• Title/Summary/Keyword: E1A

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A Functional SNP in the MDM2 Promoter Mediates E2F1 Affinity to Modulate Cyclin D1 Expression in Tumor Cell Proliferation

  • Yang, Zhen-Hai;Zhou, Chun-Lin;Zhu, Hong;Li, Jiu-Hong;He, Chun-Di
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3817-3823
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    • 2014
  • Background: The MDM2 oncogene, a negative regulator of p53, has a functional polymorphism in the promoter region (SNP309) that is associated with multiple kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to associate with accelerated tumor formation by increasing the affinity of the transcriptional activator Sp1. It remains unknown whether there are other factors involved in the regulation of MDM2 transcription through a trans-regulatory mechanism. Methods: In this study, SNP309 was verified to be associated with overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G substitution at SNP309 generates a stronger E2F1 binding site, which was confirmed by ChIP and luciferase assays. Results: E2F1 knockdown downregulates the expression of MDM2, which confirms that E2F1 is a functional upstream regulator. Furthermore, tumor cells with the GG genotype exhibited a higher proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion significantly inhibits the proliferation capacity and downregulates cyclin D1 expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA effects could be rescued by cyclin D1 overexpression. Conclusion: Taken together, a novel modulator E2F1 was identified as regulating MDM2 expression dependent on SNP309 and further mediates cyclin D1 expression and tumor cell proliferation. E2F1 might act as an important factor for SNP309 serving as a rate-limiting event in carcinogenesis.

Evidence of Greater Competitive Fitness of Erwinia amylovora over E. pyrifoliae in Korean Isolates

  • Choi, Jeong Ho;Kim, Jong-Yea;Park, Duck Hwan
    • The Plant Pathology Journal
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    • v.38 no.4
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    • pp.355-365
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    • 2022
  • Erwinia amylovora and E. pyrifoliae are the causative agents of destructive diseases in both apple and pear trees viz. fire blight and black shoot blight, respectively. Since the introduction of fire blight in Korea in 2015, the occurrence of both pathogens has been independently reported. The co-incidence of these diseases is highly probable given the co-existence of their pathogenic bacteria in the same trees or orchards in a city/district. Hence, this study evaluated whether both diseases occurred in neighboring orchards and whether they occurred together in a single orchard. The competition and virulence of the two pathogens was compared using growth rates in vitro and in planta. Importantly, E amylovora showed significantly higher colony numbers than E. pyrifoliae when they were co-cultured in liquid media and co-inoculated into immature apple fruits and seedlings. In a comparison of the usage of major carbon sources, which are abundant in immature apple fruits and seedlings, E. amylovora also showed better growth rates than E. pyrifoliae. In virulence assays, including motility and a hypersensitive response (HR), E. amylovora demonstrated a larger diameter of travel from the inoculation site than E. pyrifoliae in both swarming and swimming motilities. E. amylovora elicited a HR in tobacco leaves when diluted from 1:1 to 1:16 but E. pyrifoliae does not elicit a HR when diluted at 1:16. Therefore, E. amylovora was concluded to have a greater competitive fitness than E. pyrifoliae.

SELF-ADJOINT INTERPOLATION ON Ax = y IN CSL-ALGEBRA ALGL

  • Kang, Joo-Ho;Jo, Young-Soo
    • Journal of applied mathematics & informatics
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    • v.15 no.1_2
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    • pp.503-510
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    • 2004
  • Given vectors x and y in a Hilbert space, an interpolating operator is a bounded operator T such that Tx = y. An interpolating operator for n vectors satisfies the equation $Tx_i\;=\;y_i,\;for\;i\;=\;1,\;2,\;\cdots,\;n$. In this paper the following is proved: Let H be a Hilbert space and L be a commutative subspace lattice on H. Let H and y be vectors in H. Let $M_x\;=\;\{{\sum{n}{i=1}}\;{\alpha}_iE_ix\;:\;n\;{\in}\;N,\;{\alpha}_i\;{\in}\;{\mathbb{C}}\;and\;E_i\;{\in}\;L\}\;and\;M_y\;=\;\{{\sum{n}{i=1}}\;{\alpha}_iE_iy\;:\;n\;{\in}\;N,\;{\alpha}_i\;{\in}\;{\mathbb{C}}\;and\;E_i\;{\in}\;L\}. Then the following are equivalent. (1) There exists an operator A in AlgL such that Ax = y, Af = 0 for all f in ${\overline{M_x}}^{\bot}$, AE = EA for all $E\;{\in}\;L\;and\;A^{*}\;=\;A$. (2) $sup\;\{\frac{{\parallel}{{\Sigma}_{i=1}}^{n}\;{\alpha}_iE_iy{\parallel}}{{\parallel}{{\Sigma}_{i=1}}^{n}\;{\alpha}_iE_iy{\parallel}}\;:\;n\;{\in}\;N,\;{\alpha}_i\;{\in}\;{\mathbb{C}}\;and\;E_i\;{\in}\;L\}\;<\;{\infty},\;{\overline{M_u}}\;{\subset}{\overline{M_x}}$ and < Ex, y >=< Ey, x > for all E in L.

A Variable Latency Goldschmidt's Floating Point Number Square Root Computation (가변 시간 골드스미트 부동소수점 제곱근 계산기)

  • Kim, Sung-Gi;Song, Hong-Bok;Cho, Gyeong-Yeon
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.9 no.1
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    • pp.188-198
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    • 2005
  • The Goldschmidt iterative algorithm for finding a floating point square root calculated it by performing a fixed number of multiplications. In this paper, a variable latency Goldschmidt's square root algorithm is proposed, that performs multiplications a variable number of times until the error becomes smaller than a given value. To find the square root of a floating point number F, the algorithm repeats the following operations: $R_i=\frac{3-e_r-X_i}{2},\;X_{i+1}=X_i{\times}R^2_i,\;Y_{i+1}=Y_i{\times}R_i,\;i{\in}\{{0,1,2,{\ldots},n-1} }}'$with the initial value is $'\;X_0=Y_0=T^2{\times}F,\;T=\frac{1}{\sqrt {F}}+e_t\;'$. The bits to the right of p fractional bits in intermediate multiplication results are truncated, and this truncation error is less than $'e_r=2^{-p}'$. The value of p is 28 for the single precision floating point, and 58 for the doubel precision floating point. Let $'X_i=1{\pm}e_i'$, there is $'\;X_{i+1}=1-e_{i+1},\;where\;'\;e_{i+1}<\frac{3e^2_i}{4}{\mp}\frac{e^3_i}{4}+4e_{r}'$. If '|X_i-1|<2^{\frac{-p+2}{2}}\;'$ is true, $'\;e_{i+1}<8e_r\;'$ is less than the smallest number which is representable by floating point number. So, $\sqrt{F}$ is approximate to $'\;\frac{Y_{i+1}}{T}\;'$. Since the number of multiplications performed by the proposed algorithm is dependent on the input values, the average number of multiplications per an operation is derived from many reciprocal square root tables ($T=\frac{1}{\sqrt{F}}+e_i$) with varying sizes. The superiority of this algorithm is proved by comparing this average number with the fixed number of multiplications of the conventional algorithm. Since the proposed algorithm only performs the multiplications until the error gets smaller than a given value, it can be used to improve the performance of a square root unit. Also, it can be used to construct optimized approximate reciprocal square root tables. The results of this paper can be applied to many areas that utilize floating point numbers, such as digital signal processing, computer graphics, multimedia, scientific computing, etc.

Synthesis of Adenosine and Uridine Analogues Containing Conjugated Diene (공액 이중 결합을 갖는 Adenosine과 Uridine 유사체의 합성)

  • Ro, Bong Oh
    • Journal of the Korean Chemical Society
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    • v.45 no.4
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    • pp.312-317
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    • 2001
  • 7'-Aldehyde-nucleosides analogue (2a, 2c) were synthesized from 6-N-benzoyl-2',3'-O-isopropylideneadenosine and uridine. The condensation of 2 with ethoxycarbonylmethylene Wittig reagent produced the adenosine and uridine analogues containing extended conjugated diene and ethoxycarbonyl group, ethyl-1',5',6',7',8'-pentadeoxy-1'-(adenin-9-yl)-$\beta$-D-ribo-nona-5'(E),7'(E)-dienofuranuronate (4b) and ethyl-1'. 5',6',7',8'-pentadeoxy-1'-(uracil-1-yl)-$\beta$-D-ribo-nona-5'(E),7'-(E)-dienofuranuronate (4c). 9-[8',8'-dibromo-5',6',7',8' -tetradeoxy-$\beta$-D-ribo-octa-5'(E),7'(E)-diene]nucleosides (6b, 6c) were also prepared from 2 with similar method.

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Differential Role of Ethanol, Glycerol, 4-Methylpyrazole and Isoniazid on Human CYP2E1 Activity in Intact HepG2 Cells (HepG2 세포에서 Ethanol, Glycerol, 4-Methylpyrazole 및 Isoniazid에 의한 Human CYP2E1 활성변화)

  • 최달웅
    • Toxicological Research
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    • v.19 no.3
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    • pp.235-240
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    • 2003
  • The modification of CYP2E1 activity is of considerable interest because of its role in the metabolic activation of a variety of toxic chemicals. In the present studies, the time-course of changes in human CYP2E1 activities was determined after treatment with ethanol, glycerol, 4-methylpyrazole or isoniazid using intact HepG2 cells transfected by human CYP2E1. Hydroxylation of chlorzoxazone was chosen for the measurement of CYP2E1 activity. CYP2E1 protein levels were increased upon cultivation of cells in the presence of ethanol, glycerol, 4-methylpyrazole or isoniazid for 24 hr. After 24 hr cultivation, ethanol or glycerol increased CYP2E1 activities, whereas 4-methylpyrazole or isoniazid inhibited. This different effect of the chemical inducers on CYP2E1 activi-ties persisted to subsequent 24 hr. Competitive inhibition study suggested that 4-methylpyrazole or isoniazid has stronger binding affinity to CYP2E1 than ethanol or glycerol. These results demonstrate that different binding affinity of the chemical inducers to the active site of CYP2E1 plays important role in determining real CYP2E1 activity in intact cells after treatment with the chemical inducers. Present study would be helpful in precise understanding of human CYP2E1-mediated toxicity.

Implications of Streptomyces coelicolor RraAS1 as an activator of ribonuclease activity of Escherichia coli RNase E (Streptomyces coelicolor RraAS1의 Eschechia coli RNase E의 RNA 분해작용에 대한 활성제로서 기능 암시)

  • Heo, Jihune;Seo, Sojin;Lee, Boeun;Yeom, Ji-Hyun;Lee, Kangseok
    • Korean Journal of Microbiology
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    • v.52 no.3
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    • pp.243-248
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    • 2016
  • RNase E (Rne) is an essential enzyme involved in the processing and degradation of a large portion of RNAs in Escherichia coli. The enzymatic activity of RNase E is controlled by regulators of ribonuclease activity, namely, RraA and RraB. Gram-positive bacterium Streptomyces coelicolor also contains homologs of Rne and RraA, designated as RNase ES (Rns), RraAS1, and RraAS2. In the present study, we investigated the effect of S. coelicolor RraAS1 on the ribonucleolytic activity of RNase E in E. coli. Coexpression of RraAS1 with Rne resulted in the decreased levels of rpsO, ftsZ, and rnhB mRNAs, which are RNase E substrates, and augmented the toxic effect of Rne overexpression on cell growth. These in vivo effects appeared to be induced by the binding of RraAS1 to Rne, as indicated by the results of co-immunoprecipitation analysis. These results suggested that RraAS1 induces ribonucleolytic activity of RNase E in E. coli.

1-Methyl Substituent and Stereochemical Effects of 2-Phenylcyclopropylamines on the Inhibition of Rat Brain Mitochondrial Monoamine Oxidase A and B

  • Kang, Gun-Il;Hong, Suk-Kil;Choi, Hee-Kyung
    • Archives of Pharmacal Research
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    • v.10 no.1
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    • pp.50-59
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    • 1987
  • (E)-2-Phenylcyclopropylamine ((E)-TCP), (Z)-2-Phenylacyclopropylamine ((Z)-TCP), (E)-1-methyl-2-phenylcyclopropylamine ((E)-MTCP), and (Z)-1-methyl-2-phenylcyclopropylamine ((Z)-MTCP) were synthesized and used to determine to what extent 1-methylsubstitution and stereochemistry of 2-phenycyclopropylamines affect inhibition of monoamine oxidase (MAO). Inhibition of rat brain mitochondrial MAO-A and B by the compounds were measured using serotonin and benzylamine as the substrate, respectively and $IC_{50}$ values obtianed with 95% confidence limits by the method of computation. For the inhibition of MAO-A, (E)-MTPC ($IC_{50}$ = 6.2 * $10^{-8}$M) was found to be 37 times more potent than (Z)-MTCP ($IC_{50}$ = 7.8 * $10^{-8}$M), was 7 times more potent than (Z)-MTCP($IC_{50}$= 4.7 * $10^{-7}$M) and (E)-TCP($IC_{50}$ =7.8 * $10^{-8}$M),0.6 times as potent as (Z)- TCP ($IC_{50}$ = 4.4 * $10^{-8}$M). The results suggested that while without 1-methyl group, potency of a (Z)-isomer was comparable to that of (E)-isomer, the methyl group in its (Z)-position was very unfavorable to the inhibition of MAO and that in its (E)-position, the methyl group contributed positively to the potency as found by the fact that (E)-MTCP was 1-5 times more potent than (E)-TCP. In view of the selective inhibition of MAO-A- or B over MAO-A and 1-methyl substitution as well as the stereochemical factors did not significantly influence the selectivity.

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HPV-18 E7 Interacts with Elk-1 Leading to Elevation of the Transcriptional Activity of Elk-1 in Cervical Cancer

  • Go, Sung-Ho;Rho, Seung Bae;Yang, Dong-Wha;Kim, Boh-Ram;Lee, Chang Hoon;Lee, Seung-Hoon
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.593-602
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    • 2022
  • The human papillomavirus (HPV)-18 E7 (E7) oncoprotein is a major transforming protein that is thought to be involved in the development of cervical cancer. It is well-known that E7 stimulates tumour development by inactivating pRb. However, this alone cannot explain the various characteristics acquired by HPV infection. Therefore, we examined other molecules that could help explain the acquired cancer properties during E7-induced cancer development. Using the yeast two-hybrid (Y2H) method, we found that the Elk-1 factor, which is crucial for cell proliferation, invasion, cell survival, anti-apoptotic activity, and cancer development, binds to the E7. By determining which part of E7 binds to which domain of Elk-1 using the Y2H method, it was found that CR2 and CR3 of the E7 and parts 1-206, including the ETS-DNA domain of Elk-1, interact with each other. As a result of their interaction, the transcriptional activity of Elk-1 was increased, thereby increasing the expression of target genes EGR-1, c-fos, and E2F. Additionally, the colony forming assay revealed that overexpression of Elk-1 and E7 promotes C33A cell proliferation. We expect that the discovery of a novel E7 function as an Elk-1 activator could help explain whether the E7 has novel oncogenic activities in addition to p53 inactivation. We also expect that it will offer new methods for developing improved strategies for cervical cancer treatment.

RINGS WITH THE SYMMETRIC PROPERTY FOR IDEMPOTENT-PRODUCTS

  • Han, Juncheol;Sim, Hyo-Seob
    • East Asian mathematical journal
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    • v.34 no.5
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    • pp.615-621
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    • 2018
  • Let R be a ring with the unity 1, and let e be an idempotent of R. In this paper, we discuss some symmetric property for the set $\{(a_1,a_2,{\cdots},a_n){\in}R^n:a_1a_2{\cdots}a_n=e\}$. We here investigate some properties of those rings with such a symmetric property for an arbitrary idempotent e; some of our results turn out to generalize some known results observed already when n = 2 and e = 0, 1 by several authors. We also focus especially on the case when n = 3 and e = 1. As consequences of our observation, we also give some equivalent conditions to the commutativity for some classes of rings, in terms of the symmetric property.