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        Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

        Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

        (S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

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        Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells

        Yun, S.M.,Woo, S.H.,Oh, S.T.,Hong, S.E.,Choe, T.B.,Ye, S.K.,Kim, E.K.,Seong, M.K.,Kim, H.A.,Noh, W.C.,Lee, J.K.,Jin, H.O.,Lee, Y.H.,Park, I.C. North-Holland 2016 Molecular and cellular endocrinology Vol.422 No.-

        Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells.

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        S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma

        Lee, K,Yun, S-T,Yun, C-O,Ahn, B-Y,Jo, E-C Macmillan Publishers Limited 2012 Gene Therapy Vol.19 No.10

        S100A2, a member of the S100 family of calcium-binding proteins, has been implicated in carcinogenesis as both a tumor suppressor and stimulator. Here, we characterized promoter activity of S100A2, generated an S100A2 promoter-driven conditionally replicative adenovirus (Ad/SA), and evaluated its anti-tumor activity in vitro and in vivo. Promoter activity of S100A2 was greatly restricted to tumor cells, and the S100A2 promoter bound with typical nuclear targets of epidermal growth factor receptor (EGFR) signaling. EGF-stimulated EGFR phosphorylation induced S100A2 expression and further activated E1A expression of Ad/SA, which was restored by EGFR signal inhibition in a concentration-dependent manner in non-small-cell lung carcinoma (NSCLC). In two EGFR-activated tumor xenograft animal models, Ad/SA exhibited potent anti-tumor activity, whereas cetuximab, an EGFR-targeting anticancer drug, was active transiently or ineffective. Combined treatment with cetuximab or cisplatin plus Ad/SA resulted in enhanced anti-tumor activity. Immunohistochemical analysis of tumor sections showed moderate-to-high grade signals for EGFR and adenovirus, and a reduction in viable cells in Ad/SA-treated tumors. Collectively, these results demonstrate that the S100A2 promoter-driven adenovirus is a potent inhibitor of cancers, and further suggest that S100A2 is a target gene of EGFR signaling pathway in NSCLC.

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        High lipid composition of particulate organic matter in the northern Chukchi Sea, 2011

        Kim, B.K.,Lee, J.H.,Yun, M.S.,Joo, H.,Song, H.J.,Yang, E.J.,Chung, K.H.,Kang, S.H.,Lee, S.H. Pergamon Press 2015 Deep-sea research. Part II, Topical studies in oce Vol.120 No.-

        We investigated the biochemical compositions (lipids, proteins, and carbohydrates) of particulate organic matter (POM) as a potential food source in the northern Chukchi Sea. We aimed to understand physiological status of phytoplankton, determine important controlling factors, and estimate the energetic contents of POM. The major inorganic nutrients were generally depleted at upper mixed-layer depth (>20m). The average chlorophyll a (chl-a) concentration was 31.9mgm<SUP>-2</SUP> (S.D.=+/-31.3mgm<SUP>-2</SUP>) in this study, significantly higher than that reported previously in the northern Chukchi Sea. Small phytoplankton (0.7-5@?m) accounted for 65.9% of total chl-a concentration. The overall average compositions of lipids, carbohydrates, and proteins were 50% (S.D.=+/-10.7%), 35% (S.D.=+/-11.0%), and 15% (S.D.=+/-11.2%) for POM, respectively. Along with other evidence (e.g., low N:P and protein-carbohydrate ratios), the high lipid and low protein compositions of POM in this study suggests that phytoplankton might have had a nitrogen limitation and/or stationary growth phase in the northern Chukchi Sea during the cruise period, 2011. The overall average calorific content of food material (FM) was 149.2μgL<SUP>-1</SUP> (S.D.=+/-36.5μgL<SUP>-1</SUP>) or 1.0Kcalm<SUP>-3</SUP> (S.D.=+/-0.2Kcalm<SUP>-3</SUP>). The relatively higher calorific contents in the northern Chukchi Sea were due to high lipid contributions and the considerably high calorific content of FM per POC.

      • Streptococcus gordonii induces nitric oxide production through its lipoproteins stimulating Toll-like receptor 2 in murine macrophages

        Kim, H.Y.,Baik, J.E.,Ahn, K.B.,Seo, H.S.,Yun, C.H.,Han, S.H. Pergamon Press 2017 Molecular immunology Vol.82 No.-

        <P>Streptococcus gordonii, a Gram-positive commensal in the oral cavity, is an opportunistic pathogen that can cause endodontic and systemic infections resulting in infective endocarditis. Lipoteichoic acid (LTA) and lipoprotein are major virulence factors of Gram-positive bacteria that are preferentially recognized by Toll-like receptor 2 (TLR2) on immune cells. In the present study, we investigated the effect of S. gordonii LTA and lipoprotein on the production of the representative inflammatory mediator nitric oxide (NO) by the mouse macrophages. Heat-killed S. gordonii wild-type and an LTA-deficient mutant (Delta ltaS) but not a lipoprotein-deficient mutant (Delta lgt) induced NO production in mouse primary macrophages and the cell line, RAW 264.7.S. gordonii wild-type and Delta ItaS also induced the expression of inducible NO synthase (iNOS) at the mRNA and protein levels. In contrast, the Delta lgt mutant showed little effect under the same condition. Furthermore, S. gordonii wild-type and Delta ItaS induced NF-kappa B activation, STAT1 phosphorylation, and IFN-beta expression, which are important for the induction of iNOS gene expression, with little activation by Delta lgt. S. gordonii wild-type and Delta ltaS showed an increased adherence and internalization to RAW 264.7 cells compared to Delta lgt. In addition, S. gordonii wild-type and AIMS, but not Delta lgt, substantially increased TLR2 activation while none of these induced NO production in TLR2-deficient macrophages. Triton X-114-extracted lipoproteins from S. gordonii were sufficient to induce NO production. Collectively, we suggest that lipoprotein is an essential cell wall component of S. gordonii to induce NO production in macrophages through TLR2 triggering NF-kappa B and STAT1 activation. (C) 2016 Elsevier Ltd. All rights reserved.</P>

      • WWW 상에서의 CGI를 이용한 농업용 전문가 시스템의 추론엔진과 사용자 인터페이스의 개발

        조성인,이종수,박은우,황헌,윤진일 한국농업정보과학회 1999 농업정보과학 Vol.1 No.1

        Tuday's agriculture mainly relies on agricultural chemicals, mechanical power, and electronics. Efficiencies if labor, capital, productivity and quality are also major issues in today's agriclilture. Not only mechanization to replace human labor but information process becomes important to achieve the efficiencies. Agricultural informations consist of numerical data, text data and images. Lots of the informations come from human experiences and are in non-numerical forms. Therefore, they are difficult to be processed properly for the information process such as expert systems. This problem would be solved by using CGI (Common Cateway Interface) in WWW (World Wide Web). We developed a forward chaining inference engine for a heuristic rule-based expert system to process knowledges in agriculture. It managed many rule bases with recursion using low memory capacity. User interfaces of the expert system using the CGI improved processing specialized agricul-tural knowledges from experts in agricultural domains. By networking the expert systems in WWW, farmers could use expert systems at remote sites with ease.

      • SCISCIESCOPUS
      • Identification of stathmin 1 expression induced by Epstein–Barr virus in human B lymphocytes

        Baik, S. Y.,Yun, H. S.,Lee, H. J.,Lee, M. H.,Jung, S. E.,Kim, J. W.,Jeon, J. P.,Shin, Y. K.,Rhee, H. S.,Kimm, K. C.,Han, B. G. Blackwell Publishing Ltd 2007 Cell proliferation Vol.40 No.2

        <P>Abstract. </P><P><I>Introduction</I>: The Epstein–Barr virus transforms resting B cells into proliferating lymphoblastoid cells, the origin of cell lines. <I>Method and results</I>: Our cDNA microarray analyses led to the identification of 232 up-regulated and 112 down-regulated genes with more than a 3-fold difference in lymphoblastoid cell lines compared to resting B cells. The functional classification of these genes exhibited the distinct expression signature for cell proliferation, cell cycle and an immune response. Among them, we verified the differential expression of several oncogenes such as <I>stathmin 1</I> (<I>STMN1</I>), <I>RAB27A</I>, <I>RAB9A</I>, <I>BACH1</I> and <I>BACH2</I> using quantitative real-time reverse transcriptase-polymerase chain reactions or Western blot analysis. Expression of <I>STMN1</I> (which is involved in regulation of the microtubule filament system, cell growth and S-phase of cell cycle) was increased in lymphoblastoid cell line as well as in 7-day post-Epstein–Barr virus infection B cells, compared to resting B cells. <I>Conclusion</I>: Thus, this study suggests that Epstein–Barr virus infection induces <I>STMN1</I> expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte.</P>

      • Contribution of small phytoplankton to total primary production in the Chukchi Sea

        Lee, S.H.,Sun Yun, M.,Kyung Kim, B.,Joo, H.,Kang, S.H.,Keun Kang, C.,Whitledge, T.E. Pergamon Press ; Elsevier Science Ltd 2013 Continental shelf research Vol.68 No.-

        Given a projection of thriving small phytoplankton in the Arctic Ocean under climate-induced environmental changes, it is important to estimate the contribution of small phytoplankton (0.7-5μm) to the total primary production in the Chukchi Sea, which is an important conduit of organic matter from the North Pacific to the Arctic Ocean. Based on a <SUP>13</SUP>C-<SUP>15</SUP>N dual isotope tracer technique, small phytoplankton productivity measurements were taken during two consecutive cruises in the Chukchi Sea in 2004. The total phytoplankton carbon uptake rates ranged from 0 to 25.38mgCm<SUP>-3</SUP>h<SUP>-1</SUP>, whereas the uptake rates of small phytoplankton ranged from 0 to 2.87mgCm<SUP>-3</SUP>h<SUP>-1</SUP>. In comparison with the carbon uptake rates, total phytoplankton nitrate uptake rates ranged from 0 to 4.40mgNm<SUP>-3</SUP>h<SUP>-1</SUP> while small phytoplankton nitrate uptake rates ranged from 0 to 0.39mgNm<SUP>-3</SUP>h<SUP>-1</SUP>. Ammonium uptake rates ranged from 0 to 8.34mgNm<SUP>-3</SUP>h<SUP>-1</SUP> and from 0.01 to 2.18mgNm<SUP>-3</SUP>h<SUP>-1</SUP>, for total and small phytoplankton, respectively. Small phytoplankton contributed 24.80% (S.D.=+/-23.0%) to the total chlorophyll-a concentration, and 59.41% (S.D.=+/-52.12%) to the total carbon biomass due to its higher particulate organic carbon per chlorophyll-a unit during the two cruises in 2004. In the Chukchi Sea, the average contributions of small phytoplankton to carbon and total nitrogen (nitrate+ammonium) uptake rates were 31.72% (S.D.=+/-23.59%) and 37.31% (S.D.=+/-26.06%), respectively.

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