• Title/Summary/Keyword: Point mutation

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Inhibition of Wnt Signaling by Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.380-386
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    • 2016
  • Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-${\kappa}B$-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ${\beta}$-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ${\beta}$-catenin protein but not mRNA. The inhibition of proteasome by MG132 and $GSK3{\beta}$ inhibition by SB216763 blocked silymarin-mediated downregulation of ${\beta}$-catenin. In addition, silymarin increased phosphorylation of ${\beta}$-catenin and a point mutation of S33Y attenuated silymarin-mediated ${\beta}$-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ${\beta}$-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.

A study on the Production and distribution planning using a genetic algorithm (유전 알고리즘을 이용한 생산 및 분배 계획)

  • 정성원;장양자;박진우
    • Proceedings of the Korean Operations and Management Science Society Conference
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    • 2001.10a
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    • pp.253-256
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    • 2001
  • Today's rapid development in the computer and network technology makes the environment which enables the companies to consider their decisions on the wide point of view and enables the software vendors to make the software packages to help these decisions. To make these software packages, many algorithms should be developed. The production and distribution planning problem belongs to those problems that industry manufacturers daily face in organizing their overall production plan. However, this combinatorial optimization problem can not be solved optimally in a reasonable time when large instances are considered. This legitimates the search for heuristic techniques. As one of these heuristic techniques, genetic algorithm has been considered in many researches. A standard genetic algorithm is a problem solving method that apply the rules of reproduction, gene crossover, and mutation to these pseudo-organisms so those organisms can Pass beneficial and survival-enhancing traits to new generation. This standard genetic algorithm should not be applied to this problem directly because when we represent the chromosome of this problem, there may exist high epitasis between genes. So in this paper, we proposed the hybrid genetic algorithm which turns out to better result than standard genetic algorithms

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The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

  • Lu, Xi;Hu, Xinde;Song, Lingzhen;An, Lei;Duan, Minghui;Chen, Shulin;Zhao, Shanting
    • BMB Reports
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    • v.48 no.2
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    • pp.97-102
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    • 2015
  • Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain ($Fyn^{R176A}$) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

Multiscale self-coordination of bidimensional empirical mode decomposition in image fusion

  • An, Feng-Ping;Zhou, Xian-Wei;Lin, Da-Chao
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.9 no.4
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    • pp.1441-1456
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    • 2015
  • The bidimensional empirical mode decomposition (BEMD) algorithm with high adaptability is more suitable to process multiple image fusion than traditional image fusion. However, the advantages of this algorithm are limited by the end effects problem, multiscale integration problem and number difference of intrinsic mode functions in multiple images decomposition. This study proposes the multiscale self-coordination BEMD algorithm to solve this problem. This algorithm outside extending the feather information with the support vector machine which has a high degree of generalization, then it also overcomes the BEMD end effects problem with conventional mirror extension methods of data processing,. The coordination of the extreme value point of the source image helps solve the problem of multiscale information fusion. Results show that the proposed method is better than the wavelet and NSCT method in retaining the characteristics of the source image information and the details of the mutation information inherited from the source image and in significantly improving the signal-to-noise ratio.

Efficient Isolation and Characterization of a Cellulase Hyperproducing Mutant Strain of Trichoderma reesei

  • Zou, Zongsheng;Zhao, Yunying;Zhang, Tingzhou;Xu, Jiaxing;He, Aiyong;Deng, Yu
    • Journal of Microbiology and Biotechnology
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    • v.28 no.9
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    • pp.1473-1481
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    • 2018
  • A cellulase hyperproducing mutant strain, JNDY-13, was obtained using the ARTP mutation system and with Trichoderma reesei RUT-C30 as the parent strain. Whole-genome sequencing of JNDY-13 confirmed that 105 of the 653 SNPs were point mutations, 336 mutations were deletions and 165 were insertions. Moreover, 99 mutations were insertions and duplications. Among all the mutations, the one that occurred in the galactokinase gene might be related to the production of cellulases in T. reesei JNDY-13. Moreover, the up-regulation of cellulase and hemicellulase genes in JNDY-13 might contribute to higher cellulases production. Under optimal conditions, the highest cellulase activity by batch fermentation reached 4.35 U/ml, and the highest activity of fed-batch fermentation achieved was 5.40 U/ml.

The Spectrum of Genetic Mutations in Breast Cancer

  • Sheikh, Asfandyar;Hussain, Syed Ather;Ghori, Quratulain;Naeem, Nida;Fazil, Abul;Giri, Smith;Sathian, Brijesh;Mainali, Prajeena;Al Tamimi, Dalal M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2177-2185
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    • 2015
  • Breast cancer is the most common malignancy in women around the world. About one in 12 women in the West develop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women are linked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associated with high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation can occur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer cases are not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1, NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, we discuss the entire spectrum of mutations which are associated with breast cancer.

p53 Mutations in Ewing's Sarcoma (유잉육종의 p53 돌연변이)

  • Bae, Dae-Kyung;Sun, Seung-Deok
    • The Journal of the Korean bone and joint tumor society
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    • v.6 no.4
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    • pp.143-151
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    • 2000
  • Purpose : The p53 tumor suppressor gene is one of the most frequently altered genes in human malignancies. We try to explore the implication of p53 alteration in Ewing's sarcoma. Materials and Methods : We analyzed 35 paraffin blocks to explore the deletion and sequence alterations of p53. Results : Quantitative PCR analysis showed that 2 tumors showed a homozygous deletion of the gene. Mutational analysis of exons 4 to 9 of p53 by PCR-SSCP revealed that 3 tumors carry sequence alterations in exons 5 or 8, and DNA sequencing analysis identified missense point mutations. Conclusion : Taken together, our data demonstrate that p53 is genetically altered in a small fraction of Ewing's sarcoma.

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Cyclic AMP response element binding (CREB) protein acts as a positive regulator of SOX3 gene expression in NT2/D1 cells

  • Kovacevic-Grujicic, Natasa;Mojsin, Marija;Popovic, Jelena;Petrovic, Isidora;Topalovic, Vladanka;Stevanovic, Milena
    • BMB Reports
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    • v.47 no.4
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    • pp.197-202
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    • 2014
  • SOX3 is one of the earliest neural markers in vertebrates, playing the role in specifying neuronal fate. In this study we have established first functional link between CREB and human SOX3 gene which both have important roles in the nervous system throughout development and in the adulthood. Here we demonstrate both in vitro and in vivo that CREB binds to CRE half-site located -195 to -191 within the human SOX3 promoter. Overexpression studies with CREB or its dominant-negative inhibitor A-CREB indicate that this transcription factor acts as a positive regulator of basal SOX3 gene expression in NT2/D1 cells. This is further confirmed by mutational analysis where mutation of CREB binding site results in reduction of SOX3 promoter activity. Our results point at CREB as a positive regulator of SOX3 gene transcription in NT2/D1 cells, while its contribution to RA induction of SOX3 promoter is not prominent.

Identification of Potential Carcinogenic Biomarker Following Exposure to N-ethyl-N-nitrosourea in Mice

  • Lim, Jung-Sun;Jeong, Sung-Young;Hwang, Ji-Yoon;Cho, Kyu-Hyuk;Cho, Jae-Woo;Han, Sang-Seop;Song, Chang-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.106-110
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    • 2005
  • N-ethyl-N-nitrosourea (ENU), which is a toxin and a carcinogen, as well as a mutagen, has a variety of effects on mice. ENU induces point mutation in male germ cell. Number of mutant animals are developed with ENU treatment. However, potentiality ot ENU as a carcinogen is not fully understood, even though, mutagenicity of ENU is broadly studied, In the present study, the gene expression profiling and histopathological investigation of ENU treated mouse's liver and brain were investigated. Also, the expression patterns of cancer related genes in ENU-treated mouse were analyzed.

Trajectory Optimization for Biped Robots Walking Up-and-Down Stairs based on Genetic Algorithms (유전자 알고리즘을 이용한 이족보행 로봇의 계단 보행)

  • Jeon Kweon-Soo;Kwon O-Hung;Park Jong-Hyeon
    • Journal of the Korean Society for Precision Engineering
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    • v.23 no.4 s.181
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    • pp.75-82
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    • 2006
  • In this paper, we propose an optimal trajectory for biped robots to move up-and-down stairs using a genetic algorithm and a computed-torque control for biped robots to be dynamically stable. First, a Real-Coded Genetic Algorithm (RCGA) which of operators are composed of reproduction, crossover and mutation is used to minimize the total energy. Constraints are divided into equalities and inequalities: Equality constraints consist of a position condition at the start and end of a step period and repeatability conditions related to each joint angle and angular velocity. Inequality constraints include collision avoidance conditions of a swing leg at the face and edge of a stair, knee joint conditions with respect to the avoidance of the kinematic singularity, and the zero moment point condition with respect to the stability into the going direction. In order to approximate a gait, each joint angle trajectory is defined as a 4-th order polynomial of which coefficients are chromosomes. The effectiveness of the proposed optimal trajectory is shown in computer simulations with a 6-dof biped robot that consists of seven links in the sagittal plane. The trajectory is more efficient than that generated by the modified GCIPM. And various trajectories generated by the proposed GA method are analyzed in a viewpoint of the consumption energy: walking on even ground, ascending stairs, and descending stairs.