Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome

<p>Abstract</p> <p>Motivation</p> <p>Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. However, the factors that affect SNP density are poorly understood. The goal of this study was to estimate the relative effects of mutability and selection on SNP density in transcribed regions of human genes. It is important for prediction of the regions that harbor functional polymorphisms.</p> <p>Results</p> <p>We used frequency-validated SNPs resulting from single-nucleotide substitutions. SNPs were subdivided into five functional categories: (i) 5' untranslated region (UTR) SNPs, (ii) 3' UTR SNPs, (iii) synonymous SNPs, (iv) SNPs producing conservative missense mutations, and (v) SNPs producing radical missense mutations. Each of these categories was further subdivided into nine mutational categories on the basis of the single-nucleotide substitution type. Thus, 45 functional/mutational categories were analyzed. The relative mutation rate in each mutational category was estimated on the basis of published data. The proportion of segregating sites (PSSs) for each functional/mutational category was estimated by dividing the observed number of SNPs by the number of potential sites in the genome for a given functional/mutational category. By analyzing each functional group separately, we found significant positive correlations between PSSs and relative mutation rates (Spearman's correlation coefficient, at least r = 0.96, df = 9, <it>P </it>< 0.001). We adjusted the PSSs for the mutation rate and found that the functional category had a significant effect on SNP density (F = 5.9, df = 4, <it>P </it>= 0.001), suggesting that selection affects SNP density in transcribed regions of the genome. We used analyses of variance and covariance to estimate the relative effects of selection (functional category) and mutability (relative mutation rate) on the PSSs and found that approximately 87% of variation in PSS was due to variation in the mutation rate and approximately 13% was due to selection, suggesting that the probability that a site located in a transcribed region of a gene is polymorphic mostly depends on the mutability of the site.</p

Collective roost of corvids in Melitopol (Zaporozhye region) in 2014–2015

Показаны результаты наблюдений за формированием, существованием и распадом совместной зимовки врановых птиц на протяжении осенне-весеннего периода 2014–2015 гг. в г. Мелитополь (Запорожская область). Фиксировали и анализировали такие параметры: время начала и окончания процесса разлета с ночевки и сбора на ночевку, хронометраж летной активности птиц внутри этих интервалов, численность и видовой состав птиц, направления перелетов с нанесением на карту местности, погодные условия. Описаны процессы разлета птиц с места ночевки и сбора на ночевку. Методом абсолютного подсчета птиц оценка процесса сбора на ночевку и разлет с нее утром проведена два раза в неделю (всего 47 дней наблюдений утром и вечером). Наблюдения показали высокую степень зависимости от долготы дня и разную интенсивность этих видов суточной активности. Выявлены сезонные различия между временем разлета. В зимние месяцы этот период достоверно короче, чем осенью и весной. Продолжительность разлета птиц с ночевки меньше, чем сбора на ночевку. В работе схематически представлены основные стратегии утреннего разлета и вечернего сбора птиц на месте ночевки с их количественной характеристикой. Для утреннего разлета птиц с территории ночевки доминирующей является стратегия «разлет с паузой», а наименьший процент составила стратегия «три пика». Для вечернего сбора птиц доминирующей является стратегия «два пика», а наименее представленной – «сбор с паузой». Показаны результаты наблюдений за формированием, существованием и распадом совместной зимовки врановых птиц на протяжении осенне-весеннего периода 2014–2015 гг. в г. Мелитополь (Запорожская область). Фиксировали и анализировали такие параметры: время начала и окончания процесса разлета с ночевки и сбора на ночевку, хронометраж летной активности птиц внутри этих интервалов, численность и видовой состав птиц, направления перелетов с нанесением на карту местности, погодные условия. Описаны процессы разлета птиц с места ночевки и сбора на ночевку. Методом абсолютного подсчета птиц оценка процесса сбора на ночевку и разлет с нее утром проведена два раза в неделю (всего 47 дней наблюдений утром и вечером). Наблюдения показали высокую степень зависимости от долготы дня и разную интенсивность этих видов суточной активности. Выявлены сезонные различия между временем разлета. В зимние месяцы этот период достоверно короче, чем осенью и весной. Продолжительность разлета птиц с ночевки меньше, чем сбора на ночевку. В работе схематически представлены основные стратегии утреннего разлета и вечернего сбора птиц на месте ночевки с их количественной характеристикой. Для утреннего разлета птиц с территории ночевки доминирующей является стратегия «разлет с паузой», а наименьший процент составила стратегия «три пика». Для вечернего сбора птиц доминирующей является стратегия «два пика», а наименее представленной – «сбор с паузой». The article contains the results of observations on the formation, existence and the dissociation of the collective winter roost of corvids (crow species) in 2014–2015 in Melitopol (Zaporozhye region). A detailed study of the concentration and the dynamics of its functioning during the winter period was carried out. By the method of absolute counting of birds, the estimation of the gathering process on the roost in the night and dispersal from roost in the morning was carried out twice a week (a total of 47 days of observation in the morning and evening). We selected the following essential parameters: time of the beginning and ending of the process of dispersal from the roost in the morning and gathering at the roost in the evening; time – study of birds’ flight activity in these intervals; the number and species composition of birds; directions of flights with their mapping; weather conditions. Within the city of Melitopol during the winter period of 2014–2015, corvids (Rook, Western Jackdaw, Eurasian Magpie and Common Raven) form one central roost. The total number of birds at the roost was typically 18 thousand individuals. The collective roost exists from the beginning of October till the end of March. The analysis of dynamics of the birds’ number during the existence of the collective showed a wide amplitude of fluctuation in the range of 1,000–5,000 individuals during autumn (10 times) and spring (5 times) migration. By the end of November migration ends, the number of birds has stabilized, and the location of the night roost becomes permanent. In winter the gathering is more stable and fluctuations in number lie within the limits of 500 individuals (8 times). The number of birds that roost collectively decreased from mid – March. In this article considerable attention is paid to processes of the birds’ dispersal from the roost site and gathering at the roost at night. The observations showed a high degree of dependence on day length and different intensity of these types of daily activity. During the analysis of the process of morning dispersal of birds from the collective roost, seasonal differences in the time of dispersal were found. In the winter months this period was significantly shorter than in the autumn and spring. The duration of dispersal of birds from the roost (28.4 ± 9 min; lim – 15–45 min) was reliably less than that of gathering at the roost (87.9 ± 14.8 min; lim – 30–115 min); the difference of averages is significant for the highest probability threshold of р ≥ 0.001 for the entire observation period. As a result of research on dispersal and gathering of birds at the roost site, the basic strategies of the birds’ behaviour were revealled. For morning dispersal of birds from the territory of the roost the strategy of “gathering with a pause” (16 registrations; 35.6%) is dominant. The strategy of “the damped wave” is sub dominant (14; 31.1%). The lowest percentage was taken up by the strategy of “three peaks” (1; 2.2%). For the evening gathering of birds at the roost, the strategy of “two peaks” is dominant. The lowest percentage was taken up by the strategy of “gathering with a pause” (2; 4.5%). The overall species diversity within a gathering and on the routes of birds’ flights reached 24 species. The undisputed dominant in numbers was the Rook, and the subdominan was the Jackdaw. Thus, corvids form the basis of the ornithological complex of the forest – park zone of Melitopol in the autumn and spring period.

IMPROVING THE EFFECTIVENESS OF THE RISK MANAGEMENT SYSTEM

The article considers the importance of an effective risk management system in the conditions of uncertainty and instability for Russian companies. It concludeis that it is necessary to implement such a system to improve the management efficiency of a modern organization, using the example of PJSC “Geotek Seismo Razvedka”. The advantages and disadvantages of the existing risk management policy are identified. The authors suggest measures to improve the risk management system for this company. The article proposes to develope (define) the key risk indicators, offers to intensify risk management activities in the field of risk monitoring. To do this, the authors recommend to implement the Omnitracker Risk  Management software product as a system for automating the company’s risk management processes. The advantages of this product are considered, and a schedule for the implementation of Omnitracker Risk Management in PJSC “Geotek Seismo Razvedka”is developed

Prediction of the Gene Expression in Normal Lung Tissue by the Gene Expression in Blood

Background: Comparative analysis of gene expression in human tissues is important for understanding the molecular mechanisms underlying tissue-specific control of gene expression. It can also open an avenue for using gene expression in blood (which is the most easily accessible human tissue) to predict gene expression in other (less accessible) tissues, which would facilitate the development of novel gene expression based models for assessing disease risk and progression. Until recently, direct comparative analysis across different tissues was not possible due to the scarcity of paired tissue samples from the same individuals. Methods: In this study we used paired whole blood/lung gene expression data from the Genotype-Tissue Expression (GTEx) project. We built a generalized linear regression model for each gene using gene expression in lung as the outcome and gene expression in blood, age and gender as predictors. Results: For ~18 % of the genes, gene expression in blood was a significant predictor of gene expression in lung. We found that the number of single nucleotide polymorphisms (SNPs) influencing expression of a given gene in either blood or lung, also known as the number of quantitative trait loci (eQTLs), was positively associated with efficacy of blood-based prediction of that gene’s expression in lung. This association was strongest for shared eQTLs: those influencing gene expression in both blood and lung. Conclusions: In conclusion, for a considerable number of human genes, their expression levels in lung can be predicted using observable gene expression in blood. An abundance of shared eQTLs may explain the strong blood/lung correlations in the gene expression

INPP4B suppresses prostate cancer cell invasion

Background INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer. Results We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine IL-8 and induced PAK6. These genes were regulated in a reciprocal manner following downregulation of INPP4B in the independently derived INPP4B-positive LNCaP prostate cancer cell line. Inhibition of PI3K/Akt pathway, which is highly active in both PC-3 and LNCaP cells, did not reproduce INPP4B mediated suppression of IL-8 mRNA expression in either cell type. In contrast, inhibition of PKC signaling phenocopied INPP4B-mediated inhibitory effect on IL-8 in either prostate cancer cell line. In PC-3 cells, INPP4B overexpression caused a decline in the level of metastases associated BIRC5 protein, phosphorylation of PKC, and expression of the common PKC and IL-8 downstream target, COX-2. Reciprocally, COX-2 expression was increased in LNCaP cells following depletion of endogenous INPP4B. Conclusion Taken together, we discovered that INPP4B is a novel suppressor of oncogenic PKC signaling, further emphasizing the role of INPP4B in maintaining normal physiology of the prostate epithelium and suppressing metastatic potential of prostate tumors

The study of bats by ultrasound detector in the zone of influence of wind farms in Ukrainian Azov region

UK: За останнє десятиріччя вітрові електростанції (ВЕС) набули значної популярності у Європі. Саме з ними пов'язують розвиток майбутньої енергетики та скорочення темпів зростання парникового ефекту. Одна кВт/година вітрової енергії скорочує виділення діоксиду вуглецю приблизно на 600 т порівняно з електростанціями, що спалюють кам'яне вугілля або нафту. Так, наприклад, у Німеччині використання поновлюваних джерел енергії дало змогу уникнути викиду в атмосферу 35 млн. тон різних газів (Deutschland, 2002). Великий інтерес до виробництва електроенергії за допомогою вітру є і в Україні, де вже створено кілька парків ВЕС

Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations

© 2018 Gorlova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly due to the limited sample size of African Americans

АНАЛИЗ РАЗЛОМНО-БЛОКОВОЙ СТРУКТУРЫ И НАПРЯЖЕННОГО СОСТОЯНИЯ ОСАДОЧНОГО ЧЕХЛА НА ГАЗОКОНДЕНСАТНЫХ МЕСТОРОЖДЕНИЯХ: ОСНОВЫ ТЕКТОНОФИЗИЧЕСКОГО ПОДХОДА

Consideration is being given to the tectonophysical approach to the reconstruction of structure formation mechanisms and stress-strain state of rocks in hydrocarbon deposits localized in the platform cover, which has a complex structure in terms of rheological layering and disturbance by different-rank fractures. With the Kovykta gas condensate field, largest in Eastern Siberia, there were shown the main methods and ways of using modern achievements in tectonophysics for interpreting geological and geophysical information on the upper and lower parts of the sedimentary cover, unique in terms of volume and significance, that was obtained during geological exploration therein. Regularities of changes in the stress-strain state of rocks, found during the research, are combined into a tectonophysical model, which can be used as a base for other hydrocarbon deposits. The model is based on the concept of a zone-block structure of the platform cover, which is formed by a network of subvertical and subhorizontal fault zones that divide it into less faulted blocks. Disjunctive structures are highly fractured zones with concentration of relatively small low-amplitude faults, i.e. represent the early stages of faulting. The zone-block structure is formed mainly by tectonic or gravitational forces; in the first case, the stages and fracture characteristics are transformed onto the platform from the surrounding mobile belts, and in the second case they are determined by the presence of ductile rocks in the section capable of gravitational sliding. The graphic component of the tectonophysical model is 3D datasets that show the zone-block structure and stress state of rocks for the deposit with the degree of detail provided by key geophysical materials and, primarily, by seismic data. By modern GIS, this information can be quickly retrieved for any-size area of the studied rock mass and then used as a basis for solving production issues related to the development of deposits in fracture-pore reservoirs, or for analyzing general problems of their formation and dynamics.Рассмотрено содержание тектонофизического подхода к реконструкции механизмов структурообразования и напряженнодеформированного состояния пород на месторождениях углеводородов, локалиующихся в платформенном чехле, который отличается сложным строением в плане реологической расслоенноти и нарушенности разноранговыми разрывами. На примере крупнейшего Ковыктинского газоконденсатного месторождения в Восточной Сибири показаны основные приемы и способы использования современных достижений тектонофизики для интерпретации уникальной по объему и значимости геологогеофизической информации, полученной для верхней и нижней части осадочного чехла при проведении геологоразведочных работ. Закономерности напряженнодеформированного состояния пород, установленные в ходе исследований, объединены в тектонофизическую модель, которая может использоваться в качестве базовой для других месторождений углеводородного сырья. Основу модели составляют представления о зонноблоковой структуре платформенного чехла, которую образует сеть субвертикальных и субгоризонтальных разломных зон, разделяющих его на менее нарушенные блоки. Дизъюнктивные структуры являются зонами повышенной трещиноватости и сгущения сравнительно мелких малоамплитудных разрывов, т.е. представляют ранние стадии разломообразования. Зонноблоковая структура формируется главным образом под действием сил тектонической и гравитационной природы, причем в первом случае этапность и характер разрывообразования трансформируются на платформу со стороны окружающих подвижных поясов, а во втором – определяются наличием в разрезе пластичных пород, способных к гравитационному скольжению. Графической составляющей тектонофизической модели являются 3D объемы информации, отражающие зонноблоковую структуру и напряженное состояние пород для место рождения с той степенью детальности, которую обеспечивают ключевые геофизические материалы, и прежде всего данные сейсморазведки. При помощи современных ГИС эта информация может оперативно извлекаться для любого по размеру участка изучаемого породного массива и затем использоваться в качестве основы для решения производственных вопросов, связанных с разработкой залежей в трещиннопоровых коллекторах, или для анализа общих проблем их образования и динамики

Collimation of a Circulating Beam in the U_70 Synchrotron by Use of Reflections in Axially - Oriented Crystals

The possibilities of the extraction and collimation of a circulating beam by a new method due to the reflection of particles in crystals with axial orientation were experimentally investigated in the Fall-2010 run at the U_70 synchrotron. Such crystals have positive features, because the axial potential is five times larger than the planar potential. It has been shown that the collimation efficiency can reach 90% due to axial effects in the crystal. Losses of the circulating beam on a collimator have been reduced by several times; this makes it possible to suppress the muon jet near the steel collimator of the circulating beam.Comment: 6 pages, 7 figure