• 제목/요약/키워드: NS5B

검색결과 146건 처리시간 0.026초

Systematic Identification of Hepatocellular Proteins Interacting with NS5A of the Hepatitis C Virus

  • Ahn, Ji-Won;Chung, Kyung-Sook;Kim, Dong-Uk;Won, Mi-Sun;Kim, Li-La;Kim, Kyung-Shin;Nam, Mi-Young;Choi, Shin-Jung;Kim, Hyoung-Chin;Yoon, Mi-Chung;Chae, Suhn-Kee;Hoe, Kwang-Lae
    • BMB Reports
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    • 제37권6호
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    • pp.741-748
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    • 2004
  • The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

Interaction of Stomatin with Hepatitis C Virus RNA Polymerase Stabilizes the Viral RNA Replicase Complexes on Detergent-Resistant Membranes

  • Kim, Jung-Hee;Rhee, Jin-Kyu;Ahn, Dae-Gyun;Kim, Kwang Pyo;Oh, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • 제24권12호
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    • pp.1744-1754
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    • 2014
  • The hepatitis C virus (HCV) RNA genome is replicated by an RNA replicase complex (RC) consisting of cellular proteins and viral nonstructural (NS) proteins, including NS5B, an RNA-dependent RNA polymerase (RdRp) and key enzyme for viral RNA genome replication. The HCV RC is known to be associated with an intracellular membrane structure, but the cellular components of the RC and their roles in the formation of the HCV RC have not been well characterized. In this study, we took a proteomic approach to identify stomatin, a member of the integral proteins of lipid rafts, as a cellular protein interacting with HCV NS5B. Co-immunoprecipitation and co-localization studies confirmed the interaction between stomatin and NS5B. We demonstrated that the subcellular fraction containing viral NS proteins and stomatin displays RdRp activity. Membrane flotation assays with the HCV genome replication-competent subcellular fraction revealed that the HCV RdRp and stomatin are associated with the lipid raft-like domain of membranous structures. Stomatin silencing by RNA interference led to the release of NS5B from the detergent-resistant membrane, thereby inhibiting HCV replication in both HCV subgenomic replicon-harboring cells and HCV-infected cells. Our results identify stomatin as a cellular protein that plays a role in the formation of an enzymatically active HCV RC on a detergent-resistant membrane structure.

수도(水稻)에서 여러 질소효율의 개념(槪念)과 상호관계(相互關係) (Concepts concerning various nitrogen efficiencies and their interrelation in rice plant)

  • 박훈
    • 한국토양비료학회지
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    • 제8권2호
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    • pp.69-80
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    • 1975
  • 수도(水稻)의 수량(收量)과 여러가지 질소효율간, 질소효율 상호간(相互間), 효율과 흡수량간(吸收量間)의 관계(關係)를 설정(設定)하고 3개(個) 연간(年間)의 3요소시험(要素試驗) (30~50개지역(個地域)) 결과자료(結果資料)로 검토(檢討)하였다. 설정(設定)된 상호관계(相互關係)는 고도유의상관(高度有意相關)을 보이므로 실험결과(實驗結果)에 잘 일치(一致)하였다. 시비하(施肥下)에서 다수성(多收性)은 시료(肥料)의 이용율(利用率)(Eu)을 증가(增加)시켜 일차적(一次的)으로 질소흡수(窒素吸收)를 증가(增加)시키고 흡수시료질소吸收肥料窒素(Nf) 효율(Ef) 및 시비효율(Fe)을 증가(增加)시키며 이차적(二次的)으로 질소효율(E)을 증가(增加)시키는데 의존(依存)한다. 흡수(吸收)된 토양질소(土壤窒素)(Ns) 효율(Es)은 Ef보다 E에 대(對)한 기여도(寄與度)가 컸으며 모든 질소효율은 동반질소(同伴窒素)의 흡수량(吸收量) 및 상대(相對)되는 다른 질소효율에 역상관(逆相關)을 보였다. Es와 Ef는 1. 감법(減法) 2. Cs (Cs=Ns/Ns+Nf) 대(對) E plotting 법(法)과 3. 표식비료(標識肥料)를 사용(使用)한 E-Cs 및 Y-Ns Plotting 법(法)이 있으며 Plotting 법(法)은 E-Es Cs+B 식(式) 또는 Y=Es Ns+Ef Nf식(式)을 사용(使用)하며 B=Ef Cf로 Ef Nf와 함께 주어진 조건하(條件下에서 상수(常數)로 본다. Es는 Ef보다 대부분(大部分)의 경우 (80%) 크며 포장간(圃場間)에 Es보다 Ef에 차이가 크며 Ef는 특히 비료(肥料)의 형태(形態)에 의존(依存)한다. 설정검토(設定檢討)된 상호관계(相互關係)는 다음과 같다. 1. Y=$Es{\cdot}Ns+Ef{\cdot}Nf$ (Y는 수량(收量)) 2. E=$Es{\cdot}Cs+Ef{\cdot}Cf(Cf=Nf/Ns/Nf)$ 3. E=b-aN, E=E, Es 또는 Ef이고 N=N, Ns 또는 Nf이다. (E=Y/N, N=Ns+Nf), b는 주어진 조건(條件)에서의 E의 이론적(理論的) 최대치(最大値)이고 a는 Y=EN 곡선(曲線)의 N=0에서의 접선(接線)의 기울기이다. 4. Fe=$Ef{\cdot}Eu$, Se=$Es{\cdot}Eu$ (Se는 토양유효질소의 종조생산효율) 5. E=$Se{\cdot}Cs/Eu+Fe{\cdot}Cf/Eu$ 6. Y=$Es{\cdot}Eu{\cdot}Sf+Ef{\cdot}Eu{\cdot}Fn$ 또는 Y=$Es{\cdot}Eu{\cdot}Ea{\cdot}Sn+Ef{\cdot}Eu{\cdot}Fn(Sf=Ea{\cdot}Sn$, Ea는 비료질소(肥料窒素)와 대등(對等)한 토양유효질소(Sf)를 전토양질소(全土壤窒素)(Sn)로 나눈 유효화율).

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Evaluation of Inhibitory Effects of Thiobarbituric Acid Derivatives Targeting HCV NS5B Polymerase

  • Lee, Jong-Ho;Lee, Sang-Yoon;Park, Mi-Young;Ha, Hyun-Joon;Myung, Hee-Joon
    • Journal of Microbiology and Biotechnology
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    • 제20권3호
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    • pp.510-512
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    • 2010
  • A series of thiobarbituric acid derivatives were constructed and evaluated for inhibitory activity on hepatitis C virus NS5B polymerase. In biochemical assays using purified viral polymerase and RNA template, the $IC_{50}$ value was improved to 0.41 ${\mu}M$ from the original compound's 1.7 ${\mu}M$ value. In HCV sub genomic replicon assay, the $EC_{50}$ value was improved to 3.7 ${\mu}M$ from the original compound's 12.3 ${\mu}M$ value. $CC_{50}$ was higher than 77 ${\mu}M$ for all compounds tested, suggesting that they are useful candidates for anti-HCV therapy.

The Effects of Glucose on Blastulation and Cell Counts of Blastocysts in Mice

  • Park, Sung-Baek;Kim, Ji-Chul;Park, Kee-Sang;Lee, Taek-Hoo;Chun, Sang-Sik;Song, Hai-Bum
    • 한국발생생물학회:학술대회논문집
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    • 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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    • pp.118-118
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    • 2003
  • The aim of this study was to investigate the effect of glucose on embryonic development of mouse embryos. Two cell embryos were recovered from ICR female mice(3-4weeks) at 46~50 hrs after hCG 5 IU injection (mated just after hCG injection) and cultured in 50 $\mu m$ DMEM droplets supplemented with nothing (control: n=46), glucose 0.5mM (Group A; n=46) or glucose 3.15 mM(Group B; n=46) under mineral oil. All experimental media were supplemented with 20% human follicular fluid. Total blastocyst formation rates was lower (NS) in glucose groups (group A: 52.2% : B. 47.8%) than control group (60.9%). ZiB rates was the highest (P<0.05) in control (47.8%) than those in group A (21.7%) and B (28.3%). ZeB rates were the highest (NS) in group A (30.4%) than those in control (13.0%) and group B (19.6%). Blastocysts, cultured in group B (50.5), had the highest (NS) mean cell number compared with the others (control: 39.2 ; group A: (45.6). The ICM proportion (% ICM of total cells) in blastocysts cultured in group A (20.6%) was the highest (NS) than those of other tested groups (control: 15.2 ; group B: 13.9%). This study shows that a low dose of glucose added to culture medium increases the ICM proportion of blastocysts in mice.

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Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics

  • Bae, Sojung;Lee, Jeong Yoon;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • 제30권12호
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    • pp.1801-1809
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    • 2020
  • Chikungunya virus (CHIKV) was first identified in 1952 as a causative agent of outbreaks. CHIKV is transmitted by two mosquito species, Aedes aegypti and A. albopictus. Symptoms after CHIKV infection in human are typically fever and joint pain, but can also include headache, muscle pain, joint swelling, polyarthralgia, and rash. CHIKV is an enveloped single-stranded, positive-sense RNA virus with a diameter of approximately 70 nm. The pathogenesis of CHIKV infection and the mechanism by which the virus evades the innate immune system remain poorly understood. Moreover, little is known about the roles of CHIKV-encoded genes in the viral evasion of host immune responses, especially type I interferon (IFN) responses. Therefore, in the present study, we screened CHIKV-encoded genes for their regulatory effect on the activation of nuclear factor kappa B (NF-κB), a critical transcription factor for the optimal activation of IFN-β. Among others, non-structural protein 2 (nsP2) strongly inhibited melanoma differentiation-associated protein 5 (MDA5)-mediated induction of the NF-κB pathway in a dose-dependent manner. Elucidation of the detailed mechanisms of nsP2-mediated inhibition of the MDA5/RIG-I signaling pathway is anticipated to contribute to the development of virus-specific therapeutics against CHIKV infection.

Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia

  • Goh, Lynette;Phua, Kong Boo;Low, Yee;Chiang, Li Wei;Yong, Chen;Chiou, Fang Kuan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제24권4호
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    • pp.366-376
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    • 2021
  • Purpose: There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. Methods: Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999-2010) received PI-Abx for 5 days, Group B (2010-2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012-2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). Results: Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). Conclusion: The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.

고속 이동 멀티미디어 통신을 위한 터보 부호 적응 QAM 시스템의 성능 분석 (Performance Evaluation of Turbo coded Adaptive QAM Systems for High-speed Mobile Multimedia Communications)

  • 백흥현;정연호
    • 융합신호처리학회논문지
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    • 제5권3호
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    • pp.216-222
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    • 2004
  • 고속 멀티미디어 전송에 있어서 주파수 선택적 페이딩은 정보 전송율 및 BER 성능에 큰 영향을 미친다. 본 논문에서는 효과적인 고속 전송을 위해 터보 부호기를 적용한 적응 QAM(Adaptive Quadrature Amplitude Modulation) 시스템을 제안한다. 친사용자 환경 시뮬레이션 플랫폼 SPW를 이용하여 터보 적응 QAM 시스템을 개발하여 주파수 선택적 채널 환경에서 수율(throughput) 및 BER 성능분석을 수행하였다. 지연 확산이 700ns와 1400ns인 두 전력 지연 프로파일을 생성시켜 수율 및 성능을 조사하였는데 지연 확산 700ns인 프로파일에서 적응 변조 시스템이 고정 QAM 변조 시스템보다 평균 0.1231 bits의 수율 향상을 얻을 수 있었고 약 3dB의 BER 성능 개선을 얻을 수 있었다. 지연 확산 1400ns인 경우에서도 적응 변조 시스템이 고정 변조 시스템보다 더 나은 BER 성능 향상을 얻을 수 있었다.

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높은 격리도와 고속 스위칭의 PIN 다이오드 스위치 (A PIN Diode Switch with High Isolation and High Switching Speed)

  • 주인권;염인복;박종흥
    • 한국전자파학회논문지
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    • 제16권2호
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    • pp.167-173
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    • 2005
  • 직렬 PIN 다이오드 스위치의 격리도는 PIN 다이오드의 병렬 커패시턴스에 의해 제한을 받으며, 스위치 구동회로는 PIN 다이오드 스위치의 스위칭 속도를 제한한다. 이런 문제를 극복하기 위해, 병렬 공진 인턱턴스와 TTL 호환의 스위치 구동회로가 적용된 높은 격리도와 고속 스위칭의 PIN 다이오드 스위치를 제안하였다. 3 GHz PIN 다이오드 스위치의 측정 결과, 1 GHz의 주파수 대역폭, 1.5 dB 이내의 삽입 손실, 65 dB의 격리도, 15 dB 이상의 반사 손실 그리고 30 ns 이내의 스위칭 속도를 나타내었다. 특히, 병렬 공진 인덕턴스를 사용한 3 GHz스위치는 15 dB의 격리도 향상을 나타내었다.