• 제목/요약/키워드: deletions

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Partial Interferon-γ Receptor Deficiency in Patients with Disseminated Tuberculosis (파종성 결핵 환자에서 interferon-γ 수용체의 부분결핍에 관한 연구)

  • Hwang, Jung Hye;Koh, Won-Jung;Lee, Shin Hye;Kim, Eun Joo;Kang, Eun Hae;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong;Kwon, O Jung
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.1
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    • pp.11-17
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    • 2005
  • Background : Interferon-gamma ($IFN-{\gamma}$) is essential in the immune response to mycobacterial infections, and a complete or partial deficiency in the $IFN-{\gamma}$ receptor 1 ($IFN{\gamma}R1$) or the $IFN-{\gamma}$ receptor 2 ($IFN{\gamma}R2$) have been reported to confer susceptibility to a disseminated infection with nontuberculous mycobacteria. However, similar mutations in the $IFN-{\gamma}$ receptor have not been specifically examined in the patients with clinical tuberculosis. Methods : This study searched for mutations in the $IFN-{\gamma}$ receptor gene that resulted in a partial $IFN-{\gamma}$ receptor deficiency in six patients with disseminated tuberculosis. The previously identified $IFN{\gamma}R1$ and $IFN{\gamma}R2$ coding regions were sequenced after amplification. Results : There was no partial $IFN{\gamma}R1$ deficiency including a homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and a hotspot for small deletions (818delT, 818del4, 818insA) found in any of the patients. In addition, a partial $IFN{\gamma}R2$ deficiency of the homozygous missense mutation (R114C) was not found in any of the patients. Conclusion : Genetic defects causing a partial $IFN-{\gamma}$ receptor deficiency were not identified in our patients with disseminated tuberculosis.

Development of System-Wide Functional Analysis Platform for Pathogenicity Genes in Magnaporthe oryzae

  • Park, Sook-Young;Choi, Jaehyuk;Choi, Jaeyoung;Kim, Seongbeom;Jeon, Jongbum;Kwon, Seomun;Lee, Dayoung;Huh, Aram;Shin, Miho;Jung, Kyungyoung;Jeon, Junhyun;Kang, Chang Hyun;Kang, Seogchan;Lee, Yong-Hwan
    • 한국균학회소식:학술대회논문집
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    • 2014.10a
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    • pp.9-9
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    • 2014
  • Null mutants generated by targeted gene replacement are frequently used to reveal function of the genes in fungi. However, targeted gene deletions may be difficult to obtain or it may not be applicable, such as in the case of redundant or lethal genes. Constitutive expression system could be an alternative to avoid these difficulties and to provide new platform in fungal functional genomics research. Here we developed a novel platform for functional analysis genes in Magnaporthe oryzae by constitutive expression under a strong promoter. Employing a binary vector (pGOF1), carrying $EF1{\beta}$ promoter, we generated a total of 4,432 transformants by Agrobacterium tumefaciens-mediated transformation. We have analyzed a subset of 54 transformants that have the vector inserted in the promoter region of individual genes, at distances ranging from 44 to 1,479 bp. These transformants showed increased transcript levels of the genes that are found immediately adjacent to the vector, compared to those of wild type. Ten transformants showed higher levels of expression relative to the wild type not only in mycelial stage but also during infection-related development. Two transformants that T-DNA was inserted in the promotor regions of putative lethal genes, MoRPT4 and MoDBP5, showed decreased conidiation and pathogenicity, respectively. We also characterized two transformants that T-DNA was inserted in functionally redundant genes encoding alpha-glucosidase and alpha-mannosidase. These transformants also showed decreased mycelial growth and pathogenicity, implying successful application of this platform in functional analysis of the genes. Our data also demonstrated that comparative phenotypic analysis under over-expression and suppression of gene expression could prove a highly efficient system for functional analysis of the genes. Our over-expressed transformants library would be a valuable resource for functional characterization of the redundant or lethal genes in M. oryzae and this system may be applicable in other fungi.

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Expression of the FHIT gene Located in Chromosome 3p14.2 in Human Lung Cancer Cell Lines (폐암 세포주에서 염색체 3p14.2에 위치한 FHIT 유전자의 발현 이상에 대한 연구)

  • Kim, Cheol-Hyeon;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.984-991
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    • 1998
  • Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.

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Activation and Abnormalities of Cell Cycle Regulating Factor in Head and Neck Squamous Cell Carcinoma Cell Lines: Abnormal Expression of CDKN2 Gene in Laryngeal Squamous Cell Carcinoma (두경부 편평상피세포암 세포주에서 세포주기조절인자의 활성 및 이상 : 후두편평상피세포암에서 종양억제유전자 CDKN2 유전자의 발현이상)

  • Song, Si-Youn;Han, Tae-Hee;Bai, Chang-Hoon;Kim, Yong-Dae;Song, Kei-Won
    • Journal of Yeungnam Medical Science
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    • v.22 no.2
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    • pp.166-182
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    • 2005
  • Background: Cyclin-dependent kinase (CDK) inhibitors are family of molecules that regulate the cell cycle. The CDKN2, a CDK4 inhibitor, also called p16, has been implicated in human tumorigenesis. The CDKN2 inhibits the cyclin/CDK complexes which regulate the transition from G1 to S phase of cell cycle. There is a previous report that homozygous deletion of CDKN2 region on chromosome 9p21 was detected frequently in astrocytoma, glioma and osteosarcoma, less frequently in lung cancer, leukemia and ovarian cancer, but not detected in colon cancer and neuroblastoma. However, little is known about the relationship between CDKN2 and laryngeal cancer. Therefore this study was initiated to investigate the role of CDKN2 in human laryngeal squamous cell carcinoma development.1) Materials and methods: We used 5 human laryngeal carcinoma cell lines whether they have deletions or losses of CDKN2 gene expression by DNA-PCR or RT-PCR, respectively. We examined 8 fresh frozen human laryngeal cancer tissues to detect the loss of heterozygosity (LOH) of CDKN2. PCR was performed by using microsatellite markers of short arm of human chromosome 9 (D9S126, D9S144, D9S156, D9S161, D9S162, D9S166, D9S171, D9S200 and D9SIFNA). For informative cases, allelic loss was scored if the signal of one allele was significantly decreased in tumor DNA when compared to the same allele in normal DNA. Results: The CDKN2 DNA deletion was observed in 3 cell lines. The CDKN2 mRNA expression was observed in only one cell line, which was very weak. LOH was detected in 7 cases (87.5%). Conclusion: These results suggest that CDKN2 plays a role in the carcinogenesis of human laryngeal squamous cell carcinoma.

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Cloning of Low-molecular-weight Glutenin Subunit Genes and Identification of their Protein Products in Common Wheat (Triticum aestivum L.) (보통 밀에서 저분자글루테닌 유전자 클로닝 및 단백질 동정)

  • Lee, Jong-Yeol;Kim, Yeong-Tae;Kim, Bo-Mi;Lee, Jung-Hye;Lim, Sun-Hyung;Ha, Sun-Hwa;Ahn, Sang-Nag;Nam, Myung-Hee;Kim, Young-Mi
    • Korean Journal of Breeding Science
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    • v.42 no.5
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    • pp.547-554
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    • 2010
  • Low-molecular-weight glutenin subunit (LMW-GS) in common wheat (Triticum aestivum L.) is important for quality processing of bread and noodles. The objectives of this study were to clarify the composition of LMW-GSs and to identify their corresponding proteins. Using LMW-GS specific primers we cloned and characterized 43 LMW-GS genes in the wheat cultivar 'Jokyoung'. Some of these genes contain polypeptides different in size due to the presence of various deletions or insertions within repetitive and glutamine-rich domains. The comparison of deduced amino acid sequence of the LMW-GS genes in Jokyoung with that of 12 groups LMW-GSs of wheat cultivar Norin 61 showed that the deduced amino acid sequences were nearly the same to LMW-GS groups of 1, 2, 3/4, 5, 7, 10 and 11. All LMW-GS genes contain eight cysteine residues, which are conserved among all of the typical LMW-GS sequences. The relative positions of cysteine residues are also conserved, except those of the first and seventh. Based on phylogenetic analysis, the 43 sequences with the same N-terminal and C-terminal amino acid sequences were clustered in the same group. To identify the proteins containing the corresponding amino acid sequences, we determined the N-terminal amino acid sequence of 7 spots of LMW-GSs of Jokyoung separated by two-dimensional gel electrophoresis (2DE). Of them, Glu-B3 (LMW-m and LMW-s) and Glu-D3 (LMW-m) were detected in two and three spots, respectively and the others were not clear. Collectively, we classified diverse LMW-GSs and identified their corresponding protein products. These results will be helpful in breeding programs for improvement of wheat flour quality.

The Relations between Financial Constraints and Dividend Smoothing of Innovative Small and Medium Sized Enterprises (혁신형 중소기업의 재무적 제약과 배당스무딩간의 관계)

  • Shin, Min-Shik;Kim, Soo-Eun
    • Korean small business review
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    • v.31 no.4
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    • pp.67-93
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    • 2009
  • The purpose of this paper is to explore the relations between financial constraints and dividend smoothing of innovative small and medium sized enterprises(SMEs) listed on Korea Securities Market and Kosdaq Market of Korea Exchange. The innovative SMEs is defined as the firms with high level of R&D intensity which is measured by (R&D investment/total sales) ratio, according to Chauvin and Hirschey (1993). The R&D investment plays an important role as the innovative driver that can increase the future growth opportunity and profitability of the firms. Therefore, the R&D investment have large, positive, and consistent influences on the market value of the firm. In this point of view, we expect that the innovative SMEs can adjust dividend payment faster than the noninnovative SMEs, on the ground of their future growth opportunity and profitability. And also, we expect that the financial unconstrained firms can adjust dividend payment faster than the financial constrained firms, on the ground of their financing ability of investment funds through the market accessibility. Aivazian et al.(2006) exert that the financial unconstrained firms with the high accessibility to capital market can adjust dividend payment faster than the financial constrained firms. We collect the sample firms among the total SMEs listed on Korea Securities Market and Kosdaq Market of Korea Exchange during the periods from January 1999 to December 2007 from the KIS Value Library database. The total number of firm-year observations of the total sample firms throughout the entire period is 5,544, the number of firm-year observations of the dividend firms is 2,919, and the number of firm-year observations of the non-dividend firms is 2,625. About 53%(or 2,919) of these total 5,544 observations involve firms that make a dividend payment. The dividend firms are divided into two groups according to the R&D intensity, such as the innovative SMEs with larger than median of R&D intensity and the noninnovative SMEs with smaller than median of R&D intensity. The number of firm-year observations of the innovative SMEs is 1,506, and the number of firm-year observations of the noninnovative SMEs is 1,413. Furthermore, the innovative SMEs are divided into two groups according to level of financial constraints, such as the financial unconstrained firms and the financial constrained firms. The number of firm-year observations of the former is 894, and the number of firm-year observations of the latter is 612. Although all available firm-year observations of the dividend firms are collected, deletions are made in the case of financial industries such as banks, securities company, insurance company, and other financial services company, because their capital structure and business style are widely different from the general manufacturing firms. The stock repurchase was involved in dividend payment because Grullon and Michaely (2002) examined the substitution hypothesis between dividends and stock repurchases. However, our data structure is an unbalanced panel data since there is no requirement that the firm-year observations data are all available for each firms during the entire periods from January 1999 to December 2007 from the KIS Value Library database. We firstly estimate the classic Lintner(1956) dividend adjustment model, where the decision to smooth dividend or to adopt a residual dividend policy depends on financial constraints measured by market accessibility. Lintner model indicates that firms maintain stable and long run target payout ratio, and that firms adjust partially the gap between current payout rato and target payout ratio each year. In the Lintner model, dependent variable is the current dividend per share(DPSt), and independent variables are the past dividend per share(DPSt-1) and the current earnings per share(EPSt). We hypothesized that firms adjust partially the gap between the current dividend per share(DPSt) and the target payout ratio(Ω) each year, when the past dividend per share(DPSt-1) deviate from the target payout ratio(Ω). We secondly estimate the expansion model that extend the Lintner model by including the determinants suggested by the major theories of dividend, namely, residual dividend theory, dividend signaling theory, agency theory, catering theory, and transactions cost theory. In the expansion model, dependent variable is the current dividend per share(DPSt), explanatory variables are the past dividend per share(DPSt-1) and the current earnings per share(EPSt), and control variables are the current capital expenditure ratio(CEAt), the current leverage ratio(LEVt), the current operating return on assets(ROAt), the current business risk(RISKt), the current trading volume turnover ratio(TURNt), and the current dividend premium(DPREMt). In these control variables, CEAt, LEVt, and ROAt are the determinants suggested by the residual dividend theory and the agency theory, ROAt and RISKt are the determinants suggested by the dividend signaling theory, TURNt is the determinant suggested by the transactions cost theory, and DPREMt is the determinant suggested by the catering theory. Furthermore, we thirdly estimate the Lintner model and the expansion model by using the panel data of the financial unconstrained firms and the financial constrained firms, that are divided into two groups according to level of financial constraints. We expect that the financial unconstrained firms can adjust dividend payment faster than the financial constrained firms, because the former can finance more easily the investment funds through the market accessibility than the latter. We analyzed descriptive statistics such as mean, standard deviation, and median to delete the outliers from the panel data, conducted one way analysis of variance to check up the industry-specfic effects, and conducted difference test of firms characteristic variables between innovative SMEs and noninnovative SMEs as well as difference test of firms characteristic variables between financial unconstrained firms and financial constrained firms. We also conducted the correlation analysis and the variance inflation factors analysis to detect any multicollinearity among the independent variables. Both of the correlation coefficients and the variance inflation factors are roughly low to the extent that may be ignored the multicollinearity among the independent variables. Furthermore, we estimate both of the Lintner model and the expansion model using the panel regression analysis. We firstly test the time-specific effects and the firm-specific effects may be involved in our panel data through the Lagrange multiplier test that was proposed by Breusch and Pagan(1980), and secondly conduct Hausman test to prove that fixed effect model is fitter with our panel data than the random effect model. The main results of this study can be summarized as follows. The determinants suggested by the major theories of dividend, namely, residual dividend theory, dividend signaling theory, agency theory, catering theory, and transactions cost theory explain significantly the dividend policy of the innovative SMEs. Lintner model indicates that firms maintain stable and long run target payout ratio, and that firms adjust partially the gap between the current payout ratio and the target payout ratio each year. In the core variables of Lintner model, the past dividend per share has more effects to dividend smoothing than the current earnings per share. These results suggest that the innovative SMEs maintain stable and long run dividend policy which sustains the past dividend per share level without corporate special reasons. The main results show that dividend adjustment speed of the innovative SMEs is faster than that of the noninnovative SMEs. This means that the innovative SMEs with high level of R&D intensity can adjust dividend payment faster than the noninnovative SMEs, on the ground of their future growth opportunity and profitability. The other main results show that dividend adjustment speed of the financial unconstrained SMEs is faster than that of the financial constrained SMEs. This means that the financial unconstrained firms with high accessibility to capital market can adjust dividend payment faster than the financial constrained firms, on the ground of their financing ability of investment funds through the market accessibility. Futhermore, the other additional results show that dividend adjustment speed of the innovative SMEs classified by the Small and Medium Business Administration is faster than that of the unclassified SMEs. They are linked with various financial policies and services such as credit guaranteed service, policy fund for SMEs, venture investment fund, insurance program, and so on. In conclusion, the past dividend per share and the current earnings per share suggested by the Lintner model explain mainly dividend adjustment speed of the innovative SMEs, and also the financial constraints explain partially. Therefore, if managers can properly understand of the relations between financial constraints and dividend smoothing of innovative SMEs, they can maintain stable and long run dividend policy of the innovative SMEs through dividend smoothing. These are encouraging results for Korea government, that is, the Small and Medium Business Administration as it has implemented many policies to commit to the innovative SMEs. This paper may have a few limitations because it may be only early study about the relations between financial constraints and dividend smoothing of the innovative SMEs. Specifically, this paper may not adequately capture all of the subtle features of the innovative SMEs and the financial unconstrained SMEs. Therefore, we think that it is necessary to expand sample firms and control variables, and use more elaborate analysis methods in the future studies.