injection of a recombinant vector results in a stable prolonged expression of a therapeutic gene and a longterm therapeutic effect. In contrast to biologic therapy involving numerous systemic injections of recombinant anti-inflammatory proteins, gene therapy does not produce systemic side effects. Vectors based on retroviruses, adenoviruses, adeno-associated viruses, and recombinant plasmids could provide delivery of target genes. Of significant importance is the development of noninvasive methods of gene therapy: intranasal and peroral. The current state of research in arthritis gene therapy is discussed in this review.

On the basis of the results of hybridological analysis, it was established that significant differences in the stability of manifestation of the nptII gene expression are observed between the Nu5 and Nu6 lines obtained from the same initial Nu21 transformant (in spite of the identical genetic environment). Relatively stable expression of the marker gene is registered in the Nu5 line; the frequencies of detection of mosaic descendants are not high. The Nu6 line is characterized by a high frequency of the appearance of mosaic plants (up to 100%), indicating an increase in the marker gene inactivation in this line. When combining the nptII gene alleles in the hybrid genome, the allele coming from the Nu6 line was manifested as semidominant and had a suppressing effect on the allele coming from the Nu5 line. No transinactivation phenomena at the level of phenotype were detected during the interaction of the nptII gene alleles from the Nu5 and Nu6 lines in diheterozygote with the alleles of homologous genes inactivated at the transcriptional or post-transcriptional levels. During segregation to F₂, separation of the Nu21 line progeny into two independent groups with preservation of the different character of the marker gene expression (with a moderate level of appearance of mosaic plants for the Nu5 line and with high level for the Nu6 line) was again registered. Further studies are directed to detection of the mechanisms leading to the mosaic type of the studied gene manifestation in transgenic plants of the Nu5 and Nu6 lines.

The analysis of personal and published data on the frequency dynamics of chromosomal inversions within the range of Anopheles messeae obtained during the period from 1974 through 2014 is presented. The results showed that, in general, across the species range, during the 40 years of genetic monitoring, there was a steady (stationary) clinal distribution of inversions in the first decade (1974–1985). Then, over the period of five years (1986–1990), there was a considerable change in the inversion frequencies in favor of southwestern chromosomal variants (particularly strongly fixed in the Tomsk population), and from 1992 to the present time, these changes remained and were relatively stably reproduced in most parts of the range. It was noted that the jump in warming during the winter of 1981–1982 led to a correlated jump of the southwestern chromosomes in the Tomsk population. In connection with the general tendency toward the increase in average winter temperatures, a sharp decrease in the 2R₁ chromosome frequency in the Siberian region and Syktyvkar in the period from 1992 to the present time was observed. There is reason to assume that, over the past decade, the northern boundary of the An. messeae range moved northward to the tundra zone.

We studied the species composition and chromosomal variability of malaria mosquitoes in the Volga Basin (Upper, Middle, and Lower Volga regions). We investigated larvae karyotypes of sibling species of the Anopheles maculipennis group. We calculated the frequencies of chromosomal inversions in the local populations of the dominant species An. messeae. We discovered that karyotypic structure of An. messeae populations depends on landscape-climatic zones. Populations of the Upper, Middle and Lower Volga differ in frequency of chromosome inversions XL, 2R, 3R, and 3L.

Hereditary spastik paraplegias (HSP) are a group of neurodegenerative disorders with primary lesion of the pyramidal tract. The most frequent autosomal dominant form of the disease in Europeans is HSP associated with mutations in the spastin gene (SPG4). Analysis of the gene SPG4 was carried out in 52 unrelated families with HSP from Bashkortostan by SSCP and following sequencing. Previously undescribed frameshift mutations c.322del29 (p.Val108SerfsX18) and c.885del10 (p.Thr295ThrfsX16) were detected in two unrelated families. Clinical studies have shown that, in both families, the disease corresponds to an uncomplicated form of hereditary spastic paraplegia, a main feature of which is the lower spastic paraparesis without any other symptoms.

Permanent residents of Kharkiv (637 men and 856 women at the age of 45–65 years) are tested on the level of aggression and empathy. The average aggression level (41.7 points) is higher in migrants (born outside Kharkiv) than in indigenous people (36.3 points); the average empathy level is lower in migrants (3.2 points) than in indigenous people (5.5 points). The average values of the aggression and empathy indices are not associated with ethnicity and degree of miscegenation. The correlation between spouses (r) by these personal features is within 0.20–0.31; the marriage conjugation index (K) is 0.13–0.18. Genotyping of the married couples for the rs2235186 SNP of X-linked monoaminooxidase (MAO-A) gene detected a positive marriage assortativeness: the C × CC and T × TT pairs are developed more frequently than during panmixia; the C × TT and T × CC pairs, less frequently. The T allele is coupled with increased aggression level and decreased empathy level. The phenotypes of heterozygous women indicate the intermediate inheritance of these traits.

The present study searched for associations between gene GRIN2B (glutamate receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal Learning Test (RAVLT) as a part of a large neuropsychological battery was administered to 302 patients with schizophrenic spectrum disorders (sample PI). Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the “10 words” test that measures short-term memory. The GRIN2B rs7301328 (C366G) polymorphism was genotyped for each subject. There were no associations between the polymorphism and any measure of the RAVLT either in the whole PI sample or in a subsample of patients with a severe cognitive deficit. The GRIN2B influenced immediate recall and proactive interference in the “10 words” test in the control group: homozygotes CC recalled fewer words and showed a lower effect of proactive interference than carriers of other genotypes. The results suggest that the C366G polymorphism could influence verbal episodic memory in the general population, but this influence is absent in schizophrenic patients.

The paper provides the annotation and data on sequencing the antibiotic resistance genes in Streptomyces fradiae strain ATCC19609, highly sensitive to different antibiotics. Genome analysis revealed four groups of genes that determined the resistome of the tested strain. These included classical antibiotic resistance genes (nine aminoglycoside phosphotransferase genes, two beta-lactamase genes, and the genes of puromycin N-acetyltransferase, phosphinothricin N-acetyltransferase, and aminoglycoside acetyltransferase); the genes of ATP-dependent ABC transporters, involved in the efflux of antibiotics from the cell (MacB-2, BcrA, two-subunit MDR1); the genes of positive and negative regulation of transcription (whiB and padR families); and the genes of post-translational modification (serine-threonine protein kinases). A comparative characteristic of aminoglycoside phosphotransferase genes in S. fradiae ATCC19609, S. lividans TK24, and S. albus J1074, the causative agent of actinomycosis, is provided. The possibility of using the S. fradiae strain ATCC19609 as the test system for selection of the macrolide antibiotic oligomycin A derivatives with different levels of activity is demonstrated. Analysis of more than 20 semisynthetic oligomycin A derivatives made it possible to divide them into three groups according to the level of activity: inactive (>1 nmol/disk), 10 substances; with medium activity level (0.05–1 nmol/disk), 12 substances; and more active (0.01–0.05 nmol/disk), 2 substances. Important for the activity of semisynthetic derivatives is the change in the position of the 33rd carbon atom in the oligomycin A molecule.