New recurrent large deletion,encompassing both GJB2 and GB6 genes,results in isolated sensorineural hearing impairment with autosomal recessive mode of inheritance

Hereditary hearing loss with the autosomal recessive mode of inheritance with DFNB1 genetic type, caused by mutations in the GJB2 gene, is major cause of congenital non-syndromal hearing impairment in most developed countries of the world (including Russia). Intragenic point mutations prevail among the GJB2 gene defects; however, large deletions in the DFNB1 locus are also found with considerable frequency in some populations (for example, Spain, Great Britain, France, United States, and Brazil). Among the four known large deletions, only one deletion affects directly the GJB2 gene sequence and was described in a single family. A new large deletion encompassing both the GJB2 and GJB6 gene sequences of approximately 101 kb in size (NC_000013.10:g.20,757,021_20,858,394del), detected in three unrelated Russian patients, is described and characterized in this essay. Ingush origin of this mutation is assumed. If the new deletion is frequent, its detection is very important for the genetic consulting to families with hereditary hearing impairment.     

Functional biomarkers in the diagnostics of mental disorders: Cognitive event-related potentials

The article deals with recent research in the field of fundamental knowledge about the mechanisms of information processing in the human brain for the diagnosis of mental disorders performed in the laboratory of neurobiology for action programming of the Bechtereva Institute of the Human Brain of the Russian Academy of Sciences. These studies were connected with the analysis of functional components for cognitive event-related potentials (ERPs) obtained under various behavioral conditions. The main goal of this fundamental approach is the decomposition of multi-channel ERPs into functionally different components. These components are generated in various cortical areas, have different temporal dynamics, and reflect a variety of mental operations. The main methodology we used is the independent component analysis, applied to a large set of ERPs (from hundreds of people) obtained by varying functional conditions in the psychological test. In particular, components related to psychological processes, such as the comparison of sensory signals with a trace in working memory, inhibition of current activity, and monitoring of conflict, were identified in the GO/NOGO test. In the European project, a normative database was constructed for the components described above, and this allowed us to compare the data obtained from large groups of patients (including patients with attention deficit disorder, schizophrenia, obsessive disorders, depression, autism, dyslexia, brain trauma, and dementia) with the healthy subjects. This article presents data from patients with a diagnosis of attention deficit disorder and schizophrenia.     

The role of interphase prenucleolar bodies in the recovery of the nucleolar structure after reversible hypotonic treatment

Interphase prenucleolar bodies are globular bodies which accumulate in large numbers in the nucleoplasm of cultivated cells after hypotonic treatment and subsequent return to isotonic conditions; detailed studies of the role of these structures in the recovery of the nucleolus have not yet been performed. The limited mobility of interphase pronucleoli within the nucleus has been demonstrated. Exchange of the major nucleolar protein B23 between prenucleolar bodies and the surrounding nucleoplasm, rather than stable binding of this protein to the prenucleolar bodies, has been demonstrated using fluorescence recovery after photobleaching method. Gradual accumulation of B23 in the recovering nucleolus with concomitant disappearance of prenucleolar bodies has been demonstrated.     

Physicochemical Properties and Anti-Opisthorchosis Effect of Mechanochemically Synthesized Solid Compositions of Praziquantel with Glycyrrhizic Acid Disodium Salt

The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.     

Diminished plasma cGMP during weightlessness

We performed an experiment within the project "RLF" (Russian long-term flight) on a cosmonaut onboard the space station MIR. For creating an analogue to orthostatic stress, we used lower body negative pressure (LBNP) as stimulus. Decrease in central and peripheral baroreceptor load by LBNP can be used as a cardiovascular countermeasure in cosmonauts or for inducing endocrine responses. Altered steady-state plasma concentration values of volume sensitive hormones have been observed inflight as well as postflight. Within this project we measured plasma ANP and cGMP as second messenger. Changes in plasma cGMP concentration are generally considered to be a good indicator of those in ANP activity. However, in our experiments depression of cGMP during space flight was more impressive than ANP decline. We are not aware of previous measurements of plasma cGMP under these conditions, and believe to be the first to report complete suppression of plasma cGMP during long-term stay in space.     

Chromonema and chromomere

A study of ultrathin sections of normal Chinese hamster cells and cells treated with decreasing concentrations of bivalent cations (Ca²⁺ and Mg²⁺) in situ revealed several discrete levels of compaction of DNA-nucleoprotein (DNP) fibrils in mitotic chromosomes and the chromatin of interphase nuclei. At concentrations ranging from 3 mM CaCl₂ and 1 mM MgCl₂ to ten times less, the chromosomes are found to contain fibrous elements (chromonemata) about 100 nm in diameter. As Ca²⁺ concentration is gradually decreased to 0.2–0.1 mM, the chromosomes decondense into a number of discrete chromatin structures, the chromomeres. As decondensation proceeds, these chromomeres acquire a rosettelike structure with DNP fibrils radiating from an electron-dense core. Upon complete decondensation of chromosomes, individual chromomeres persist only in the centromeric regions. The following levels of DNP compaction in mitotic chromosomes are suggested: a 10-nm nucleosomal fibril, a 25-nm nucleomeric fibril, and the chromonema, a fibrous structure, about 100 nm in diameter, composed of chromomeres. Interphase nuclei also contain structures which are morphologically similar to the chromomeres of mitotic chromosomes.     

Low Diversity of T Haplotypes in the Eastern Form of the House Mouse, Mus Musculus L

In previous studies, 13 different recessive embryonic lethal genes have been associated with t haplotypes in the wild mice of the species Mus domesticus. In this communication we have analyzed five populations of Mus musculus for the presence and identity of t haplotypes. The populations occupy geographically distant regions in the Soviet Union: Altai Mountains, western and eastern Siberia, Azerbaijan and Turkmenistan. No t haplotypes were found in mice from eastern Siberia. In the remaining four populations, t haplotypes occurred with frequencies ranging from 0.07 to 0.21. All the t haplotypes extracted from these populations and analyzed by the genetic complementation test were shown to carry the same lethal gene tcl-w73. In one population (that of western Siberia), another lethal gene (tcl-w5) was found to be present on the same chromosome as tcl-w73. This situation is in striking contrast to that found in the populations of the western form of the house mouse, M. domesticus. In the latter species, tcl-w73 has not been found at all and the different populations are characterized by the presence of several different lethal genes. The low diversity of t haplotypes in M. musculus is consistent with lower genetic variability of other traits and indicates a different origin and speciation mode compared to M. domesticus. Serological typing for H-2 antigenic determinants suggests that most, if not all, of the newly described t haplotypes might have arisen by recombination of tw73 from M. musculus with t haplotypes from M. domesticus either in the hybrid zone between the two species or in regions where the two species mixed accidentally.