• Title/Summary/Keyword: Member function

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Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

  • Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.6813-6823
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    • 2015
  • Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

Characterization of Hrq1-Rad14 Interaction in Saccharomyces cerevisiae (효모에서 Hrq1과 Rad14의 상호작용에 대한 연구)

  • Min, Moon-Hee;Kim, Min-Ji;Choi, You-Jin;You, Min-Ju;Kim, Uy-Ra;An, Hyo-Bin;Kim, Chae-Hyun;Kwon, Chae-Yeon;Bae, Sung-Ho
    • Korean Journal of Microbiology
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    • v.50 no.2
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    • pp.95-100
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    • 2014
  • Hrq1 is a novel member of RecQ helicase family, found in fungal genomes by bioinformatics analyses. It is most homologous to human RECQL4 and recent genetic and biochemical studies suggested that it may play roles in the maintenance of genome stability. In this study, we investigated yeast two-hybrid interactions between Hrq1 and the yeast genes homologous to the human genes that are known to interact with RECQL4. Among the 11 genes tested, Rad14, a nucleotide excision repair (NER) factor, was found to interact with Hrq1. In addition, pull-down assay with the purified proteins revealed direct protein-protein interaction between Hrq1 and Rad14. The yeast two-hybrid interaction was enhanced by the DNA damage induced by 4-nitroquinoline-1-oxide, which was dependent on the presence of Rad4, a key NER factor. These results suggest that Hrq1 may function in NER through interaction with Rad14.

Cytological analysis of pregnancy-associated plasma protein-A expression in porcine neonatal testis (미성숙 돼지 정소에서 pregnancy-associated plasma protein-A의 발현의 세포학적 분석)

  • Kim, Ji-youn;Oh, Keon Bong;Byun, Sung June;Ock, Sun-A;Lee, Hwi-Cheul;Hwang, Seong-Su;Park, SangHyun;Ha, Wootae;Woo, Jae-Seok;Song, Hyuk
    • Journal of Embryo Transfer
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    • v.33 no.3
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    • pp.177-183
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    • 2018
  • The identification of biomarkers of a living tissues is essentially required to understand specific functions of the cells. In previous study, we reported IGFBP 3 as one of the putative biomarkers, by showing specific expression at porcine spermatogonial stem cells (SSCs) of early stage of porcine testis. In this study, we analyzed the expression of seven members of IGFBP family (IGFBPs) in SSCs and histological expression pattern of pregnancy-associated plasma protein-A (PAPP-A), which plays a role on the growth promoting enzyme by cleavage of IGFBPs in testis of 5 days old pig. RT-PCR analysis showed that IGFBP 1, 2, 3, 4, and 6 were expressed at high level specifically in porcine SSCs compared with whole testis. We performed immunohisotochemical staining of testis sections with PAPP-A and protein gene product 9.5 (PGP9.5) which are the known biomarkers for SSCs. We were not able to find co-expression of PAPP-A and PGP9.5; PAPP-A was expressed only in Sertoli cells and PGP9.5 expression was confirmed in spermatogonium. Additionally, we were able to confirm the GATA4 expression in Sertoli and Leydig cells as a regulator of Sertoli cell function was not detected PGP9.5 expressing cells, indicating indirect evidence of that cytolocalization of PAPP-A expression is limited in Sertoli cells. These results suggested that the PAPP-A expressed in Sertoli cells may play role on regulation of development and differentiation of testicular cells through the IGF axis in neonatal porcine testis.

Evaluation of Potential Biomarkers for Thioacetamide-induced Hepatotoxicity using siRNA

  • Kang, Jin-Seok;Yum, Young-Na;Han, Eui-Sik;Kim, Joo-Hwan;Lee, Eun-Mi;Ryu, Doug-Young;Kim, Young-Hee;Yang, Sung-Hee;Kim, Seung-Hee;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.16 no.3
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    • pp.197-202
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    • 2008
  • In our previous publication we compared the gene expression profiles on hepatotoxicants exposure to assess the comparability between in vivo and in vitro test systems. We investigated global gene expression from both mouse liver and mouse hepatic cell line treated with thioacetamide (TAA) and identified several common genes. In this study, we selected genes to validate them as potential biomarkers for hepatotoxicity on the relevance of in vitro and in vivo system. Three up-regulated, aquaporin 8 (Aqp8), glutathione peroxidase 1 (Gpx1), succinate-CoA ligase, GDP-forming, alpha subunit (Suclg1) and two down-regulated, DnaJ (Hsp40) homolog subfamily C member 5 (Dnajc5) and tumor protein D52 (Tpd52) genes were tested for their effects in vitro. For characterization of gene function, short interfering RNA (siRNA) for each gene was synthesized and transfected in mouse hepatic cell line, BNL CL.2. Cell viability, mRNA expression level and morphological alterations were investigated. We confirmed siRNA transfection against selected five genes induced down-regulation of respective mRNA expression. siRNA transfection in general decreased cell viability in different degrees and induced morphological changes such as membrane thickening and alterations of intracellular structures. This suggests that these genes could be associated with TAA-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity for better understanding of its mechanism.

Functional Screening for Cell Death Suppressors and Development of Multiple Stress-Tolerant Plants

  • Moon, Hae-Jeong;Baek, Dong-Won;Lee, Ji-Young;Nam, Jae-Sung;Yun, Dae-Jin
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2003.04a
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    • pp.65-71
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    • 2003
  • Bax, a mammalian pro-apoptotic member of the Bcl-2 family, induces cell death when expressed in yeast. To investigate whether Bax expression can induce cell death in plant, we produced transgenic Arabidopsis plants that contained murine Bax cDNA under control of a glucocorticoid-inducible promoter. Transgenic plants treated with dexamethasone, a strong synthetic glucocorticoid, induced Bax accumulation and cell death, suggesting that some elements of cell death mechanism by Bax may be conserved among various organisms. Therefore, we developed novel yeast genetic system, and cloned several Plant Bax Inhibitors (PBIs). Here, we report the function of two PBIs in detail. PBI1 is ascorbate peroxidase (sAPX). Fluorescence method of dihydrorho-damine 123 oxidation revealed that expression of Bax in yeast cells generated reactive oxygen species (ROS), and which was greatly reduced by co-expression with sAPX. These results suggest that sAPX inhibits the generation of ROS by Bax, which in turn suppresses Baxinduced cell death in yeast. PBI2 encodes nucleoside diphosphate kinase (NDPK). ROS stress strongly induces the expression of the NDPK2 gene in Arabidopsis thaliana (AtNDPK2). Transgenic plants overexpressing AtNDPK2 have lower levels of ROS than wildtype plants. Mutants lacking AtNDPK2 had higher levels of ROS than wildtype. $H_2O_2$ treatment induced the phosphorylation of two endogenous proteins whose molecular weights suggested they are AtMPK3 and AtMPK6. In the absence of $H_2O_2$ treatment, phosphorylation of these proteins was slightly elevated in plants overexpressing AtNDPK2 but markedly decreased in the AtNDPK2 deletion mutant. Yeast two-hybrid and in vitro protein pull-down assays revealed that AtNDPK2 specifically interacts with AtMPK3 and AtMPK6. Furthermore, AtNDPK2 also enhances the MBP phosphorylation activity of AtMPK3 in vitro. Finally, constitutive overexpression of AtNDPK2 in Arabidopsis plants conferred an enhanced tolerance to multiple environmental stresses that elicit ROS accumulation in situ. Thus, AtNDPK2 appears to play a novel regulatory role in $H_2O_2$-mediated MAPK signaling in plants.

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Molecular Cloning of Glycoside Hydrolase Family 74 Genes and Analysis of Transcript Products from the Basidiomycete Phanerochaete chrysosporium (담자균 Phanerochaete chrysosporium으로부터 유래한 Glycoside Hydrolase Family 74 유전자 클로닝과 전사산물 분석)

  • Lee, Jae-Won;Samejima, Masahiro;Choi, In-Gyu
    • Journal of the Korean Wood Science and Technology
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    • v.34 no.3
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    • pp.56-63
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    • 2006
  • In order to evaluate the mechanism of cellulose hydrolysis, the complementary DNA encoding Glycoside Hydrolase Family (GHF)74 was cloned from Phanerochaete chrysosporium. Depending on the presence of Cellulose Binding Module (CBM), it can be classified as GHF74A or GHF74B. The GHF74A gene from P. chrysosporium (PcGHF74A) consists of 2163 bp encoding a protein of 721 amino acid residues. The PcGHF74A showed homology of 70~77% compared with the GHF74 from other filamentous fungi. The PcGHF74B, which contains CBM and is a member of family 1, was transcribed to various transcripts depending on the nature of carbon sources and their concentration. To study the possible presence of splice variants in GHF74B transcripts in P. chrysospoium, we carried out RT-PCR analysis using primers that designed based on the annotation data and sequenced data. Our result indicated that PcGHF74B was transcribed to several splicing variants in various culture conditions. Especially in the culture of 2% cellulose, three transcript products were observed. First transcript was presumed to be a full length ORF that contained 11th intron with stop codon at position 2562 bp. The second one consisted of 12 exons and 11 introns with stop codon at position 1187 bp with 7th exon. The shortest transcript consisted of 10 exons and 9 introns with stop codon at 910 bp in the 7th exon. These premature stop codon might prevent the synthesis of fully active GHF74 or contribute for the production of protein with distinct function depending on the ambient carbon sources.

Bi-Axial Stress Field Analysis on Shear-Friction in RC Members (2축-응력장 이론을 이용한 철근콘크리트 부재의 전단마찰 해석)

  • Kim, Min-Joong;Lee, Gi-Yeol;Lee, Jun-Seok;Kim, Woo
    • Journal of the Korea Concrete Institute
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    • v.24 no.1
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    • pp.25-35
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    • 2012
  • For a member subjected to direct shear forces, forces are transferred across interface concrete area and resisted by shear transfer capacity. Shear-friction equations in recent concrete structural design provisions are derived from experimental test results where shear-friction capacity is defined as a function of steel reinforcement area contained in the interface. This empirical equation gave too conservative values for concrete members with large amounts of reinforcement. This paper presents a method to evaluate shear transfer strengths and to define ultimate conditions which result in crushing of concrete struts after yielding of longitudinal reinforcement perpendicular to the interface concrete. This method is based on the bi-axial stress field theory where different constitutive laws are applied in various means to gain accurate shear strengths by considering softening effects of concrete struts based on the modified compression-field theory and the softened truss model. The validity of the proposed method is examined by applying to some selected test specimens in literatures and results are compared with recent design code provisions. A general agreement is observed between predicted and measured values at ultimate loading stages in initially uncracked normal-strength concrete test.

Development of Sorption Database (KAERI-SDB) for the Safety Assessment of Radioactive Waste Disposal (방사성폐기물 처분안전성 평가 자료 제공을 위한 핵종 수착 데이터베이스(KAERI-SDB) 개발)

  • Lee, Jae-Kwang;Baik, Min-Hoon;Jeong, Jongtae
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.11 no.1
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    • pp.41-54
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    • 2013
  • Radionuclide sorption data is necessary for the safety assessment of radioactive waste disposal. However the use of sorption database is often limited due to the accessability. A web-based sorption database program named KAERI-SDB has been developed to provide information on the sorption of radionuclides onto geological media as a function of geochemical conditions. The development of KAERI-SDB was achieved by improving the performance of pre-existing sorption database program (SDB-21C) developed in 1998 and considering user's requirements. KAERI-SDB is designed that users can access it by using a web browser. Main functions of KAERI-SDB include (1) log-in/member join, (2) search and store of sorption data, and (3) chart expression of search results. It is expected that KAERI-SDB could be widely utilized in the safety assessment of radioactive waste disposal by enhancing the accessibility to users who wants to use sorption data. Moreover, KAERI-SDB opened to public would also improve the reliability and public acceptance on the radioactive waste disposal programs.

Video Event Analysis and Retrieval System for the KFD Web Database System (KFD 웹 데이터베이스 시스템을 위한 동영상 이벤트 분석 및 검색 시스템)

  • Oh, Seung-Geun;Im, Young-Hee;Chung, Yong-Wha;Chang, Jin-Kyung;Park, Dai-Hee
    • The Journal of the Korea Contents Association
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    • v.10 no.11
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    • pp.20-29
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    • 2010
  • The typical Kinetic Family Drawing (KFD) Web database system, a form of prototype system, has been developed, relying on the suggestions from family art therapists, with an aim to handle large amounts of assessment data and to facilitate effective implement of assessment activities. However, unfortunately such a system has an intrinsic problem that it fails to collect clients' behaviors, attitudes, facial expressions, voices, and other critical information observed while they are drawing. Accordingly we propose the ontology based video event analysis and video retrieval system in this paper, in order to enhance the function of a KFD Web database system by using a web camera and drawing tool. More specifically, a newly proposed system is designed to deliver two kinds of services: the client video retrieval service and the sketch video retrieval service, accompanied by a summary report of occurred events and dynamic behaviors relative to each family member object, respectively. The proposed system can support the reinforced KFD assessments by providing quantitative and subjective information on clients' working attitudes and behaviors, and KFD preparation processes.

Research on the Actual Conditions of Elementary Schoolchildren's Internet Addication and Teachers' Consciousness of It (초등학생의 인터넷 중독에 대한 실태와 교사들의 인식에 관한 연구)

  • Bae, Young-Kwon;Ahn, Seong-Hun;Kim, Gyu-Seog;Kho, Dae-Ghon
    • The Journal of the Korea Contents Association
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    • v.8 no.4
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    • pp.285-293
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    • 2008
  • Internet addiction is currently regarded as a problem for its negative function in the information-oriented society. Particularly in cases of elementary schoolchildren in their growth period, it is very important to grasp the schoolchildren's conditions in advance and guide them on a systematic basis before they get into the habit of addiction to the Internet. For this purpose, several research papers have already discussed the seriousness of Internet addiction. This research is aimed at conducting a positive research work on to what extent such academic research results had affected educational fields, and also at what level the seriousness of Internet addiction is staying at the present moment. For this, this research conducted a survey of the Internet addiction level for fourth, fifth, and sixth graders totalling in 448 from one elementary school located within the jurisdiction of Gyeongsangbuk-do through the on-line system and questionnaires from March 31 to April 3, 2008. And also looked into the level of perception on Internet addiction for 29 teachers within the surveyed school. The results of this study show that 90.1 percent(408 children) of the surveyed children were a member of a general user group. Such aspects are thought to have resulted from some factors that functioned in a positive way, such as teachers' proper perception on Internet addiction and their proper guidance against this, and plenty of conversation at the children's homes, and the children's smooth relationship between their friends and teachers.