• Title/Summary/Keyword: pathway analysis

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The Anti-Cancer Effect of Apamin in Bee-Venom on Melanoma cell line SK-MEL-2 and Inhibitory Effect on the MAP-Kinase Signal Pathway (약침용(藥鍼用) 봉독성분(蜂毒成分) 중(中) Apamin의 항암효과(抗癌效果)와 MAP-Kinase 신호전달체계에 관한 연구(硏究))

  • Kim, Youn-Mi;Lee, Jae-Dong;Park, Dong-Seok
    • Journal of Acupuncture Research
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    • v.18 no.4
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    • pp.101-115
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    • 2001
  • Objective : To characterize the antitumorigenic potential of Apamin, one of the major components of bee venom, its effects on cell proliferation and the mitogen-activated protein kinase (MAPK) signal transduction pathway were characterized using the human melanoma cell line SK-MEL-2. Methods & Results : Cell counting analysis for cell death demonstrated that consistent with a previous results, SK-MEL-2 cells treated with $0.5-2.0{\mu}g/ml$ of Apamin showed no recognizable cytotoxic effect whereas detectable induction of cell death was identified at concentrations over $5.0{\mu}g/ml$. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin in a dose- and time-dependent manner. To explore whether Apamin-induced growth suppression is associated with the MAPK signaling pathway, phosphorylation of Erk, a function mediator of MAPK growth-stimulating signal, was examined Western blot assay using a phospho-specific Erkl/2 antibody. A significant increase of Erkl/2 phosphorylation level was observed in Apamin-treated cells compared with untreated control cells. Qantitative RT-PCR analysis revealed that Apamin inhibit expression of MAPK downstream genes such as c-Jun, c-Fos, and cyclin D1 but not expression of MAPK pathway component genes including Ha-Ras, c-Raf-1, MEK1, and Erk. Conclusion : It is strongly suggested that the antitumorigenic activity of Apamin might result in part from its inhibitory effect on the MAPK signaling pathway in human melanoma cells SK-MEL-2.

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Rapamycin-Induced Abundance Changes in the Proteome of Budding Yeast

  • Shin, Chun-Shik;Chang, Yeon-Ji;Lee, Hun-Goo;Huh, Won-Ki
    • Genomics & Informatics
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    • v.7 no.4
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    • pp.203-207
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    • 2009
  • The target of rapamycin (TOR) signaling pathway conserved from yeast to human plays critical roles in regulation of eukaryotic cell growth. It has been shown that TOR pathway is involved in several cellular processes, including ribosome biogenesis, nutrient response, autophagy and aging. However, due to the functional diversity of TOR pathway, we do not know yet some key effectors of the pathway. To find unknown effectors of TOR signaling pathway, we took advantage of a green fluorescent protein (GFP)-tagged collection of budding yeast Saccharomyces cerevisiae. We analyzed protein abundance changes by measuring the GFP fluorescence intensity of 4156 GFP-tagged yeast strains under inhibition of TOR pathway. Our proteomic analysis argues that 83 proteins are decreased whereas 32 proteins are increased by treatment of rapamycin, a specific inhibitor of TOR complex 1 (TORC1). We found that, among the 115 proteins that show significant changes in protein abundance under rapamycin treatment, 37 proteins also show expression changes in the mRNA levels by more than 2-fold under the same condition. We suggest that the 115 proteins indentified in this study may be directly or indirectly involved in TOR signaling and can serve as candidates for further investigation of the effectors of TOR pathway.

NGSEA: Network-Based Gene Set Enrichment Analysis for Interpreting Gene Expression Phenotypes with Functional Gene Sets

  • Han, Heonjong;Lee, Sangyoung;Lee, Insuk
    • Molecules and Cells
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    • v.42 no.8
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    • pp.579-588
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    • 2019
  • Gene set enrichment analysis (GSEA) is a popular tool to identify underlying biological processes in clinical samples using their gene expression phenotypes. GSEA measures the enrichment of annotated gene sets that represent biological processes for differentially expressed genes (DEGs) in clinical samples. GSEA may be suboptimal for functional gene sets; however, because DEGs from the expression dataset may not be functional genes per se but dysregulated genes perturbed by bona fide functional genes. To overcome this shortcoming, we developed network-based GSEA (NGSEA), which measures the enrichment score of functional gene sets using the expression difference of not only individual genes but also their neighbors in the functional network. We found that NGSEA outperformed GSEA in identifying pathway gene sets for matched gene expression phenotypes. We also observed that NGSEA substantially improved the ability to retrieve known anti-cancer drugs from patient-derived gene expression data using drug-target gene sets compared with another method, Connectivity Map. We also repurposed FDA-approved drugs using NGSEA and experimentally validated budesonide as a chemical with anti-cancer effects for colorectal cancer. We, therefore, expect that NGSEA will facilitate both pathway interpretation of gene expression phenotypes and anti-cancer drug repositioning. NGSEA is freely available at www.inetbio.org/ngsea.

CysQ of $Cryptosporidium$ $parvum$, a Protozoa, May Have Been Acquired from Bacteria by Horizontal Gene Transfer

  • Lee, Ji-Young;Kim, Sang-Soo
    • Genomics & Informatics
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    • v.10 no.1
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    • pp.9-15
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    • 2012
  • Horizontal gene transfer (HGT) is the movement of genetic material between kingdoms and is considered to play a positive role in adaptation. $Cryptosporidium$ $parvum$ is a parasitic protozoan that causes an infectious disease. Its genome sequencing reported 14 bacteria-like proteins in the nuclear genome. Among them, cgd2_1810, which has been annotated as CysQ, a sulfite synthesis pathway protein, is listed as one of the candidates of genes horizontally transferred from bacterial origin. In this report, we examined this issue using phylogenetic analysis. Our BLAST search showed that $C.$ $parvum$ CysQ protein had the highest similarity with that of proteobacteria. Analysis with NCBI's Conserved Domain Tree showed phylogenetic incongruence, in that $C.$ $parvum$ CysQ protein was located within a branch of proteobacteria in the cd01638 domain, a bacterial member of the inositol monophosphatase family. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the sulfate assimilation pathway, where CysQ plays an important role, is well conserved in most eukaryotes as well as prokaryotes. However, the Apicomplexa, including $C.$ $parvum$, largely lack orthologous genes of the pathway, suggesting its loss in those protozoan lineages. Therefore, we conclude that $C.$ $parvum$ regained cysQ from proteobacteria by HGT, although its functional role is elusive.

Analysis of Enzymes of Stenotrophomonas maltophilia LK-24 Associated with Phenol Degradation (Stenotrophomonas maltophilia LK-24의 페놀분해 관련 효소)

  • Kim, Jeong-Dong;Kang, Kook-Hee
    • Microbiology and Biotechnology Letters
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    • v.32 no.1
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    • pp.37-46
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    • 2004
  • The analysis of enzymes associated with metabolism of phenolics by Stenotrophomonas maltophilia LK-24 was conducted. To identify metabolites of phenol and phenol compound, we investigated enzymes of S. maltophilia LK-24 associated with degradation of phenolics. We found that phenol hydrolase, catechol-2.3-dioxygenase, 2-hydroxymuconic semialdehyde dehydrogenase, 2-hydroxymuconic semialdehyde hydroxylase and acetaldehyde dehydrogenase were activated. The results showed that phenolics were gone through the meta-pathway ring cleavage. The results will contribute greatly to understand metabolic pathways of phenol and it is possible to make some assessment of the feasibility of using S. maltophilia LK-24 for the treatments of phenolic-contaminated waste streams.

Analysis of Sediment Transport Pathway using the STA Method in Nakdong Estuary (STA 기법에 의한 낙동강 하구역의 토사이동경로 예측)

  • Yoon, Eun-Chan;Lee, Jong-Sup
    • Journal of Korean Society of Coastal and Ocean Engineers
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    • v.20 no.6
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    • pp.540-552
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    • 2008
  • We predicted to seasonal sediment transport pathway of the estuary area of the Nakdong river using the STA method. The eCSedtrend model was used to flexible application of the previous STA methods. The analysis of the seasonal interpretation of sediment transport pathway showed that the most dominant trend in the Nakdong estuary was CB+ and CB-. In case of CB+, it was identified around the area where the mud sediment was distributed and formed transport vector toward the north. Also, in case of CB-, it was identified mostly around the sand bar where the sand sediment was distributed and generally showed transport vector toward the north even though there was seasonal difference.

Effect analysis of ISLOCA pathways on fission product release at Westinghouse 2-loop PWR using MELCOR

  • Kim, Seungwoo;Park, Yerim;Jin, Youngho;Kim, Dong Ha;Jae, Moosung
    • Nuclear Engineering and Technology
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    • v.53 no.9
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    • pp.2878-2887
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    • 2021
  • As the amount of fission product released from ISLOCA was overestimated because of conservative assumptions in the past, several studies have been recently conducted to evaluate the actual release amount. Among several pathways for the ISLOCA, most studies were focused on the pathway with the highest possibility. However, different ISLOCA pathways may have different fission product release characteristics. In this study, fission product behavior was analyzed for various pathways at the Westinghouse two-loop plant using MELCOR. Four pathways are considered: the pipes from a cold leg, from a downcomer, from a hot leg to the outlet of RHR heat exchanger, and the pipe from the hot leg to the inlet of RHR pump (Pathway 1-4). According to the analysis results, cladding fails at around 2.5 h in Pathways 1 and 2, and on the other hand, about 3.3 h in Pathways 3 and 4 because the ISLOCA pathways affect the safety injection flow path. While the release amount of cesium and iodine ranges between 20 and 26% in Pathways 1 to 3, Pathway 4 allows only 5% to the environment because the break location is submerged. Also, as more than 90% of cesium released to the environment passes through the personnel door, reinforcing the pressure capacity of the doors would be a significant factor in the accident management of the ISLOCA.

Biominerlization and Possible Endosulfan Degradation Pathway Adapted by Aspergillus niger

  • Bhalerao, Tejomyee S.
    • Journal of Microbiology and Biotechnology
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    • v.23 no.11
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    • pp.1610-1616
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    • 2013
  • Endosulfan is a chlorinated pesticide; its persistence in the environment and toxic effects on biota are demanding its removal. This study aims at improving the tolerance of the previously isolated fungus Aspergillus niger (A. niger) ARIFCC 1053 to endosulfan. Released chloride, dehalogenase activity, and released proteins were estimated along with analysis of endosulfan degradation and pathway identification. The culture could tolerate 1,000 mg/ml of technical grade endosulfan. Complete disappearance of endosulfan was seen after 168 h of incubation. The degradation study could easily be correlated with increase in released chlorides, dehalogenase activity and protein released. Comparative infrared spectral analysis suggested that the molecule of endosulfan was degraded efficiently by A. niger ARIFCC 1053. Obtained mass ion values by GC-MS suggested a hypothetical pathway during endosulfan degradation by A. niger ARIFCC 1053. All these results provide a basis for the development of bioremediation strategies to remediate the pollutant under study in the environment.

Radionuclide-Specific Exposure Pathway Analysis of Kori Unit 1 Containment Building Surface

  • Byon, Jihyang;Park, Sangjune;Ahn, Seokyoung
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.18 no.3
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    • pp.347-354
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    • 2020
  • Site characterization for decommissioning Kori Unit 1 is ongoing in South Korea after 40 years of successful operation. Kori Unit 1's containment building is assumed to be mostly radioactively contaminated, and therefore radiation exposure management and detailed contamination investigation are required for decommissioning and dismantling it safely. In this study, site-specific Derived Concentration Guideline Levels (DCGLs) were derived using the residual radioactivity risk evaluation tool, RESRAD-BUILD code. A conceptual model of containment building for Kori Unit 1 was set up and limited occupational worker building inspection scenario was applied. Depending on the source location, the maximum contribution source and exposure pathway of each radionuclide were analyzed. The contribution of radionuclides to dose and exposure pathways, by source location, is expected to serve as basic data in the assessment criteria of survey areas and classification of impact areas during further decommissioning and decontamination of sites.

Java DOM Parsers to Convert KGML into SBML and BioPAX Common Exchange Formats

  • Lee, Kyung-Eun;Jang, Myung-Ha;Rhie, A-Rang;Thong, Chin Ting;Yang, San-Duk;Park, Hyun-Seok
    • Genomics & Informatics
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    • v.8 no.2
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    • pp.94-96
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    • 2010
  • Integrating various pathway data collections to create new biological knowledge is a challenge, for which novel computational tools play a key role. For this purpose, we developed the Java-based conversion modules KGML2SBML and KGML2BioPAX to translate KGML (KEGG Markup Language) into a couple of common data exchange formats: SBML (Systems Biology Markup Language) and BioPAX (Biological Pathway Exchange). We hope that our work will be beneficial for other Java developers when they extend their bioinformatics system into SBML- or BioPAX-aware analysis tools. This is part of our ongoing effort to develop an ultimate KEGG-based pathway enrichment analysis system.