Влияние вируса клещевого энцефалита на ход метаморфоза напитавшихся личинок и нимф клеща Ixodes ricinus

In laboratory experience the conditions for development engorged larvaes (n = 2 500) and nymphs (n = 800) of Ixodes ricinus with diapause (6 h of light) are simulated. In contrast to control (diapause), the ticks with tick-borne encephalitis virus (strain EK- 328), developed under three variants; namely with diapause, with acceleration metamorphosis, and without diapause. The distinc- tions are caused by a season of the year and influence of the virus. The realization of variants carries out by stimulation or blocking of moult hormone.В лабораторном опыте смоделированы условия для развития напитавшихся личинок (n = 2 500) и нимф (n = 800) Ixodes ricinus с диапаузой (6 ч света). В отличие от контрольных (диапауза) клещи, зараженные вирусом клещевого энце- фалита (штамм «ЭК-328»), развивались по трем различным сценариям: с диапаузой, с ускорением метаморфоза, без диа- паузы. Различия обусловлены сезоном года и действием вируса. Реализация различных сценариев осуществлялась через стимуляцию или блокировку гормона линьки

Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children

Background: The biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes. Methods: The participants were 52 children of Mexican or Central American origin aged 11.6–15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood. Results: Overall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures. Conclusions: Assessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance

QSAR ANALYSIS OF COMPLEXATION OF ETHERS OF 7-BROM-3-HYDROXY-5-(2'-CHLORO) PHENYL-1,2-DIHYDRO-3H-1,4-BENZODIAZEPIN-2-ONES WITH CENTRAL BENZODIAZEPINE RECEPTORS CNS

QSAR analysis of the structural infl uence of 3-substituted 1,2-dihydro-3Н-1,4-benzodiazepine derivatives on the thermodynamic characteristics (ΔН0, ΔS0 and ΔG0) of their complexation with compounds was the main problem of QSAR analysis in this study. For small sets a new approach was developed for constructing statistical models and estimating their predictive ability. The developed special procedure for the generation of ensembles of QSAR models made it possible to construct adequate «structure – thermodynamic parameters» models for an «extremely small» set (6 compounds). 2D-PLS QSAR models were developed using the structural descriptors calculated by Dragon program and the descriptors calculated by the method based on the simplex representation of the molecular structure. The consensus models with quite good statistical characteristics (R2 > 0.95 for work set, R2 test > 0.78 for test set) were obtained for thermodynamic charact eristics complexation of investigated compounds. The prognosis of the thermodynamic parameters of binding of the related compounds with R = H, iso-C4H9, sec.-C4H9 to the CBDR was carried out using the simplex descriptors and Dragon descriptors. The increa se in the corresponding alkyl substituent from ethyl to isomeric butyl does not signifi cantly affect the interaction of ligands with the CBDR. It is assumed that the amount of Hydrogen atoms bounding to the Carbon atom adjacent to the carbonyl group has a certain infl uence on the thermodynamic characteristics of ligands interaction with CBDR; this may be due to the hyperconjugation effect. Exner’s method has revealed that the mechanism of interaction of the methyl-substituted compound with the CBDR differs from the mechanism of interaction with the CBDR of other investigated compounds

QSAR АНАЛІЗ КОМПЛЕКСОУТВОРЕННЯ ЕСТЕРІВ 7-БРОМ-3-ГІДРОКСИ-5-(2’-ХЛОР)ФЕНІЛ-1,2-ДИГІДРО-3Н-1,4-БЕНЗДІАЗЕПІН-2-ОНІВ З ЦЕНТРАЛЬНИМИ БЕНЗДІАЗЕПІНОВИМИ РЕЦЕПТОРАМИ ЦНС

QSAR analysis of the structural infl uence of 3-substituted 1,2-dihydro-3Н-1,4-benzodiazepine derivatives on the thermodynamic characteristics (ΔН0, ΔS0 and ΔG0) of their complexation with compounds was the main problem of QSAR analysis in this study. For small sets a new approach was developed for constructing statistical models and estimating their predictive ability. The developed special procedure for the generation of ensembles of QSAR models made it possible to construct adequate «structure – thermodynamic parameters» models for an «extremely small» set (6 compounds). 2D-PLS QSAR models were developed using the structural descriptors calculated by Dragon program and the descriptors calculated by the method based on the simplex representation of the molecular structure. The consensus models with quite good statistical characteristics (R2 > 0.95 for work set, R2 test > 0.78 for test set) were obtained for thermodynamic charact eristics complexation of investigated compounds. The prognosis of the thermodynamic parameters of binding of the related compounds with R = H, iso-C4H9, sec.-C4H9 to the CBDR was carried out using the simplex descriptors and Dragon descriptors. The increa se in the corresponding alkyl substituent from ethyl to isomeric butyl does not signifi cantly affect the interaction of ligands with the CBDR. It is assumed that the amount of Hydrogen atoms bounding to the Carbon atom adjacent to the carbonyl group has a certain infl uence on the thermodynamic characteristics of ligands interaction with CBDR; this may be due to the hyperconjugation effect. Exner’s method has revealed that the mechanism of interaction of the methyl-substituted compound with the CBDR differs from the mechanism of interaction with the CBDR of other investigated compounds.Проведено QSAR аналіз впливу структури похідних 3-заміщених 1,4-бенздіазепінів на термодинамічні характеристики (ΔН0, ΔS0 и ΔG0) їх комплексоутворення з центральними бенздіазепіновими рецепторами (ЦБДР) ЦНС. Основною проблемою аналізу виявилась незначна кількість досліджуваних сполук, у зв’язку з чим було розроблено новий підхід для малих вибірок щодо побудови статистичних моделей та оцінки їхньої прогнозувальної здатності. Використовуючи спеціальну процедуру для формування навчальних та тестових вибірок, структурні дескриптори, розраховані за допомогою програми Dragon, і дескриптори, розраховані в рамках методу, що базується на симплексному представленні молекулярної структури, було побудовано адекватні 2D-PLS моделі «структура - термодинамічні параметри» для «надзвичайно малого» набору досліджуваних речовин (6 сполук). Отримані моделі мають задовільні статистичні характеристики: R2 > 0.95 для навчальної вибірки, R2 test > 0.78 для тестової вибірки. З метою більш детального аналізу впливу замісника на термодинамічні характеристики похідних 3-заміщених 1,4-бенздіазепінів було спрогнозовано значення ΔН0, ΔS0 і ΔG0 комплексеутворення з ЦБДР для сполук з R = H, i-C4H9, s-C4H9.Встановлено, що збільшення довжини і розгалуженості відповідного алкільного заступника від етилу до ізомерних бутилів не суттєво впливає на взаємодію лігандів з ЦБДР. Зроблено припущення, що певний вплив на термодинамічні характеристики взаємодії лігандів з ЦБДР має кількість атомів Гідрогену, які зв’язані з атомом Карбону алкілу, що знаходиться поряд з карбонільною групою, що може бути пов’язано з ефектом гіперкон’югації. Метод Екснера дозволив виявити, що механізм взаємодії метил-заміщеної сполуки з ЦБДР відрізняється від механізму взаємодії з ЦБДР інших досліджуваних сполук

Ixodid ticks and tick-borne encephalitis virus prevalence in the South Asian part of Russia (Republic of Tuva)

The most significant processes of arbovirus evolution can be expected to occur in the territories where ticks of different species cohabitate and at the boundaries of virus occurrence, where the probability of the appearance of new virus variants is high due to the possible shift in the main vectors and/or vertebrate hosts. One of the most interesting regions in this regard is the Republic of Tuva. Since most of its territory is covered by mountain ranges and intermountain basins, we were able to study the distribution of vectors and viruses in geographically isolated areas at different altitudes and in various landscapes. From 2008 to 2017, we conducted six expeditions to Tuva and collected 3,077 adult ticks and 24 nymphs. The distribution of tick species was confined to specific landscapes, as follows: Dermacentor nuttalli occurred in steppes, D. silvarum inhabited forest-steppe areas, and Ixodes persulcatus inhabited mixed forests. All three species of ticks were collected on plains and mountain slopes. The range of D. silvarum was shown to be lower than 1300 m above sea level (a.s.l.). Only D. nuttalli and I. persulcatus were collected at higher altitudes. According to our observations, single nymphs of D. nuttalli appear on animals one month before larvae appear. This finding confirms the hypothesis that the immature forms of D. nuttalli are able to overwinter under favourable conditions. We isolated 9 strains and 3 isolates of tick-borne encephalitis virus (TBEV) from I. persulcatus, one strain from D. nuttalli and one strain from D. silvarum. The TBEV strain from D. nuttalli was isolated from the territory inhabited only by Dermacentor ticks. All isolated strains belong to the Siberian subtype of TBEV. TBEV was detected in ticks from all the investigated altitudes. There were no statistically significant differences in the virus prevalence between the Dermacentor and Ixodes ticks. The results of our work provide additional support for the hypothesis of the existence of TBEV foci in areas with an absolute dominance of D. nuttalli. © 2019 The Author

Effects of early social deprivation on epigenetic statuses and adaptive behavior of young children: A study based on a cohort of institutionalized infants and toddlers

Early social deprivation (i.e., an insufficiency or lack of parental care) has been identified as a significant adverse early experience that may affect multiple facets of child development and cause long-term outcomes in physical and mental health, cognition and behavior. Current research provides growing evidence that epigenetic reprogramming may be a mechanism modulating these effects of early adversities. This work aimed to investigate the impact of early institutionalization—the immersion in an extreme socially depriving environment in humans—on the epigenome and adaptive behavior of young children up to 4 years of age. We conducted a cross-sectional study involving two comparison groups: 29 children raised in orphanages and 29 children raised in biological families. Genome-wide DNA methylation profiles of blood cells were obtained using the Illumina MethylationEPIC array; the level of child adaptive functioning was assessed using the Vineland Adaptive Behavior Scales-II. In comparison to children raised in families, children residing in orphanages had both statistically significant deficits in multiple adaptive behavior domains and statistically significant differences in DNA methylation states. Moreover, some of these methylation states may directly modulate the behavioral deficits; according to preliminary estimates, about 7–14% of the deviation of adaptive behavior between groups of children may be determined by their difference in DNA methylation profiles. The duration of institutionalization had a significant impact on both the adaptive level and DNA methylation status of institutionalized children