The binding of monomeric amyloid ß peptide to serum albumin is affected by major plasma unsaturated fatty acids.

Human serum albumin (HSA) serves as a natural depot of amyloid ß peptide (Aß). Improvement of Aß binding to HSA should impede Alzheimer's disease (AD). We developed a method for quantitation of the interaction between monomeric Aß40/42 and HSA using surface plasmon resonance spectroscopy. The dissociation constant of HSA complex with recombinant Aß40/42 is 0.2-0.3 µM. Flemish variant of Aß40 has 2.5-10-fold higher affinity to HSA. The parameters of the HSA-Aß interaction are selectively sensitive to HSA binding of major plasma unsaturated fatty acids and Cu2+. Linoleic and arachidonic acids promote the HSA-Aß42 interaction. The developed methodology for quantitation of HSA-Aß interaction may serve as a tool for search of compounds favoring HSA-Aß interaction, thereby preventing AD progression.

Metagenomic analysis of microbial community of a parasitoid wasp Megaphragma amalphitanum.

The vast majority of multicellular organisms coexist with bacterial symbionts that may play various roles during their life cycle. Parasitoid wasp Megaphragma amalphitanum (Hymenoptera: Trichogrammatidae) belongs to the smallest known insects whose size is comparable with some bacteria. Using 16S rRNA gene sequencing and Whole Genome Sequencing (WGS), we described microbiota diversity for this arthropod and its potential impact on their lifecycle. Metagenomic sequences were deposited to SRA database which is available at NCBI with accession number SRX2363723 and SRX2363724. We found that small body size and limited lifespan do not lead to a significant reduction of bacterial symbionts diversity. At the same time, we show here a specific feature of microbiota composition in M. amalphitanum - the absence of the Rickettsiaceae family representatives that are known to cause sex-ratio distortion in arthropods and well represented in other populations of parasitoid wasps.

Epigenetics of Ancient DNA.

Initially, the study of DNA isolated from ancient specimens had been based on the analysis of the primary nucleotide sequence. This approach has allowed researchers to study the evolutionary changes that occur in different populations and determine the influence of the environment on genetic selection. However, the improvement of methodological approaches to genome-wide analysis has opened up new possibilities in the search for the epigenetic mechanisms involved in the regulation of gene expression. It was discovered recently that the methylation status of the regulatory elements of the HOXD cluster and MEIS1 gene changed during human evolution. Epigenetic changes in these genes played a key role in the evolution of the limbs of modern humans. Recent works have demonstrated that it is possible to determine the transcriptional activity of genes in ancient DNA samples by combining information on DNA methylation and the DNAaseI hypersensitive sequences located at the transcription start sites of genes. In the nearest future, if a preserved fossils brain is found, it will be possible to identify the evolutionary changes in the higher nervous system associated with epigenetic differences.

Identification of novel microRNA genes in freshwater and marine ecotypes of the three-spined stickleback (Gasterosteus aculeatus).

The three-spined stickleback (Gasterosteus aculeatus L.) is an important model organism for studying the molecular mechanisms of speciation and adaptation to salinity. Despite increased interest to microRNA discovery and recent publication on microRNA prediction in the three-spined stickleback using bioinformatics approaches, there is still a lack of experimental support for these data. In this paper, high-throughput sequencing technology was applied to identify microRNA genes in gills of the three-spined stickleback. In total, 595 miRNA genes were discovered; half of them were predicted in previous computational studies and were confirmed here as microRNAs expressed in gill tissue. Moreover, 298 novel microRNA genes were identified. The presence of miRNA genes in selected 'divergence islands' was analysed and 10 miRNA genes were identified as not randomly located in 'divergence islands'. Regulatory regions of miRNA genes were found enriched with selective SNPs that may play a role in freshwater adaptation.

Nonhydrolyzable ATP analog 5'-adenylyl-imidodiphosphate (AMP-PNP) does not inhibit ATP-dependent scanning of leader sequence of mRNA.

The objective of the present work was to determine whether it is possible to use a nonhydrolyzable analog of ATP (AMP-PNP) as an inhibitor of ATP-dependent scanning of the leader sequence of eukaryotic mRNA in translation initiation-. The formation of ribosomal 48S initiation complexes at the start codon of the capped mRNA leader sequence of rabbit ß-globin mRNA was studied. The study was carried out in a system composed of individual components of translation initiation. The dependences of the efficiency of formation of 48S initiation complexes on ATP concentration and incubation time were obtained in the absence and presence of AMP-PNP. It was found that AMP-PNP did not affect the efficiency of formation of 48S initiation complexes in all cases under study. We conclude that the uncleavable analog of ATP, AMP-PNP, is not an inhibitor of translation initiation in eukaryotes.

No DNA damage response and negligible genome-wide transcriptional changes in human embryonic stem cells exposed to terahertz radiation.

Terahertz (THz) radiation was proposed recently for use in various applications, including medical imaging and security scanners. However, there are concerns regarding the possible biological effects of non-ionising electromagnetic radiation in the THz range on cells. Human embryonic stem cells (hESCs) are extremely sensitive to environmental stimuli, and we therefore utilised this cell model to investigate the non-thermal effects of THz irradiation. We studied DNA damage and transcriptome responses in hESCs exposed to narrow-band THz radiation (2.3 THz) under strict temperature control. The transcription of approximately 1% of genes was subtly increased following THz irradiation. Functional annotation enrichment analysis of differentially expressed genes revealed 15 functional classes, which were mostly related to mitochondria. Terahertz irradiation did not induce the formation of γH2AX foci or structural chromosomal aberrations in hESCs. We did not observe any effect on the mitotic index or morphology of the hESCs following THz exposure.

Analysis of the Mitochondrial Genome of a Novosvobodnaya Culture Representative using Next-Generation Sequencing and Its Relation to the Funnel Beaker Culture.

The Novosvobodnaya culture is known as a Bronze Age archaeological culture in the North Caucasus region of Southern Russia. It dates back to the middle of the 4th millennium B.C. and seems to have occurred during the time of the Maikop culture. There are now two hypotheses about the emergence of the Novosvobodnaya culture. One hypothesis suggests that the Novosvobodnaya culture was a phase of the Maikop culture, whereas the other one classifies it as an independent event based on the material culture items found in graves. Comparison between Novosvobodnaya pottery and Funnelbeaker (TRB) pottery from Germany has allowed researchers to suggest that the Novosvobodnaya culture developed under the influence of Indo-European culture. Nevertheless, the origin of the Novosvobodnaya culture remains a matter of debate. We applied next-generation sequencing to study ~5000-year-old human remains from the Klady kurgan grave in Novosvobodnaya stanitsa (now the Republic of Adygea, Russia). A total of 58,771,105 reads were generated using Illumina GAIIx with a coverage depth of 13.4x over the mitochondrial (mt) DNA genome. The mtDNA haplogroup affiliation was determined as V7, suggesting a role of the TRB culture in the development of the Novosvobodnaya culture and supporting the model of sharing between Novosvobodnaya and early Indo-European cultures.

[Phosphorescent microanalysis as a new technical platform for molecular diagnostics].

The authors developed a method of phosphorescent multiplex microanalysis (PHOSPHAN) as a new technological platform for a wide scope of molecular diagnostic tasks, and consider the prospects of its application in the article. PHOSPHAN combines the potential of solid-phase microplate analysis with the principle of microarray laser scanning of microzonules with biospecifically bound analyte on the surface of the bottom of microplate holes with consequent real-time registration of the phosphorescent signal. The sensitivity of the instrumental detection system is approximately 1000 molecules of Pt coproporphyrin mark in the illuminated area of scanning of 30 microns in diameter. PHOSPHAN makes it possible to detect separate microbial cells in samples and increases the sensitivity of analyte detection in microaliquots eluted from blood spots dried on paper blanks. All the key elements of this technology are protected with Russian patents.

[The effect of the Russian inhalant glucocorticosteroid budesonide on bronchial inflammation and hyperreactivity during the long-term treatment of bronchial asthma patients]. / Vliianie otechestvennogo ingaliatsionnogo gliukokortikosteroida budesonida na vospalenie i giperreaktivnost' bronkhov pri dlitel'nom lechenii bol'nykh bronkhial'noi astmoi.

11 patients with severe bronchial asthma entered a randomized trial of glucocorticosteroid budesonide of Russian produce. Of them 6 patients received inhalations of budesonide (800 micrograms/day for 6 months), 5 control patients did not receive the drug. As shown by investigations of external respiration and bronchoalveolar lavage with estimation of cytogram, metacholine provocative tests, fiber bronchoscopy, budesonide inhalations relieved clinical symptoms of asthma, bronchial hyperreactivity and inflammation.

[An attempt to use ofloxacin in patients with mucoviscidosis]. / Opyt primeneniia ofloksatsina u bol'nykh mukovistsidozom.

The literature data and the data of the authors on the pathogenesis and pathogenetic and etiotropic therapy of mucoviscidosis are presented. The use of ofloxacin as an antibacterial agent in the complex treatment of mucoviscidosis is considered expedient. The drug was administered intravenously in a dose of 400 mg twice a day for 5 days followed by the oral use of the drug in the form of tablets according to the same scheme. The microbiological investigation of the sputum specimens revealed diagnostically significant titers of Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella spp. The isolates except for one case (Ps.aeruginosa) were susceptible to ofloxacin. The treatment with ofloxacin in accordance with the above scheme resulted in a rapid improvement of the patient state: the intoxication lowered, the expectoration and the sputum viscosity decreased, the body temperature normalized by the 5th day. The drug tolerance after the intravenous and enteral administration was good. The intravenous injections of ofloxacin induced a 1.5-fold increase in the intensity of the neutrophil oxygen burst. After the drug enteral administration there was observed a 2-fold increase the intensity of the neutrophil oxygen burst.

[Treatment of patients with pneumonia, chronic obstructive bronchitis and mucoviscidosis with cefpirome]. / Lechenie bol'nykh s pnevmoniiami, khronicheskim obstruktivnym bronkhitom i mukovistsidozom tsefpiromom.

Twenty two patients with inflammatory respiratory tract infection were treated with cefpirome. Among the patients 14 were with severe pneumonia, 4 with exacerbated obstructive chronic purulent bronchitis and 4 with mucoviscidosis. All the patients were subjected to clinical, laboratory and x-ray examinations, electrocardiography, estimation of the external respiration and sputum bacteriological tests. The cefpirome susceptibility was determined by the agar diffusion assay with standard disks from Roussel Uclaf. Cefpirome was administered by slow intravenous infusion in a daily dose of 2 to 4 g every 12 hours depending on the disease severity. After 2 or 3 days of the patient afebrile temperature and normal differential blood count the therapy was discontinued. The favourable time course of the disease was recorded in 12 out of the 14 patients with pneumonia. Recovery and clinical improvement were stated in 64.3 and 21.4 per cent of the cases respectively. In 2 patients the treatment failed. In all the patients with exacerbated severe chronic purulent bronchitis the cefpirome therapy resulted in the disease remission. The clinical effect of the mucoviscidosis treatment was observed in 3 out of the 4 patients. The drug tolerance in the doses used was good.

[The dependence of the cytokinetic effects of alkylating antitumor preparations on the phase of the hepatocyte cell cycle in regenerating liver]. / Zavisimost' tsitokineticheskikh éffektov alkiliruiushchikh protivoopukholevykh preparatov ot fazy kletochnogo tsikla gepatotsitov regeneriruiushchei pecheni.

Effects of alkylating antitumor drugs on resting (G0 phase of cell cycle) and proliferating (G1, S, G2 and M phases) hepatocytes were studied in regenerating mouse liver. Cell cycle kinetics (fraction of labeled mitoses, labeling and mitotic indices) were determined by 3H-thymidine autoradiography. Dipin and fotrin as a DNA-damaging agents attack mainly resting (G0) and proliferating (G1) cells. Effect of the damage results in the inhibition of DNA synthesis and G2 phase arrest in the following mitotic cycle. An alkylating drug phopurin as well as ara-C both suppress the mitotic progression in proliferating hepatocytes and do not influence the resting cells.

Interpretation of snow-climate feedback as produced by 17 general circulation models.

Snow feedback is expected to amplify global warming caused by increasing concentrations of atmospheric greenhouse gases. The conventional explanation is that a warmer Earth will have less snow cover, resulting in a darker planet that absorbs more solar radiation. An intercomparison of 17 general circulation models, for which perturbations of sea surface temperature were used as a surrogate climate change, suggests that this explanation is overly simplistic. The results instead indicate that additional amplification or moderation may be caused both by cloud interactions and longwave radiation. One measure of this net effect of snow feedback was found to differ markedly among the 17 climate models, ranging from weak negative feedback in some models to strong positive feedback in others.

[Bioavailability of dalargin and its metabolism during intranasal administration to rats]. / Biodostupnost' dalargina i ego metabolizm pri intranazal'nom vvedenii krysam.

Bioavailability and metabolism of a peptide drug Dalargin with a chemical structure Tyr-D-Ala-Gly-Phe-Leu-Arg have been examined. Dalargin is applied for the treatment of gastric and duodenal ulcers. Bioavailability was estimated following intramuscular (i/m) and intranasal (i/n) routes of administration of 3H-dalargin in anesthetized dogs. The highest dalargin concentration was achieved about 10 min after i/m and i/n administration. Absolute dalargin bioavailability was 15% and 8%, while its elimination half-life was 23.2 min and 21.3 min, respectively. Tyrosine, N-terminated tetra- and pentapeptides were the main metabolites detected in the blood. The intranasal route of dalargin administration is concluded to be possible in the clinical practice.