Mosquitoes of Anopheles hyrcanus (Diptera, Culicidae) group: species diagnostic and phylogenetic relationships

Herein, we report the results of study of Anopheles species in Primorsk and Khabarovsk regions of Russia. Three species of the Anopheles hyrcanus group: An. kleini, An. pullus, and An. lesteri were identified by molecular taxonomic diagnostics for the first time in Russia. Surprisingly, An. sinensis, which earlier was considered the only species of Anopheles in Russian Far East, was not observed. We analyzed nucleotide variation in the 610-bp fragment of the 5' end of the cytochrome c oxidase subunit I (COI) region. All species possessed a distinctive set of COI sequences. A maximum likelihood phylogenetic tree was constructed for members of the hyrcanus group. The examined Anopheles hyrcanus group members could be divided into two major subgroups: subgroup 1 (An. hyrcanus and An. pullus) and subgroup 2 (An. sinensis, An. kleini, and An. lesteri), which were found to be monophyletic

The policy of import substitution as the basis for economic security and well-being of society

The study presents the analysis of import substitution opportunities on separate branches of economic activity, preceding the realization of import substitution policy with the aim to support national economic security, which is essential for the contemporary society welfare insurance. Currently, social well-being is considered to be the reflection of economic activity, the instrument of state influence on the society, as well as an indicator of the social security system. Due to the fact that Russia is integrated into the world economy, the foreign-economic policy currently is playing an important role in the development of national security and the state's interest to the spheres of economy considering external and internal threats. Decline in external economic conditions may result in serious consequences for the functioning and development of the country as well as for the trade and investment activities, which will further lead to the decline in export, withdrawal of capital, recession of industrial production, trade and investment sphere, fall of GDP and living standards. Thus, considering the current state of instability in the world economy and the growing political tension in relation to Russian Federation, the measures to increase economic security in the country should be taken. The policy of import substitution is considered to be one of the major solutions nowadays

Оптимальне шкалювання для вимірювання стресу раннього періоду життя

BACKGROUND: Early life stress is associated with high risk for both negative psychological and physical health outcomes. However, many of the stressful life events inventories that have been used in epidemiological research have not been validated or checked for reliability or consistency. The aim of our study is to use optimal scaling and correspondence analysis that employ categorical principal components analysis (CATPCA) algorithm to consider the internal structure and the geometry of the space of variables obtained through the questions measuring early life stress. This approach was chosen because it allows quantification of categorical (both nominal and ordinal) scales and reduction of initial number of variables with interval quantification of the resulting dimensions. METHODS: A questionnaire for measuring early life stress was applied to the participants of the Ukrainian component of European Longitudinal Study of Pregnancy and Childhood at the age of three and seven years. CATPCA algorithm was used to elaborate a tool for estimating related integral quantified characteristics.RESULTS: Application of quantification and dimension reduction techniques to the categorical variables measuring stress in three- and seven-year-old children resulted in two dimensions. The first dimension that accounts for a major part of initial variance and is associated with all the collected variables can be interpreted as the overall value of stress. The second dimension accounts for smaller but still considerable part of variance and can be related to child’s attachment to mother and acquiring new experience as the route of development.CONCLUSIONS: Application of optimal scaling to the empirical data of early life stress measurement resulted in construction of two integral indicators – first measuring overall stress and second contrasting security related to child’s attachment to mother and new experiences – consistent across age groups of three and seven-year-old children.АКТУАЛЬНОСТЬ: Стресс в ранний период жизни связан с высоким риском как психологических, так и физиологических проблем. При этом многие инструменты, используемые для регистрации стрессовых событий в жизни в эпидемиологических исследованиях, не прошли проверку на валидность, надежность и согласованность. Целью нашего исследования было использование оптимального шкалирования и анализа соответствий по методу главных компонент для категориальных признаков с целью рассмотрения внутренней структуры и пространственной геометрии переменных, полученных из вопросника по измерению стресса в ранний период жизни. Выбор такого подхода был обусловлен тем, что он делает возможным количественное выражение категориальных (номинальных и порядковых) переменных и уменьшение размерности данных с интервальным выражением выявленных размерностей.  МЕТОДЫ: Вопросник по измерению стресса в ранние периоды жизни был предложен участникам украинской компоненты Европейского лонгитюдного исследования беременности и детства, когда их дети достигли 3-х и 7-ми лет. Алгоритм анализа соответствий по методу главных компонент для категориальных величин использовался для оценки соответствующих интегральных характеристик.РЕЗУЛЬТАТЫ: Применение количественного выражения и сокращения размерностей к категориальным переменным, измеряющим стресс у 3-х и 7-ми-летних детей, позволило выделить две размерности.Первая размерность, которая учитывает основную часть дисперсии и связана со всеми переменными в исследовании, может быть интерпретирована как общий уровень стресса. Вторая размерность, которая учитывает меньшую, но все же значительную часть дисперсии, сопоставляет привязанность ребенка к матери и получение нового опыта как важные элементы развития. ВЫВОДЫ: Применение оптимального шкалирования к эмпирическим данным по стрессу в ранний период жизни позволило сконструировать два интегральных индикатора. Первый индикатор служит для измерения общего стресса, а второй – для противопоставления ощущения безопасности, выражаемой в привязанности к матери, и получения нового опыта. Оба индикатора были выявлены как в возрастной группе 3-х-летних, так и 7-ми-летних детей.АКТУАЛЬНІСТЬ: Стрес у ранній період життя пов’язаний з високим ризиком як психологічних, так і фізіологічних проблем. Однак, інструменти, що використовують для реєстрації стресових подій у житті в епідеміологічних дослідженнях, не пройшли перевірку на валідність, надійність та узгодженість. Метою нашого дослідження було використання оптимального градуювання і аналізу відповідностей за методом головних компонент для категоріальних величин з метою виявлення внутрішньої структури і просторової геометрії змінних, отриманих з опитувальника, що вимірює стрес у ранній період життя. Вибір такого підходу був зумовлений його здатністю квантифікації категоріальних (номінальних і порядкових) шкал і зменшення розмірності даних з їх інтервальним визначенням.МЕТОДИ: Опитувальник стресу у ранні періоди життя був запропонований учасникам української компоненти Європейського лонгітюдного дослідження вагітності і дитинства, коли їх діти досягли 3-х і 7-ми років. Алгоритм аналізу відповідностей за методом головних компонент для категоріальних величин використовували для оцінки відповідних інтегральних характеристик.РЕЗУЛЬТАТИ: Використання вирахування і скорочення розмірностей щодо категоріальних змінних, які вимірюють стрес в 3-х і 7-ми-літніх дітей, дозволило виділити дві розмірності.Перша розмірність, яка враховує основну частину дисперсії і пов’язана з усіма змінними у дослідженні, може бути проінтерпретована як загальний рівень стресу. Друга розмірність, яка враховує меншу, але все ж значну частину дисперсії, співставляє прив’язаність дитини до матері й отримання нового досвіду як елементи процесу розвитку. ВИСНОВКИ: Використання оптимального градуювання до емпіричних даних зі стресу у ранній період життя дозволило сконструювати два інтегральні індикатори. Перший індикатор служить для вимірювання загального рівня стресу, а другий – для визначення відчуття безпеки, що проявляється через прив’язаність до матері, і отримання нового досвіду. Обидва індикатора були виявлені як у віковій групі 3-х-річних, так і 7-ми-річних дітей.  

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

BACKGROUND: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16(ink4a )drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16(ink4a )overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16(ink4a )overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas METHODS: Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16(ink4a )was analyzed by RT-PCR and by immunohistochemical technique. RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16(ink4a )cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. CONCLUSION: Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16(ink4a). Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16(ink4a )is a feature of cervical carcinomas

Prediction of catalytic residues using Support Vector Machine with selected protein sequence and structural properties

BACKGROUND: The number of protein sequences deriving from genome sequencing projects is outpacing our knowledge about the function of these proteins. With the gap between experimentally characterized and uncharacterized proteins continuing to widen, it is necessary to develop new computational methods and tools for functional prediction. Knowledge of catalytic sites provides a valuable insight into protein function. Although many computational methods have been developed to predict catalytic residues and active sites, their accuracy remains low, with a significant number of false positives. In this paper, we present a novel method for the prediction of catalytic sites, using a carefully selected, supervised machine learning algorithm coupled with an optimal discriminative set of protein sequence conservation and structural properties. RESULTS: To determine the best machine learning algorithm, 26 classifiers in the WEKA software package were compared using a benchmarking dataset of 79 enzymes with 254 catalytic residues in a 10-fold cross-validation analysis. Each residue of the dataset was represented by a set of 24 residue properties previously shown to be of functional relevance, as well as a label {+1/-1} to indicate catalytic/non-catalytic residue. The best-performing algorithm was the Sequential Minimal Optimization (SMO) algorithm, which is a Support Vector Machine (SVM). The Wrapper Subset Selection algorithm further selected seven of the 24 attributes as an optimal subset of residue properties, with sequence conservation, catalytic propensities of amino acids, and relative position on protein surface being the most important features. CONCLUSION: The SMO algorithm with 7 selected attributes correctly predicted 228 of the 254 catalytic residues, with an overall predictive accuracy of more than 86%. Missing only 10.2% of the catalytic residues, the method captures the fundamental features of catalytic residues and can be used as a "catalytic residue filter" to facilitate experimental identification of catalytic residues for proteins with known structure but unknown function

Erot spatiaalisissa ja ajallisissa reaktionormeissa kevään ja syksyn fenologisille tapahtumille

For species to stay temporally tuned to their environment, they use cues such as the accumulation of degree-days. The relationships between the timing of a phenological event in a population and its environmental cue can be described by a population-level reaction norm. Variation in reaction norms along environmental gradients may either intensify the envi- ronmental effects on timing (cogradient variation) or attenu- ate the effects (countergradient variation). To resolve spatial and seasonal variation in species’ response, we use a unique dataset of 91 taxa and 178 phenological events observed across a network of 472 monitoring sites, spread across the nations of the former Soviet Union. We show that compared to local rates of advancement of phenological events with the advancement of temperature-related cues (i.e., variation within site over years), spatial variation in reaction normsPeer reviewe

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

Chronicles of nature calendar, a long-term and large-scale multitaxon database on phenology

We present an extensive, large-scale, long-term and multitaxon database on phenological and climatic variation, involving 506,186 observation dates acquired in 471 localities in Russian Federation, Ukraine, Uzbekistan, Belarus and Kyrgyzstan. The data cover the period 1890-2018, with 96% of the data being from 1960 onwards. The database is rich in plants, birds and climatic events, but also includes insects, amphibians, reptiles and fungi. The database includes multiple events per species, such as the onset days of leaf unfolding and leaf fall for plants, and the days for first spring and last autumn occurrences for birds. The data were acquired using standardized methods by permanent staff of national parks and nature reserves (87% of the data) and members of a phenological observation network (13% of the data). The database is valuable for exploring how species respond in their phenology to climate change. Large-scale analyses of spatial variation in phenological response can help to better predict the consequences of species and community responses to climate change.Peer reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease