• Title/Summary/Keyword: TRAF2

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Deletion Analysis of the Major NF-${\kappa}B$ Activation Domain in Latent Membrane Protein 1 of Epstein-Barr Virus

  • Cho, Shin;Lee, Won-Keun
    • Journal of Microbiology
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    • v.37 no.4
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    • pp.256-262
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    • 1999
  • Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-${\kappa}B$ activation. NF-${\kappa}B$ activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-${\kappa}B$ activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-${\kappa}B$ activation. In this study, we dissected the CTAR2 region, which is the major NF-${\kappa}B$ signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-${\kappa}B$ activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-${\kappa}B$ activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.

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Study On The Heavy Metal Pollution in Soils and Barks of Roadside Trees in Taejon (대전시의 가로수 수피 및 표사의 중금속 오염에 관한 연구)

  • O, In-Hye
    • The Journal of Natural Sciences
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    • v.5 no.2
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    • pp.19-24
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    • 1992
  • To find out the extent of air pollution in Taejon city, we investigated the concents of heavy metals in barks of trees in principal roadside, the outer block of a roadside and Pomunsan Park. Among the road-side trees in these areas, Platanus orientalis, Ginkgo biloba and Liriodendron tulipifera have been chosen. And we analyzed the relationship between the content of heavy metal of the barks and the traffic volume expressed by cars passing through for an hour. The range of contents of the lead in barks of the trees in the roadside and Pomunsan Park were respectively 2-1109 ppm and 5-11 ppm. Generally the contents of lead of barks of the trees in roadside was much higher than that in Pomunsan Park. And there has been positive correlation between the traf-fic volume and the content of lead in the barks. The more cars passing through for an hour, the higher the maximum in contents of lead in the barks of roadside trees. By the way the contents of cadmium in barks of the roadside trees was slightly higher than that in Pomunsan Park and was little variable.

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Marein Prevented LPS-Induced Osteoclastogenesis by Regulating the NF-κB Pathway In Vitro

  • Li, Yuling;Zhang, Jing;Yan, Caiping;Chen, Qian;Xiang, Chao;Zhang, Qingyan;Wang, Xingkuan;Jiang, Ke
    • Journal of Microbiology and Biotechnology
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    • v.32 no.2
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    • pp.141-148
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    • 2022
  • Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

Endoplasmic Reticulum Stress Response and Apoptosis via the CoCl2-Induced Hypoxia in Neuronal Cells (CoCl2 처리로 유도된 hypoxia상태에서 세포자살과 ER stress에 관련된 인자의 발현)

  • Kim, Seon-Hwan;Kwon, Hyon-Jo;Koh, Hyeon-Song;Song, Shi-Hun;Kwon, Ki-Sang;Kwon, O-Yu;Choi, Seung-Won
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1820-1828
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    • 2010
  • Cobalt(II) chloride, a chemical compound with the formula$CoCl_2$, has been widely used in the treatment of anemia, as a chemical agent for the induction of hypoxia in cell cultures, and is known to activate hypoxic signaling. However, excessive exposure to cobalt is associated with several clinical conditions, including asthma, pneumonia, and hematological abnormalities, and can lead to tissue and cellular toxicity. It is also known to induce apoptosis. One of the questions was that of whether $CoCl_2$ might induce apoptosis via endoplasmic reticulum (ER) stress in neurons. To address this question, first, the level of DNA fragmentation was measured for assay of apoptotic rates using $CoCl_2$ with neuron PC12 cells. After confirmation of apoptosis inductions, under the same conditions, the expression levels of ER stress associated factors [ER chaperones Bip, calnexin, ERp72, ERp29, PDI, and ER membrane kinases (IRE1, ATF6, PERK)] were examined by RT-PCR and Western blotting. These results indicated that apoptosis is induced through activation of ER membrane kinases via ER stress. In conclusion, during induction of apoptosis through $CoCl_2$-induced hypoxia in neuron PC12 cells, ER membrane kinase of IRE1 was dominantly up-expressed, and, consecutively, TRAF2, which has been suggested to be one of the links connecting apoptosis and ER stress, was strongly up-expressed.

TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells

  • Zahra Zandieh;Azam Govahi;Azin Aghamajidi;Ehsan Raoufi;Fatemehsadat Amjadi;Samaneh Aghajanpour;Masoomeh Golestan;Reza Aflatoonian
    • Clinical and Experimental Reproductive Medicine
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    • v.50 no.1
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    • pp.44-52
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    • 2023
  • Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions

  • Yang, Yanyan;Lee, Jongsung;Rhee, Man Hee;Yu, Tao;Baek, Kwang-Soo;Sung, Nak Yoon;Kim, Yong;Yoon, Keejung;Kim, Ji Hye;Kwak, Yi-Seong;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.61-68
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    • 2015
  • Background: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods: We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results: PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-${\alpha}$, and prostaglandin $E_2$], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-${\alpha}$, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion: These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).

교통량에 따른 배기가스량 산정에 관한 연구 -교차로를 중심으로-

  • 홍창의
    • Proceedings of the KOR-KST Conference
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    • 1996.02a
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    • pp.29-58
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    • 1996
  • 현재 서울은 교통사고문제, 교통혼잡문제와 자동차로부터 배출되는 유해가스에 의한 대기환경오염문제를 갖고 있다. 본 논문의 목적은 대기환경오염을 악화시키는 자동차의 주된 배출오염가스인 일산화탄소, 탄화수소 및 질소화합물량을 교차로 교통량을 중심으로 어떻게 계산하는가에 있다. 연구의 대상지역은 서울시의 송파구 교차로들과 도심지역의 링크들을 선택하였다. 그리고 교통량, 지체시간, 링크길이, 정지회수, 운행속도, 주행속도 등을 고려하여, 제작차 배출가스 허용기준, 총량기준, 불량차 기준, 속도기준 등에 의한 계수산정 및 TRAF-NETSIM에 의한 시뮬레이션을 통하여 일정 도로상의 제한된 범위내의 배출량 산출을 시도하였다. 본 연구의 결과에 의하면 첫째, 어느 방법이든 실제배출량의 정확한 값을 표현 할 수는 없는 것이고, 단지 상대적인 비교에 의하면 배출가스량의 수준을 추정 할 수 있었다. 또한, 시뮬레이션 배출율표를 우리 현실에 맞는 자료에 의해 수정할 수 있다면, 그 결과는 실제량에 보다 근접할 수 있을 것이다. 둘째, 서울도로의 현재 혼잡상태에서 속도의 저감에 배출량이 민감한 반응을 보이고 있다는 사실이다. 셋째, 교통량변화에 따른 배출량의 변화가 일산화탄소에서 가장 심하게 나타남을 알 수 있었고, 신호운영상의 옵셋값이 잘못 설정되면 탄화수소는 35%, 일산화탄소는 40%, 질소산화물은 75%까지 초과발생할 수 있으며, 유해배출가스량을 최소화시키는 측면에서의 신호최적화를 위해서는 현재의 Stop Penalty는 상향 조정되어야 함이 밝혀졌다. 앞으로는 자동차로 인한 대기환경오염 농도의 저감을 위해서는 도로별 자동차 유해가스 배출 총량규제 방안도 고려해 볼 가치가 있으며, 이를 위해 환경공학과 교통공학의 다학제적 공동연구가 지속적으로 필요하며 교통정책에 반영되어야 할 것이다.분석, 리용수 학모형대이십일세기상해항공운량진행예측, 제출발전상해항공운수적전 략목표급발전중점. 예측2020년 상해항공항총객운탄토량4300만인/년, 화운량달120만돈; 2050년객운량장달18150만인차/년, 화운량518만돈. 사, 발전상해민항기출경제정책, 제출위료$\ll$진흥상해, 개발포동, 복무전국, 면향세계$\gg$ 화도이십일세기중기국민경제달도중등발달국가수 평굉관전략목표적실현, 제료필수재지도사상상파교통운수진정방도전략 산업지위, 환응재관리체제상채취과단유효적개혁조시, 재기출경제정책 상급여대력부지. 오, 전략목표, 위파상해건설성위태평양서안최대적경제, 김융, 무역적중심, 요구상해항공항성위화동지구통향세계각지항선망출발참, 구성대외개방선면축심, 실현국제항선적함접화국내항반적전항, 형성다축심복사식항선망; 가강기장건설, 개피포동제이국제기장건설, 괄응포동개발경제발전적수요. 부화개시일은 각 5월 26일과 5월 22일이었다. 11. 6월 중순에 애벌레를 대상으로 처리한 Phenthoate EC가 96.38%의 방제가로 약효가 가장 우수하였고 3월중순 및 4월중순 월동후 암컷을 대상으로 처리한 Machine oil, Phenthoate EC 및 Trichlorfon WP는 비교적 약효가 낮았다.>$^{\circ}$E/$\leq$30$^{\circ}$NW 단열군이 연구지역 내에서 지하수 유동성이 가장 높은 단열군으로 추정된다. 이러한 사실은 3개 시추공을 대상으로 실시한 시추공 내 물리검층과 정압주입시험에서도 확인된다.. It was resulted from increase of weight of single cocoon. "Manta"2.5ppm produced 22.2kg of cocoon. It is equal to 9% increase i

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Basic Study to Establish Marine Activity Criteria Based on the Seakeeping Performance of Less Than 10-tons Fishing Vessels(I) (내항성능 기반 10톤 미만 어선의 해양활동 기준 마련 기초 연구(I))

  • Choi, Gwang-Young;Song, Chae-Uk;Park, Young-Soo;Park, Jun-Bum
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.28 no.6
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    • pp.965-972
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    • 2022
  • This is a basic study to establish marine activity criteria based on the seakeeping performance of less than 10-tons fishing vessels. These vessels account for approximately 95% of Korea's currently registered fishing vessels, and accidents and loss of life are also occurring during marine activities such as navigation, and fishing. Accordingly, the Ministry of Oceans and Fisheries has set a regulation of vessel traf ic control to restrict the operation of fishing vessels when the high seas watch takes effect, but it is applied equally without criteria according to the ship ton level and wave height; therefore, many differences may exist in ship fluctuations. Because the fluctuation of the ship owing to the wave height can be a factor in marine accidents by reducing the sense of boarding and performance of equipment, the seakeeping performance must be reviewed during waves to secure safe marine activities such as navigation and fishing. However, the review for the fishing vessel of established marine activity criteria based on the seakeeping performance is insufficient. Accordingly, the seakeeping performance was evaluated for a 10-ton class (G/T 9.77 tons) fishing vessel in Korea, and the level of marine activity according to the significant wave height and ship speed was interpreted by applying the operation and survival of the established seakeeping performance criteria. The analysis results indicated that the roll of the ship exceeded the operation criteria from 0.4m and the survival criteria from 2.2m. The pitch of the ship exceeded the operation criteria from 1.7m and did not exceed the survival criteria until 3.0m. However, the rolling exceeding the survival criteria from 2.2m may not be safe. Therefore, fishing vessels with less than 10-tons can leave before the high seas watch takes effect. However, they did not satisfy the criteria for evaluating the performance of the sea in relation to marine activities. Although this study was limitedly evaluated for 10-ton fishing vessels, it is expected to be of great help in preparing marine activity criteria.