[Variability of Fragments of Nuclear Brca1 Gene, Exon 11, and Mitochondrial Cox1 Gene in House Mice Mus musculus].

To clarify genetic differences between subspecies of the house mouse Mus musculus, their distribution, and hybridization, we first conducted a comparative analysis of variability of nucleotide sequences of fragments of the nuclear gene Brca1, exon 11 (2331 bp), and mitochondrial gene Cox1 (1260 bp) in 40 house mice from West and East Europe, Transcaucasia, Siberia, and Central and South Asia. Brca1 genotypes were divided into five main groups, which differed in a number of fixed substitutions. Genotypes of each group are characteristic for the certain geographical region and the following subspecies: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. wagneri together with M. m. gansuensis; a fifth group corresponds to an unidentified subspecies or a distinct genetic form of M. musculus from India (Sikkim State). Besides the homozygous specimens, we revealed mice, which were heterozygous for all diagnostic loci simultaneously; these specimens were determined as hybrid. Hybrid mice were mainly found in the zones of contact of subspecies, but in some cases, quite far from one of the parent subspecies (possibly, due to transportation). In two hybrid mice (from Bakhtiari Province of Iran and Transbaikalia of Russia), unique Brca1 haplotypes were detected. It cannot be ruled out that, at least partly, they may be characteristic of the M. m. bactrianus and M. m. gansuensis subspecies, respectively. Thus, the results of the study showed that the nuclear Brca1 gene is a promising molecular genetic marker for the analysis of variability, differentiation, and hybridization of house mice as well for subspecific identification of M. musculus specimens. Despite more rapid evolution of the Cox1 gene, it is not well suited for discrimination of M. m. musculus, M. m. wagneri, M. m. gansuensis specimens and Transcaucasian representatives of M. m. domesticus due to introgression and long-term maintenance of foreign mitochondrial DNA in populations. However, Cox1 gene analysis (along with the diagnostics of animals by nuclear DNA) may be useful for estimation of population differences in M. m. castaneus and M. m. domesticus subspecies.

['Masks' of acute neuroinfections and markers of differencial diagnosis]. / 'Maski' ostrykh neiroinfektsii i markery differentsial'noi diagnostiki.

AIM: To compare thе medical history, clinical features, composition of cerebrospinal fluid (CSF), results of laboratory and instrumental examinations of patients with acute neuroinfections and differentiable diseases including a pseudoinflammatory variant of the acute stage of uncomplicated subarachnoid hemorrhage (SAH), consequences of traumatic brain injury (traumatic SAH, SAN combination with secondary purulent meningitis, posttraumatic nasal liquorrhea, intracerebral hematomas), abscesses and tumors of the brain, lymphoma with proven CNS. These diagnoses were mistakenly made to patients admitted to an infectious department. MATERIAL AND METHODS: Forty-six patients, aged from 18 to 83 years, hospitalized in the Department of neuroinfections and intensive care in 2010-2016 were examined. Conventional clinical neurological, laboratory, instrumental (including MRI) examinations of patients, comprehensive examination of CSF samples, the study of markers of inflammation (C - reactive protein, CSF lactate), immunophenotyping of CSF cells were performed. RESULTS AND CONCLUSION: The misdiagnosis can be explained by the overestimation of such symptoms as the acute (in most cases) onset of the disease with increased body temperature to febrile levels, presence of meningeal syndrome, disorders of consciousness and focal symptoms of varying severity. The authors showed the errors and difficulties in the diagnosis, the role and importance of an integrated, interdisciplinary approach taking into account history, clinical data, results of CSF study, conventional and special methods of laboratory and instrumental examination of patients.

Genetic Differentiation of the Steppe Field Mouse Sylvaemus witherbyi Populations: The Results of the Mitochondrial DNA Control Region Analysis.

The degree of genetic diversity of the steppe field mouse was estimated on the basis of the mtDNA control region variability data. Polymorphism of this mtDNA marker in S. witherbyi was more pronounced than previously assumed. The steppe field mouse population from the northern shore of Lake Manych-Gudilo includes several mitochondrial lines, which may be due to the existence of several migration flows to this area from Southwest Asia.

Role of estrogen receptor α and ß in the induction of progesterone receptors in hypothalamic ventromedial neurons.

The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is critical for the regulation of female sexual behavior. VMNvl neurons express PRs and both types of estrogen receptors (ERα and ERß), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvl of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ERα, propyl-pyrazole triol (PPT), and of the ERß, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons. The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvl does not involve solely the activation of the ERα and suggests that it might also implicate the activation of membrane receptors. The present results also show that ERß activation averts the action of ERα in the induction of PRs.

Regulation of ERα protein expression by 17ß-estradiol in cultured neurons of hypothalamic ventromedial nucleus.

The activation of the subtype α of estrogen receptors (ERα) in the hypothalamic ventromedial nucleus (VMNvl) is required to stimulate female sexual receptivity. Moreover, the hormone was found to govern the expression of the receptor. Its removal due to ovariectomy and subsequent substitution suggest that the hormone down-regulates the expression of ERα. In contrast, in normally cycling animals the expression of the receptor peaks at proestrus, the phase of highest concentration of 17ß-estradiol in estrous cycle. Therefore, in this study we examined the influence of the hormone on ERα expression in primary dissociated cultures of neurons isolated from the VMNvl of young adult female rats. Measurements of ERα immunofluorescence revealed that both supraphysiological and physiological concentrations of 17ß-estradiol increase the expression of ERα. Analyses with selective agonists showed that both nuclear ERs are able to mediate the action of the hormone. However, the activation of ERα had a stronger effect on the expression of its own receptor than the activation of ERß. Simultaneous activation of both receptors attenuated the influence of ERα alone. Physiological concentrations of progesterone were found to revoke the effect of 17ß-estradiol, whereas the expression of ERα is up-regulated by progesterone alone. These data indicate that the expression of ERα in VMNvl neurons is under the control of both types of nuclear ERs and, in addition, progesterone receptors (PRs). The particular contribution of the receptors is dependent on their level of expression and the hormonal context. In neurons expressing high quantity of ERα, ERß attenuates the overall expression of the receptor, whereas in cells containing mostly ERß it contributes to the up-regulation of ERα synthesis. Simultaneous activation of ERs and PRs reverses the influences of the receptors due to inter-inhibition of their transcriptional activities.

[Correlation between the receptor specificity of pandemic influenza A (H1N1)pdm09 virus strains isolated in 2009-2011 and the structure of the receptor-binding site and the probability of fatal primary viral pneumonia].

The receptor specificity (RS) of pandemic influenza A(H1N1) pdm09 virus strains deposited into the State Collection of Viruses of the Russian Federation, D. I. Ivanovsky Research Institute of Virology, Ministry of Health and Social Development of Russia, in the 2009-2010 and 2010-2011 epidemic seasons to a panel of 9 sialoglycopolymers (SGP). The strains were divided into 3 groups according to the W(3/6) index proposed by the authors, which was equal to the amount of reactivities to unbranched alpha2-3-SGP to that of reactivities to unbranched alphal-6-SGP: W(3/6) < or = 1.0; 1.0 < W(3/6) < or = 1.5. The W(3/6) < or = 1.5 group showed a predominance of a2-3-RS, attended by the high incidence of fatal primary viral pneumonias (FPVP) (60.0%) and amino acid replacements in the HA1 receptor-binding site (RBS) (80.0%): D222{G, N} and Q223R. The 1.0 < W(3/6) < or = 1.5 group was characterized by mixed alpha2-3/alpha2-6-RS with the incidence of FPVP (29.7%) and amino acid replacements in the HA1 RBS (40.5%) (D222{G, N, V} and Q223), respectively. In the W(3/6) < or = 1.0 group, alpha2-6-RS was prevalent, FPVPs were absent and amino acid replacements in HA1 RBS (D222{G, E}) were seen only in 6.0% of cases. The number of strains with increased specificity to alpha2-3-sialosides increased in the 2010-2011 epidemic season as compared to the previous season. With their further spread among the population, there may be a rise in cases of severe primary viral pneumonias with possible fatal outcomes, which can be, however, accompanied by a decrease in the capacity of mutants to air-dropwise transmission.

[The specific features of the cocirculation of influenza viruses in the 2010-2011 postpandemic period according to the results of activities of the D. I. Ivanovsky Research Institute of Virology, Ministry of Health and Social Development of Russia].

The paper gives the results of monitoring the circulation of influenza viruses in the 2010-2011 season, that covers the second year of circulation of pandemic A(H1N1)v virus strains, and their interaction with seasonal A (H3N2) and B strains. Unlike the previous season, the beginning of an increase in morbidity was recorded in January 2011; its peak in the most of contiguous areas was noted at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of 2011. Preschool and school children were most involved in the epidemic process. Three influenza virus strains (A(H1N1)v, A(H3N2), and B) were found to circulate. Differences were found in the level of participation of the isolated strains in individual areas of the Russian Federation. Detailed typing of the isolated strains determined the compliance of the vast majority of them with vaccine viruses. The pandemic influenza A(H1N1)v virus strains retained their susceptibility to oseltamivir and were resistant to rimantadine. The participation of non-influenza acute respiratory viral infection pathogens was estimated as follows: 11.9% for parainfluenza viruses, 5.9% for adenoviruses, and 3.5% for PC viruses, and 0.7% for pneumonia Mycoplasma, which was comparable with the previous epidemic seasons.

[Satellite DNA as a phylogenetic marker: case study of three genera of the Murinae subfamily].

Satellite DNA (satDNA) represent tens percent of any of the vertebrate genome. Still, a complete set of sat-DNA fragments is not determined for either species. It is known that some genus with species-specific modifications possess a satDNA characteristic for the genus. So, satDNA was used as a phylogenetic marker in some cases when precise satDNA fragment was cloned. We used the probe of the whole pericentromeric region and 4 cloned satDNA fragments of Mus musculus in order to consider probes value for phylogenesis of 3 Murinae genera. Fluorescent in situ hybridization (FISH) revealed similar pattern on metaphase spreads inside genus Mus, though some difference was noted. None of the satDNA fragment gave signal in the centromeric region on chromosomes from genera Sylvaemus and Apodemus. These data are in agreement with those on satDNA fragments in the genome determined by dot-blot hybridization: M musculus satDNA fragments are absent in the genomes of both remote genera while they are present in the genomes of the genera Mus, though in different amounts. SatDNA of each genera should be cloned for the phylogenetic purposes.

[Comparative analysis of methods for laboratory diagnosis of Lyme's disease in early stages of infection]. / Sravnitel'nyi analiz metodov laboratornoi diagnostiki bolezni laima na rannei stadii infektsii.

Different methods of laboratory diagnostics were comparatively analyzed in examining 25 patients at the early infection stage. Sera were measured by using various serological reactions. Specific antibodies were determined by using the reaction of indirect immune-fluorescence (RIIF), the immune-enzyme analysis (IEA) and the complement-binding reaction (CBR) in 83.1%, 54.4% and 12.5% of cases, respectively. Essential differences in sensitivity were detected between the above methods. RIIF was proven to be a reliable and sufficiently sensitive method in the laboratory diagnostics of Lyma's disease. While the use of two methods, i.e. RIIF and IEA, ensures the highest percentage of detection of antibodies to the causative agent of Lyma's disease.

Self-organization of a radial microtubule array by dynein-dependent nucleation of microtubules.

Polarized radial arrays of cytoplasmic microtubules (MTs) with minus ends clustered at the cell center define the organization of the cytoplasm through interaction with microtubule motors bound to membrane organelles or chromosomes. It is generally assumed that the radial organization results from nucleation of MTs at the centrosome. However, radial MT array can also be attained through self-organization that requires the activity of a minus-end-directed MT motor, cytoplasmic dynein. In this study we examine the role of cytoplasmic dynein in the self-organization of a radial MT array in cytoplasmic fragments of fish melanophores lacking the centrosome. After activation of dynein motors bound to membrane-bound organelles, pigment granules, the fragments rapidly form polarized radial arrays of MTs and position pigment aggregates at their centers. We show that rearrangement of MTs in the cytoplasm is achieved through dynein-dependent MT nucleation. The radial pattern is generated by continuous disassembly and reassembly of MTs and concurrent minus-end-directed transport of pigment granules bearing the nucleation sites.

Dissociative mechanism of thermal denaturation of rabbit skeletal muscle glycogen phosphorylase b.

The thermal stability of rabbit skeletal muscle glycogen phosphorylase b was characterized using enzymological inactivation studies, differential scanning calorimetry, and analytical ultracentrifugation. The results suggest that denaturation proceeds by the dissociative mechanism, i.e., it includes the step of reversible dissociation of the active dimer into inactive monomers and the following step of irreversible denaturation of the monomer. It was shown that glucose 1-phosphate (substrate), glucose (competitive inhibitor), AMP (allosteric activator), FMN, and glucose 6-phosphate (allosteric inhibitors) had a protective effect. Calorimetric study demonstrates that the cofactor of glycogen phosphorylase-pyridoxal 5'-phosphate-stabilizes the enzyme molecule. Partial reactivation of glycogen phosphorylase b preheated at 53 degrees C occurs after cooling of the enzyme solution to 30 degrees C. The fact that the rate of reactivation decreases with dilution of the enzyme solution indicates association of inactive monomers into active dimers during renaturation. The allosteric inhibitor FMN enhances the rate of phosphorylase b reactivation.

Notes on mites of the family Myobiidae (Acari: Prostigmata) parasitising rodents (Mammalia: Rodentia) in Iran.

Six mite species of the family Myobiidae, Radfordia (Austromyobia)persica sp. n., Radfordia (Austromyobia) merioni Bochkov, Dubinina et Chirov, 1990, Radfordia (Radfordia) acomys Fain et Lukoschus, 1977, Radfordia (Radfordia) affinis (Poppe, 1896), Radfordia (Graphiurobia) dyromys Fain et Lukoschus, 1973, and Myobia (Myobia) murismusculi (Schrank, 1781) were found in Iran on the rodents Gerbillus cheesmani Thomas, Meriones libycus Lichtenstein, Acomys cahirinus (Desmarest), Alus musculus L., Dryomys nitedula (Pallas), and Mus muscullus, respectively. R. (A.) persica is described as a new species from the female, male and tritonymph. The other five myobiid species are new to Iran.

Comparative cytogenetics of hamsters of the genus Calomyscus.

Karyotypes of Calomyscus from different regions of Turkmenistan, Iran, and Azerbaijan were studied using chromosome banding (G- and C-banding) and analyses of meiosis in laboratory hybrids. Extensive variation in the diploid number and the number of autosomal arms (FNa) was revealed (2n = 30, FNa = 44; 2n = 32, FNa = 42; 2n = 44, FNa = 46; 2n = 44, FNa = 58; 2n = 37, FNa = 44; 2n = 50, FNa = 50; 2n = 52, FNa = 56). Centric and tandem fusions and heterochromatin changes were identified as the major modes of karyotype evolution in this group. Natural hybrids between individuals with different karyotypes were recorded, and regular chromosome pairing in meiosis was observed in laboratory hybrids. Fluorescence in situ hybridization with a 353-bp BspRI complex tandem repeat indicated that chromosomal repatterning occurred recently within the genus. There is no unequivocal evidence suggesting the role of chromosomal change in the speciation of the populations of Calomyscus examined.

Mitochondrial DNA and chromosomal studies of wild mice (Mus) from Turkey and Iran.

Complete D-loop sequences of 20 Mus from three localities in Turkey and seven in Iran were characterized. These countries are thought to be close to the place of origin of the subspecies Mus musculus domesticus. Five new M. m. domesticus haplotypes were added to the nine already known for the region. Four of these 14 haplotypes were very similar to the consensus D-loop sequence for western Europe defined by Nachman et al. (1994), which may represent the ancestral condition for M. m. domesticus. A divergent mtDNA lineage is found in various parts of Turkey and northern Iran; it has spread into western Europe, but other European lineages were not found in either Turkey or Iran. The other Mus D-loop sequences were of M. m. castaneus and Mus macedonicus and confirmed M. macedonicus as a monotypic species with low nucleotide diversity. The prevalence of the standard 40-chromosome complement in this region is particularly interesting with regards M. m. domesticus, as it is consistent with the in situ origin of Robertsonian karyotypic races (2n < 40) in western Europe.

[Bacterial endotoxinemia in children with intestinal dysbacteriosis]. / Bakterial'naia éndotoksinemiia u detei s disbiozom kishechnika.

34 children with gastrointestinal diseases of infectious, allergic and mixed etiology were examined. The state of normal microflora in the large intestine as indicated by fecal bacterial charts and the level of secretory immunoglobulin A (sIgA) in the contents of the intestine as indicated by the results of radial immunodiffusion were studied. In addition, the content of endotoxin in the children's plasma was determined with the use of the Limulus (LAL) test. The presence of endotoxin in the plasma of children with intestinal dysbiosis was determined in 71.1% of cases. The frequency of the detection of antigenemia was found to be related to the severity of manifestations of dysbiotic changes in the intestine and to the level of sIgA in fecal supernatants. The inclusion of the probiotic preparation Bifidumbacterin forte containing live bifidobacteria adsorbed on activated charcoal into the complex therapy of digestive tract diseases ensured a decrease in the detection rate of endotoxinemia, which correlated with the tendency towards the normalization of defective intestinal microflora.

[The results of a multicenter study of the comparative activity of cefepime and other antibiotics against the causative agents of severe hospital infections (the Micromax program)]. / Rezul'taty mnogotsentrovogo issledovaniia sravnitel'noi aktivnosti tsefepima i drugikh antibiotikov v otnoshenii vozbuditelei tiazhelykh gospital'nykh infektsii (programma "Micromax").

A multicentre trial was performed on the activity of cefepime in comparison with ceftazidime, ceftriaxone, piperacillin/tazobactam, imipenem and ciprofloxacin against severe hospital infection pathogens in intensive care units. The isolates of Escherichia coli and Proteus spp. from the majority of the centres were highly susceptible to the antibiotics (90 to 100 per cent of the isolates). In some centres up to 40 per cent of the isolates produced ESBL. The isolates of Klebsiella spp. were characterized by lower susceptibility, in some centres the frequency of the strains producing ESBL exceeded 90 per cent, by the MIC geometric mean cefepime was superior to the third generation cephalosporins, the frequency of resistance to ciprofloxacin ranged from 0 to 31 per cent, no resistance to imipenem was recorded. The frequency of resistance to the third generation cephalosporins and piperacillin/tazobactam in Enterobacter spp., Serratia spp., Citrobacter spp., Morganella spp., and Providencia spp. ranged from 10 to 52 per cent, the resistance to cefepime equaled 0-11 per cent, 0 to 17 per cent of the isolates were resistant to ciprofloxacin, some isolates were resistant to imipenem. As for the nonfermenting microorganisms their resistance to all the antibiotics tested was comparatively high and markedly differed in various centres. As a whole, 7 per cent of all the isolates of the nonfermenting organisms was resistant to cefepime, 10 per cent was resistant to imipenem, 17 per cent was resistant to ceftazidime, 21 per cent was resistant to piperacillin/tazobactam and 36 per cent was resistant to ciprofloxacin.

Trichoecius calomysci sp. n. (Acari: Myocoptidae), a new mite species from Iran.

A new species of myocoptid mite, Trichoecius calomysci sp. n. (Acari: Myocoptidae), from Calomyscus sp. (Rodentia: Cricetidae) from Iran is described.

[Rehabilitation of patients with ischemic heart disease after aortocoronary bypass surgery]. / Reabilitatsiia bol'nykh ishemicheskoi bolezn'iu serdtsa posle operatsii aortokoronarnogo shuntirovaniia.

The paper outlines some experience in rehabilitating 1250 patients with coronary heart disease (CHD) undergone aortocoronary bypass surgery (ACBS). Rehabilitative measures promoted more rapid and maximally full recovery of physical fitness and cardiorespiratory parameters. The recommended groups of physical activity allow one to differentially approach to the choice of the optimum training regimen and hence to achieve the maximum training effect. The groundlessly high proportion of disabled patients with CHD after ACBS is due not to the quality of surgical treatment, but to the absence of a rehabilitative programme for this group of patients and to the presence of obsolete standard acts for definitions of disability groups by the medical-and-labor examination commission.

[Dirithromycin in the treatment of infections of the lower respiratory tract]. / Diritromitsin v lechenii infektsii nizhnikh dykhatel'nykh putei.

Good results of the treatment of patients with lower respiratory tract infections with dirithromycin (Eli Lilly, USA), a new semisynthetic macrolide, were recorded. The trial included 15 patients: 6 with acute bronchitis (AB) and 9 with exacerbation of chronic bronchitis (AB) and 9 with exacerbation of chronic bronchitis (ECB). The antibiotic was administered orally in a single dose of 500 mg once a day for 7 days. The treatment efficacy was estimated by the clinical results and laboratory findings. The sputum specimens were investigated bacteriologically with testing the microflora for the drug susceptibility by using the diffusion disks. 50 per cent of the patients with AB isolated Streptococcus viridans with low (the diameter of the growth inhibition zones < 16 mm) and intermediate (16-17 mm) susceptibility to the antibiotic, 33.3 per cent of the patients isolated highly susceptible (19 mm) strains of Str. pneumonia and 16.7 per cent of the patients isolated resistant (15 mm) strains of Staphylococcus epidermidis. Highly susceptible (17-19 mm) strains of Haemophilus influenzae and Str. viridans were isolated respectively from 55.5 and 45.5 per cent of the patients with ECB. In 4 patients with ECB a clinical improvement of the state was recorded. In the other patients with AB and ECB the recovery was stated. The bacteriological tests revealed a new pathogen in 2 patients with ECB and the failure of the treatment in another 2 patients with ECB. In all the other patients the pathogen was shown to be eradicated. In the patients isolating the new pathogen the symptomatic recovery was stated in the posttherapeutic period. Therefore, diritromycin proved to be efficient in 13 out of the 15 patients with lower respiratory tract infections. It should be noted that the drug tolerance was excellent. None of the patients showed any adverse reactions.