Restriction fragment length polymorphism of the apolipoprotein A-I gene among inhabitants of Novosibirsk]

Restriction fragments' length polymorphism in the region of apolipoprotein A-I (apo A-I) gene was investigated in Novosibirsk (Siberia, USSR) population. Correlation between PstI apo A-I alleles (2,2 kb-P1; 3,3 kb-P2) and total cholesterol, triglycerides, high density polyproteins cholesterol, and apolipoprotein A-I level was analysed. A tendency to increase in cholesterol index of atherogenicity and to decrease in high density lipoproteins cholesterol as well as apolipoprotein A-I level was shown to occur for P1P2 genotype patients.     

Characteristics of immunomodulating effect of histamine in inbred strain mice]

The activity of 5'-nucleotidase of peritoneal exudate in subcutaneous injection of histamine in a dose of 1.0-100 microliters was studied in mice of different lines (CBA, C57, B1/6, Balb/c, NFS/n, NFR/n). There were interline differences in the influence of histamine on this metabolic index.     

Outlook for the use of microsecond plasma opening switches to generate high-power nanosecond current pulses

An analysis is made of the current break process in microsecond plasma opening switches and their possible application in high-current generators. Necessary conditions are determined for generating megavolt pulses in the erosion mode of a plasma opening switch with the gap insulated by an external magnetic field. Under these conditions, efficient sharpening of high-power submegampere current pulses can be achieved. The possibility of using plasma opening switches operating at voltages of 5–6 MV to generate X-ray and gamma emission is discussed. The main operating and design parameters of a six-module plasma opening switch with a current pulse amplitude of 3.7 MA and voltage of 4–6 MV for use in the MOL generator, which is the prototype of one of the 24 modules of the projected Baikal multimegajoule generator, are estimated by using the available scalings.     

Structure and Conformational Heterogeneity of a Weak Toxin from the Cobra Naja kaouthiaVenom

Resonances in the two-dimensional ¹H NMR spectra of a weak toxin (WTX) from the venom of cobra Naja kaouthiafor all 65 amino acid residues were assigned. The amino acid sequence of WTX, determined by the sequential assignment of spin systems, was found to be similar to that of the CM-9a toxin from the N. kaouthiavenom. Unlike CM-9a, WTX contains an additional Trp36 residue; Lys50 and Tyr52 are interchanged; and there is a Thr residue in place of Arg2. For some residues of WTX, the presence of two components of approximately equal intensities in the spectra was shown, which is explained by the conformational heterogeneity of the polypeptide owing to the cis–transisomerization of the peptide bond Arg32–Pro33. The data (contacts of the nuclear Overhauser effect, constants of spin–spin coupling of protons, and rates of exchange of amide protons for deuterium of the solvent) made it possible to determine the secondary structure of two forms of WTX, which is characterized by the presence of two antiparallel -sheets, one of which consists of two strands (regions 1–5 and 13–17) and the other, of three strands (regions 23–28, 38–43, and 55–59).     

Mutation in the structure of exon 7 of the phenylalanine hydroxylase in phenylketonuria patients from the Novosibirsk area

The spectrum and frequency of mutations of exon 7 of the gene for phenylalanine hydroxylase (PAH) were studied in 34 phenylketonuria (PKU) patients living in Novosibirsk oblast. The five most prevalent mutations constituted 17.64% of defective alleles: R243Q (1.47%), R252W (1.47%), R261Q (5.88%), E280K (1.47%), and P281L (7.35%). A neutral polymorphic locus V245V was found within exon 7.     

Study of solid-phase catalytic isotopic exchange of hydrogen in alpha-conotoxin G1 under the effect of spillover-tritium

Tritium-labeled alpha-conotoxin G1 with a molar radioactivity of 35 Ci/mmol and full biological activity (according to the binding to nicotinic acetylcholine receptor) was obtained by the high-temperature solid-state catalytic isotope exchange (HSCIE). The tritium distribution in the molecule of alpha-conotoxin G1 was revealed by 3H NMR spectroscopy. Tritium was found in all amino acid residues except for the Asn4-Pro5-Ala6 fragment. The data on the comparative reactivity of C-H bonds, the ab initio quantum-chemical calculation of the hydrogen exchange reaction, and the information on the spatial structures of alpha-conotoxin G1 in solution and in crystal state allowed us to establish that the reactivity of H atoms may be increased by their interaction with the electron donor O and N atoms at the transition state of the HSCIE reaction. A decrease in the rate of the HSCIE reaction could be caused by both a poor spatial accessibility of C-H bonds and a limited mobility of the peptide fragment containing these bonds.     

Polymer-based cell-free expression of ligand-binding family B G-protein coupled receptors without detergents

G-protein coupled receptors (GPCRs) constitute the largest family of intercellular signaling molecules and are estimated to be the target of more than 50% of all modern drugs. As with most integral membrane proteins (IMPs), a major bottleneck in the structural and biochemical analysis of GPCRs is their expression by conventional expression systems. Cell-free (CF) expression provides a relatively new and powerful tool for obtaining preparative amounts of IMPs. However, in the case of GPCRs, insufficient homogeneity of the targeted protein is a problem as the in vitro expression is mainly done with detergents, in which aggregation and solubilization difficulties, as well as problems with proper folding of hydrophilic domains, are common. Here, we report that using CF expression with the help of a fructose-based polymer, NV10 polymer (NVoy), we obtained preparative amounts of homogeneous GPCRs from the three GPCR families. We demonstrate that two GPCR B family members, corticotrophin-releasing factor receptors 1 and 2β are not only solubilized in NVoy but also have functional ligand-binding characteristics with different agonists and antagonists in a detergent-free environment as well. Our findings open new possibilities for functional and structural studies of GPCRs and IMPs in general.     

Genetic aspects of sexual behavior in malaria mosquitoes on the basis of specific acoustic signals at mating

Acoustic characteristics were studied in two species of the "Anopheles maculipennis" species complex, A. messeae and A. atroparvus. The species were found to clearly differ in sound frequencies, which was assumed to play a key role in species identification during mating in regions of their sympatric distribution. The sound spectrum in A. messeae was far more diverse than in A. atroparvus, which was associated with intraspecific inversion polymorphism of the former. Mosquitoes with the inversion combinations that were most common in populations of the central region of the A. messeae species area specifically differed in acoustic signal spectrum from each other. Hence, sound communication within the species was considered to be the main mechanism that is responsible for sexual partner selection and determines the chromosome associations observed earlier in individual karyotypes. Since males carrying different inversion combinations significantly differed in acoustic characteristics, females were assumed to play a main role in selecting the sexual partner.     

Dynamics of the plasma injected into the gap of a plasma opening switch across a strong magnetic field

A method is proposed to increase the linear charge density transferred through a plasma opening switch (POS) and, accordingly, reduce the POS diameter by enhancing the external magnetic field in the POS gap. Results are presented from experimental studies of the dynamics of the plasma injected into the POS gap across a strong magnetic field. The possibility of closing the POS gap by the plasma injected across an external magnetic field of up to 60 kG is demonstrated.     

Genome‐wide SNP analysis unveils genetic structure and phylogeographic history of snow sheep (Ovis nivicola) populations inhabiting the Verkhoyansk Mountains and Momsky Ridge (northeastern Siberia)

Insights into the genetic characteristics of a species provide important information for wildlife conservation programs. Here, we used the OvineSNP50 BeadChip developed for domestic sheep to examine population structure and evaluate genetic diversity of snow sheep (Ovis nivicola) inhabiting Verkhoyansk Range and Momsky Ridge. A total of 1,121 polymorphic SNPs were used to test 80 specimens representing five populations, including four populations of the Verkhoyansk Mountain chain: Kharaulakh Ridge–Tiksi Bay (TIK, n = 22), Orulgan Ridge (ORU, n = 22), the central part of Verkhoyansk Range (VER, n = 15), Suntar‐Khayata Ridge (SKH, n = 13), and Momsky Ridge (MOM, n = 8). We showed that the studied populations were genetically structured according to a geographic pattern. Pairwise F_ST values ranged from 0.044 to 0.205. Admixture analysis identified K = 2 as the most likely number of ancestral populations. A Neighbor‐Net tree showed that TIK was an isolated group related to the main network through ORU. TreeMix analysis revealed that TIK and MOM originated from two different ancestral populations and detected gene flow from MOM to ORU. This was supported by the f3 statistic, which showed that ORU is an admixed population with TIK and MOM/SKH heritage. Genetic diversity in the studied groups was increasing southward. Minimum values of observed (Ho) and expected (He) heterozygosity and allelic richness (Ar) were observed in the most northern population—TIK, and maximum values were observed in the most southern population—SKH. Thus, our results revealed clear genetic structure in the studied populations of snow sheep and showed that TIK has a different origin from MOM, SKH, and VER even though they are conventionally considered a single subspecies known as Yakut snow sheep (Ovis nivicola lydekkeri). Most likely, TIK was an isolated group during the Late Pleistocene glaciations of Verkhoyansk Range.