Vitamin D Insufficiency in Overweight and Obese Children and Adolescents

Excessive body weight and obesity in childhood and adolescence are becoming more and more important unfavorable factors that entail extremely adverse consequences and require close attention of physicians of any specialty. Along with the high prevalence of obesity and metabolic syndrome in pediatric patients, children and adolescents in the majority of countries are diagnosed with vitamin D deficiency. Among the non-calcaemic effects of vitamin D, a significant role is played by its impact on the hormonal regulation of glucose metabolism and the synthesis of adipokines by fat tissue. The review presents literature data indicative of a close pathogenic relationship between vitamin D insufficiency and impaired tissue insulin sensitivity. It demonstrates the role of vitamin D insufficiency in immune reactions resulting in development of subclinical inflammation in fat tissue infiltrated with macrophages and lymphocytes. It also shows the role of adipokines, immune system cells and pro-inflammatory cytokines produced by them in the pathogenesis of obesity, as well as the function of vitamin D as an endocrine and paracrine regulator of the process of inflammation in adipose tissue. The relationships between the principal adipokines (leptin, adiponectin, resistin) are revealed in the presence of normal vitamin D content and in vitamin D deficiency. The carbohydrate and lipid metabolism parameters in overweight children and adolescents with vitamin D insufficiency are analyzed. A high prevalence of vitamin D insufficiency in overweight and obese children and adolescents (increasing along with the severity of obesity) is demonstrated. The review also presents the current recommendations for the correction of vitamin D insufficiency and underlines the need for higher cholecalciferol doses to achieve serum calcifediol targets in overweight and obese children and adolescents

Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

Relevance. Abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta is associated with many pregnancy pathologies. Aim. The aim of this work was to analyze the prevalence of abnormal methylation of the PRDM16 and PTPRN2 genes in chorionic villi of spontaneous abortions with normal karyotype and with the most frequent aneuploidies (trisomy 16 and monosomy X). Materials and Methods. The methylation profile was evaluated using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 10), spontaneous abortions with normal karyotype (n = 39), trisomy 16 (n = 17) and monosomy X (n = 20) and peripheral blood lymphocytes of healthy volunteers (n = 6). Results and Discussion. In analyzed genes, differential methylation of individual CpG sites was found in chorionic villi of spontaneous abortions. Despite the absence of significant differences between the groups in the average level of methylation in analyzed gene regions, abnormal methylation of the PRDM16 and PTPRN2 genes were detected for 33 % and 5 % of spontaneous abortions, respectively, indicating a high incidence of epigenetic abnormalities in these genes in the chorionic villi of spontaneous abortions. The level of methylation of the PRDM16 gene significantly correlated with the level of methylation of the retrotransposon LINE-1, which indicates the generalized nature of methylation disorders in spontaneous abortions. Finally, the level of methylation of the PTPRN2 gene depended on the age of mothers of spontaneous abortions with monosomy X, which raises the question of the influence of maternal factors on the methylation profile in this group of spontaneous abortions. Conclusion. The results indicate that epigenetic disorders of the PRDM16 gene may be associated with spontaneous termination of pregnancy in the first trimester

МОДЕЛИРОВАНИЕ КАК МЕТОД НАУЧНОГО ПОЗНАНИЯ СЛОЖНЫХ МЯСНЫХ СИСТЕМ

The paper examines the issues associated with the integration of knowledge in meat product technology + computers + mathematical methods. The possibilities to use a computer system and mathematical methods for an optimal solution to tasks in the field of food biotechnology and meat product technology are demonstrated.The applied software program SSS Bio realized in the computer system was developed and described. Using the one-way analysis of variance, which is one of the system modules, a comprehensive amount of statistical data for interpretation of the results was obtained. The program modules (correlation and regression analysis) allow establishing the model structure and parameters that link quantitative resulting and factorial variables, as well as assessing a degree of their correspondence with the experimental data. This kind of statistical analysis makes it possible to solve the main task of an experiment when the observed and resulting variables are quantitative.Based on the experimental data obtained with the use of the computer system SSS Bio, the mathematical models of moisture binding capacity (MBC), moisture holding capacity (MHC) and fat binding capacity (FBC) in sausage meat were calculated for sausages with isolated soya protein depending on the fat and protein content using the module of multiple regression of the computer system.The obtained stochastic dependence of changes in MBC (Y) on the total protein (X1) and fat (X2) content in sausage meat shows that at the constant level of fat, an increase in total protein favors a growth in MBC of sausage meat. However, a growth in MBC per unit of protein decreases with an increase in the fat amount.В статье рассмотрены вопросы, связанные с  интеграцией знаний «технология мясных продуктов + компьютеры + математические методы». Показаны возможности использования компьютерной системы и математических методов для оптимального решения задач в  области пищевой биотехнологии и технологии мясных продуктов.Разработана и описана прикладная программа SSS Bio, реализованная в  компьютерной системе. При помощи однофакторного дисперсионного анализа, являющегося одним из модулей системы, получены исчерпывающее количество статистических данных для интерпретации результатов. Модули программы (корреляционный и  регрессионный анализ) позволяют установить структуру и  параметры модели, связывающей количественные результирующую и факторные переменные, и оценить степень ее согласованности с экспериментальными данными. Этот вид статистического анализа позволяет решать главную задачу эксперимента в  случае, если наблюдаемые и  результирующие переменные являются количественными.На основе экспериментальных данных при помощи компьютерной системы SSS Bio рассчитаны математические модели влагосвязывающей (ВСС), влагоудерживающей (ВУС) и жиросвязывающей (ЖСС) способностей в фарше для колбасных изделий с использованием соевого изолированного белка в зависимости от содержания жира и белка с использованием модуля множественной регрессии компьютерной системы.Полученная стохастическая зависимость изменения ВСС (Y) от содержания общего белка (X1) и жира (X2) в колбасном фарше показывает, что при постоянном уровне жира увеличение общего содержания белка способствует росту ВСС фарша. Однако рост ВСС на единицу белка уменьшается с увеличением количества жира

The Telomere Binding Protein TRF2 Induces Chromatin Compaction

Mammalian telomeres are specialized chromatin structures that require the telomere binding protein, TRF2, for maintaining chromosome stability. In addition to its ability to modulate DNA repair activities, TRF2 also has direct effects on DNA structure and topology. Given that mammalian telomeric chromatin includes nucleosomes, we investigated the effect of this protein on chromatin structure. TRF2 bound to reconstituted telomeric nucleosomal fibers through both its basic N-terminus and its C-terminal DNA binding domain. Analytical agarose gel electrophoresis (AAGE) studies showed that TRF2 promoted the folding of nucleosomal arrays into more compact structures by neutralizing negative surface charge. A construct containing the N-terminal and TRFH domains together altered the charge and radius of nucleosomal arrays similarly to full-length TRF2 suggesting that TRF2-driven changes in global chromatin structure were largely due to these regions. However, the most compact chromatin structures were induced by the isolated basic N-terminal region, as judged by both AAGE and atomic force microscopy. Although the N-terminal region condensed nucleosomal array fibers, the TRFH domain, known to alter DNA topology, was required for stimulation of a strand invasion-like reaction with nucleosomal arrays. Optimal strand invasion also required the C-terminal DNA binding domain. Furthermore, the reaction was not stimulated on linear histone-free DNA. Our data suggest that nucleosomal chromatin has the ability to facilitate this activity of TRF2 which is thought to be involved in stabilizing looped telomere structures

Deciphering the origin and therapeutic targets of cancer of unknown primary: a case report that illustrates the power of integrative whole-exome and transcriptome sequencing analysis

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p