The 8200 calBP climate event and the spread of the Neolithic in Eastern Europe

At 8200 calBP, the beginning of the Atlantic period, there was a drastic change from warm and humid climatic conditions to cold conditions. The abrupt cooling at 8200 calBP has been documented in different parts of Europe. In western, and some parts of southern, Europe, this event was a trigger for new forms of economy and migrations of groups of Neolithic farmers. This paper considers the different ways in which ceramic traditions developed in eastern Europe in the steppe,steppe-forest and forest zones as a result of the rapid climate changes at about 8200 calBP.V času okoli 8200 calBP, to je na začetku obdobja atlantika, je prišlo do korenite spremembe klime, od toplih in vlažnih pogojev do ohladitev. Nenadna ohladitev v času 8200 calBP je dokumentirana v različnih delih Evrope. V zahodni in v delu južne Evrope je dogodek sprožil nove oblike gospodarstev in preseljevanje skupin neolitskih poljedelcev. V članku razpravljamo o različnih oblikah razvoja keramičnih tradicij na stepskih, gozdno-stepskih in gozdnih območjih v vzhodni Evropi kot posledico te hitre klimatske spremembe v času 8200 calBP

Comparative MLVA-Analysis of Vibrio cholerae Strains of Classical Biovar, Isolated in the Russian Federation and Abroad

Objective of the study is to determine phylogenetic affinity of the Vibrio cholerae strains of classical biovar, isolated between 1937 and 1969 in Russia, to the strains from near and far abroad countries. Materials and methods. Utilized were 27 Vibrio cholerae strains of classical biovar. PCR was carried out applying “BIS M112” amplifier. Genetic analyzer ABI 3500xl was used for sequencing of the strains. MLVA-analysis was performed by reference to 5 MLVA-loci: VC0147, VC0436-0437, VC1650, VCA0171, and VCA0238. Nutrient requirement and soluble hemagglutinin/protease production was established using plate method. Results and conclusions. Identified have been 8 MLVA-clusters and 21 MLVA-types. It is determined that the strains, isolated during atypical cholera outbreak 1942–1943 in Russia, are inhomogeneous as regards phenotype and genotype and fall into two separate groups, one of which is related to the strain, isolated during cholera outbreak 1938 in Khabarovsk, and another group – to the strains from India and China, isolated in 1946 and 1949, respectively

Construction of PCR Test-System for Differentiation between Genetically Altered Toxigenic Vibrio cholerae Strains, Biovar El Tor, with Varied Epidemic Potential

Designed is a multi-locus PCR test-system that allows for differentiation between genetically altered Vibrio cholerae strains, biovar El Tor, with high and low epidemic potential respectively, based on identification of genetic marker structure in the agent of the seventh cholera pandemic - pandemicity island VSP-II. In the course of investigations selected have been three target genes allocated in the central region and terminal end of the mobile genetic element. This test-system offers the possibility to identify the strains containing intact VSP-II, the ones containing VSP-II with a short-length deletion, and the strains with VSP-II with extended deletion. The first two are classified as the variants with low epidemic potential, while the last ones - as the variants with high epidemic potential. Specificity and efficacy of the test-system is shown by the experiments with 28 toxigenic genetically altered V. cholerae strains, biovar El Tor, and 6 strains of closely related species and enterobacteria. The results obtained coincide with the data on mono-locus PCR assay and in a number of instances are verified by sequencing

Molecular MLVA Typing of Typical and Genetically Altered Natural Strains of <I>Vibrio cholerae</I> El Tor Biovar

Displayed is the possibility of differentiation between typical and genetically altered strains of Vibrio cholerae biovar El Tor, which vary in their virulence and epidemic potential, by means of MLVA. Determined is a significant genetic diversity of the gene-variants, probably, due to their polyclonal origin and continuous alterations within genome under the influence of varying environmental factors

Prevalence of Different Types of Integrative Conjugative Element SXT/R391 Encoding Multiple Antibiotic Resistance Among Clinical Strains of Cholera Agent

The aim of the work was to study the prevalence of different types of SXT element with different composition of antibiotic resistance genes among clinical strains of the El Tor cholera pathogen isolated in Russia, Ukraine and cholera-endemic countries in Asia and Africa.Materials and methods. The subject of the study was 27 strains and nucleotide sequences of 77 strains of Vibrio cholerae El Tor available from the NCBI GenBank. The structure of the SXT element and its type were determined using the Mauve and BLAST v.2.9.0 programs. Phylogenetic relations of strains with different types of SXT were identified using Snippy v.4.6.0 and MrBayes v.3.2.7 software. Assessment of strain sensitivity to antibiotics was carried out in accordance with Methodological Regulations 4.2.2495-09.Results and discussion. Two types of SXT element (ICEVchInd5 and ICEVchBan9) have been identified among the studied strains from Russia and Ukraine, which have different composition of antibiotic resistance genes: floR, strAB, sul2, dfrA1 and floR, tetAR, strAB, sul2, dfrA1, respectively. At the same time, the studied strains from Asia and Africa contain five types of SXT: ICEVchInd5, ICEVchBan9, ICEVchBan5, SXTTET, ICEVchInd5ΔVRIII, which differ in size and/or composition of resistance genes. Of these, the last three have not been found in Russia and Ukraine. Due to the high level of genomic diversity of SXT in the population of V. cholerae in endemic regions, there is a risk of importation of cholera pathogen strains with altered resistance to antibiotics into Russia. Phylogenetic relations of 76 strains with different SXT types and different alleles of the ctxB gene encoding the B subunit of cholera toxin have been assessed based on SNP analysis. A close phylogenetic relation between strains with the same type of SXT isolated in Russia and Asian countries has been demonstrated, which confirms the importation of the causative agent of cholera with multiple resistance to antibiotics from this region and the need for constant monitoring of the sensitivity of V. cholerae to antimicrobial drugs

EFFECT OF THE PROPHAGE CTXΦ DELETION UPON PHENOTYPIC PROPERTIES IN STRAINS OF VIBRIO CHOLERAE BIOVAR EL TOR, ASSOCIATED WITH VIRULENCE AND PERSISTENCE

Objective of the study is to evaluate the influence of CTXφ prophage deletion, which carries ctxAB genes, on phenotypical properties associated with pathogenicity or biofilm formation in non-toxigenic mutants. Materials and methods. Utilized have been the clinical strains of Vibrio cholerae biovar El Tor and their spontaneous non-toxigenic mutants that lost CTXφ prophage. Applied have been microbiological and biochemical methods, inoculation of model animals with cells of the strains under study. Results and conclusions. The results of comparative analysis of phenotypic properties in isogenic toxigenic and non-toxigenic strains of Vibrio cholerae biovar El Tor, which lost CTXφ prophage encoding the cholera toxin, are represented. It is established that the deletion of CTXφ prophage leads to the simultaneous change of several phenotypic properties associated with virulence (colonizing ability, production of soluble hemagglutinin/protease and heat labile hemolysin/cytolysin) and biofilm formation (motility, exopolysaccharide biosynthesis) in spontaneous non-toxigenic mutants. It is suggested that the reason for these phenotypic changes in the mutants might be the changes in activity of the related to each other regulatory genes controlling virulence and biofilm formation process in cholera agent

Tenascin-C as a cardiovascular marker

Novel biological markers, such as fibrosis marker galectin-3, peptide hormone adrenomedullin, soluble ST2, chemokine CX3CL1, surrogate marker of vasopressin, and others, are every year one step closer to being introduced into health practice. Over the past decades, significant progress has been made in the study of cardiovascular biomarkers. A key moment was the introduction of deter mining the concentration of natriuretic peptides used as markers for the diagnostic and prognostic evaluation of patients with heart failure. Currently, in order to search for novel markers for early diagnosis and risk stratification, studies have been conducted on the analysis of promising inflammatory marker tenascin-C (TNC) in cardiovascular patients. Data have been obtained that allow us to consider TNC as a tool for risk stratification and assessment of cardiovascular disease prognosis. The combination of TNC with other biological markers, in particular brain natriuretic peptide, may improve prognostic power. Nevertheless, serial testing to assess the prognosis and effectiveness of ongoing treatment, including in the conditions of a multimarker model, requires further research

ОСОБЕННОСТИ ЛЕГИРОВАНИЯ КРЕМНИЯ МЕТОДОМ ТЕРМОМИГРАЦИИ

Characteristics of crystal doping with electrically active impurities by the thermomigration method for two− and three−component liquid zones in comparison with diffusion alloying (for the example of silicon) have been analyzed.We have  found  that  the  concentration range of doping for the  two− component migration zone is much narrower than the range of diffusion doping. Introduction of a third component into the liquid phase allows extending the range of doping thermomigration to values  exceeding the diffusion doping range for the same impurity. For silicon crystals this technological advantage of thermomigration is achieved with the use of three zones, GaxAl1−xSi and SnxAl1−xSi.We show  that  the  speed of crystal  doping by the  thermomigration method in technologically relevant situations is by orders of magnitude higher  than that of diffusion alloying. Thermomigration doped layers with steadily moving liquid zones have higher structural perfection than diffusion doped layers.We show that the thermomigration alloying method can be used in the technology of semiconductor device  structures, provided that  their planar dimensions and thickness are tens  micrometers or more. Quantitative results obtained for the example of liquid zone migration in silicon, but the features of thermomigration as a doping method are true for other  semiconductor materials.Рассмотрены особенности легирования кристаллов электрически активными примесями методом термомиграции  (ТМ) двух− и трехкомпонентных жидких зон в сравнении с диффузионным легированием (на примере кремния).Установлено, что концентрационный диапазон легирования миграцией двухкомпонентной зоны значительно уже диапазона легирования диффузией. Введение в жидкую фазу  третьего компонента позволяет расширить диапазон легирования термомиграцией до значений, превышающих диапазон  легирования той же примесью методом диффузии. Применительно к кристаллам кремния указанная технологическая особенность метода ТМ обеспечивается при использовании трехкомпонентных зон GaxAl1−xSi и SnxAl1−xSi.Показано, что скорость легирования кристаллов методом ТМ в технологически значимых  ситуациях на порядки превышает скорость легирования диффузией. Слои, легированные термомиграцией стабильно движущихся жидких зон, структурно  более совершенны, чем диффузионные слои. Показано, что легирование методом ТМ может быть реализовано в технологии получения полупроводниковых приборных структур при условии, что их планарные размеры и толщины составляют десятки микрометров и более

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Identification of pyrimethamine- and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998: genotyping of archive blood samples

<p>Abstract</p> <p>Background</p> <p>Understanding the geographical distribution of drug resistance of <it>Plasmodium falciparum </it>is important for the effective treatment of malaria. Drug resistance has previously been inferred mainly from records of clinical resistance. However, clinical resistance is not always consistent with the parasite's genetic resistance. Thus, molecular identification of the parasite's drug resistance is required. In Africa, clinical resistance to pyrimethamine (Pyr) and chloroquine (CQ) was evident before 1980 but few studies investigating the genetic resistance to these drugs were conducted before the late 1990s. In this study, genotyping of genes involved in resistance to Pyr and CQ was performed using archive blood samples from Africa between 1984 and 1998.</p> <p>Methods</p> <p>Parasite DNA was extracted from <it>P. falciparum</it>-infected blood smears collected from travellers returning to Japan from Africa between 1984 and 1998. Genotypes of the dihydrofolate reductase gene (<it>dhfr</it>) and CQ-resistance transporter gene (<it>pfcrt) </it>were determined by polymerase chain reaction amplification and sequencing.</p> <p>Results</p> <p>Genotyping of <it>dhfr </it>and <it>pfcrt </it>was successful in 59 and 80 samples, respectively. One wild-type and seven mutant <it>dhfr </it>genotypes were identified. Three <it>dhfr </it>genotypes lacking the S108N mutation (NRSI, ICSI, IRSI; amino acids at positions 51, 59, 108, and 164 with mutations underlined) were highly prevalent before 1994 but reduced after 1995, accompanied by an increase in genotypes with the S108N mutation. The <it>dhfr </it>IRNI genotype was first identified in Nigeria in 1991 in the present samples, and its frequency gradually increased. However, two double mutants (ICNI and NRNI), the latter of which was exclusively found in West Africa, were more frequent than the IRNI genotype. Only two <it>pfcrt </it>genotypes were found, the wild-type and a Southeast Asian type (CVIET; amino acids at positions 72-76 with mutations underlined). The CVIET genotype was already present as early as 1984 in Tanzania and Nigeria, and appeared throughout Africa between 1984 and 1998.</p> <p>Conclusions</p> <p>This study is the first to report the molecular identification of Pyr- and CQ-resistant genotypes of <it>P. falciparum </it>in Africa before 1990. Genotyping of <it>dhfr </it>and <it>pfcrt </it>using archive samples has revealed new aspects of the evolutionary history of Pyr- and CQ-resistant parasites in Africa.</p