Promoter DNA Methylation in GWAS-Identified Genes as Potential Functional Elements for Blood Pressure: An Observational and Mendelian Randomization Study

Genome-wide association studies have identified numerous genetic loci for blood pressure (BP). However, the relationships of functional elements inside these loci with BP are not fully understood. This study represented an effort to determine if promoter DNA methylations inside BP-associated loci were associated with BP.We conducted a cross-sectional study investigating the association between promoter DNA methylations of 10 candidate genes and BP in 1,241 Chinese individuals. Twenty-one genomic fragments in the CpG Islands were sequenced. The associations of methylation levels with BP and hypertension were assessed in regression models. Mendelian randomization (MR) analysis was then applied to find supporting evidence for the identified associations.A total of 413 DNA methylation sites were examined in an observational study. Methylation levels of 24 sites in PRDM6, IGFBP3, SYT7, PDE3A, TBX2 and C17orf82 were significantly associated with BP. Methylation levels of PRDM6 and SYT7 were significantly associated with hypertension. Methylation levels of five sites (including cg06713098) in IGFBP3 were significantly associated with DBP. MR analysis found associations between the methylation levels of six CpG sites (cg06713098, cg14228300, cg23193639, cg21268650, cg10677697 and cg04812164) around the IGFBP3 promoter and DBP. Methylation levels of cg14228300 and cg04812164 were associated with SBP. By further applying several MR methods we showed that the associations may not be due to pleiotropy. Association between IGFBP3 mRNA levels in blood cells and BP was also found in MR analysis. This study identified promoter methylation as potential functional element for BP. The identified methylations may be involved in the regulatory pathway linking genetic variants to BP.

Appearance and Basic Functional Elements of an Interactive Multimodal Hybrid Conformal Microsystem for Real-Time Transdermal Biomedical Monitoring and Correction of the Body State

The constructive and technological solutions of a new generation interactive multimodal hybrid conformal sensor-correcting microsystem are presented. The functional modules of the microsystem made in the form of an ultrathin bracelet or patch with the possibility of fixation on human skin are considered. The advantages of the proposed microsystem, its purpose and possible applications are discussed.

Determination of the Model Basis for Assessing the Vehicle Energy Efficiency in Urban Traffic

The paper studies the problem of assessing the vehicle energy efficiency on the streets of urban road network. As a result of morphological analysis of the system “Vehicle—Traffic flow—Road—Traffic Environment” 18 significant morphological attributes of its functional elements, that affect the energy efficiency of vehicles, were identified. Each attribute is characterized by 3–6 implementation variants, which are evaluated by the relevant quantitative or qualitative parameters. The energy efficiency of vehicles is determined by the criteria of their energy consumption considering the vehicle category, type of energy unit, mode of vehicle movement and adjustment factors—road, climatic and others. The input parameters values of the system in the process of traffic flow on the linear fragments of streets and road networks of the cities of Ukraine and Poland were measured. The set of independent system parameters is determined by applying the Farrar-Glober method based on statistical estimates. The specified set is the basis of the studied system and is formed of 10 independent input parameters. The presence in the basis of parameters that correspond to the morphological features of all four functional elements, confirmed the importance of these elements of the system. The mathematical dependence of the impact of vehicle characteristics, traffic flow, road and environment on vehicle energy efficiency is built. The standard deviation of the model values from the tabular ones equals σ´=0.0091. Relative standard deviation equals S´r=1.5%. The results of the study could be used in the development of new and optimization of existing intelligent traffic control systems of urban transport.

Comparative Enhancer Map of Cattle Muscle Genome Annotated by ATAC-Seq

Annotating regulatory elements could benefit the interpretation of the molecular mechanism of genome-wide association study (GWAS) hits. In this work, we performed transposase-accessible chromatin with sequencing (ATAC-seq) to annotate the cattle muscle genome's functional elements. A total of 10,023 and 11,360 peaks were revealed in muscle genomes of adult and embryo cattle, respectively. The two peak sets produced 8,850 differentially accessible regions (DARs), including 2,515 promoters and 4,319 putative enhancers. These functional elements were associated with the cell cycle, muscle development, and lipid metabolism. A total of 15 putative enhancers were selected for a dual-luciferase reporter assay, and 12 of them showed enhancer activity in cattle myoblasts. Interestingly, the GeneHancer database has annotated the interactions of eight active enhancers with gene promoters, such as embryo-specific peak1053 (log2FC = 1.81, embryo/adult, E/A) with ligand-dependent nuclear receptor corepressor-like protein (LCORL) and embryo-specific peak4218 (log2FC = 1.81) with FERM domain-containing 8 (FRMD8). A total of 295 GWAS loci from the animal QTL database were mapped to 183 putative enhancers, including rs109554838 (associated with cattle body weight and average daily gain) to peak1053 and rs110294629 (associated with beef shear force and tenderness score) to peak4218. Notably, peak4218 has been found to be involved in mouse embryo development. Deleting peak4218 clearly reduced luciferase activity (P = 3.30E-04). Our comparative enhancer map is expected to benefit the area of beef cattle breeding.

RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse

Eukaryotic genomes contain many nongenic elements that function in gene regulation, chromosome organization, recombination, repair or replication, and mutation of those elements can affect genome function and cause disease. While numerous epigenomic studies provide high coverage of gene regulatory regions, those data are not usually exposed in traditional genome annotation, and can be difficult to access and interpret without field-specific expertise. The National Center for Biotechnology Information (NCBI) therefore provides RefSeq Functional Elements (RefSeqFEs), which represent experimentally validated human and mouse nongenic elements derived from the literature. The curated dataset is comprised of richly annotated sequence records, descriptive records in the NCBI Gene database, reference genome feature annotation, and activity-based interactions between nongenic regions, target genes and each other. The dataset provides succinct functional details and transparent experimental evidence, leverages data from multiple experimental sources, is readily accessible and adaptable, and utilizes a flexible data model. The data have multiple uses for basic functional discovery, bioinformatics studies, genetic variant interpretation, as known positive controls for epigenomic data evaluation, and as reference standards for functional interactions. Comparisons to other gene regulatory datasets show that the RefSeqFE dataset includes a wider range of feature types representing more areas of biology, but it is comparatively smaller and subject to data selection biases. RefSeqFEs thus provide an alternative and complementary resource for experimentally assayed functional elements, with future dataset growth expected.

Book Reviews

Paul N. Courant of Edward M. Gramlich Distinguished University Professor and Provost Emeritus, University of Michigan reviews “Like Nobody’s Business: An Insider’s Guide to How US University Finances Really Work” by Andrew C. Comrie. The Econlit abstract of this book begins: “Discusses the essentials of university funding, reviewing the business and finances of higher education in terms of its six functional elements—state and trustee governance, university administration, teaching, research, public service, and students and the broader community.”

Structure of the human SAGA coactivator complex

The SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.

Analysis of Cyber Networks in a System Concept

The aim of the paper is to show that all cyber networks (such as telecommunication, IT or ICT networks) are systemically identical or very similar, although each of them is applied in another industry or economy field or includes other added functional elements. The effort is to show that systemic identity (similarity) of the mentioned networks identifies the same set of network security threats that can be solved using the same approaches and techniques. The integrative approach based on the systematic approach enables to effectively use the efforts of professionals and all means target to the actual problem solving. The mentioned networks classification to the cyber critical infrastructures is also made based on this concept. Cyber system and cyber networks are threatened by both, the internal system deficits (technical and organisational nature) and the wide range of disasters: natural disasters - impacts primarily on the technical resources; intentional events caused by human vandalism, theft, terrorist attacks; technological accidents; and failure of electricity supply; etc. They threaten individual humans, human groups and states by their technical and organisational deficits and by the IT disuse.

Assessment of the Benefits of Information and Communication Technologies (ICT) Adoption on Downstream Supply Chain Performance of the Retail Industry

Background: The COVID-19 pandemic-driven supply chain disruptions have pushed supply chain decision-makers in the retail industry to implement information and communication technologies (ICT) to improve the efficiency and resiliency of their supply chain. However, they need some guidance to identify the functional elements of the supply chain for ICT adoption and the benefits of implementing ICT on their supply chain performance. Methods: We conducted an empirical study that provides guidance on the performance benefits of ICT adoption specifically for the downstream supply chain of the retail industry. This study employed the feature engineering technique to prioritize the functional elements of the supply chain to maximize the benefits of ICT adoption on supply chain performance. Results: ICT adoption benefits the retail industry’s overall downstream supply chain performance in the range of 9–41%. Moreover, the study discovered the key functional elements of the supply chain for ICT adoption that significantly improve the overall supply chain performance. Conclusions: The study presents a definite view of the quantitative benefits of ICT adoption to the supply chain decision-makers of the retail industry and aids them in selecting appropriate functional elements for ICT adoption to maximize their supply chain performance.