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

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

Long Distance Electron Transfer at the Metal/Alkanethiol/Ionic Liquid Interface

The rate constants of simple electron transfer (ET) reactions in room temperature ionic liquids (ILs) available now are rather high, typically at the edge of experimental accuracy. To consider ET phenomena in these media in view of theory developed earlier for molecular solvents, it is crucial to provide quantitative comparison of experimental kinetic data for certain reactions. We report this comparison for ferrocene/ferrocenium reaction. The ET distance is fixed by Au surface modification by alkanethiol self-assembled monolayers, which were characterized by in situ scanning tunneling microscopy. The dependence of ln kapp on barrier thickness in the range of ca. 6–20 Å is linear, with a slope typical for the same plots in aqueous media. This result confirms diabatic mode of Fc oxidation at long distance. The data for shorter ET distances point to the adiabatic regime of ET at a bare gold surface, although more detailed computational studies are required to justify this conclusion

Maximizing Roughness Factors in Oxide-Derived Copper Coatings through Electrodeposition Parameters for Enhanced Electrocatalytic Performance

The pursuit of novel techniques for obtaining dispersed copper-based catalysts is crucial in addressing environmental issues like decarbonization. One method for producing nanostructured metals involves the reduction of their oxides, a technique that has found widespread use in CO2 electroreduction. Currently, the intrinsic activities of oxide-derived copper electrocatalysts produced via different routes cannot be compared effectively due to the lack of information on electrochemically active surface area values, despite the availability of electrochemical methods that enable estimation of surface roughness for highly dispersed copper coatings. In this study, we aim to explore the potential of oxide-derived copper to achieve a high electrochemically active surface area by examining samples obtained from acetic and lactic acid deposition solutions. Our results revealed that Cu2O oxides had distinct morphologies depending on the electrodeposition solution used; acetate series samples were dense films with a columnar structure, while electrodeposition from lactic acid yielded a fine-grained, porous coating. The roughness factors of the electroreduced films followed linear relationships with the deposition charge, with significantly different slopes between the two solutions. Notably, a high roughness factor of 650 was achieved for samples deposited from lactic acid solution, which represents one of the highest estimates of electrochemically active surface area for oxide-derived copper catalysts. Our results highlight the importance of controlling the microstructure of the electrodeposited oxide electrocatalysts to maximize surface roughness

MODELING AS A METHOD FOR SCIENTIFIC COGNITION OF COMPLEX MEAT SYSTEMS

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