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Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism in Cryptococcus neoformans

  • Choi, Yoojeong;Do, Eunsoo;Hu, Guanggan;Caza, Melissa;Horianopoulos, Linda C.;Kronstad, James W.;Jung, Won Hee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1142-1148
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    • 2020
  • Mitochondria play a vital role in iron uptake and metabolism in pathogenic fungi, and also influence virulence and drug tolerance. However, the regulation of iron transport within the mitochondria of Cryptococcus neoformans, a causative agent of fungal meningoencephalitis in immunocompromised individuals, remains largely uncharacterized. In this study, we identified and functionally characterized Mrs3/4, a homolog of the Saccharomyces cerevisiae mitochondrial iron transporter, in C. neoformans var. grubii. A strain expressing an Mrs3/4-GFP fusion protein was generated, and the mitochondrial localization of the fusion protein was confirmed. Moreover, a mutant lacking the MRS3/4 gene was constructed; this mutant displayed significantly reduced mitochondrial iron and cellular heme accumulation. In addition, impaired mitochondrial iron-sulfur cluster metabolism and altered expression of genes required for iron uptake at the plasma membrane were observed in the mrs3/4 mutant, suggesting that Mrs3/4 is involved in iron import and metabolism in the mitochondria of C. neoformans. Using a murine model of cryptococcosis, we demonstrated that an mrs3/4 mutant is defective in survival and virulence. Taken together, our study suggests that Mrs3/4 is responsible for iron import in mitochondria and reveals a link between mitochondrial iron metabolism and the virulence of C. neoformans.

PROTECTIVE EFFECT OF TAURINE ON INDOMETHACIN-INDUCED GASTRIC MUCOSAL INJURY

  • Miwon Son;Kim, Hee-Kee;Kim, Won-Bae;Junnick Yang;Kim, Byong-Kak
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.92-92
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    • 1995
  • It has been suggested that oxygen-derived free radicals have an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDS-induced gastric injury by its antioxidant properties, Protect ive effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats, Pretreatment with 0.25 g/kg of taurine for 3 days significantly reduced the gastric lesion formation and Inhibited the elevation of lipid peroxide level In gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of indomethacin. 5-20mM of taurine inhibited chemiluminescence of neutrophils activated by indomethacin and/or FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to confluent monolayer of human umbilical vein endothelial cells(HUVEC) after coincubation with aspirin or indomethacin. Also taurine prevented neutrophil adhesion induced by these drugs to HUVEC in dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDS-induced gastric mucosal Injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

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Effect of ${\alpha}$-Glycosidase Inhibitor in Multidrug Resistant Cell Lines

  • Paek, Nam-Soo;Namgung, Jun;Lee, Jung-Joon;Choi, Yong-Jin;Kim, Tae-Han;Kim, Kee-Won
    • BMB Reports
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    • v.31 no.3
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    • pp.269-273
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    • 1998
  • The objective of this study was to evaluate the reversal of multi drug resistance of human cell lines by specific inhibitors of ${\alpha}-glycosidase$ and mannosidases that had been reported to be involved in N-linked oligosaccharide processing of glycoproteins. N-methyldeoxynojirimycin, I-deoxynojirimycin, and castanospermine, which were known to be potent inhibitors of both ${\alpha}-glycosidase$ I and II, showed no activity against the multidrug resistant phenotype of the cell lines of SNU1DOX, KB-V1, and MCF-7/ADR. In contrast, I-deoxymannojirimycin, an inhibitor of mannosidase I, resulted in a slight reversal for the vinblastine resistance of the KB-V1 cell line, but did not show any activity toward the other cell lines. Parallel experiments with tunicamycin, an inhibitor of N-linked glycosylation, also resulted in no significant changes in multidrug resistant (MDR) phenotype of the cell lines tested in this work. These observations suggest that the unglycosylation of P-glycoprotein associated with the inhibitor treatments might not be correlated with the reversal of multidrug resistance of the cell lines tested in this study.

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Automated Protein-Expression Profiling System using Crude Protein Direct Blotting Method

  • Kobayashi, Hironori;Torikoshi, Yasuhiro;Kawasaki, Yuko;Ishihara, Hideki;Mizumoto, Hiroshi
    • 제어로봇시스템학회:학술대회논문집
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    • 2003.10a
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    • pp.2356-2361
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    • 2003
  • Proteome research in the medical field is expected to accelerate the understanding of disease mechanism, and to create new diagnostic concept. For protein profiling, this paper proposes a new methodology named CPDIB (Crude Protein Direct Blotting). In the CPDIB procedure, crude protein sample is directly immobilized on a membrane and the expression of protein molecules in the sample are analyzed quantitatively by using a special device called ImmobiChip, where the membrane is used as a field of the immune reaction. The over-all structure of the ImmobiChip is based on the conventional Slot blot device. Mechanical improvement in the air-tightness of the case holding the membrane realizes the direct blotting and results in high performance of stability in the immune reaction. In the measurement of multiple proteins, a dispensing robot is used for increasing the efficiency of handling of liquid. Cooperation of the dispensing robot with the ImmobiChip for immobilizing proteins realizes automated and stable performance of the CPDIB procedure. This paper shows the evaluation of the air-tightness of the ImmobiChip, the ability of analyzing proteins using the CPDIB procedure and the performance of the automated equipment.

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An Experimental Study for Manufacture of High Quality Recycled Aggregate by Heating (가열방법을 이용한 고품질 순환골재 제조를 위한 실험적 연구)

  • Yoo, Sung-Won;Min, Gyeong-Oan;Her, Yoon;Ha, Heon-Jae;Moon, Jae-Heum
    • Journal of the Korean Society of Safety
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    • v.26 no.5
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    • pp.65-72
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    • 2011
  • The use of waste concrete can resolve the environmental pollution and shortage of natural aggregate. However, recycled aggregate includes substantial amount of cement paste. So, these aggregates are more porous, and less resistant to mechanical actions than natural aggregates. So, recently, the new manufacture processes of high quality recycled aggregates were suggested such as heating and solving to acid liquid. But the method of solving to acid liquid is not economical and produces additional environmental pollution. In this paper, for the purpose of manufacture of high quality recycled aggregates, the heating processes was added to the existing process of recycled aggregates. To find the optimum process, the experiment was performed by using the method of statistical experiment design, and the heating temperatures(4 levels : 300, 450, 600 and $750^{\circ}C$) and heating times(4 levels : 5, 20, 40, 60 minute) were main experimental variables. By the test results, the optimum manufacturing condition of coarse recycled aggregate was $600^{\circ}C$ and 40 minute, and for the fine recycled aggregate, a little heating made a satisfaction to the KS standard quality code.

Effect of DW282 on the Induction of Methemoglobinemia, Hypoglycemia or WBC Count and Hematological Changes

  • Moon, Eun-Yi;Hwang, Hyun-Sook;Choi, Chung-Ha;Jung, Sang-Hun;Yoon, Sung-June
    • Archives of Pharmacal Research
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    • v.22 no.6
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    • pp.565-570
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    • 1999
  • DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induced methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it dose produce.

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Liquid Crystal Alignment on Patterned Micro-grooved Polyimide Surfaces

  • Chiou, D.R.;Chen, L.J.;Lee, C.D.;Liu, H.M.
    • 한국정보디스플레이학회:학술대회논문집
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    • 2005.07a
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    • pp.774-777
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    • 2005
  • In this work, a soft embossing method is proposed to fabricate microgrooves on polyimide surfaces. Apply these resulting patterned micro-grooved polyimide surfaces as the liquid crystal alignment layers. The director of liquid crystal molecules aligns perfectly along the direction of microgrooves.

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Production of 1-Deoxynojirimycin by Streptomyces sp. SID9135

  • Paek, Nam-Soo;Kang, Dae-Jung;Choi, Yong-Jin;Lee, Jung-Jun;Kim, Tae-Han;Kim, Kee-Won
    • Journal of Microbiology and Biotechnology
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    • v.7 no.4
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    • pp.262-266
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    • 1997
  • To increase the high production of 1-deoxynojirimycin (DNJ) from Streptomyces sp. SID9135, the effect of various carbon sources, nitrogen sources, cationic metal ions, the initial pH of the medium, and agitation speed were investigated. The most effective carbon and nitrogen sources were found to be lactose 2.5% (w/v) and soybean meal 2.0% (w/v), respectively. None of the cationic metal ions examined had any detectable stimulating effect on DNJ production except $Fe^{+2}$ ion. The initial optimum pH for DNJ production ranged from 6-8 and agitation speed was most effective at 400 rpm. In the jar fermentor experiments under optimal culture conditions, the accumulation of DNJ reached about $640{\mu}g$/ml after 5 days of cultivation and the level remained the same for a further two days.

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Fabrication and Characteristics of HARP Image Pickup Tube Using a-Se Photoconductive Film (a-Se 광도전막을 이용한 HARP 촬상관의 제작 및 특성)

  • Park, Wug-Dong;Kim, Ki-Wan;Kubota, Misao;Kato, Tsutomu;Suzuki, Shiro;Tanioka, Kenkichi
    • Journal of Sensor Science and Technology
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    • v.7 no.1
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    • pp.17-22
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    • 1998
  • A HARP (high-gain avalanche rushing amorphous photoconductor) image pickup tube using $4{\mu}m$ thick a-Se photoconductive film was fabricated and its characteristics were investigated. When the target voltage was increased more than 360 V, the signal current increases rapidly but the dark current of the tube was suppressed less than 3.2 nA up to the voltage of 490 V And the quantum efficiency of the target was about 4.3 at the electric field of $1.1{\times}10^{6}V/cm$ and the wavelength of 440 nm. Also the amplitude response of the HARP tube was 7.5% at 800 TV lines, and the decay lag was 3.4%.

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Laboratory Management Status of Vestibular Function Test in Korea (국내 전정기능검사실의 운영 현황)

  • Kim, Tae Su;Kim, Mi Joo;Kim, Byung-Kun;Kim, Hyun Ah;Bae, Dae Woong;Bae, Miran;Bae, Seong-Cheon;Lee, Eeksung;Jeon, Eun-Ju
    • Research in Vestibular Science
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    • v.17 no.4
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    • pp.160-166
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    • 2018
  • Objectives: This study was conducted to assess the current management status of the vestibular function test laboratories in Korea. Methods: Questionnaire about the management status of the vestibular function test laboratories was sent by email to the entire members of the Korean Balance Society. The contents of questionnaire included situation of employees who perform the tests, the types of vestibular function tests and equipment, frequency of the test and types of dizziness related questionnaires. Results: Forty-nine hospitals and clinics responded. All the 49 respondents answered that they have videonystagmography. Spontaneous nystagmus analysis by videonystagmogrphy was the most frequently tests for patients with dizziness. Questionnaires for dizziness were used by 27 respondents (55.1%) for initial evaluation of the dizziness patients. The Korean version of dizziness handicap inventory was the most frequently used dizziness related questionnaire. Conclusions: We analyzed the current management status of vestibular function test laboratories to comprehend the present condition of the vestibular function test. We think that these results will help to provide a standard for laboratory operations and prepare for the education, focusing on high-demand tests.