Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation.

Bronchial asthma (BA) is a disease that still lacks an exhaustive treatment protocol. In this regard, the global medical community pays special attention to the genetic prerequisites for the occurrence of this disease. Therefore, the search for the genetic polymorphisms underlying bronchial asthma has expanded considerably. As the present study progressed, a significant amount of scientific medical literature was analyzed and 167 genes reported to be associated with the development of bronchial asthma were identified. A group of participants (n = 7,303) who had voluntarily provided their biomaterial (venous blood) to be used in the research conducted by the Federal Medical Biological Agency of Russia was formed to subsequently perform a bioinformatic verification of known associations and search for new ones. This group of participants was divided into four cohorts, including two sex-distinct cohorts of individuals with a history of asthma and two sex-distinct cohorts of apparently healthy individuals. A search for polymorphisms was made in each cohort among the selected genes, and genetic variants were identified whose difference in occurrence in the different cohorts was statistically significant (significance level less than 0.0001). The study revealed 11 polymorphisms that affect the development of asthma: four genetic variants (rs869106717, rs1461555098, rs189649077, and rs1199362453), which are more common in men with bronchial asthma compared to apparently healthy men; five genetic variants (rs1923038536, rs181066119, rs143247175, rs140597386, and rs762042586), which are more common in women with bronchial asthma compared to apparently healthy women; and two genetic variants (rs1219244986 and rs2291651) that are rare in women with a history of asthma.

The Effect of Contact Non-equilibrium Plasma on Structural and Magnetic Properties of Mn Х Fe3 - X О4 Spinels.

Nano-sized manganese ferrites Mn х Fe3 - Ñ… О4 (х = 0-1.3) were prepared using contact non-equilibrium plasma (CNP) in two different pH (11.5 and 12.5). The influence of synthesis conditions (e.g., cation ratio and initial pH) on phase composition, crystallite size, and magnetic properties were investigated employing X-ray diffraction (XRD), differential thermal analysis (DTA), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and magnetic measurement techniques. The formation of monodispersed faceted ferrite particles at х = 0-0.8 was shown. The FTIR spectra revealed reflection in region 1200-1700 cm-1 caused by the presence of water adsorbed on the surface of Fe3 - x Mn x O4 micro-granules or embedded into their crystal lattice. The most sensitivity of reflection spectra to the composition changes takes place within a 400-1200 cm-1 range, typical to the stretching vibrations of Fe(Mn)-O (up to 700 cm-1 ), Fe(Mn)-OH, and Fe(Mn)-OH2 bonds (over 700 cm-1). The XRD results showed that the nanocrystalline Mn х Fe3 - Ñ… О4 (0 < x < 1.0) had cubic spinel crystal structure with average crystallite size 48-49 A. The decrease of crystalline size with the x increase was also observed.

Intraretinal variability and specialization of cones in Japanese anchovy (Engraulis japonicus, Engraulidae).

The retina of anchovies is characterized by an unusual arrangement and ultrastructure of cones. In the retina of Japanese anchovies, Engraulis japonicus, three types of cones are distributed into rows. The nasal, central, temporal, and ventro-temporal regions of the retina were occupied exclusively by the long and short cones. Triple cones, made up of two lateral components and one smaller central component, were found only in the dorsal and ventro-nasal retinal regions. In the outer segments of all short and long cones from the ventro-temporal region, the lamellae were oriented along the cell axis and were perpendicular to the lamellae in the long cones, providing a morphological basis for the detection of polarization. This lamellar orientation is unique to all vertebrates. The cones were examined with respect to regional differentiation in their size and spectral properties via light microscopy, transmission electron microscopy, and microspectrophotometry. Various dimensions of cones were measured in preparations of isolated cells. The cones from the ventro-temporal region had different dimensions than cones of the same type located in other retinal regions. Triple cones from the dorsal region were significantly larger than triple cones from the ventro-nasal region. The spectral absorbance of the lateral components of triple cones in the ventro-nasal retina was identical to the absorbance of all long and short cones from the ventro-temporal region. These are shifted to shorter wavelengths relative to the absorbance of the lateral components of the triple cones located in the dorsal retina. Thus, the retina of the Japanese anchovy shows some features of regional specialization common in other fishes that improves spatial resolution for the upwards and forwards visual axis and provides spectral tuning in downwelling light environment. That results from the differentiation of cone types by size and by different spectral sensitivity of various retinal areas.

[THE APPLICATION OF SELECTIVE CHROMOGENIC AGAR FOR DETECTING ENTEROBACTERIA WITH PRODUCTION OF BETA-LACTAMASES].

The detection of enterobacteria with production of beta-lactamases of extended spectrum in selective chromogenic agar was analyzed The results ofdetection of beta-lactamases of extended spectrum was compared with "double disc" technique. The smears from mucous membrane of guttur and rectum from patients were analyzed in parallel on solid growth agar (Endo or Mac Conkey) and on selective agar CHROMagartm ESBL (CHROMagar France). The production of beta-lactamases of extended spectrum was confirmed using "double discs" technique. To exclude hyper-production of ampC beta-lactamases E-test was applied containing cefotetan and cefotetan with cloxacillin. The sampling consisted of 1552 samples from patients. The study permitted to isolate 1243 strains of enterobacteria on agar Endo or Mac Conkey and 409 strains of enterobacteria on selective agar CHROMagartm ESBL (Escherichia coli n = 226, Klebsiella pneumoniae n = 105, enterobacter spp. n = 35, Citrobacter spp. n = 21, others n = 22). The application of "double discs" technique confirmed production of beta-lactamases of extended spectrum in 386 (94%) out of 409 strains isolated on agar CHROMagartm ESBL. In 23 (6%) of strains no confirmation was established and hyper-production of ampC of beta-lactamases was established 15 out of total. Additionally, 8 were sensitive to cephalosporin of third generation. All enterobacteria isolated on agar Endo or Mac Conkey also were tested by "double discs" technique. Overall, 394 strains of enterobacteria with production of beta-lactamases of extended spectrum were obtained. On all agars (agar Endo or Mac Conkey and CHROMagartm ESBL)--263 (67%) strains; only on CHROMagartm ESBL--123 (31%) and only on agar Endo or Mac Conkey--8 (2%) (p < 0.0001). The sensitivity of selective agar CHROMagartm ESBL made up to 98% and specificity--97%. The resolution about detection of enterobacteria producing beta-lactamases of extended spectrum were submitted to clinic in 18-24 hours after arrival ofsamplesfrom patients in laboratory. The CHR OMagartm ESBL has higher sensitivity and specificity to detect enterobacteria with production of beta-lactamases of extended spectrum and can be applied in common laboratory practice.

The morphology of the digestive tract and respiratory organs of the holothurian Cladolabes schmeltzii (Holothuroidea, Dendrochirotida).

The microanatomy of the digestive and respiratory systems of the holothurian Cladolabes schmeltzii was studied. The digestive tube of C. schmeltzii is divided into seven parts. The pharynx, esophagus, and stomach are lined with cuticular immersed epithelium. In these regions, the epithelial cells are connected via desmosomes, septate junctions, and rivet-like structures. The presence of the cuticle and rivet-like structures suggests an ectodermal origin for these parts of the digestive tube. The luminal intestinal epithelium is formed by vesicular enterocytes, which have different structures in different intestinal regions. Moreover, the epithelium of the first descending part of the intestine contains the granular enterocytes. The respiratory system consists of paired respiratory trees lined by a luminal epithelium that is formed by cells of irregular shape. The apical surface of these epithelial cells has few lamellae. The cells are connected to each other through a system of intercellular junctions, consisting of both desmosomes and well-developed septate junctions. The coelomic epithelium of the intestine and the respiratory trees consists of peritoneal and myoepithelial cells.

[Translation termination factor of eRFI of the ciliate Blepharisma japonicum recognizes all three stop codons].

We have determined the type of stop codon specificity of Blepharisma japonicum translation termination factor eRF1 in an in vitro reconstituted eukaryotic translation system and in in vivo assay (the dual reporter system). We have shown that B. japonicum eRF1 retained specificity towards all three stop codons although efficiency of peptydyl-tRNA hydrolysis in the presence of UGA is reduced in an in vitro assay. We suggest that since the heterotrich B. japonicum represents the earliest diverged lineage on phylogenetic tree of ciliates, B. japonicum has the universal genetic code as ancestor group for all ciliates.

[The association between the NRG1 gene polymorphism and cognitive functions in patients with schizophrenia and healthy controls].

NRG1 is a strong candidate for schizophrenia though its role in the pathogenesis of the disease remains unknown. One of the approaches to study mechanisms underlying the association between NRG1 and schizophrenia is to investigate the association between a gene and an endophenotype of schizophrenia, e.g., cognitive dysfunctions. Authors looked for the association of 478B14-848 и 420M9-1395 microsatellites with semantic verbal fluency, working and episodic memory in 338 patents with schizophrenia, 162 their unaffected relatives and 316 healthy controls from the Russian population. It was found associations between allele 0 at 478B14-848 (220 bp) and long-term episodic memory and between allele 0 at 420M9-1395 (274 bp) and short-term memory in schizophrenic patients. The frequency of homozygotes for 420M9-1395 was higher in the group of patients as compared to controls. In conclusion, the risk allele 0 at 420M9-1395 is associated with the short-term memory deficit while allele 0 at 478B14-848 is protective for long-term memory deficits.

[Molecular-genetic study of early-onset schizophrenia].

Schizophrenia with early onset is a relatively rear form of the disease which characterized by severe chronic course and poor outcome. In the present paper, we studied several genes possibly involved in the pathogenesis of this form. These are genes for brain-derived neurotrophic factor (Val66Met polymorphism), serotonin transporter (5-HTTLPR), serotonin receptor type 2A (T102C) and dopamine receptor D2 (Taq1A). Sixty-five patients (age at onset before 15 years) and 111 healthy controls were included in the study. Out of all genes tested, the association was found only for the Val66Met BDNF polymorphism. Frequency of the ValVal genotype was higher in the group of patients (p=0.03; OR 2.1 CI 1.1-4.0) compared to the controls. These results were consistent with our previous study which was carried out on the sample of schizophrenic patients with later age of disease onset. In this study, the frequency of the ValVal genotype was higher only in the group of patients with chronic schizophrenia compared to the controls. It is concluded that the ValVal BDNF genotype may be considered as a marker of schizophrenia with more severe course.

[Regional "occupational medicine" system--effective model of occupational risks evaluation and management].

Sverdlovsk regional government specified and approved a concept of diversified system "Occupational medicine" to preserve and improve health of workers in Sverdlovsk region. Implementation of the concept enables to put new organizational approaches into practice for improved management of available medical care for all workers, for increased quality of this care, for better clinical work and better health of economically active population in Sverdlovsk region.

[Protein S3 fragments neighboring mRNA during elongation and translation termination on the human ribosome].

Protein S3 fragments were determined that crosslink to modified mRNA analogues in positions +5 to +12 relative to the first nucleotide in the P-site binding codon in model complexes mimicking states of ribosomes at the elongation and translation termination steps. The mRNA analogues contained a Phe codon UUU/UUC at the 5'-termini that could predetermine the position of the tRNA(Phe) on the ribosome by the location of P-site binding and perfluorophenylazidobenzoyl group at a nucleotide in various positions 3' of the UUU/UUC codon. The crosslinked S3 protein was isolated from 80S ribosomal complexes irradiated with mild UV light and subjected to cyanogen bromide-induced cleavage at methionine residues with subsequent identification of the crosslinked oligopeptides. An analysis of the positions of modified oligopeptides resulting from the cleavage showed that, in dependence on the positions of modified nucleotides in the mRNA analogue, the crosslinking sites were found in the N-terminal half of the protein (fragment 2-127) and/or in the C-terminal fragment 190-236; the latter reflects a new peculiarity in the structure of the mRNA binding center in the ribosome, unknown to date. The results of crosslinking did not depend on the type of A-site codon or on the presence of translation termination factor eRF1.

[Investigation of association of the brain-derived neurotrophic factor (BDNF) and a serotonin receptor 2A (5-HTR2A) genes with voluntary and involuntary attention in schizophrenia].

To investigate the effect of Val66Met BDNF and 5-HTR2A T102C polymorphisms on the characteristics of voluntary and involuntary visual attention, 89 patients with schizophrenia, 91 their well relatives and 163 controls have been studied. Attention was assessed using a modified version of the Munsterberg test. The significant interaction effect of the BDNF, 5-HTR2A and diagnosis on attention characteristics was found (p=0,04). Carriers of the Val/Val genotype demonstrated higher scores of both voluntary and involuntary attention and those with the A1 (T) allele needed more time for the performance of the test. The combination of the A1 allele with a Met BDNF allele was associated with lower scores of voluntary attention and higher scores of involuntary attention. The study confirmed the impairment of selective attention in patients with schizophrenia and their relatives while any pathological changes in involuntary attention were not observed. The effect of genotypes was presented irrespective of diagnostic group studied. The data obtained suggest that carriers of the Val/Val genotype are able to allocate more attentional resources to process external stimuli. At the same time, the possibility that this polymorphism is likely associated with specific visual-spatial abilities than with attention as such or general cognitive resources can not be excluded.

[How translation termination factor eRF1 Euplotes does not recognise UGA stop codon].

In universal-code eukaryotes, a single class-1 translation termination factor eRF1 decodes all three stop codons, UAA, UAG, and UGA. In some ciliates with variant genetic codes one or two stop codons are used to encode amino acid(s) and are not recognized by eRF1. In Stylonychia, UAG and UAA codons are reassigned as glutamine codons, and in Euplotes, UGA is reassigned as cysteine codon. In omnipotent eRF1s, stop codon recognition is associated with the N-terminal domain of eRF1. Because variant-code ciliates most likely evolved from universal code ancestor(s), structural features should exist in ciliate eRF1s that restrict their stop codon recognition. To find out amino acid residues which confer UAR-only specificity to Euplotes aediculatus eRF1, eRFI chimeras were constructed by swapping eRF1 E. aediculatus N-terminal domain sequences with the matching ones from the human protein. In these chimeras the MC-domain was from human eRF1. Functional analysis of these chimeric eRFI highlighted the crucial role of the two regions (positions 38-50 and 123-145) in the N-terminal domain of E. aediculatus eRF1 that restrict E. aediculatus eRF1 specificity toward UAR codons. Possibly, restriction of eRF1 specificity to UAR codons might have been an early event occurring in independent instances in ciliate evolutionary history, possibly facilitating the reassignment of UGA to sense codons.

[C-domain of translation termination factor eRF1 neighbors stop codon at the 80S ribosomal A site].

Positioning of stop codon and the adjacent triplet downstream of it with respect to the components of human 80S termination complex was studied with the use of mRNA analogues that bore stop signal UPuPuPu (Pu is A or G) and photoactivatable perfluoroaryl azide group. This group was attached to one of nucleotides of the stop signal or 3' of it (in positions +4 to +9 with respect to the first nucleotide of the P site codon). It was shown that upon mild UV irradiation the mRNA analogues crosslinked to components of model complexes imitating state of 80S ribosome in the course of translation termination. It was found that termination factors eRF1 and eRF3 do not affect mutual arrangement of stop signal and the 18S rRNA. Factor eRF1 was shown to cross-link to modified nucleotides in positions +5 to +9 (ability of eRF1 to cross-link to stop codon nucleotide in position +4 was shown earlier). Fragments of eRF1 containing cross-linking sites of the mRNA analogues were determined. In fragment 52-195 (containing the N-domain and a part of the M-domain) we have found cross-linking sites of the analogues that bore modifying groups on A or G in positions +5 to +9 or at the terminal phosphate of nucleotide in position +7. For mRNA analogues bearing modifying groups on G site of cross-linking from positions +5 to +7 was found in the eRF1 fragment

Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83, Lactobacillus casei) influences the severity of dextran sodium sulfate-induced colitis in BALB/c mice.

Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.

[Angiotensin converting enzyme inhibitor moexipril in the treatment of arterial hypertension. Possibilities of moexipril in the treatment of postmenopausal women].

Data on efficacy and safety of angiotensin converting enzyme inhibitor moexipril in the treatment of arterial hypertension are reviewed. Such advantages of this preparation as 24-hour duration of action, lack of loss of hypotensive effect during long term administration, metabolic neutrality, and low rate of side effects are discussed. Antihypertensive action of moexipril is compared with other medicines. Special attention is devoted to various aspects of the use of moexipril in women in postmenopause, including positive effect on metabolism of bones and combination with hormonal replacement therapy.

[Influence of individual domains of the translation termination factor eRF1 on induction of the GTPase activity of the translation termination factor eRF3].

Translation termination in eukaryotes is governed by two proteins, belonging to the class-1 (eRF1) and class-2 (eRF3) polypeptide release factors. eRF3 catalyzes hydrolysis of GTP to GDP and inorganic phosphate in the ribosome in the absence of mRNA, tRNA, aminoacyl-tRNA and peptidyl-tRNA but needs the presence of eRF1. It's known that eRF1 and eRF3 interact with each other in vitro and in vivo via their C-terminal regions. eRF1 consists of three domains - N, M, and C. In this study we examined the influence of individual domains of the human eRF1 on induction of the human eRF3 GTPase activity in the ribosome in vitro. It was shown that none of the N-, M-, C- and NM-domains induces eRF3 GTPase activity in presence of the ribosomes. MC-domain does induce GTPase activity of eRF3 but four times less efficient than full-length eRF1, therefore, MC-domain (and very likely M-domain) binds to the ribosome in the presence of eRF3. Based on these data and taking into account the data available in literature, a conclusion was drawn that the N domain of eRF1 is not essential for eRF1-dependent induction of the eRF3 GTPase activity. A working hypothesis is formulated, postulating that GTPase activity eRF3 during the translation termination is associated with the intermolecular interactions of GTP/GDP, GTPase center of the large ribosomal subunit (60S), MC-domain of eRF1, C-terminal region and GTP-binding domains of eRF3, but without participation of the N-terminal region of eRF3.

Interaction of mucosal microbiota with the innate immune system.

Organisms live in continuos interaction with their environment; this interaction is of vital importance but at the same time can be life threatening. The largest and most important interface between the organism and its environment is represented by surfaces covered with epithelial cells. Of these surfaces, mucosae comprise in humans approximately 300 m2, and the skin covers approximately 1.8 m2 surface of the human body. Mucosal tissues contain two effector arms of the immune system, innate and adaptive, which operate in synergy. Interaction with commensal bacteria, which outnumber the nucleated cells of our body, occurs physiologically on epithelial surfaces; this interaction could pose the risk of inflammation. The mucosal immune system has developed a complex network of regulatory signalling cascades that is a prerequisite for proper activation but also for a timely inactivation of the pathway. As demonstrated in gnotobiotic animal models of human diseases, impaired regulation of mucosal responses to commensal bacteria plays an important role in the development of several inflammatory and autoimmune diseases.

[Peculiarities of attention in families with schizophrenia: correlation between psychological and neurophysiological characteristics].

A relationship between neurophysiological and psychological characteristics of attention was studied in 18 patients with schizophrenia and their 34 mentally healthy relatives: parents and siblings (20 subjects) and children (14 subjects). In patients, a decrease of P300 auditory evoked potentials significantly correlated with disturbances of attention stability and volume as well as characteristics of involuntary attention. At the same time, in the groups of relatives the anomalies of attention stability and attention in conditions of prolonged concentration were positively related to P300 latency.