• Title/Summary/Keyword: gene behavior

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Histone Deacetylase in Carcinogenesis and Its Inhibitors as Anti-cancer Agents

  • Kim, Dong-Hoon;Kim, Min-Jung;Kwon, Ho-Jeong
    • BMB Reports
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    • v.36 no.1
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    • pp.110-119
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    • 2003
  • The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.

Defensive Behavior against Noxious Heat Stimuli Is Declined with Aging Due to Decreased Pain-Associated Gene Expression in Drosophila

  • Ghimire, Saurav;Kim, Man Su
    • Biomolecules & Therapeutics
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    • v.23 no.3
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    • pp.290-295
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    • 2015
  • Aging is defined as a collective process that alters organism's functional capacity and appearance over the course of life. Apart from an increase in susceptibility to many diseases, aging affects the cellular system that is responsible for decoding painful stimuli. Yet, aging-associated molecular mechanisms of pain perception remains elusive. Using Drosophila, we showed a decrease in temperature tolerance and a reduction in high temperature thermal avoidance with aging. Locomotor activity assay demonstrated that the age-dependent changes in heat nociception did not stem from the general decline in muscular activity. However, we identified pain-related gene expression alteration with aging. We anticipate that our findings would help opening a new window onto developing the optimal pain treatment for the elderly.

Normal Anxiety, Fear and Depression-related Behaviors in Mice Lacking ${\alpha}-Calcitonin$ Gene-Related Peptide

  • Lee, Jong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.6
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    • pp.299-304
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    • 2002
  • Calcitonin gene-related peptide (CGRP) expressing neurons are distributed widely throughout the central and peripheral nervous systems. Due to its distribution and pharmacological studies, CGRP has been implicated to be involved in anxiety, fear and depression. In this study, ${\alpha}CGRP-knockout$ mice were used to assess the consequences of removing this neuropeptide to the mice behaviors. ${\alpha}CGRP-knockout$ mice performed equally as well as wild type mice in the light-dark transition test and in the elevated plus maze test of anxiety. ${\alpha}CGRP-null$ mice behaved similarly as wild-type mice in the Porsolt swim test of depression. They also exhibited normal learning and memory in the fear conditioning tasks. It is concluded that ${\alpha}CGRP$ is not essential for mice to be able to perform these tests, despite the presence of ${\alpha}CGRP$ in the relevant regions of the brain.

Genetic Structure in Korean Populations of Hosta capitata (Liliaceae)

  • Chung, Myong-Gi
    • Journal of Plant Biology
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    • v.37 no.3
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    • pp.277-284
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    • 1994
  • I investigated levels of genetic diversity, population genetic structure, and gene flow in Hostacapitata, a herbaceous perennial native to South Korea and southwestern Japan. Starch gel electrophoresis was conducted on leaves collected from 310 plants in 19 Korean populations. Twenty-two of 25 putative loci examined were polymorphic in at least one populatin and the mean number of alleles per locus was 1.65. In addition, mean expected heterozygosity within populations (Hep=0.153) was higher than average values for species with similar life history traits. Significant differences in allele frequency were detected between populations at all loci (P<0.01), and slightly over 30% of the genetic variation was found among populatins (GST=0.308). Indirect estimates of the number of migrants per generation (Nm) (0.506, calculated from GST; 0.852, calculated from the mean frequency of ten private alleles) indicate that gene flow is restricted among the isolated Korean populations of H. capitata. Factors contributing to the high levels of genetic differentiation among populations of H. capitata include small and discrete populations, human disturbance, and low frequencies of pollinator foraging behavior.

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MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

  • Li, Ping;Xie, Xiao-Bing;Chen, Qian;Pang, Guo-Lian;Luo, Wan;Tu, Jian-Cheng;Zheng, Fang;Liu, Song-Mei;Han, Lu;Zhang, Jian-Kun;Luo, Xian-Yong;Zhou, Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6949-6954
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    • 2014
  • Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

Optimal Design for Marker-assisted Gene Pyramiding in Cross Population

  • Xu, L.Y.;Zhao, F.P.;Sheng, X.H.;Ren, H.X.;Zhang, L.;Wei, C.H.;Du, L.X.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.6
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    • pp.772-784
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    • 2012
  • Marker-assisted gene pyramiding aims to produce individuals with superior economic traits according to the optimal breeding scheme which involves selecting a series of favorite target alleles after cross of base populations and pyramiding them into a single genotype. Inspired by the science of evolutionary computation, we used the metaphor of hill-climbing to model the dynamic behavior of gene pyramiding. In consideration of the traditional cross program of animals along with the features of animal segregating populations, four types of cross programs and two types of selection strategies for gene pyramiding are performed from a practical perspective. Two population cross for pyramiding two genes (denoted II), three population cascading cross for pyramiding three genes(denoted III), four population symmetry (denoted IIII-S) and cascading cross for pyramiding four genes (denoted IIII-C), and various schemes (denoted cross program-A-E) are designed for each cross program given different levels of initial favorite allele frequencies, base population sizes and trait heritabilities. The process of gene pyramiding breeding for various schemes are simulated and compared based on the population hamming distance, average superior genotype frequencies and average phenotypic values. By simulation, the results show that the larger base population size and the higher the initial favorite allele frequency the higher the efficiency of gene pyramiding. Parents cross order is shown to be the most important factor in a cascading cross, but has no significant influence on the symmetric cross. The results also show that genotypic selection strategy is superior to phenotypic selection in accelerating gene pyramiding. Moreover, the method and corresponding software was used to compare different cross schemes and selection strategies.

Tracking of the $Km^r$ Gene in Conjugal Transfer by Using DNA Probe (DNA Probe에 의한 $Km^r$ 유전자의 전이 추적)

  • 이성기;김치경
    • Microbiology and Biotechnology Letters
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    • v.20 no.4
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    • pp.483-490
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    • 1992
  • In order to understand the transfer behavior of a particular gene in water environments, kanamycin resistance ($Km^r$) gene was tracked by Southern hybridization with DNA probe in its conjugal transfer. A $Km^r$ natural bacterial isolate and genetically modified microorganisms (GMMs) constructed from the isolate were used as donor for conjugal transfer of the $Km^r$ gene. The transfer frequencies of the $Km^r$ gene from GMM strains were generally 10 to 100 times higher than those from the natural isolate. The conjugants obtained from GMM strains in LB broth had more plasmids newly appeared, and particularly the conjugants in A Wand FW waters revealed more rearrangement in their plasmids as a function of conjugation time. When plasmids of the conjugants obtained in LB broth were Southern hybridized with DNA probe of the $Km^r$ gene, the $Km^r$ plasmids in the conjugants were detected at the same position of the plasmids in donor cells, in spite of the fact that the plasmids were highly rearranged in conjugant cells. But the $Km^r$ plasmids in the donor of DKI and DKC601, and DKC600 were not identified in the conjugants obtained after 50 h conjugation in AW and after 30 h in AW, respectively. The size of the $Km^r$ plasmids showing hybridization signal were a little changed in the conjugants obtained in A Wand FW waters. Therefore, the method of Southern hybridization with DNA probe was proved to be very specific and useful for tracking of particular genes in water environments.

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A Discrete Mathematical Model Applied to Genetic Regulation and Metabolic Networks

  • Asenjo, J.A.;Ramirez, P.;Rapaport, I.;Aracena, J.;Goles, E.;Andrews, B.A.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.3
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    • pp.496-510
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    • 2007
  • This paper describes the use of a discrete mathematical model to represent the basic mechanisms of regulation of the bacteria E. coli in batch fermentation. The specific phenomena studied were the changes in metabolism and genetic regulation when the bacteria use three different carbon substrates (glucose, glycerol, and acetate). The model correctly predicts the behavior of E. coli vis-a-vis substrate mixtures. In a mixture of glucose, glycerol, and acetate, it prefers glucose, then glycerol, and finally acetate. The model included 67 nodes; 28 were genes, 20 enzymes, and 19 regulators/biochemical compounds. The model represents both the genetic regulation and metabolic networks in an integrated form, which is how they function biologically. This is one of the first attempts to include both of these networks in one model. Previously, discrete mathematical models were used only to describe genetic regulation networks. The study of the network dynamics generated 8 $(2^3)$ fixed points, one for each nutrient configuration (substrate mixture) in the medium. The fixed points of the discrete model reflect the phenotypes described. Gene expression and the patterns of the metabolic fluxes generated are described accurately. The activation of the gene regulation network depends basically on the presence of glucose and glycerol. The model predicts the behavior when mixed carbon sources are utilized as well as when there is no carbon source present. Fictitious jokers (Joker1, Joker2, and Repressor SdhC) had to be created to control 12 genes whose regulation mechanism is unknown, since glycerol and glucose do not act directly on the genes. The approach presented in this paper is particularly useful to investigate potential unknown gene regulation mechanisms; such a novel approach can also be used to describe other gene regulation situations such as the comparison between non-recombinant and recombinant yeast strain, producing recombinant proteins, presently under investigation in our group.

Analysis of Non-segregated S-allele Strain by Single-Locus Hypothesis in Self-incompatible Brassica campestris (자가불화합성 Brassica campestris에 있어서 단일유전자좌가설에 의해 분리되지 않는 S-유전자 계통의 분석)

  • 노일섭
    • Journal of Plant Biology
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    • v.36 no.2
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    • pp.127-132
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    • 1993
  • Self-incompatibility in Brassica campestris is controlled by multi-allele system in a single genetic locus, the S locus, and it is elucidated that S-glycoproteins are S gene products. In this experiments, we examined the genetic mode(pollen tube behavior and segregation of S-glycoprotein), characteristic of S-glycoproteins and DNA constitution within nuclear genome on S gene family that unexplained by single locus model, and investigated the segregation pattern of S-glycoproteins in bred F1 generation. By diallel cross among the 15 plants within one family the existence of three types of homozygotes and three types of heterozygotes were observed, and segregation of S-allele could not explained by single locus model. From the results of IEF-immunoblot analysis for non-segregated individual plant, the segregation pattern of S specific bands was corresponded with results of diallel cross except with one case(SaSa genotype). The molecular weight of 6 different S-genotype varied in near by 50 kD, and each genotype expressed with 2 or 3 bands. Specific bands in SaSa, SbSb, ScSc has almost similar molecular weight between them. Southern analysis of genomic DNA probed with S-glycoprotein cDNA for 6 different genotypes revealed that there are clear difference in polymorphism, multiple bands of hybridization, when restriction enzymes of EcoR I were used. It could be assumed that there are several sequences related to the S-glycoprotein structural genes within their nuclear genome. Therefore, we suggested the possibilities that S-allele system could be controlled by multi-locus, that dominance-recessive interactions could be explained by modifier gene or supressor gene based on the results of abnormal segregation of S-glycoprotein in bred F1. The F2 analyses are progressing in now.

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The Dopamine $D_2$ Receptor Locus as a Modifying Gene in Korean Schizophrenia, Alcoholism and Drug Addiction (정신분열증, 알코올중독, 약물중독에서 도파민 $D_2$ 수용체 유전자의 조절유전자(modifying gene)로서의 역할 - 충동적.강박적.탐닉적 행동을 나타내는 정신질환들에서 도파민 $D_2$ 수용체의 조절유전자로서의 역할 -)

  • Jung, Hyun-Mo;Lee, Hong-Seock;Chang, Dong-Won;Lee, Min-Soo
    • Korean Journal of Biological Psychiatry
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    • v.4 no.2
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    • pp.225-233
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    • 1997
  • The authors attempted to examine the allelic association between the A1 allele of Dopamine $D_2$ receptor and schizophrenia, alcoholism, drug addiction in Koreans. Schizophrenic patients(n=31), alcoholism(n=65), drug addiction(n=18) and controls(n=52) were examined by case-control study for distribution of the TaqI polymorphism of the dopamine $D_2$ receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. In schizophrenics, the numbers of schizophrenics with A1A1, A1A2, A2A2 were 9(29.0%), 15(48.4%) and 7(22.6%) respectively and in alcoholics with A1A1, A1A2, A2A2 were 14(21.5%), 36(55.4%) and 15(23.1%) respectively and in drug addiction with A1A1, A1A2, A2A2 were 2(11.1%), 10(55.6%) and 6(33.3%) respectively and in controls with A1A1, A1A2, A2A2 were 4(7.6%), 24(46.2%) and 24(46.2%) respectively. The prevalence of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 77%, 76.9%, 67% and 53.8% respectively. And the frequency of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 0.53, 0.49 0.39 and 0.31 respectively. There was significant difference in the frequency of the A1 allele between schizophrenics, alcoholics and controls. We also classified our alcoholic population. For classification by severity, we used the median MAST score 30 in our samples. There was also significant difference in the frequency of the A1 allele between less severe group(0.42) and more severe group(0.57). This data suggest that the A1 allele is associated with schizophrenia and alcoholism in Koreans. Furthermore the prevalence of the A1 allele increassed in more severely affected alcoholics. The authors conclude that our data support an allelic association between the A1 allele at dopamine $D_2$ receptor and schizophrenia, alcoholism. These results suggest the A1 allele of the $DRD_2$ gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

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