Telomere length in the population of long-lived persons of North-West region of Russia

Interdisciplinary study of telomere length, polymorphism of genes of renin-angiotensin (ACE) and serotonin (5HTR2A and 5HTTPR) systems in population of aged and old inhabitants of the North-West of Russia was conducted, in their relations to data from clinical and geriatric anamnesis, and psychological functioning. Regular link between telomere length and respondent's age was demonstrated in subgroups of old respondents and long-livers, by method of factor analysis.     

Role of extracellular DNA oxidative modification in radiation induced bystander effects in human endotheliocytes

The development of the bystander effect induced by low doses of irradiation in human umbilical vein endothelial cells (HUVECs) depends on extracellular DNA (ecDNA) signaling pathway. We found that the changes in the levels of ROS and NO production by human endothelial cells are components of the radiation induced bystander effect that can be registered at a low dose. We exposed HUVECs to X-ray radiation and studied effects of ecDNA(R) isolated from the culture media conditioned by the short-term incubation of irradiated cells on intact HUVECs. Effects of ecDNA(R) produced by irradiated cells on ROS and NO production in non-irradiated HUVECs are similar to bystander effect. These effects at least partially depend on TLR9 signaling. We compared the production of the nitric oxide and the ROS in human endothelial cells that were (1) irradiated at a low dose; (2) exposed to the ecDNA(R) extracted from the media conditioned by irradiated cells; and (3) exposed to human DNA oxidized in vitro. We found that the cellular responses to all three stimuli described above are essentially similar. We conclude that irradiation-related oxidation of the ecDNA is an important component of the ecDNA-mediated bystander effect.     

The synthesis and antituberculosis activity of 5′-nor carbocyclic uracil derivatives

A series of new carbocyclic uracil derivatives were synthesized and evaluated as potential antituberculosis agents. Racemic 1-[4′-hydroxy-2′-cyclopenten-1′-yl]-5-tetradecynyluracil completely inhibited the growth of Mycobacterium tuberculosis H37Rv in vitro at a concentration of 10 μg/ml. Individual (+) and (?) isomers of the above uracil derivative were isolated and showed the same level of activity against two strains of Mycobacterium tuberculosis: laboratory sensitive (H37Rv) and clinical resistant to five top antituberculosis drugs (MS-115).     

A study of the prevalence of regulatory genes controlling virulence gene expression among Vibrio choleraeeltor biovariant strains varying in their pandemic potential

The evolution of the genome of the pathogenic agent of the seventh cholera pandemia Vibrio cholerae eltor biovariant was thought to occur by acquiring not only structural genes of virulence but also regulatory systems as a result of horizontal transfer events. The polymerase chain reaction revealed the presence of the following regulatory genes that control the virulence gene expression in the chromosome of pre-pandemic and pandemic strains of cholera vibrios eltor: toxR, toxT, tcpP, tcpH, luxS, luxO, crp, vicH, pepA. The avirulent V. cholerae strain ATCC14033 isolated in 1910 (hypothetical predecessor of the cholera eltor agent) was shown to be lacking the regulatory genes toxT, tcpP, tcpHlocalized in the pathogenicity island VPI-1, and to be capable of realizing positive control over the expression of the virulence genes involved in the ToxR regulon. The virulent strains isolated from cholera patients during the local cholera outbreak in Indonesia in 1937 did not differ from the strains that caused cholera eltor pandemic in 1961. The strains had identical content of the regulatory genes tested. Only one strain of the four isolates studied contained no tcpPgene. Two key regulatory genes, toxR and toxT, were sequenced in all the isolates. The toxR nucleotide sequence of three pre-pandemic strains was shown to be indistinguishable from that of the pandemic isolates. On the other hand, the clinical strain MAK757 isolated prior to the emergence of the epidemic demonstrated an altered nucleotide sequence in its toxR gene. Experiments with the intra-intestinal challenge of suckling rabbits were indicative of similar virulence levels for the pre-pandemic and pandemic clinical strains. These results may serve as the evidence of the in vivo activity of the pre-pandemic strains of the toxT, tcpH, and tcpP positive regulatory genes that acquired in V. cholerae during the evolutionary process.     

Microbiocenosis of nasal mucous membrane during allergic rhinosinusitis

Overall quantity of microorganisms and their relative prevalence on nasal mucous membrane in patients with allergic rhinosinusitis are determined. Microbial flora in studied group was characterized qualitatively and quantitatively. Obtained results showed that there were changes of microbiocenosis of nasal mucous membrane during allergic rhinosinusitis and in characteristics of species in Staphylococcus genus.     

A simple Markov model of sodium channels with a dynamic threshold

Characteristics of action potential generation are important to understanding brain functioning and, thus, must be understood and modeled. It is still an open question what model can describe concurrently the phenomena of sharp spike shape, the spike threshold variability, and the divisive effect of shunting on the gain of frequency-current dependence. We reproduced these three effects experimentally by patch-clamp recordings in cortical slices, but we failed to simulate them by any of 11 known neuron models, including one- and multi-compartment, with Hodgkin-Huxley and Markov equation-based sodium channel approximations, and those taking into account sodium channel subtype heterogeneity. Basing on our voltage-clamp data characterizing the dependence of sodium channel activation threshold on history of depolarization, we propose a 3-state Markov model with a closed-to-open state transition threshold dependent on slow inactivation. This model reproduces the all three phenomena. As a reduction of this model, a leaky integrate-and-fire model with a dynamic threshold also shows the effect of gain reduction by shunt. These results argue for the mechanism of gain reduction through threshold dynamics determined by the slow inactivation of sodium channels.     

Measurements of the parameters of a condensed deuterated Z-pinch on the angara-5-1 facility

Results are presented from measurements of the parameters of high-temperature plasma in the Z-pinch neck formed when a current of up to 3.5 MA flows through a low-density polymer load. To enhance the effect of energy concentration, a deuterated microporous polyethylene neck with a mass density of 100 mg/cm³ and diameter of 1–1.3 mm was placed in the central part of the load. During the discharge current pulse, short-lived local hot plasma spots with typical dimensions of about 200–300 μm formed in the neck region. Their formation was accompanied by the generation of soft X-ray pulses with photon energies of E > 0.8 keV and durations of 3–4 ns. The plasma electron temperature in the vicinity of the hot spot was measured from the vacuum UV emission spectra of the iron diagnostic admixture and was found to be about 200–400 eV. The appearance of hot plasma spots was also accompanied by neutron emission with the maximum yield of 3 × 10¹⁰ neutrons/shot. The neutron energy spectra were studied by means of the time-of-flight method and were found to be anisotropic with respect to the direction of the discharge current.     

First data on the shell structure of the Early Cretaceous (Berriasian) rhynchonellids from Crimea

The shell structure of the Early Cretaceous rhynchonellids from Crimea has not been previously studied. First data on the shell structure of Berriasian rhynchonellids from the family Praecyclothyrididae Makridin, 1964 from southwestern and central Crimea are presented. Sulcirhynchia semenovi (Moisseev, 1939), S. berriasensis (Lobacheva, 1980), S. gracilis (Lobacheva, 1977), Belbekella airgulensis Moisseev, 1939, B. mutabilis Lobacheva, 1983, B. minor Lobacheva, 1983 and partly Lamellaerhynchia rectimarginata (Smirnova, 1972) are studied. The shell wall of most species consists of three layers: external (finely or coarsely crystalline), fibrous, and prismatic layers. The layers are usually strongly recrystallized, especially external and prismatic layers. New fibers were formed by repeated dichotomy of ridges in different areas of the fibrous layer independently of the distance from the anterior margin.     

The comparative analysis of gene and structural somatic mutations in inhabitants of Orel district areas contaminated with radionuclides as a result of Chernobyl accident

The results of comparative analysis of gene and structural mutations found in peripheral blood lymphocytes of inhabitants of Orel district areas contaminated with radionuclides as a result of Chernobyl accident are presented. The average level of 137Cs contamination in those areas ranged about 22-113 kBq/m2. In the study group was found the enhanced frequency of somatic cells with gene and structural mutations compared with laboratory control level by synchronous applying a T-cell receptor (TCR) loci mutation assay and cytogenetic analysis of unstable aberrations. The case-control comparison was carried out using the measured mutation frequencies and cases of various thyroid gland sickness recognized by ultrasonic examination. The cytogenetic assay did not show the statistical difference between healthy group and subjects with thyroid gland sickness. The average frequency of TCR loci mutation cells in the subjects with thyroid gland sickness was found to be statistically higher comparing with healthy persons. This finding was true for each study region and for Orel district in total. The subgroup of subject exposed in utero in 1986, soon after accident was analyzed. Both cytogenetic and TCR loci mutation assays shown enhancement of average mutation frequency in somatic cells in the subjects of this subgroup with thyroid gland sickness comparing with healthy persons.