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Transcription Factor PU.1 Inhibits Aspergillus fumigatus Infection via Surfactant Protein-D

  • Kim, Sung-Su
    • Biomedical Science Letters
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    • v.24 no.3
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    • pp.175-182
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    • 2018
  • Aspergillosis is a life-threatening disease in individuals with compromised immune systems. Fungal invasion is a highly critical process during host cellular infection. Several papers have reported that transcription factors are responsible for the infection process. To investigate what transcription factors are involved in the process in an effort to inhibit fungal infection into cells, I checked the surfactant protein family and PU.1 transcription factor levels in A549 cells infected with A. fumigatus conidia. PU.1 and surfactant protein-D levels were reduced in cells infected with fungal conidia. I then observed an increase in surfactant protein-D on PU.1-overexpressed cells. Infection of A. fumigatus conidia was decreased in PU.1-overexpressed cells, whereas the suppression of PU.1 did not lead to any changes in cases of A. fumigatus conidia infection. These results indicate that PU.1 inhibits the infection of A. fumigatus conidia via the expression of surfactant protein-D, suggesting that PU.1 is a key transcription factor for protection against A. fumigatus invasion.

Cytotoxic Effects of an Oncolytic Adenoviral Vector AdLPCDIRESE1A in Hepatocellular Carcinoma Cells (암세포 용해성 AdLPCDIRESE1A 벡터의 간암 세포독성효과)

  • Chung, In-Jae
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.75-79
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    • 2011
  • The replication competent adenoviral vector (AV), AdLPCDIRESE1A was generated and reported previously to have cytotoxic effects in some cell lines. In AdLPCDIRESE1A, the expression of cytosine deaminse (CD) and E1A genes are under the control of tumor-specific L-plastin promoter. CD enzyme can deaminate the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic 5-fluorouracil (5-FU). E1A gene is essential for viral replication. Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. Thus, we have conducted in vitro preclinical study to evaluate effectiveness of AdLPCDIRESE1A on HCC. The efficacy of cytotoxicity was measured by generation of cytopathic effect (CPE) and cell counting. We infected HepG2 cells with various MOI of vector alone or concurrent with 5-FC. Exposure of cells to AdLPCDIRESE1A generated a significant cytotoxic effect as compared to the control. Almost 83% of the cell had manifested the characteristic cytotoxic effect on day 9 after infection of cells with 10 MOI of vector. We also observed the additive cytotoxic effects when AdLPCDIRESE1A vector had been coadministrated with 5-FC. The results suggest that the use of AdLPCDIRESE1A/5FC may be value in treatment of liver cancer. Further animal studies are needed for clinical trial.

Biochemical and molecular characterization of a tetrachloroethylene (PCE) dechlorinating Clostridium bifermentans DPH-1

  • Chang, Young-Cheol;Toyama, Tadashi;Kikuchi, Shintaro
    • Journal of environmental and Sanitary engineering
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    • v.23 no.2
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    • pp.1-18
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    • 2008
  • The tetrachloroethylene (PCE) dehalogenase of Clostridium bifermentans DPH-1 (a halorespiring organism) was purified, cloned, and sequenced. This enzyme is a homodimer with a molecular mass of ca. 70 kDa and exhibits dehalogenation of dichloroethylene isomers along with PCE and trichloroethylene (TCE). Broad range of substrate specificity for chlorinated aliphatic compounds (PCE, TCE, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, 1,1-dichloroethylene, 1,2-dichloropropene, and 1,1,2-trichloroethane) for this enzyme was also observed. A mixture of propyl iodide and titanium citrate caused a light-reversible inhibition of enzymatic activity suggesting the involvement of a corrinoid cofactor. A partial sequence (81 bp) of the encoding gene for PCE dehalogenase was amplified and sequenced with degenerateprimers designed from the N-terminal sequence (27 amino acid residues). Southern analysis of C. bifermentans genomic DNA using the polymerase chain reaction product as a probe revealed restriction fragment bands. A 5.0 kb ClaI fragment, harboring the relevant gene (designated pceC) was cloned (pDEHAL5) and the complete nucleotide sequence of pceC was determined. The gene showed homology mainly with microbial membrane proteins and no homology with any known dehalogenase, suggesting a distinct PCE dehalogenase. So, C. bifermentans could play some important role in the initial breakdown of PCE and other chlorinated aliphatic compounds in sites contaminated with mixtures of halogenated substances.

Association of PPARGC1A Gene Variants with Hypertension in Korean Population

  • Jin, Hyun-Seok;Park, Sangwook
    • Biomedical Science Letters
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    • v.27 no.1
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    • pp.12-18
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    • 2021
  • Hypertension (HTN) is one of the cardiovascular disease risk factors. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is involved in a master modulator of mitochondrial biogenesis, and pulmonary arterial hypertension. In this study, we report results of PPARGC1A were associated with hypertension and its intermediate phenotype of systolic (SBP) and diastolic blood pressure (DBP) in the Korean population. In detail, identifying a susceptibility locus, 3 SNPs for HTN, 2 SNPs for SBP, 3 SNPs for DBP at P<0.05. Among them, rs1472095 in PPARGC1A gene statistically demonstrated one of the significant correlations with Hypertension (P-value=0.00359, OR=0.8, 95% CI=0.68~0.93). The minor allele (T) of PPARGC1A was statistically associated with the increased value of DBP, SBP, and the increase risk of hypertension. We aim to manifest a significant association between genetic variant in PPARGC1A and hypertension. This finding suggested that association of PPARGC1A genetic polymorphism and HTN accelerates our understanding of blood pressure control and underlines potential drug targets for treatment of hypertension.

EQUIMULTIPLE GOOD IDEALS WITH HEIGHT 1

  • Kim, Mee-Kyoung
    • Journal of the Korean Mathematical Society
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    • v.39 no.1
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    • pp.127-135
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    • 2002
  • Let I be an ideal in a Gorenstein local ring A with the maximal ideal m. Then we say that I is an equimultiple good ideal in A, if I contains a reduction Q = ( $a_1$, $a_2$,ㆍㆍㆍ, $a_{s}$ ) generated by s elements in A and G(I) =(equation omitted)$_{n 0}$ $I^{n}$ / $I^{n+1}$ of I is a Gorenstein ring with a(G(I)) = 1 - s, where s = h $t_{A}$ I and a(G(I)) denotes the a-invariant of G(I). Let $X_{A}$$^{s}$ denote the set of equimultiple good ideals I in A with h $t_{A}$ I = s, R(I) = A [It] be the Rees algebra of I, and $K_{R(I)}$ denote the canonical module of R(I). Let a I such that $I^{n+l}$ = a $I^{n}$ for some n$\geq$0 and $\mu$$_{A}$(I)$\geq$2, where $\mu$$_{A}$(I) denotes the number of elements in a minimal system of generators of I. Assume that A/I is a Cohen-Macaulay ring. We show that the following conditions are equivalent. (1) $K_{R(I)}$(equation omitted)R(I)+as graded R(I)-modules. (2) $I^2$ = aI and aA : I$\in$ $X^1$$_{A}$._{A}$./.

Genome Type Analysis of Adenovirus Serotypes 1, 2 and 5 Isolated from Children with Lower Respiratory Tract Infections in Korea (하기도 감염 환아에서 분리된 Adenovirus 1, 2, 5 혈청형의 유전체형 분석)

  • Park, Ki-Won;Choi, Eun-Hwa;Choun, Ji-Tae;Lee, Hoan-Jong;Park, Ki-Ho
    • Pediatric Infection and Vaccine
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    • v.12 no.2
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    • pp.166-177
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    • 2005
  • Purpose : The purpose of this study was to examine the molecular epidemiology and genetic variability of adenovirus(Ad) serotypes Ad1, Ad2, and Ad5 over 14 years in Korea. Methods : A total of 382 adenoviral strains isolated from the nasopharyngeal aspirates of children with lower respiratory tract infections in Seoul, Korea from November 1990 to February 2003 were serotyped by neutralization assay with type-specific antisera. Viral DNAs were extracted from infected cell lysates by the modified Hirt procedure. Genome type(GT) was determined by DNA restriction analysis with 12 restriction enzymess(BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). To evaluate the genetic relatedness, pairwise comigrating restriction fragments(PCRF) analysis was performed. Results : Of 382 strains, 33 strains(9%) were Ad1, 45 strains(12%) were Ad2, and 24 strains(6%) were Ad5. Eighteen GTs(Ad1p1-Ad1p7, Ad1a, Ad1b, Ad1b1-Ad1b3, Ad1c, Ad1d, Ad1e, Ad1e1, Ad1e2, Ad1f) among Ad1, 24(Ad2p1-Ad2p11, Ad2a, Ad2a1-Ad2a6, Ad2b, Ad2c, Ad2d, Ad2e, Ad2e1-Ad2e3) among Ad2, and 10(Ad5p1, Ad5p2, Ad5a, Ad5a1-Ad5a7) among Ad5 strains were identified. One or two strains of the vast majority of GTs were isolated during the study period while a few GTs were identified sporadically with more than 2 strains. It is notable that some GTs such as Ad1p5 and Ad5a1 appeared in cluster during a short period. In analysis of genetic relatedness, the degree of PCRFs(pairwise comigrating restriction fragments) for Ad1 varied from 79 to 99%, for Ad2, 82 to 99%, and for Ad5, 85 to 99%. Conclusion : This study established the comprehensive nomenclature systems of Ad1, Ad2, and Ad5. Diverse GTs identified in this study have crucial implications in the genomic diversity and epidemiological characteristics of Ad1, Ad2, and Ad5.

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CERTAIN CLASS OF FRACTIONAL CALCULUS OPERATOR WITH TWO FIXED POINTS

  • Kwon, Oh-Sang
    • East Asian mathematical journal
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    • v.14 no.1
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    • pp.107-116
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    • 1998
  • This paper deals with functions of the form $f(z)=a_1z-{\sum}{\limits}_{n=2}^{\infty}a_nz^n(a_1>0,\;a_n{\geqslant}0)$ with $(1-{\mu})f(z_0)/z_0+{\mu}f'(z_0)=1(-1. We introduce the class $\varphi({\mu},{\eta},{\gamma},{\delta},A,B;\;z_0)$ with generalized fractional derivatives. Also we have obtained coefficient inequalities, distortion theorem and radious problem of functions belonging to the calss $\varphi({\mu},{\eta},{\gamma},{\delta},A,B;\;z_0)$.

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BLYP and mPW1PW91 Calculated Structures and IR Spectra of the Stereoisomers of Tetra-O-methylsulfinylcalix[4]arene

  • Choe, Jong-In
    • Bulletin of the Korean Chemical Society
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    • v.31 no.11
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    • pp.3247-3251
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    • 2010
  • Molecular structures of the various conformers for the four stereoisomers of tetra-t-butyl-tetra-O-methylsulfinylcalix[4]arene (1) were optimized using DFT BLYP and mPW1PW91/6-31G(d,p) (hybrid HF-DF) calculation methods. We have analyzed the total electronic and Gibbs free energies and normal vibrational frequencies of 16 different structures from four major conformations (cone (CONE), partial cone (PC), 1,2-alternate (1,2-A), 1,3-alternate (1,3-A)) of the four stereoisomers [1(rccc), 1(rcct), 1(rctt), 1(rtct)]. The mPW1PW91/6-31G(d,p) calculations suggested that the $1(rccc)_{CONE}$, $1(rcct)_{PC}$, $1(rctt)_{PC}$, and $1(rtct)_{1,3-A}$ were the most stable conformations of the respective stereoisomers. These outcomes are in accordance with the experimental structures obtained from X-ray crystallography. The electrostatic repulsion between the sulfinyl and methoxy groups is a primary factor for the relative stabilities of the four different conformations. The IR spectra of the most stable conformers [$1(rccc)_{CONE}$, $1(rcct)_{PC}$, $1(rctt)_{PC}$, $1(rtct)_{1,3-A}$] of each stereoisomer were compared to each other.

Identification of Differentially Expressed Genes by TCDD in Human Bronchial Cells: Toxicogenomic Markers for Dioxin Exposure

  • Park, Chung-Mu;Jin, Kyong-Suk;Lee, Yong-Woo
    • Biomedical Science Letters
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    • v.18 no.1
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    • pp.1-9
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    • 2012
  • Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

Synthesis and Guest Binding Properties of Cyclophanes Containing Two Benzo[b]furan Rings

  • Park, Kwang-Hee;Kim, Sun-Hyuk;Park, Joon-Woo
    • Bulletin of the Korean Chemical Society
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    • v.25 no.11
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    • pp.1635-1640
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    • 2004
  • The cyclophanes 1a-d containing two benzo[b]furan rings connected by various bridges have been prepared and their binding behaviors with N-benzylphenethylammonium cation 2 were examined by NMR titration method. The successive alkylation reactions of 4-hydroxyl groups and then 2-hydroxyl groups of 2,4-dihydroxybenzophenonse gave macrocycles 5a-c. Photoirradiation of the macrocycles 5a-c with 350 nm mercury lamp followed by dehydration afforded the cyclophanes 1a-c. Hydrolysis of two ester groups pendant on a bridge of 1b produced the carboxyl group-containing cyclophane 1d. The cyclophane 1a having a p-xylene bridge showed 1 : 1 binding with 2 with the binding constant of $36{\pm}6M^{-1}$ in 3 : 1 $CDCl_3$/methanol-$d_4$ solvent, while 1b and 1c which have neutral flexible bridges exhibited no appreciable binding with 2. The disodium salt of 1d showed much higher binding affinity for 2 forming 1 : 1 and 1 : 2 complexes.