[Geometric Approach to Phylogeographic Analysis Molecular Genetic Sequences: Principal Components and Dendrograms].

Currently, the search for manifestations of selection under the influence of the environment in molecular sequences is usually carried out within closely related species or at the intraspecific level. It is believed that at high taxonomic levels this is unpromising due to phylogenetic relationship. Cytochrome b amino acid sequences of 67 rodent and lagomorph species with known geographic coordinates were digitized using the AAindex database. Based on more than 200 thousand characters, the principal components were obtained. A well-known statistical method, which has not been previously used for such problems, was used, which makes it possible to orthogonally decompose multidimensional variability into intra- and intertaxon variability and analyze them separately. The subfamily level was selected. For the second principal component (17.05% of intertaxon variability), a correlation with latitude was found (r = 0.561; n = 67; p < E-5). The clear division into two groups, revealed by the first principal component (39.48% of intertaxon variability), which does not coincide with the taxonomic one, indicates a possible physicochemical underlying cause for the differences between them. This requires further research.

Low-filled suspensions of α-chitin nanorods for electrorheological applications.

Highly anisometric α-chitin nanoparticles isolated by TEMPO-oxidation were investigated as filler for electrorheological fluids. The dimensions of rod-like particles were determined by AFM and cryo-TEM methods. The rheological behavior of α-chitin nanoparticles in polydimethylsiloxane changes from viscous to elastic under electric field. The yield stress reaches about 220 Pa at 7 kV/mm for 1.0 wt% fluid. Despite the nanosize of particles, the suspensions sedimentation ratio was found to be low (~23%). The electrorheological behavior of the fluids was discussed in terms of the Mason numbers. The stability of fluids response under switching electric field was shown. The activation energy of polarization processes in suspensions was calculated as 58 ± 2 and 64 ± 1 kJ/mol for 0.5 and 1.0 wt% filler content from the impedance spectra. The high aspect ratio (~70) and dielectric permittivity result in high electrorheological activity of α-chitin suspensions at extremely low concentrations (≤1.0 wt%).

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

[THE CONTENT OF LIPIDS AND PRODUCTS OF THEIR PEROXIDATION OF RAT THYMOCYTES IN EXPERIMENTAL ULCEROGENESIS].

The work is dedicated to the research of the content of lipids and products of their peroxidation in rats thymocytes in experimental ulceration. It was found significant increase of the content of lipid peroxidation products diene conjugates (DC), malondialdehyde (MDA), schiff base (SB) in experimental models of gastric ulcers (ethanol and stress). It was established that under ethanol gastric the contents of DC increases by 1.8 times, MDA by 2.1 and SB by 1.3 times relative to control values. Under stress model it was observed an increase in the number of DC by 2 times, MDA by 1.9 and SB by 1.3 times relative to control. When ethanol and stress ulcers cholesterol increased by 1.7 and 1.5 times, triacylglycerol by 2 and 2.3 times and fatty acids by 2.2 and 1.9 times, respectively, relative to controls. Phosphatidylethanolamine content decreases by 1.5 and 1.3 times compared to control. Also, the stress model, it was observed reduction of phosphatidylinositol by 1.3 times and increased lizofosfatydylholinu by 1.7 times compared to control. Therefore, our studies indicate quantitative changes of lipid content (neutral- and phospholipids) in rats' thymocytes under experimental (ethanol and stress) ulceration. The reason of this changes may be activation of lipid peroxidation, as shown by the increase of lipid peroxidation products' (DK, MDA, SB) content.

[Cytogenetic effects in peripheral blood lymphocytes in the offspring of Chernobyl nuclear power plant accident liquidators under the influence of mitomycin C in vitro and folic acid in vivo].

The data on cytogenetic examination concerning the offspring of the Chernobyl accident liquidators (cleanup personnel) have been obtained. It has been established that spontaneous chromosomal aberrations level before folic acid administration was 1,8 times higher than that value after its employment (4,45 to 2,42 %, p < 0,01). In lymphocyte cultures treated with mitomycin C accompanied by folic acid it was 4,5 times higher before their administration (23,95 to 5,36 %, p < 0,001). The data obtained confirm a possibility of stabilization of genetic apparatus in offspring of the Chernobyl disaster liquidators after folic acid administration.

[Correspondence analysis and combination of molecular genetic and morphological data in zoological systematics].

A new algorithmic approach is proposed for correspondence analysis of different types of data in zoological systematics. The algorithm is tested on actual data. A high degree of correspondence is shown for morphometric and genetic distances in the tested set of species. Two directions of variation in both character spaces have clearly appeared. The first direction discriminates families; the second discriminates orders. The characters responsible for these differences have been revealed. After uniting both distance matrixes, the morphological one and the molecular genetic one, into a single matrix, and displaying the summarized distances between species on a plane, the configuration of species remained principally unchanged. The principal directions of variations were preserved and marked the differences between orders, families, and genera.

[Tiotropium bromide for treating chronic obstructive pulmonary disease].

Five different types of muscarine-sensitive receptors were identified until now. In routine practice, the nonselective antagonist of cholinoreceptors are replaced by ipratropium bromide that is selectively blocking M1, M2, and M3 subtypes with the same affinity to each of them. However, the blockage of M2 subtype leads to bronchoconstriction and is accompanied by inhibition of M3 receptors in bronchial smooth muscles. The new drug tiotropium bromide selectively inhibits only the M1 and M3 types of receptors and does not affect the M2 subtype. This drug is administered only once a day, which is very important in clinical practice. Thus tiotropium bromide is the drug of choice for basic therapy of COPD.

[Mechanisms of the therapeutic effect of immunoglobulins in the treatment of bronchial asthma].

Data on the therapeutic effectiveness of intravenous injections of immunoglobulins in high doses in patients with bronchial asthma are analyzed. Some possible mechanisms of this therapeutic effect are considered, which are related to of immunoglobulin fragments capable of interacting with cytochrome P-450 and NO-synthase systems of the liver.

[The protector properties of a pseudopeptide drug ingamine studied on a model of bronchospasm in guinea pigs].

The original pseudopeptide drug ingamine (4-[N-[2-(imidazol-4-yl)ethyl]-carbamoyl] butyric acid) was studied on the traditional model of antigen-induced bronchospasm in actively sensitized guinea pigs. The drug was introduced using various methods (by inhalation, via intragastric tube, and by intraperitoneal injections) in a range of doses (20, 50, 150, or 500 mg/kg). The new drug exhibited a pronounced dose-dependent protector action for all ways of introduction, but the most significant effect was observed upon inhalation, whereby the degree of bronchospasm inhibition exceeded 80%. In comparison to the reference drug sodium cromoglycate, ingamine (in equimolar doses) showed a higher activity with respect to the antigen-dependent bronchospasmic reactions. It can be expected that ingamine will provide for the effective treatment of bronchial obstruction under clinical conditions.

A new approach to the study of genetic variability of complex characters.

A new approach to multivariate genetic analysis of complex organismal traits is developed. It is based on examination of the distribution of parental strains and the F1 and F2 hybrids in a multidimensional space, and the determination of the directions corresponding to heterozygosity, epistatic and additive gene effects. The effect of heterozygosity includes variability produced by interaction between and within heterozygous loci. The additive gene effects and the remaining epistatic interactions between the homozygous loci can be visualized separately from the effects of heterozygosity by an appropriate projection of the points in multidimensional space. In all, 20 morphological, physiological and behavioural characters and 21 craniometric measures were studied in crosses between two laboratory rat strains. Linear combinations of craniometric and of morphophysiological characters with a high narrow-sense heritability could be identified. These combinations characterized the organismal stress response, which had been selected for in one of the strains. The prospects for the practical application of the new approach and also for the evaluation of the contribution of the genetic diversity to phenotypic variability in animals in natural populations are discussed.

[The effect of a potential drug ingamine on a model of noninfectious pneumonia]. / Issledivanie éffektivnosti potentsial'nogo lekarstvennogo sredstva - ingamina TM na modeli neinfektsionnogo vospaleniia legkikh.

The potential drug ingamine (glutarylhistamine) showed pronounced anti-inflammatory activity on a model of acute noninfectious pneumonia and in the stage of chronic inflammation induced by singe instillation of Sephadex (5 mg/kg) in Wistar rats. A 6-day treatment with ingamine (50-500 microg/kg) by inhalation, intragastric, and intraperitoneal administration produced an anti-inflammatory effect (expressed to various degrees), which was manifested by a decrease in alveolitis, bronchitis, obstructive emphysema, lymphocyte-neutrophile infiltration of interalveolar septa, cytosis, and neutrophile component of bronchoalveolar lavage and by normalization of the cytogram. The most pronounced effect was observed upon inhalation in a dose of 500 microg/kg. In the stage of chronic inflammation, the inhalation of ingamine in a dose of 500 microg/kg produced a significant antiinflammatory action for both 10- and 20-day treatment. The effect was comparable with that of the inhaled glucocorticoid budesonide.

Antitussive activity of Anar.

Affinity-purified antibodies to morphine (mixture of homeopathic dilutions C30+C200) produced an antitussive effect on male and female guinea pigs with cough induced by citric acid and capsaicin.

Ultralow doses of antibodies to inflammatory mediators: antitussive properties of antibodies to bradykinin, histamine, and serotonin.

We studied antitussive activity of antibodies to inflammatory mediators (bradykinin, histamine, and serotonin) in ultralow doses. Experiments were performed on guinea pigs with cough induced by citric acid and capsaicin. Test preparations suppressed cough produced by citric acid. Antibodies to bradykinin in ultralow doses were most potent in relieving capsaicin-induced cough (up to 85%); antibodies to serotonin and, particularly, to histamine produced a smaller effect. Potentiated histamine and serotonin possessed polymodal properties.

Interactions between syntaxins identify at least five SNARE complexes within the Golgi/prevacuolar system of the Arabidopsis cell.

The syntaxin family of soluble N-ethyl maleimide sensitive factor adaptor protein receptors (SNAREs) is known to play an important role in the fusion of transport vesicles with specific organelles. Twenty-four syntaxins are encoded in the genome of the model plant Arabidopsis thaliana. These 24 genes are found in 10 gene families and have been reclassified as syntaxins of plants (SYPs). Some of these gene families have been previously characterized, with the SYP2-type syntaxins being found in the prevacuolar compartment (PVC) and the SYP4-type syntaxins on the trans-Golgi network (TGN). Here we report on two previously uncharacterized syntaxin groups. The SYP5 group is encoded by a two-member gene family, whereas SYP61 is a single gene. Both types of syntaxins are localized to multiple compartments of the endomembrane system, including the TGN and the PVC. These two groups of syntaxins form SNARE complexes with each other, and with other Arabidopsis SNAREs. On the TGN, SYP61 forms complexes with the SNARE VTI12 and either SYP41 or SYP42. SYP51 and SYP61 interact with each other and with VTI12, most likely also on the TGN. On the PVC, a SYP5-type syntaxin interacts specifically with a SYP2-type syntaxin, as well as the SNARE VTI11, forming a SNARE complex likely involved in TGN-to-PVC trafficking.

VACUOLELESS1 is an essential gene required for vacuole formation and morphogenesis in Arabidopsis.

Most plant cells are characterized by the presence of a large central vacuole that in differentiated cells accounts for more than 90% of the total volume. We have undertaken a genetic screen to look for mutants that are affected in the formation of vacuoles in plants. In this study, we report that inactivation of the Arabidopsis gene VACUOLELESS1 (VCL1) blocks vacuole formation and alters the pattern of cell division orientation and cell elongation in the embryo. Consistent with a role in vacuole biogenesis, we show that VCL1 encodes the Arabidopsis ortholog of yeast Vps16p. In contrast to yeast mutants that lack a vacuolar compartment but are viable and morphologically normal, loss of the plant vacuole leads to aberrant morphogenesis and embryonic lethality.

Antiinflammatory effect of russian-made budesonide in experimental noninfectious pulmonary granulomatosis.

We studied the antiinflammatory effect of a Russian-made glucocorticoid budesonide administered by inhalation and intraperitoneal injection to rats with experimental noninfectious pulmonary granulomatosis. The antiinflammatory effects of budesonide at both administration routes were similar. Intraperitoneal injection, in contrast to inhalation, produced a systemic effect manifested in suppression of hyperplasia of non-encapsulated lymphoid formations in the mucosa.

[The effect of gamma-L-glutamylhistamine analogues on the severity of experimental anaphylactic reaction, hormonal status and liver cytochrome P450 system]. / Vliianie analogov gamma-L-glutamilgistamina na izmenenie tiazhesti proiavlenii éksperimental'noi anafilakticheskoi reaktsii, gormonal'nogo statusa i sistemy tsitokhroma P450 pecheni.

The influence of gamma-L-glutamylhistamine analogues on the hexenal-induced sleeping, glucocorticoid hormone content in blood plasma and severity of experimental anaphylactic reaction was studied. It was observed that gamma-L-glutamylhistamine analogues caused decrease in the sleeping time and severity of experimental anaphylactic reaction, the elevation of glucocorticoids content in blood plasma. The present results indicate that substances have the wide spectrum of biological activity which depends on the length of the N-acyl radical.