• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.275-280
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• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• Journal of Microbiology and Biotechnology
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• 제23권4호
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• pp.451-458
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• 2013

The human gastric pathogen Helicobacter pylori (Hp) has been considered a microaerophile. However, we recently reported that, when supplied with 10% $CO_2$, Hp growth is stimulated by an atmospheric level of $O_2$, suggesting that Hp is a capnophilic aerobe. In this study, we investigated the effects of aerobic $O_2$ tension on Hp cells by comparing gene expression profiles of cultures grown under microaerobic and aerobic conditions in the presence of 10% $CO_2$. The results showed that overall differences in gene expression in Hp cells grown under the two $O_2$ conditions were predominantly growth-phase-dependent. At 6 h, numerous genes were down-regulated under the aerobic condition, accounting for our previous observation that Hp growth was retarded under this condition. At 36 h, however, diverse groups of genes involved in energy metabolism, cellular processes, transport, and cell envelope synthesis were highly up- or down-regulated under the aerobic condition, indicating a progression of the cultures from the log phase to the stationary phase. The expression of several oxidative stress-associated genes including tagD, katA, and rocF was induced in response to aerobic $O_2$ level, whereas trxA, trxB, and ahpC remained unchanged. Altogether, these data demonstrate that aerobic $O_2$ tension is not detrimental to Hp cells but stimulates Hp growth, supporting our previous finding that Hp may be an aerobic bacterium that requires a high $CO_2$ level for its growth.

• 원예과학기술지
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• 제32권1호
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• pp.91-99
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• 2014

본 연구는 배추에서의 저온 저항성 유전자를 개발하는데 목적이 있으며 이를 위해 먼저 저온($4^{\circ}C$) 스트레스가 처리된 내혼계배추를 대상으로 한 KBGP-24K oligo chip의 결과 [BrEMD(Brassica rapa EST and Microarray Database)]를 분석하였다. 그 결과 23,929개의 배추 unigene 중 저온 처리시 대조군 대비 5배 이상 발현이 증가하는 417개(1.7%)의 저온 반응 유전자를 1차 선발하고, 이들 중 기능이 정확히 알려지지 않았으나 완전장을 갖추고 있는 BrCSR로 명명한 유전자를 선발하였다. 이 유전자의 저온 저항성을 분석하기 위하여 형질전환용 과발현 vector인 pSL101 binary vector를 제작하여 담배에 형질전환시켰다. BrCSR이 과발현된 $T_1$ 세대 담배 형질전환체들은 PCR과 Southern hybridization 분석에 의해 선발하였고, BrCSR의 기능은 저온 처리 시 유전자의 발현 수준 분석과 표현형 검정을 통해 확인하였다. Quantitative real-time RT-PCR과 Northern blot hybridization 분석 결과, 형질전환 담배에서 BrCSR의 발현이 대조군보다 약 2배 정도 높게 발현되었으며 실제로 $4^{\circ}C$ 처리 후 표현형 분석에서 BrCSR이 과발현된 형질전환체들이 대조군보다 우수한 저온 저항성을 보여 주었다. 위 결과들에 근거하여 BrCSR 유전자가 저온 환경 하에서 식물의 생장과 저항성 향상에 중요한 역할을 담당하고 있음을 확인할 수 있었다.

• 한국환경성돌연변이발암원학회지
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• 제25권1호
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• pp.40-46
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic compound and tumor promoter. In our experiment, we investigated the effects of TCDD on gene expression in mouse skin carcinogenesis. We used cDNA microarray to detect the differential gene expression in tumors induced in hairless mouse skin by MNNG plus TCDD protocol. We found that erb-2, c-ets2 and p27$^{kip1}$ were significantly up-regulated, but TNFR2, AKT-l, integrin $\beta$l, maspin, IGF-l, c-raf-l, Rb were significantly down-regulated, in tumor region, respectively. We also found that the expression of 53 genes involved in cen cycle, signal transduction, apoptosis, adhesion molecule, angiogenesis, and invasion, were changed two fold more, in tumor surrounding region. These data suggest that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis in mouse skin carcinogenesis.

• 한국통계학회:학술대회논문집
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• 한국통계학회 2003년도 추계 학술발표회 논문집
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• pp.173-177
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• 2003

When we have both a paired data set and two independent data sets, neither a paired t-test nor a two-sample t-test can be used to detect differences between two samples. In order to identify differentially expressed genes in a mixed data set, a new test statistic is proposed.

• Korean Journal of Acupuncture
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• 제23권3호
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• pp.133-160
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• 2006

Objectives : Scolopendrae Corpus has a broad array of clinical applications in Korean medicine, including treatment of inflammatory conditions such as arthritis. To explore the global gene expression profiles in human Raw cell lines treated with Scolopendrae Corpus herbal-acupuncture solution (SCHAS), cDNA microarray analysis was performed. Methods : The Raw 264.7 cells were treated with lipopolysaccharide (LPS), SCHAS, or both. The primary data was normalized by the total spots of intensity between two groups, and then normalized by the intensity ratio of reference genes such as housekeeping genes in both groups. The expression ratio was converted to log2 ratio. Normalized spot intensities were calculated into gene expression ratios between the control and treatment groups. Greater than 2 fold changes between two groups were considered to be of significance. Results : Of the 8 K genes profiled in this study, with a cut-off level of two-fold change in the expression, 20 genes (BCL2-related protein A1, MARCKS-like 1, etc.) were upregulated and 5 genes (activated RNA polymerase II transcription cofactor 4, calcium binding atopy-related autoantigen 1, etc.) downregulated following LPS treatment. 139 genes (kell blood group precursor (McLeod phenotype), ribosomal protein S7, etc.) were upregulated and 42 genes (anterior gradient 2 homolog (xenopus laevis), phosphodiesterase 8B, etc.) were downregulated following SCHAS treatment. And 10 genes (yeast saccharomyces cerevisiae intergeneic sequence 4-1, mitogen-activated protein kinase 1, etc.) were upregulated and 8 genes (spermatid perinuclear RNA binding protein, nuclear receptor binding protein 2, etc.) were downregulated following co-stimulation of SCHAS and LPS. Discussions : It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacological actions of SCHAS in the treatment of arthritis. But further studies are required to concretely prove the effectiveness of SCHAS.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.177-185
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• 2017

Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells.

• 한국지능시스템학회논문지
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• 제22권6호
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• pp.786-792
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• 2012

마이크로어레이는 수만 가지 이상의 DNA 또는 RNA를 기판위에 배열해 놓은 것이며 이 기술을 이용하여 대량의 유전자 발현을 탐색할 수 있게 되었다. 그렇지만 마이크로어레이는 실험자가 탐색하려는 특정 표현형에 대해서 설계된 실험방법을 이용하므로 제한된 숫자의 유전자 발현만을 관찰할 수 있다. 본 논문에서는 MicroRNAs(miRNAs)와 Protein-Protein Interaction(PPI) 정보를 포함하고 있는 데이터베이스를 활용하여 마이크로어레이 데이터의 의미적 확장 방법을 제시하고자 한다. 또한 Online Mendelian Inheritance in Man(OMIM) 및 International Statistical Classification of Diseases and Related Health Problems, $10^{th}$ Revision(ICD-10)을 이용하여 질병 간 유전적 공통점 파악을 시도하였다. 이러한 접근방법을 통하여 새로운 생물학적 시각을 제공할 수 있을 것으로 기대된다.

• 유전체소식지
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• 제5권4호
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• pp.9-16
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• 2005

Bioinformatics is a rapidly emerging field of biomedical research. A flood of large-scale genomic expression data transforms the challenges m biomedical research into ones in bioinformatics. Clinical informatics has long developed technologies to imp개ve biomedical research by integrating experimental and clinical information systems. Biomedical informatics, powered by high throughput techniques, genomic-scale databases and advanced clinical information system, is likely to transform our biomedical understanding forever much the same way that biochemistry did to biology a generation ago. The emergence of healthcare and biomedical informatics revolutionizing both bioinformatics and clinical informatics will eventually change the current practice of medicine, including diagnostics, therapeutics and prognostics.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2007년도 추계학술발표대회
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• pp.733-736
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• 2007

최근 생명 공학 기술의 발달로 마이크로 단위의 실험이 가능해지고 하나의 칩상에 수 만개의 유전자들의 발현 양상을 보다 쉽게 관찰할 수 있게 되었다. DNA 칩 기술에 의해 얻어지는 마이크로어레이(microarray) 데이터는 세포나 조직 내의 유전자 발현도(expression level)를 측정한 것으로 질병 진단이나 유전자 기능 예측 등에 이용되고 있다. 본 논문에서는 대량의 시계열 마이크로어레이 데이터 분석을 위해 효율적으로 데이터의 차원을 판단하는 점진적 주성분 분석을 이용하여 데이터의 차원을 축소 한다. 제안된 방법은 실제 시계열 마이크로어레이 데이터인 yeast cell cycle 데이터에 적용되었고, 데이터 차원 축소에 대한 효율성을 검증하기 위해 클러스터링을 수행하였다. 그 결과 데이터를 축소하여 클러스터링을 수행한 경우 학습 성능이 향상 된 결과를 보였다.