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Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.5917-5935
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    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

Assessment of New Algicide Thiazolidinedione (TD49) for the Control of Marine Red Tide Organisms (해양적조생물제어를 위한 살조물질 Thiazolidinedione 유도체(TD49) 평가)

  • Baek, Seung-Ho;Jang, Min-Chul;Joo, Hae-Mi;Son, Moon-Ho;Cho, Hoon;Kim, Young-Ok
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.17 no.1
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    • pp.9-15
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    • 2012
  • Worldwide development of harmful algal blooms causes serious problem for public health and fisheries industries. To evaluate the algicidal impact on the harmful algae bloom species in aquatic ecosystems of coast, a new algicide thiazolidinedione derivative (TD49) were tentatively examined in the growth stages (i.e., lag, logarithmic and stationary phase) of rapidophyceae $Heterosigma$ $akashiwo$, $Chattonella$ $marina$ and $Chattonella$ sp..Three strains could easily destroy in the lag phase due to relatively weak cell walls than those of the logarithmic and stationary phase. It is thought that inoculation of TD49 substances into initial or developmental natural blooms with a threshold concentration ($2{\mu}M$) can maximize the algicidal activity. Also, bio-chemical assays revealed that the algicidal substances from all culture strains were likely to be extracellular substances because those cells have easily destroyed in cell walls. On the other hand, natural zooplankton communities were influenced within the exposure experiments of $2{\mu}M$, which is showed the maximum algcidal activity of tested organisms. These results indicate that although the TD49 substance is potential agents for the control of $H.$ $akashiwo$, $C.$ $marina$ and $Chattonella$ sp. in the enclosed eutrophic bay and coastal water, more detailed research of acute toxicity effect on high trophic organism in marine ecosystems need to be conducted.

Gluconacetobacter persimmonis sp. nov., Isolated from Korean Traditional Persimmon Vinegar

  • Yeo, Soo-Hwan;Lee, Oh-Seuk;Lee, In-Seon;Kim, Hyun-Soo;Yu, Tae-Shick;Jeong, Yong-Jin
    • Journal of Microbiology and Biotechnology
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    • v.14 no.2
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    • pp.276-283
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    • 2004
  • Screening was performed to isolate cellulose-producing microorganisms from the Korean traditional fermented persimmon vinegar. The resulting strain, KJ $145^{T}$, was then taxonomically investigated by phenotypic characterization, particularly chemotaxonomic, and by phylogenetic inference based on a 16S rDNA sequence analysis including other related taxa. Strain KJ $145^{T}$ was found to grow rapidly and form pale white colonies with smooth to rough surfaces on a GYC agar. Strain KJ $145^T$ also produced acetate from ethanol, and was tolerable to 10% ethanol in SM medium. In a static culture, a thick cellulose pellicle was produced, and in GYC broth, the strain grew at temperatures ranging from 28 to $40^\circ{C}$ with an optimum pH of 4.0. The genomic DNA G+C content of strain KJ $145^T$ was 61.9 mol%, and the predominant ubiquinone was Q 10 as the major quinone and Q9 as the minor quinone. The major cellular fatty acids were $C_{16:0}$ and the sum in feature 7 ($C_{18:1}$ w9c, w12t and/or w7c). A 16S rRNA-targeted oligonucleotide probe specific for strain KJ $145^T$was constructed, and the phylogenetic position of the new species was derived from a 16S rDNA-based tree. When comparing the 16S rDNA nucleotide sequences, strain KJ $145^T$ was found to be most closely related to G. hansenii LMG $1527^T$ (99.2%), although KJ $145^T$ was still distinct from G. hansenii LMG $l527^T$ and G. xylinus LMG $1515^T$ in certain phenotypic characteristics. Therefore, on the basis of 16S rDNA sequences and taxonomic characteristics, it is proposed that strain KJ $145^T$ should be placed in the genus Gluconacetobacter as a new species, Gluconacetobacter persimmonis sp. nov., under the type-strain KJ $145^T$ (=KCTC =$10175BP^T$=KCCM=$10354^T$).

A Cytotaxonamical study of Rubus (Rosaceae) in Korea (한국산 산딸기속(Rubus)의 세포분류학적 연구)

  • Yang, Ji Young;Pak, Jae-Hong
    • Korean Journal of Plant Taxonomy
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    • v.35 no.2
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    • pp.129-142
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    • 2005
  • Somatic chromosome numbers of 19 taxa of Korean Rubus was investigated. Subg. Anoplobatus (2 species), subg. Cylactis (1 species), subg. Idaeobatus (15 taxa) and subg. Malachobatus (1 species) are found in Korea. All taxa belonging to subg. Idaeobatus except for R. parvifolius which shows tetrapolid and hexaploid are diploid. The basic chromosome number of the genus was x=7. New chromosome numbers for 5 taxa were reported here: R. hongnoensis of Jeju-island endemic species, 2n=14; R. longisepalus, 2n=14; R. longisepalus var. tozawai, 2n=14; R. parvifolius, 2n=28; R. parvifolius var. taquetii, 2n=28. The rest 12 taxa except for R. coreanus Miq was well counted as 2n=14 and well consistent with previous reports from China and Japan. Our new chromosome level for R. parvifolius as 6x may indicate that speciation by polyploidization has occurred within Korean population. Unlikely to Japanese population (2n=42), Korean population of R. buergeri has same ploidy level with Taiwanese population as 2n=56.

In vitro Antimicrobial Activity of a New Isolate Streptomyces sp. BCNU 1030 (신규 분리균주 Streptomyces sp. BCNU 1030의 in vitro 항균활성)

  • Bang, Ji-Hun;Choi, Hye-Jung;Ahn, Cheol-Soo;Kim, Dong-Wan;Jeong, Yong-Kee;Joo, Woo-Hong
    • Journal of Life Science
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    • v.21 no.4
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    • pp.589-595
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    • 2011
  • This work focused on screening and characterizing antibiotic-producing actinomycetes to develop new antibiotics that can overcome the growing resistance of disease-causing microbes. One-hundred actinomycetes strains were isolated from soil samples from Chungcheongbuk-do, Korea using various kinds of actinomycetes isolation media, including a starch casein agar medium and potato dextrose agar (PDA). Among them, strain BCNU 1030 was determined to show strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Biochemical, physiological, and 16S rRNA sequence analyses indicated that strain BCNU 1030 belonged to the genus Streptomyces. Strain BCNU 1030 exhibited antibiotic activity against a wide range of bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of BCNU 1030 dichloromethane extract was determined to be $0.78\;{\mu}g/ml$ for MRSA CCARM 3090. Therefore, Streptomyces sp. BCNU 1030 has potential for anti-MRSA drug development.

Phylogenetic diversity and UV resistance analysis of radiation-resistant bacteria isolated from the water in Han River (한강물로부터 분리된 방사선 내성 세균들의 계통학적 다양성 및 UV 내성 분석)

  • Lee, Jae-Jin;Joo, Eun Sun;Lee, Do Hee;Jung, Hee-Young;Kim, Myung Kyum
    • Korean Journal of Microbiology
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    • v.52 no.1
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    • pp.65-73
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    • 2016
  • The aim of this study was to investigate the UV-resistance of radiation-resistant bacteria isolated from the water of Han River, South Korea. The water sample was irradiated with 3 kGy gamma radiation prior to isolation. Radiation-resistant bacterial strains were isolated by standard serial dilution method on R2A and 1/10 diluted R2A agar. The resulting purely isolated 60 cultures of bacteria were analysed for UV resistance and used in further studies. Based on the comparative analyses of 16S rRNA gene sequences, the bacterial isolates were divided into 3 phyla (4 genera): the phylum Deinococcus-Thermus (the genus Deinococcus) was 61.7%, Bacteroidetes (Hymenobacter and Spirosoma) was 23.4%, and Firmicutes (Exiguobacterium) was 15%. The results suggested that twenty-nine isolates are candidates new species belonging to Deinococcus, Hymenobacter, and Spirosoma, or other new genera. Nine bacterial strains were selected among the novel candidates and the UV-resistance analysis was conducted. All the candidate bacterial strains showed high UV resistance, similar to that of D. radiodurans R1.

A New Selective Medium for the Isolation and the Detection of Leuconostocs in Foodstuffs (식품중에 함유된 Leuconostocs 균주의 새로운 선택배지 개발)

  • Choi, Hak-Jong;Shin, Young-Jae;Yu, Ju-Hyun;Yoon, Sung-Sik
    • Korean Journal of Food Science and Technology
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    • v.28 no.2
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    • pp.279-284
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    • 1996
  • To develop a selective medium for the isolation and the detection of leuconostocs from the various samples including fermented vegetables, ten strains of leuconostocs and seven strains of lactobacilli were tested for their sensitivity to various antibiotics. The basal-medium containing 5 ${\mu}g/ml$ of novobiocin inhibited the growth of lactobacilli completely, but not that of leuconostocs. On the basis of this result, a new selective medium was developed and to be named NLS medium. This medium contains 1% Tryptone (Difco), 0.1% Yeast Extract (Difco), 2% sucrose, 0.1% Beef Extract (BBL), 0.5% sodium acetate, 0.2% ammonium sulfate, 0.01% magnesium sulfate, 0.2% dipotassium phosphate, 0.05% sorbic acid, 75 ppm sodium azide (Sigma), 0.1% (vol/vol) Tween 80, 30 ${\mu}g/ml$ of Vancomycin (Sigma), 5${\mu}g/ml$ of Novobiocin (Sigma), 0.5${\mu}g/ml$ of cysteine HCI, and 1.5% Agar (Difco). All of the eighty six isolates obtained from some foodstuffs were identified as members of the genus Leuconostoc. Comparative counts with the MRS, PES, LUSM, and NLS medium indicated that the recovery percent was lower than other selective media. Therefore, this result suggested that NLS medium was suitable for the isolation of leuconostocs, but not for counting or enumerating.

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Characterization of a Restriction Endonuclease AspJI from Alcaligenes sp. J-482 (Alcaligenes sp. J-482 로부터 분리한 제한효소 AspJI의 특성)

  • Lee, Jeong-Taek;;Lim, Jai-Yun
    • Korean Journal of Microbiology
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    • v.32 no.4
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    • pp.285-290
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    • 1994
  • About 500 bacterial and fungal strains from a wide variety of natural habitats were screened for a new type II restriction endonuclease. Among the 500 species, we selected one species that produced a new restriction endonuclease. This strain has an optimum temperature of $30^{circ}C$ for growth. Morphological, cultural, and physiological characteristics were examined for identification of the isolated strain J-482. This strain was found to belong to the genus Alcaligenes. The restriction endonuclease was named as AspJI and partially purified from Alcaligenes sp. J-482 by DEAE-Sephadex A-50 column chromatography and gel filtration. Most of other nucleases were removed by the purification steps. The AspJI has a substrate specificity to ${lambda}$ DNA, pBR322 and Adenovirus-2 DNA. For its maximal activity, the isolated enzyme requires $MgCl_2$, which should be at least 12.5 mM and it does not need any other cofactors. It is maximally active in the absence of NaCl and is completely inactivated at 100 mM NaCl. The pH and temperature optima for activity were pH 7.5 and $37^{circ}C$, respectively. The DNA fragments generated by digesting ${lambda}$ DNA, pBR322, and Adenovirus-2 DNA with AspJI were the same as that produced by AatII. This suggests that AspJI is an isoschizomer of AatII.

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Development of New Vector Systems as Genetic Tools Applicable to Mycobacteria (Mycobacteria에 적용 가능한 genetic tool로서의 새로운 vector system 개발)

  • Jeong, Ji-A;Lee, Ha-Na;Ko, In-Jeong;Oh, Jeong-Il
    • Journal of Life Science
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    • v.23 no.2
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    • pp.290-298
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    • 2013
  • The genus Mycobacterium includes crucial animal and human pathogens such as Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium bovis. Although it is important to understand the genetic basis for their virulence and persistence in host, genetic analysis in mycobacteria was hampered by a lack of sufficient genetic tools. Therefore, many functional vectors as molecular genetic tools have been designed for understanding mycobacterial biology, and the application of these tools to mycobacteria has accelerated the study of mechanisms involved in virulence and gene expression. To overcome the pre-existing problems in genetic manipulation of mycobacteria, this paper reports new vector systems as effective genetic tools in Mycobacterium smegmatis. Three vectors were developed; pKOTs is a suicide vector for mutagenesis containing a temperature-sensitive replication origin (TSRO) and the sacB gene encoding levansucrase as a counterselectable marker. pMV306lacZ is an integrative lacZ transcriptional fusion vector that can be inserted into chromosomal DNA by site-specific recombination. pTnMod-OKmTs is a minitransposon vector harboring the TSRO that can be used in random mutagenesis. It was demonstrated in this study that these vectors effectively worked in M. smegmatis. The vector systems reported here are expected to successfully applicable to future research of mycobacterial molecular genetics.

First Report of a Bracken Blight Disease Caused by Didymella sp. (Didymella sp.에 의한 고사리 신규 마름병 발생 보고)

  • Lee, Jung Eun;Kim, Ki Beom;Park, Ju Eun;Kim, Da-Woon;Shin, Yoo-Kyoung;Yun, Sung-Hwan;Chung, Young-Ryun
    • Research in Plant Disease
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    • v.25 no.3
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    • pp.143-148
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    • 2019
  • An outbreak of new disease with leaf and stem blight symptom occurred at bracken-growing fields in Namhae-gun, Gyeongsangnam-do, Korea during the last 4 years. This new disease caused significant yield losses on bracken production in this area. We have collected diseased leaves and stems showing the blight symptom in May, July, and October 2018 to investigate causal pathogens. A total of 92 fungal isolates were obtained from the diseased samples and their pathogenicity was tested on healthy bracken leaves. From the total isolates, 22 isolates were able to produce the leaf blight symptom similar to the original one found in the fields. To identify two fungal pathogens which showed higher virulence levels compared to other pathogenic isolates, we constructed phylogenetic trees using the nucleotide sequences of genes for ribosomal RNA, RNA polymerase beta subunit, beta tubulin, and internal transcribed region. Most phylogenetic trees constructed indicate that both isolates, which are identical to each other, reside in a clade of the genus Didymella and possibly similar to D. rumicicola or D. acetosellae. Nevertheless, the exact identification of these pathogens at the species level needs further investigations. This is the first report of a blight disease on bracken by Didymella sp.