• 제목/요약/키워드: IRF-3

검색결과 75건 처리시간 0.021초

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism

  • Lee, Jeong Yoon;Kim, Seong-Jun;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • 제29권12호
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    • pp.2014-2021
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.

위성 레이다용 QM급 주파수합성기 설계 및 제작 (Design and Implementation on Frequency Synthesizer Qualification Model Level for SAR payload)

  • 김동식;김현철;허전;김완식
    • 한국인터넷방송통신학회논문지
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    • 제20권3호
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    • pp.9-14
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    • 2020
  • 본 논문에서는 SAR 탑재체에 적용할 수 있는 X-band 주파수합성기 인증모델(QM)을 설계 및 제작하고, 우주환경모의 시험을 통해 그 성능을 검증하였다. 제작된 주파수합성기는 상하향변환에 필요한 13.XXGHz 의 저잡음 국부신호를 생성하는 역할을 수행하며, 10Hz에서 1MHz 까지 측정된 적분 위상잡음은 -37.91 dBc 이다. 측정된 위상잡음을 통해 SAR 성능지표인 IRF성능 영향분석을 수행하였으며, 0.2 ps 의 지터로 PSLR과 ISLR에 영향 없이 SAR 시스템에 적용 가능함을 확인하였다. 또한, 열분석, 구조분석을 수행하여 안정성을 확인하였으며, 열진공, 열주기, 진동, 충격 시험을 통해 우주환경 내성을 확인하였다. 제작된 QM 급 주파수합성기는 L-band, C-band, Ku-band 주파수를 출력하며, 6U모듈 2개로 설계를 하였다. 본 연구를 통해 국내 위성용 RF 모듈의 국산화 기술 확보와 SAR 위성용 주파수합성기 기술 개발에 활용이 가능하다.

Apoptosis of Human Islet Cells by Cytokines

  • Kim, Sun-Shin;Kim, Kyoung-Ah;Suk, Kyoung-Ho;Kim, Yun-Hee;Oh, Seung-Hoon;Lee, Moon-Kyu;Kim, Kwang-Won;Lee, Myung-Shik
    • IMMUNE NETWORK
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    • 제12권3호
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    • pp.113-117
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    • 2012
  • FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

하이브리드 슈퍼커패시터 DC-DC 컨버터를 이용한 LED 비상 유도등 동작 디밍 제어 (Dimming Control of the LED Luminaire Emergency Exit Sign Operation using a Hybrid Super Capacitor of DC-DC Convertor)

  • 황락훈;김진선;나용주
    • 한국항행학회논문지
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    • 제21권3호
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    • pp.220-229
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    • 2017
  • 본 연구는 다양한 DC 전원을 활용할 수 있는 승압형 DC-DC 컨버터로 설계사양을 통한 인덕터 L과 커패시터 C의 값을 산출하여 PSPICE를 통한 최적의 값을 추정하였다. 승압형 DC-DC 컨버터는 스위치 소자로 IRF840을 사용하였으며 역회복 시간(reverse recovery time)이 뛰어난 쇼트키 다이오드(schottky rectifiers)인 D10SC6M을 사용하여 정전류 제어 (constant current controller)가 가능하도록 구성하였으며 열저항을 고려한 파워 LED 모듈 (power LED module)을 제작하여 구동하였다. 컨버터의 스위칭 주파수는 50 kHz로 최초 듀티비는 10 %에서 출력전압의 검출 값에 따라 점차적으로 증가시키도록 하였다. 그 결과로 승압형 파워 LED 구동기를 시뮬레이션 한 특성은 설계사양과 비교하여 5 %이하의 오차로 근사적으로 나타났고, 입력전압 15 V를 인가하여 안정된 24 V의 안정된 출력전압을 얻었으며 디밍제어 (dimming control)를 통한 밝기 조절 및 소비전류의 조정이 가능하였다.

국내 원전에서 $^{131}I$ 내부 흡입 에 따른 섭취량 산정과 내부피폭 방사선량 평가 경험 몇 개선방향에 대한 연구 (The Experience on Intake Estimation and Internal Dose Assessment by Inhalation of Iodine-131 at Korean Nuclear Power Plants)

  • 김희근;공태영
    • Journal of Radiation Protection and Research
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    • 제34권3호
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    • pp.129-136
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    • 2009
  • 국내 원전의 계획예방정비기간 중에 원자로계통의 개방과정에서 원자로건물내 공기 중으로 누설된 $^{131}I$의 체내 흡입으로 원전종사자의 내부피폭이 발생하였다. 이에 따라 원전에서 보유하고 있는 전신계측기(Whole body counter)를 이용하여 내부방사능을 측정하였다. 이들 측정값을 근거로 국제방사선방호위원회(ICRP)의 내부피폭 선량평가 지침을 적용하여 섭취량을 산정하고, 내부 피폭 방사선량을 평가하였다. $^{131}I$은 체내에서 섭취와 배설이 빠르고 갑상선으로 재축적이 일어나기 때문에 섭취 후 측정시점에 따라 섭취량이 차이를 보였다. 또한 ICRP 간행물에서 $^{131}I$의 전선에 대한 섭취잔류분율 자료를 제공하고 있지 않아 갑상선 섭취잔류분율 자료를 이용함으로써 섭취량 평가에서 오차를 나타내었다. 이에 따라 수계산과정으로 섭취량을 산정하고 예탁유효선량을 평가하였다. 한편 전선에 대한 섭취잔류분율을 새로 계산하였으며, 이 결과를 검증하였다. 또한 국제적으로 이용되고 있는 내부 피폭 선량평가 전신코드들 이용하여 섭취량 산정과 내부피폭 선량평가 평가결과에 대한 비교 계산이 병행하여 이루어졌다.

TNF-induced genes and Proteins

  • 이태호
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1993년도 제1회 추계심포지움 and 제2회 생리분자과학연구센터워크숍
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    • pp.17-20
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    • 1993
  • As a step toward a more complete understanding of the molecular actions of TNF, we prepared a cDNA library from TNF-treated human FS-4 fibroblasts and used differential hybridization to identify cDNA clones corresponding to mRNAs enriched in TNF-treated eells. In Quiescent FS-4 cells n induces an increase in the level of some mRNAs within 20 to 30 min. Some of these immediate-early response mRNAs are elevated only transiently for about 30 to 120 min, e. g., c-fos and c-myc (Lin and Vilcek,1987) or the transcription factor IRF-1 (Fujita et al.1989). Such immediate-early gene products may be important for the activation of other genes, but their transient induction suggests that they are not the actual effector molecules responsible for the phenotypic changes induced by TNF. We chose a 3-h incubation with W because we were seeking cDNAs corresponding to messages that are more stably elevated after TNF treatment. Indeed, the results shown in Figure 8 and 9 indicate that all of the mRNAs corresponding to the eight TSG cDNAs isolated remained significantly elevated after 16h of continuous treatment with TNF, and their kinetics of induction were clearly different from those of the immediate-early response mRNAs such as c-fos, c-myc or IRF-1. Nevertheless, only the induction of TSG-21 (collagenase) and TSG-27 (stromelysin) nNAs was completely inhibited by cycloheximide and the induction of TSG-37 (metallothionein-II) was reduced in the presence of this inhibitor of protein synthesis. Induction of the other five TSG mRNAs by TNF was completelyresistant to cycloheximide, suggest ins that no protein intermediate is needed for the upregulation of these mRNAs.

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Multi-channel analyzer based on a novel pulse fitting analysis method

  • Wang, Qingshan;Zhang, Xiongjie;Meng, Xiangting;Wang, Bao;Wang, Dongyang;Zhou, Pengfei;Wang, Renbo;Tang, Bin
    • Nuclear Engineering and Technology
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    • 제54권6호
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    • pp.2023-2030
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    • 2022
  • A novel pulse fitting analysis (PFA) method is presented for the acquisition of nuclear spectra. The charging process of the feedback capacitor in the resistive feedback charge-sensitive preamplifier is equivalent to the impulsive pulse, and its impulse response function (IRF) can be obtained by non-linear fitting of the falling edge of the nuclear pulse. The integral of the IRF excluding the baseline represents the energy deposition of the particles in the detector. In addition, since the non-linear fitting process in PFA method is difficult to achieve in the conventional architecture of spectroscopy system, a new multi-channel analyzer (MCA) based on Zynq SoC is proposed, which transmits all the data of nuclear pulses from the programmable logic (PL) to the processing system (PS) by high-speed AXI-Stream in order to implement PFA method with precision. The linearity of new MCA has been tested. The spectrum of 137Cs was obtained using LaBr3(Ce) scintillator detector, and was compared with commercial MCA by ORTEC. The results of tests indicate that the MCA based on PFA method has the same performance as the commercial MCA based on pulse height analysis (PHA) method and excellent linearity for γ-rays with different energies, which infers that PFA method is an effective and promising method for the acquisition of spectra. Furthermore, it provides a new solution for nuclear pulse processing algorithms involving regression and iterative processes.

Induction of IFN-β through TLR-3- and RIG-I-Mediated Signaling Pathways in Canine Respiratory Epithelial Cells Infected with H3N2 Canine Influenza Virus

  • Park, Woo-Jung;Han, Sang-Hoon;Kim, Dong-Hwi;Song, Young-Jo;Lee, Joong-Bok;Park, Seung-Yong;Song, Chang-Seon;Lee, Sang-Won;Choi, In-Soo
    • Journal of Microbiology and Biotechnology
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    • 제31권7호
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    • pp.942-948
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    • 2021
  • Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-β in a canine respiratory epithelial cell line (KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-β induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (p < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-β significantly (p < 0.001) decreased, and the protein expression of IFN-β also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I significantly reduced IRF3 (p < 0.001) and IFN-β (p < 0.001) mRNA levels. Moreover, the protein concentration of IFN-β was significantly (p < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIG-I alone. Also, the antiviral protein MX1 was only expressed in KU-CBE cells infected with CIV or treated with IFN-β or IFN-α. Thus, we speculate that IFN-β further induces MX1 expression, which might suppress CIV replication. Taken together, these data indicate that TLR3 and RIG-I synergistically induce IFN-β expression via the activation of IRF3, and the produced IFN-β further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.

Toll-like receptor 2, 3, 4의 신호전달체계 조절을 통한 curcumin의 항암${\cdot}$항염증 효과 (Anti-cancer and Anti-inflammatory Effects of Curcumin by the Modulation of Toll-like Receptor 2, 3 and 4)

  • 강순아;;윤형선
    • 한국식품과학회지
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    • 제39권2호
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    • pp.175-180
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    • 2007
  • TLRs는 병원균이 숙주의 몸 속에 들어 왔을 때, 병원균들이 가지고 있는 독특한 구조를 인식하여 선천성 면역반응과 뒤이어 후천성 면역반응을 유도하는 중요한 역할을 한다. 우리는 이번 실험을 통하여 curcumin이 선행연구에서 밝혀낸 TLR4 뿐만 아니라 TLR2와 TLR6 그리고 TLR3를 또한 분자학적인 타깃으로 할 수 있다는 것을 알아내었다. Curcumin이 MALP-2(TLR2,6 agonist)에 의해서 유도된 IRAK-1 degradation을 억제시켰다. 이러한 결과는 curcumin의 분자학적인 타깃이 IRAK-1위에 놓여 있으며, TLR2와 TLR6가 될 것이라는 가능성을 제시해 준다고 할 수 있다. 또한 curcumin은 viral 자극제인 poly[I:C](TLR3 agonist)에 의해서 유도된 IRF3나 $NF-{\kappa}B$ 활성화를 억제하였지만, TRIF에 의해서 유도된 IRF3 활성화는 억제시키지를 못하였다. 이러한 결과 또한 TLR3 자체가 curcumin의 분자학적인 타깃이라는 가능성을 제시해 준다고 할 수 있겠다. 이러한 결과를 종합해 볼때, curcumin의 분자학적인 타깃이 $IKK{\beta}$ 이외에 모든 TLRs가 될 수 있다는 가능성을 제시해 준다고 할 수 있겠다. 이러한 결과는 curcumin이 그람음성균 뿐만이 아니라 바이러스나 박테리아 등 여러 병원균들로부터 유도되는 염증반응이나 만성적인 질병들을 조절할 수 있다는 것을 보여주는 결과라 할 수 있겠다.

The Anti-Inflammatory Effects of Phytochemicals by the Modulation of Innate Immunity

  • Youn, Hyung-Sun
    • 대한의생명과학회지
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    • 제18권3호
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    • pp.181-192
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    • 2012
  • Toll-like receptors (TLRs) induce innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways; myeloid differential factor 88 (MyD88) and Toll/IL-1R domain-containing adaptor inducing IFN-${\beta}$ (TRIF) leading to the activation of NF-${\kappa}B$ and IRF3. Numerous studies demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit NF-${\kappa}B$ activation induced by pro-inflammatory stimuli including lipopolysaccharide and tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$). However, the direct molecular targets for such anti-inflammatory phytochemicals are not fully identified. In this paper, we will discuss about the molecular targets of phytochemicals in TLRs signaling pathways. These results present a novel anti-inflammatory mechanism of phytochemicals in TLRs signaling.