ЛЕКСИКО-СЕМАНТИЧЕСКИЕ ОСОБЕННОСТИ АНТРОПОНИМОВ

The purpose of this paper is studying of the poetic onomasticon of R.Minin, defining the role of onomastic system in creating linguostylistic structure of the works, the description of the aspects of text’s space, the novelty of the research is to generalize the author’s numerous works, offers his own vision of a problem "in the name of a literary text," and also devoted to issues specific implementation of expressive possibilities of anthroponyms in children's poetry.Целью данной статьи является изучение поэтического ономастикона Р.Миннуллина, определение роли ономастической системы в создании лингвостилистической структуры произведений, описание особенности текстового онимического пространства, новизна предлагаемого исследования заключается в обобщении наблюдений автора многочисленных трудов, предлагавших свое видение проблемы «имя в художественном тексте», а также посвященных вопросам особенностей реализации выразительных возможностей антропонимов в текстах детской поэзии

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

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

Design of BET Inhibitor Prodrugs with Superior Efficacy and Devoid of Systemic Toxicities

Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic index of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive design and optimization. Here, using BET bromodomain inhibitors (BETi)—a class of epigenetic regulators with proven anti-cancer activity but clinical development hindered by systemic adverse effects–– we introduce a platform that overcomes these challenges. Through tuning of traceless linkers appended to a “brush prodrug” scaffold, we demonstrate that it is possible to correlate in vitro prodrug activation kinetics with in vivo tumor pharmacokinetics, leading to novel BETi prodrugs with enhanced anti-tumor efficacy and devoid of dose-limiting toxicities. This work has immediate clinical implications, introducing principles for the predictive design of prodrugs and potentially overcoming hurdles in drug development. </div