• Title/Summary/Keyword: X Inactivation

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Functions of TET Proteins in Hematopoietic Transformation

  • Han, Jae-A;An, Jungeun;Ko, Myunggon
    • Molecules and Cells
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    • v.38 no.11
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    • pp.925-935
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    • 2015
  • DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven-translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5-hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti-cancer agents.

Inactivation of Mycobacteria by Radicals from Non-Thermal Plasma Jet

  • Lee, Chaebok;Subhadra, Bindu;Choi, Hei-Gwon;Suh, Hyun-Woo;Uhm, Han. S;Kim, Hwa-Jung
    • Journal of Microbiology and Biotechnology
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    • v.29 no.9
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    • pp.1401-1411
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    • 2019
  • Mycobacterial cell walls comprise thick and diverse lipids and glycolipids that act as a permeability barrier to antibiotics or other chemical agents. The use of OH radicals from a non-thermal plasma jet (NTPJ) for the inactivation of mycobacteria in aqueous solution was adopted as a novel approach. Addition of water vapor in a nitrogen plasma jet generated OH radicals, which converted to hydrogen peroxide ($H_2O_2$) that inactivated non-pathogenic Mycobacterium smegmatis and pathogenic Mycobacterium tuberculosis H37Rv. A stable plasma plume was obtained from a nitrogen plasma jet with 1.91 W of power, killing Escherichia coli and mycobacteria effectively, whereas addition of catalase decreased the effects of the former. Mycobacteria were more resistant than E. coli to NTPJ treatment. Plasma treatment enhanced intracellular ROS production and upregulation of genes related to ROS stress responses (thiolrelated oxidoreductases, such as SseA and DoxX, and ferric uptake regulator furA). Morphological changes of M. smegmatis and M. tuberculosis H37Rv were observed after 5 min treatment with $N_2+H_2O$ plasma, but not of pre-incubated sample with catalase. This finding indicates that the bactericidal efficacy of NTPJ is related to the toxicity of OH and $H_2O_2$ radicals in cells. Therefore, our study suggests that NTPJ treatment may effectively control pulmonary infections caused by M. tuberculosis and nontuberculous mycobacteria (NTM) such as M. avium or M. abscessus in water.

Loss of a Strain-Specific Protein by Bacterial Infection in Amoeba proteus (Amoeba proteus에 있어서 박테리아 감염에 의한 변이주 특이성 단백질의 손실)

  • Ahn, Tae-In;Park, Eui-Yul
    • The Korean Journal of Zoology
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    • v.28 no.1
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    • pp.21-30
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    • 1985
  • By two-dimensional gel electrophoresis loss of a cell-specific protein was detected in tD strain of Amoeba proteus that had been infected by symbiotic bacteria extracted from xD strain. In 50 days of experimental infection by induced phagocytosis the host amoeba lost the ability to synthesize the tD cell-specific protein even after removal of the infective bacteria and xD cell-specific protein by growing the amoebae at $27^\\circC$. By this time the host amoebae were obligately dependent on the bacteria. From these and other results (Lorch and Jeon, Science 221:549), it is clear that the incompatibility of the infected nuclei with the cytoplasm of the uninfected amoeba and the obligate dependence of the host on bacteria are due to the irreversible inactivation or the loss of the cell-specific gene by bacterial infection in this amoeba.

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Novel Purification Method of Kv 4.2 Potassium Channel from Rat Brain Membrane

  • Park, Sung-Soo
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.96-103
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    • 2012
  • Kv 4.2 ion channel protein has an ability to open at subthreshold membrane potentials and to recover quickly from inactivation. That is very important for neuronal signal transmission in vertebrate brain. In order to purify Kv 4.2 protein, the novel purification methods were experimented. The purification procedure utilized chromatography on DE-52 ion exchange column and affinity chromatography on a WGA-Sepharose 4B, and Kv 4.2 affinity column chromatography. It was found that 0.5% (wt./vol.) Triton X-100 detergent in lysis buffer worked well for Kv 4.2 protein solubilization from rat brain membrane. Protein quantitative determination was conducted by BCA method at 562 nm for each purification step to avoid determination interference of protein at 280 nm by detergent. The confirmation of Kv 4.2 existence and amount is performed using by SDS-PAGE/immunoblotting or 96-well dot blotting. The Kv 4.2 without interacting protein that contains carbohydrate, was purified from novel biochemical 3-steps purification method for further research.

Novel non-apoptotic cell death: ferroptosis (새로운 non-apoptotic 세포사멸: ferroptosis)

  • Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Yeungnam Medical Science
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    • v.34 no.2
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    • pp.174-181
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    • 2017
  • Ferroptosis is a newly recognized type of cell death that results from iron-dependent lipid peroxidation and is different from other types of cell death, such as apoptosis, necrosis, and autophagic cell death. This type of cell death is characterized by mitochondrial shrinkage with an increased mitochondrial membrane density and outer mitochondrial membrane rupture. Ferroptosis can be induced by a loss of activity of system $X_c{^-}$ and the inhibition of glutathione peroxidase 4, followed by the accumulation of lipid reactive oxygen species (ROS). In addition, inactivation of the mevalonate and transsulfuration pathways is involved in the induction of ferroptosis. Moreover, nicotinamide adenine dinucleotide phosphate oxidase and p53 promote ferroptosis by increasing ROS production, while heat shock protein beta-1 and nuclear factor erythroid 2-related factor 2 inhibit ferroptosis by reducing iron uptake. This article outlines the molecular mechanisms and signaling pathways of ferroptosis regulation, and explains the roles of ferroptosis in human disease.

Removal and Inactivation of Viruses during Manufacture of a High Purity Antihemophilic Factor VII Concentration from Human Plasma

  • Kim, In-Seop;Choi, Yong-Woon;Lee, Sung-Rae;Woo, Hang-Sang;Lee, Soung-Min
    • Journal of Microbiology and Biotechnology
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    • v.11 no.3
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    • pp.497-503
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    • 2001
  • The purpose of this study was to examine the efficacy and mechanism of the cryo-precipitation, solvent/detergent (S/D) treatment, monoclonal anti-FVIIIc antibody (mAb) column chromatography, Q-Sepharose column chromatography, and lyophilization involved in the manufacture of antithemophilic factor VII(GreenMono) from human plasma, in the removal and/or inactivation of blood-borne viruses. A variety of experimental model viruses for human pathogenic viruses, including the bovine viral diarrhoea virus (BVDV), bovine herpes virus (BHV), murine encephalomyocarditis virus (EMCV), and porcine parvovirus (PPV), were all selected for this study. BHV and EMCV were effectively partitioned from a factor VII during the cryo-precipitation with a log reduction factor of 2.83 and 3.24, respectively. S/D treatment using the organic solvent, tri(n-butyl) phosphate (TNBP), and the detergent, Triton X-100, was a robust and effective step in inactivating enveloped viruses. The titers of BHV and BVDV were reduced from the initial titer of 8.85 and $7.89{log_10} {TCID_50}$, respectively, reaching undetectable levels within 1 min of the S/D treatment. The mAb chromatography was the most effective step for removing nonenveloped viruses, EMCV and PPV, with the log reduction factors of 4.86 and 3.72, respectively. Q-Sepharose chromatography showed a significant efficacy for partitioning BHV, BVDV, EMCV, and PPV with the log reduction the log reduction factors of 2.32, 2.49, 2.60, and 1.33 respectively. Lyophilization was an effective step in inactivating g nonenveloped viruses rather than enveloped viruses, where the log reduction factors of BHV, BVDV, DMCV, and PPV were 1.41, 1.79, 4.76, and 2.05, respectively. The cumulative log reduction factors of BHV, BVDV, EMCV, and PPV were ${\geqq}$11.12, ${\geqq}$7.88, 15.46, and 7.10, respectively. These results indicate that the production process for GreenMono has a sufficient virus-reducing capacity to achieve a high margin of the virus safety.

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UNDERSTANDING OF EPIGENETICS AND DNA METHYLATION (후생유전학 (Epigenetics)과 DNA methylation의 이해)

  • Oh, Jung-Hwan;Kwon, Young-Dae;Yoon, Byung-Wook;Choi, Byung-Jun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.3
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    • pp.302-309
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    • 2008
  • Epigenetic is usually referring to heritable traits that do not involve changes to the underlying DNA sequence. DNA methylation is known to serve as cellular memory. and is one of the most important mechanism of epigenetic. DNA methylation is a covalent modification in which the target molecules for methylation in mammalian DNA are cytosine bases in CpG dinucleotides. The 5' position of cytosine is methylated in a reaction catalyzed by DNA methyltransferases; DNMTl, DNMT3a, and DNMT3b. There are two different regions in the context of DNA methylation: CpG poor regions and CpG islands. The intergenic and the intronic region is considered to be CpG poor, and CpG islands are discrete CpG-rich regions which are often found in promoter regions. Normally, CpG poor regions are usually methylated whereas CpG islands are generally hypomethylated. DNA methylation is involved in various biological processes such as tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. In general. cancer cells are characterized by global genomic hypomethylation and focal hypermethylation of CpG islands, which are generally unmethylated in normal cells. Gene silencing by CpG hypermethylation at the promotors of tumor suppressor genes is probably the most common mechanism of tumor suppressor inactivation in cancer.

Pericentric Inversion of the X Chromosome in a Male with Azoospermia and in the Family of a Pregnant Female Carrier (무정자증을 보이는 남성과 정상 생식력을 가진 여성의 가계에서 관찰된 X 염색체의 Pericentric Inversion)

  • Lee, Bom-Yi;Ryu, Hyun-Mee;Lee, Moon-Hee;Park, Ju-Yeon;Kim, Jin-Woo;Lee, Joong-Shik;Kim, Hye-Ok;Kim, Min-Hyung;Park, So-Yeon
    • Journal of Genetic Medicine
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    • v.5 no.2
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    • pp.139-144
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    • 2008
  • We report on two cases of pericentric inversion of X chromosome. The cases were found in a 40-year-old man with azoospermia and in a family of a 38-year-old pregnant woman. The first case with 46,Y,inv(X)(p22.1q27) had concentrations of LH, prolactin, estradiol, and testosterone that were within normal ranges; however, FSH levels were elevated. Testis biopsy revealed maturation arrest at the primary and secondary spermatocytes without spermatozoa. There were no microdeletions in the 6 loci of chromosome Y. For the second case, the cytogenetic study of thepregnant woman referring for advanced maternal age and a family history of inversion X chromosome was 46,X,inv(X)(p22.11q27.2). The karyotype of her fetus was 46,X,inv(X)(p22.1q27). Among other family members, the karyotypes of an older sister in pregnancy and her fetus were 46,X,inv(X)(p22.11q27.2), and 46,Y,?inv(X), respectively. The proband's father was 46,Y,inv(X)(p22.11q27.2). All carriers in the family discussed above were fertile and phenotypically normal. In addition, the ratio of inactivation of inv(X) by RBG-banding was discordant between the two sisters, with the older sister having only 4.1% of cells carrying inactivated inv(X) while the proband had a 69.5% incidence of late replicating inv(X). Therefore, we suggest that the cause of azoospermia in the first case might be related to inversion X chromosome with positional effect. Also, the family of the second case showing normal phenotype of the balanced inv(X) might be not affected any positional effect of genes.

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Combination of Light Emitting Diode at 375 nm and Photo-reactive TiO2 Layer Prepared by Electrostatic Spraying for Sterilization

  • Hwang, Kyu-Seog;Jeon, Young-Sun;Choi, Tae-Il;Hwangbo, Seung
    • Journal of Electrical Engineering and Technology
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    • v.8 no.5
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    • pp.1169-1174
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    • 2013
  • The objective of this work was to increase the efficiency of ultraviolet-light emitting diodes at 375 nm for sterilization. Since $TiO_2$ had antibacterial properties, which were attributed to the appearance of hydroxyl radicals and superoxide radical anions on the surface species under ultra violet radiation at about 387 nm, photo-reactive layers such as Ag-doped $TiO_2$ were coated on aluminum substrates by electrostatic spraying. Crystallinity and surface morphology of the coating layer were examined by X-ray diffraction ${\theta}-2{\theta}$ scan and field emission-scanning electron microscope, respectively. In an antibacterial test, we observed above 99% reduction of Escherichia coli populations on 3 or 5 mol% Ag-doped $TiO_2$ layers after irradiation for 2 hrs at 375 nm, while very low inactivation on bare aluminum substrates occurred after irradiation as the same condition.