Structure and Functional Role of Bacterial CRISPR System

Presented is the review of literature data on the recently discovered system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), which takes part in the defense against penetration of alien genetic information in prokaryotes. CRISPR structural peculiarities and functions, and putative mechanism of action are described. Also presented are data on the availability of this system in particularly dangerous infections agents and on the possibility of its application for molecular typing

The limits of normal approximation for adult height

Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait

Phenotypic and Genetic Analysis of Altered Variants of <i>Vibrio cholerae</i> Biovar El Tor

Determined is cholera toxin production by altered Vibrio cholerae O1 eltor strains, isolated on the territory of Russia in 1993-2010, which contain classical type ctxB gene. Studied are their genetic characteristics related to the production of this virulence factor. Determined is that altered eltor variants yield 10 to 20 times more cholera toxin than typical eltor strains. Changes in promotor region of ctxAB operon are not detected but elucidated is that 90 % of studied altered strains contain two copies of CTXϕ prophage in their genome whereas typical strains carry one copy of CTXϕ prophage. Despite the higher copy number of CTXϕ prophage, the identified differences in production of cholera toxin can be associated mostly with a change of transcriptional activity of regulatory genes. That causes the active production of cholera toxin by the altered variants of Vibrio cholerae eltor in non typical environment

Сравнение альтернативных методов разделения смеси метилацетат – метанол – уксусная кислота – уксусный ангидрид

Objectives. The paper is a comparative analysis of methyl acetate + methanol + acetic acid + acetic anhydride industrial mixture separation flowsheets based on the use of special distillation methods (extractive distillation and pressure-swing distillation). The results obtained illustrate the variability of the structure of the technological separation flowsheet.Methods. Mathematical modeling using the software package Aspen Plus V. 10.0 was chosen as the research method. The simulation was based on the local composition equation NRTL and the Hayden–O’Connell equation of state. The relative uncertainties of phase equilibrium description do not exceed 3%.Results. The vapor–liquid diagram of the quaternary mixture of methyl acetate + methanol + acetic acid + acetic anhydride was studied using thermodynamic topological analysis. It was shown that the system contains one binary azeotrope and is characterized by one distillation region. Although the structure is not complex, there is a possibility of using several methods for mixture separation: pressure-swing distillation, and extractive distillation with different entrainers. Twelve flowsheets with different structure were proposed, and 29 variants of separation were compared.Conclusions. It was shown that the most perspective structure for the separation of a methyl acetate + methanol + acetic acid + acetic anhydride mixture is a combination of distributed sequence separation and extractive distillation.Цели. Целью работы является сравнительный анализ технологических схем разделения промышленной смеси метилацетат – метанол – уксусная кислота – уксусный ангидрид, основанных на использовании специальных методов разделения: экстрактивная ректификация и варьирование давления. Полученные результаты иллюстрируют вариативность структуры технологической схемы разделения.Методы. В качестве метода исследования выбрано математическое моделирование в программном комплексе Aspen Plus V. 10.0. Моделирование основывалось на уравнении локального состава NRTL и уравнении состояния Хейдена–О'Коннелла. Относительные ошибки описания фазового равновесия не превышают 3%.Результаты. С помощью термодинамико-топологического анализа изучена диаграмма парожидкостного равновесия четырехкомпонентной системы метилацетат – метанол – уксусная кислота – уксусный ангидрид. Показано, что система содержит один бинарный азеотроп и характеризуется одной областью дистилляции. Несмотря на то, что структура не является сложной, существует возможность использования нескольких методов разделения смеси: ректификация с варьированием давления, экстрактивная ректификация с различными разделяющими агентами. Предложено 12 технологических схем различной структуры и проведен сравнительный анализ 29 вариантов разделения.Заключение. Показано, что наиболее эффективным для разделения смеси метилацетат – метанол – уксусная кислота – уксусный ангидрид является сочетание промежуточного режима разделения смеси и экстрактивной ректификации

Regression of lumbar disk herniation

Compression of the spinal nerve root, giving rise to pain and sensory and motor disorders in the area of its innervation is the most vivid manifestation of herniated intervertebral disk. Different treatment modalities, including neurosurgery, for evolving these conditions are discussed. There has been recent evidence that spontaneous regression of disk herniation can regress. The paper describes a female patient with large lateralized disc extrusion that has caused compression of the nerve root S1, leading to obvious myotonic and radicular syndrome. Magnetic resonance imaging has shown that the clinical manifestations of discogenic radiculopathy, as well myotonic syndrome and morphological changes completely regressed 8 months later. The likely mechanism is inflammation-induced resorption of a large herniated disk fragment, which agrees with the data available in the literature. A decision to perform neurosurgery for which the patient had indications was made during her first consultation. After regression of discogenic radiculopathy, there was only moderate pain caused by musculoskeletal diseases (facet syndrome, piriformis syndrome) that were successfully eliminated by minimally invasive techniques

Phenotypic and Molecular-Genetic Analysis of Genetically Modified Toxigenic <I>Vibrio cholerae</I> El Tor Strain 301, Isolated in 2011 in Russia

The phenotypic and molecular-genetic analysis of Vibrio cholerae O1 El Tor Inaba strain 301, isolated in 2011 from sea water in recreation zone in Taganrog, demonstrated this isolate to be a genetic variant of El Tor cholera causative agent. Its genome was shown to carry a hybrid prophage, containing gene ctxB of classical type and gene rstR of El Tor type, as well as altered pathogenicity island VPI-1 and pandemicity island VSP-II. This strain produced much more cholera toxin (0,12 mcg/ml) than typical strains of this causative agent

Microbiome Responses to an Uncontrolled Short-Term Diet Intervention in the Frame of the Citizen Science Project

Personalized nutrition is of increasing interest to individuals actively monitoring their health. The relations between the duration of diet intervention and the effects on gut microbiota have yet to be elucidated. Here we examined the associations of short-term dietary changes, long-term dietary habits and lifestyle with gut microbiota. Stool samples from 248 citizen-science volunteers were collected before and after a self-reported 2-week personalized diet intervention, then analyzed using 16S rRNA sequencing. Considerable correlations between long-term dietary habits and gut community structure were detected. A higher intake of vegetables and fruits was associated with increased levels of butyrate-producing Clostridiales and higher community richness. A paired comparison of the metagenomes before and after the 2-week intervention showed that even a brief, uncontrolled intervention produced profound changes in community structure: resulting in decreased levels of Bacteroidaceae, Porphyromonadaceae and Rikenellaceae families and decreased alpha-diversity coupled with an increase of Methanobrevibacter, Bifidobacterium, Clostridium and butyrate-producing Lachnospiraceae- as well as the prevalence of a permatype (a bootstrapping-based variation of enterotype) associated with a higher diversity of diet. The response of microbiota to the intervention was dependent on the initial microbiota state. These findings pave the way for the development of an individualized diet.</p

The GWAS-MAP platform for aggregation of results of genome-wide association studies and the GWAS-MAP|homo database of 70 billion genetic associations of human traits

Hundreds of genome-wide association studies (GWAS) of human traits are performed each year. The results of GWAS are often published in the form of summary statistics. Information from summary statistics can be used for multiple purposes – from fundamental research in biology and genetics to the search for potential biomarkers and therapeutic targets. While the amount of GWAS summary statistics collected by the scientific community is rapidly increasing, the use of this data is limited by the lack of generally accepted standards. In particular, the researchers who would like to use GWAS summary statistics in their studies have to become aware that the data are scattered across multiple websites, are presented in a variety of formats, and, often, were not quality controlled. Moreover, each available summary statistics analysis tools will ask for data to be presented in their own internal format. To address these issues, we developed GWAS-MAP, a high-throughput platform for aggregating, storing, analyzing, visualizing and providing access to a database of big data that result from region- and genome-wide association studies. The database currently contains information on more than 70 billion associations between genetic variants and human diseases, quantitative traits, and “omics” traits. The GWAS-MAP platform and database can be used for studying the etiology of human diseases, building predictive risk models and finding potential biomarkers and therapeutic interventions. In order to demonstrate a typical application of the platform as an approach for extracting new biological knowledge and establishing mechanistic hypotheses, we analyzed varicose veins, a disease affecting on average every third adult in Russia. The results of analysis confirmed known epidemiologic associations for this disease and led us to propose a hypothesis that increased levels of MICB and CD209 proteins in human plasma may increase susceptibility to varicose veins