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        De novo assembly and phasing of a Korean human genome

        Seo, Jeong-Sun,Rhie, Arang,Kim, Junsoo,Lee, Sangjin,Sohn, Min-Hwan,Kim, Chang-Uk,Hastie, Alex,Cao, Han,Yun, Ji-Young,Kim, Jihye,Kuk, Junho,Park, Gun Hwa,Kim, Juhyeok,Ryu, Hanna,Kim, Jongbum,Roh, Mira Nature Publishing Group, a division of Macmillan P 2016 Nature Vol.538 No.7624

        <P>Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing(2), next-generation mapping(3), microfluidics-based linked reads(4), and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.</P>

      • KCI등재

        Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

        Kim, Arang,Lee, Wooje,Yun, Jung-Mi The Korean Nutrition Society 2017 Nutrition research and practice Vol.11 No.5

        BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

      • SCIESCOPUSKCI등재

        Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

        Arang Kim,Wooje Lee,Jung-Mi Yun 한국영양학회 2017 Nutrition Research and Practice Vol.11 No.5

        BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

      • KCI등재
      • SCISCIESCOPUS

        Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection

        Rhie, Arang,Park, Weon Seo,Choi, Moon Kyung,Kim, Ji-Hyun,Ryu, Junsun,Ryu, Chang Hwan,Kim, Jong-Il,Jung, Yuh-Seog Williams & Wilkins Co 2015 Medicine Vol.94 No.50

        ABSTRACT: Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV−) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection.For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed.p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39–0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66–1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16 and p16− groups. A region containing PRDM2 was amplified only in the p16 group, whereas EGFR and 11q13.3 showed increased amplification in p16− counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16 OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS.p16 OSCC exhibit distinct CNV patterns compared with p16− counterpart. Specific patterns of CNVs predict better survival, especially in p16 OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV− OSCC.

      • KCI등재
      • KCI등재

        한국 성인 남녀에서 당뇨병 유병률과 혈중 비타민 D 농도와의 관련성 : 제6기 국민건강영양조사(2013∼2014)에 근거하여

        김아랑 ( Arang Kim ),윤정미 ( Jung-mi Yun ) 대한영양사협회 2017 대한영양사협회 학술지 Vol.23 No.1

        Insufficient vitamin D intake is a major health problem around the world. Recently, many studies have suggested that vitamin D intake may influence insulin resistance. However, little is known about the association between vitamin D and diabetes mellitus. The aim of this study was to investigate the association between serum 25-hydroxy vitamin D (25(OH)D) levels and diabetes mellitus in Korean adults. This study was a cross-sectional analysis of 3,686 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) 2013∼2014 aged 19 years and higher. The results showed that the mean serum 25-hydroxy vitamin D (25(OH)D) level in Korean adults was 16.77 ng/mL, and 74.2% of them had an insufficient serum 25-hydroxy vitamin D (25(OH)D) level (below 20 ng/mL). In normal and pre-diabetic groups, the serum 25-hydroxy vitamin D (25(OH)D) level significantly increased with age (P<0.001), but there was no significant difference relative to age in the diabetic group. Low vitamin D levels (25-hydroxy vitamin D <10 ng/mL) were associated with increased fasting blood glucose levels, compared with optimal vitamin D levels (25-hydroxy vitamin D >30 ng/mL), after adjusting for variables that may affect fasting blood glucose, but this result was not significant. In conclusion, although no significant association was observed between diabetes prevalence and vitamin D levels in this study, further studies are needed because the effect of vitamin D on diabetes remains controversial. This nutrient plays a crucial role in the body, and levels are insufficient in the Korean population.

      • KCI우수등재

        Influence of dietary organic trace minerals on enteric methane emissions and rumen microbiota of heat-stressed dairy steers

        Arang Son,Mahfuzul Islam,Seon-Ho Kim,이성실,이상석 한국축산학회 2023 한국축산학회지 Vol.65 No.1

        Ruminants are the main contributors to methane (CH4), a greenhouse gas emitted by livestock, which leads to global warming. In addition, animals experience heat stress (HS) when exposed to high ambient temperatures. Organic trace minerals are commonly used to prevent the adverse effects of HS in ruminants; however, little is known about the role of these minerals in reducing enteric methane emissions. Hence, this study aimed to investigate the influence of dietary organic trace minerals on rumen fermentation characteristics, enteric methane emissions, and the composition of rumen bacteria and methanogens in heat-stressed dairy steers. Holstein (n=3) and Jersey (n=3) steers were kept separately within a 3×3 Latin square design, and the animals were exposed to HS conditions (Temperature-Humidity Index [THI], 82.79 ± 1.10). For each experiment, the treatments included a Control (Con) consisting of only basal total mixed rations (TMR), National Research Council (NRC) recommended mineral supplementation group (NM; TMR + [Se 0.1 ppm + Zn 30 ppm + Cu 10 ppm]/kg dry matter), and higher concentration of mineral supplementation group (HM; basal TMR + [Se 3.5 ppm + Zn 350 ppm + Cu 28 ppm]/kg dry matter). Higher concentrations of trace mineral supplementation had no influence on methane emissions and rumen bacterial and methanogen communities regardless of breed (p > 0.05). Holstein steers had higher ruminal pH and lower total volatile fatty acid (VFA) concentrations than Jersey steers (p < 0.05). Methane production (g/d) and yield (g/kg dry matter intake) were higher in Jersey steers than in Holstein steers (p < 0.05). The relative abundances of Methanosarcina and Methanobrevibacter olleyae were significantly higher in Holstein steers than in Jersey steers (p < 0.05). Overall, dietary organic trace minerals have no influence on enteric methane emissions in heat-stressed dairy steers; however, breed can influence it through selective alteration of the rumen methanogen community.

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