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Prediabetes (PD) is a high-risk state of developing type 2 diabetes, and cardiovascular and metabolic diseases. Metabolomics-based biomarker studies can provide advanced opportunities for prediction of PD over the conventional methods. Here, we aimed to identify metabolic markers and verify their abilities to predict PD, as compared to the performance of the traditional clinical risk factor (CRF) and previously reported metabolites in other population-based studies. Targeted metabolites quantification was performed in 1723 participants in the Korea Association REsource (KARE) cohort, from which 500 normal individuals were followed up for 6 years. We selected 12 significant metabolic markers, including five amino acids, four glycerophospholipids, two sphingolipids, and one acylcarnitine, at baseline, resulting in a predicted incidence of PD with an area under the curve (AUC) of 0.71 during follow-up. The performance of these metabolic markers compared to that of fasting glucose was significantly higher in obese patients (body mass index: BMI ≥ 25 kg/m2, 0.79 vs. 0.58, P

IntroductionObesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.Research design and methodsWe performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).ResultsSeven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.ConclusionsOur finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.

// Suman Lee 1 , Hyo Jin Kim 2 , Sohee Han 1 , Jae-Pil Jeon 1 , Sang-Ick Park 2 , Ho-Yeong Yu 1 , Mi Yeong Hwang 1 and Juyoung Lee 1 1 Center for Genome Science, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea 2 Center for Biomedical Sciences, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea Correspondence to: Suman Lee, email: smnl93@gmail.com Keywords: cg16672562, HIF3A , obesity, CpG methylation, cis-meQTL Received: January 16, 2017 Accepted: May 27, 2017 Published: June 27, 2017 ABSTRACT Differential methylations of the HIF3A (hypoxia-inducible factor 3a) gene have been linked to body mass index (BMI). To explore the association of these methylations to childhood obesity, we measured 5 CpG methylation sites (cg27146050, cg46801562, cg22891070, cg16672562 and cg46801675) in intron 1 of the HIF3A gene by pyrosequencing, in the Korean population (mean age: 13.9 yrs, 305 obese cases and 387 controls). Two CpG methylations, cg46801562 and cg16672562, had statistically significant association with childhood obesity ( P = 2.09E-9 and 1.66E-7, respectively). Notably, in the case of cg16672562, all correlations were significantly positive with BMI ( beta = 0.285, P = 1.652E-13), waist-hip ratio ( beta = 0.0028, P = 1.42E-15) and fasting plasma glucose level ( beta = 0.0645, P = 2.61E-4), when analyzed by linear regression, with age and sex as covariates. We investigated any genetic effect of cg16672562 methylation by using 14 single nucleotide polymorphisms (SNP) identified by exome sequencing of the HIF3A locus . cg16672562 methylation showed no statistically significant changes due to the 14 polymorphisms. In this study, we show that cg16672562 is the most significant blood DNA methylation marker for childhood obesity in the Korean population, and might be independent of any underlying HIF3A genetic background.

Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1].

This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene&ndash, disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs&rsquo, expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.

Copy number variation is a well-known genetic variation. microRNAs (miRNAs/miRs) are non-coding RNAs that mediate gene expression by regulating target mRNAs. In the present study, copy number deletions encompassing miRNA coding regions were investigated to determine the association between the deletion of miRNA and its phenotypic effects. A total of 38 human miRNAs in copy number variants were identified and miR-650, which is functional in the human osteosarcoma MG-63 cell line, was selected. Overexpression of miR-650 decreased the expression of inhibitor of growth family member 4 (ING4) in the MG-63 cells and increased interleukin (IL)6 transcription, as well as IL6 secretion in IL1B-stimulated cells. Furthermore, miR-650 downregulated the amount of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor α and increased the transcriptional activity of nuclear factor (NF)κB. Downregulation of ING4 also increased the production of IL6, similar to miR-650 overexpression. Taken together, these data indicate that miR-650 plays a significant role in the production of IL6 by regulating ING4 expression and NFκB signaling in IL1B-stimulated MG-63 osteosarcoma cells.

Dilated cardiomyopathy (DCM) is one of the main causes of heart failure (called cardiomyopathies) in adults. Alterations in epigenetic regulation (i.e., DNA methylation) have been implicated in the development of DCM. Here, we identified a total of 1828 differentially methylated probes (DMPs) using the Infinium 450K HumanMethylation Bead chip by comparing the methylomes between 18 left ventricles and 9 right ventricles. Alterations in DNA methylation levels were observed mainly in lowly methylated regions corresponding to promoter-proximal regions, which become hypermethylated in severely affected left ventricles. Subsequent mRNA microarray analysis showed that the effect of DNA methylation on gene expression regulation is not unidirectional but is controlled by the functional sub-network context. DMPs were significantly enriched in the transcription factor binding sites (TFBSs) we tested. Alterations in DNA methylation were specifically enriched in the cis-regulatory regions of cardiac development genes, the majority of which are involved in ventricular development (e.g., TBX5 and HAND1).

Recently, the technologies of mobile robots have been growing rapidly in the fields such as cleaning robot, explosive ordnance disposal robot, patrol robot, etc. However, the researches about the autonomous underwater robots have not been done so much, and they still remain at the low level of technology. This paper describes a model of 3-joint (4 links) fish robot type. Then we calculate the dynamic motion equation of this fish robot and use Singular Value Decomposition (SVD) method to reduce the divergence of fish robot’s motion when it operates in the underwater environment. And also, we analysis response characteristic of fish robot according to the parameters of input torque function and compare characteristic of fish robot with 3 joint and fish robot with 2 joint. Next, fish robot’s maximum velocity is optimized by using the combination of Hill Climbing Algorithm (HCA) and Genetic Algorithm (GA). HCA is used to generate the good initial population for GA and then use GA is used to find the optimal parameters set that give maximum propulsion power in order to make fish robot swim at the fastest velocity.

The single nucleotide polymorphism rs9939609 of the gene FTO, which encodes fat mass and obesity–associated protein, is strongly associated with obesity and type 2 diabetes (T2D) in multiple populations; however, the underlying mechanism of this association is unclear. The present study aimed to investigate FTO genotype–dependent metabolic changes in obesity and T2D. To elucidate metabolic dysregulation associated with disease risk genotype, genomic and metabolomic datasets were recruited from 2,577 participants of the Korean Association REsource (KARE) cohort, including 40 homozygous carriers of the FTO risk allele (AA), 570 heterozygous carriers (AT), and 1,967 participants carrying no risk allele (TT). A total of 134 serum metabolites were quantified using a targeted metabolomics approach. Through comparison of various statistical methods, seven metabolites were identified that are significantly altered in obesity and T2D based on the FTO risk allele (adjusted p < 0.05). These identified metabolites are relevant to phosphatidylcholine metabolic pathway, and previously reported to be metabolic markers of obesity and T2D. In conclusion, using metabolomics with the information from genome-wide association studies revealed significantly altered metabolites depending on the FTO genotype in complex disorders. This study may contribute to a better understanding of the biological mechanisms linking obesity and T2D.