• Title/Summary/Keyword: differential mechanism

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Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain

  • Itoh, Ken;Wakabayashi, Nobunao;Katoh, Yasutake;Ishii, Tetsuro;Igarashi, Kazuhiko;Engel, James Douglas;Yamamoto, Masayuki
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2002.05a
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    • pp.25-35
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    • 2002
  • Transcription factor Nrf2 is essential for the antioxidant responsive element (ARE)-mediated induction of phase II detoxifying and oxidative stress enzyme genes. Detailed analysis of differential Nrf2 activity displayed in transfected cell lines ultimately led to the identification of a new protein, which we named Keap1, that suppresses Nrf2 transcriptional activity by specific binding to its evolutionarily conserved amino-terminal regulatory domain. The closest homolog of Keap1 is a Drosophila actin-binding protein called Kelch, implying that Keap1 might be a Nrf2 cytoplasmic effector. We then showed that electrophilic agents antagonize Keap1 inhibition of Nrf2 activity in vivo, allowing Nrf2 to traverse from the cytoplasm to the nucleus and potentiate the ARE response. We postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel Nrf2 nuclear shuttling mechanism. The activation of Nrf2 leads in turn to the induction of phase II enzyme and antioxidative stress genes in response to electrophiles and reactive oxygen species.

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AUTO-GUIDING SYSTEM FOR CQUEAN (CAMERA FOR QUASARS IN EARLY UNIVERSE)

  • Kim, Eun-Bin;Park, Won-Kee;Jeong, Hyeon-Ju;Kim, Jin-Young;Kuehne, John;Kim, Dong-Han;Kim, Han-Geun;Odoms, Peter S.;Chang, Seung-Hyuk;Im, Myung-Shin;Pak, Soo-Jong
    • Journal of The Korean Astronomical Society
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    • v.44 no.4
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    • pp.115-123
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    • 2011
  • To perform imaging observations of optically red objects such as high redshift quasars and brown dwarfs, the Center for the Exploration of the Origin of the Universe (CEOU) recently developed an optical CCD camera, Camera for QUasars in EArly uNiverse (CQUEAN), which is sensitive at 0.7-1.1 ${\mu}m$. To enable observations with long exposures, we develop an auto-guiding system for CQUEAN. This system consists of an off-axis mirror, a baffle, a CCD camera, a motor and a differential decelerator. To increase the number of available guiding stars, we design a rotating mechanism for the off-axis guiding camera. The guiding field can be scanned along the 10 arcmin ring offset from the optical axis of the telescope. Combined with the auto-guiding software of the McDonald Observatory, we confirm that a stable image can be obtained with an exposure time as long as 1200 seconds.

Differential Expression of Ubiquitin-Specific Protease 16 Gene by Methylprednisolone in Neuronal Cells

  • Choi, Seung-Won;Kwon, Hyon-Jo;Koh, Hyeon-Song;Song, Shi-Hun;Kwon, O-Yu;Kim, Seon-Hwan
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.105-112
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    • 2010
  • Methylprednisolone (MPD) is a synthetic glucocorticoid drug used in treatment of many neurological diseases and neurotraumas, including spinal cord injuries. Little is known of the mechanism of MPD in neuronal cells, particularly the genetic expression aspect. DD-PCR was used in identification of genes expressed during MPD treatment of PC12 cells. We have isolated 3 predicted up- or down-regulated genes, which are differentially expressed in neurons by MPD. One of these genes, USP16 (ubiquitin specific protease 16), is the deubiquitinating enzyme that is up-regulated by MPD in neurons. In order to observe the effect of MPD on USP16 gene expression, PC12 cells were treated under several experimental conditions, including endoplasmic reticulum stress drugs. We have isolated the total RNAs in PC12 cells and detected USP16 and ER related genes by RT-PCR. Because its expression pattern is similar to expression of ER chaperons, USP16 gene expression is strongly associated with unfolded protein response. A meaningful negative effect on each tissue treated by methylprednisolone is not shown in vivo. USP16 gene expression is suppressed by LY294002 (phosphatidylinositol 3-kinase inhibitor), which suggests that USP16 gene expression is regulated by the phosphatidylinositol 3-kinase pathway.

Non-uniform Distribution of Magnetic Fluid in Multistage Magnetic Fluid Seals

  • Zhongzhong, Wang;Decai, Li;Jing, Zhou
    • Journal of Magnetics
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    • v.22 no.2
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    • pp.299-305
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    • 2017
  • Magnetic fluid, a new type of magnetic material, is a colloidal liquid constituted of nano-scale ferromagnetic particles suspended in carrier fluid. Magnetic fluid sealing is one of the most successful applications of magnetic fluid. As a new type of seal offering the advantages of no leakage, long life and high reliability, the magnetic fluid seal has been widely utilized under vacuum- and low-pressure-differential conditions. In practical applications, for improved pressure capacity, a multistage sealing structure is always used. However, in engineering applications, a uniform distribution of magnetic fluid under each tooth often cannot be achieved, which problem weakens the overall pressure capacity of the seals. In order to improve the pressure capacity of magnetic fluid seals and broaden their applications, the present study theoretically and experimentally analyzed the degree of non-uniform distribution of multistage magnetic fluid seals. A mathematical model reflecting the relationship between the pressure capacity and the distribution of magnetic fluid under a single tooth was constructed, and a formula showing the relationship between the volume of magnetic fluid and its contact width with the shaft was derived. Furthermore, the relationship of magnetic fluid volume to capacity was analyzed. Thereby, the causes of non-uniform distribution could be verified: injection of magnetic fluid; the assembly of magnetic fluid seals; the change of magnetic fluid silhouette under pressure loading; the magnetic fluid sealing mechanism of pressure transmission, and seal failure. In consideration of these causes, methods to improve the pressure capacity of magnetic fluid seals was devised (and is herein proposed).

Differential Induction of Septic Shock by Lipopolysacchrides from E. coli and S. abortus (S. abortus 유래 LPS와 E. coli 유래 LPS에 의한 패혈증성 쇽 유도 작용 비교)

  • Cho, Jae-Youl;Yoo, Eun-Sook
    • YAKHAK HOEJI
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    • v.51 no.1
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    • pp.44-50
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    • 2007
  • Acute septic shock is one of inflammatory diseases mediated by pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. In this study, we examined the pathological difference and mechanism of lipopolysaccharides isolated from E. coli (E-LPS) or S. abortus (S-LPS) on inducing acute septic shock in ICR mouse. All mice were died by intraperitoneal treatment of S-LPS with 0.75 mg/kg, whereas E-LPS treated with even 3 mg/kg only showed 30% of mice lethal, indicating that S-LPS may be more feasible in triggering a strong septic shock condition. The secretion pattern of TNF-${\alpha}$, a critical pro-inflammatory cytokine in septic shock condition, was also distinct between E-LPS- and S-LPS-treated groups. Thus, S-LPS strikingly increased serum level of TNF-${\alpha}$ (6 ng/ml) at 1 h, while E-LPS just displayed at 2 ng/ml level. However the interaction of S-LPS with LPS receptor toll like receptor (TLR)-4, was not stronger than that of E-LPS, according to experiments with macrophage cell line RAW264.7 cells. Thus, E-LPS rather than S-LPS strongly enhanced the production of TNF-${\alpha}$. Interestingly, S-LPS more strongly up-regulated splenocyte proliferation, compared to E-LPS group, whereas there was no difference between S- or E-LPS treated groups in proliferation of Balb/c- or C57BL/6-originated splenic lymphocytes. Therefore, our data suggest that S-LPS is a more active endotoxin and that the strong septic shock-inducing effect of S-LPS seems due to the enhancement of early TNF-${\alpha}$ production and S-LPS-sensitive lymphocyte proliferation.

Investigating the Effect of Value Characteristics of SNS Users on SNS Usage Motivation, Social Capital, and Usage Behavior (SNS 이용자의 가치체계의 특징이 SNS 이용동기, 사회적 자본, 이용행위 등에 미치는 영향 분석)

  • Cho, Hyong-Oh
    • Journal of Digital Contents Society
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    • v.19 no.2
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    • pp.351-362
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    • 2018
  • This study investigated how Schwartz' value system(1992) would interfere with SNS users' motivations and behavioral responses. The study result shows that values are characterized in terms of openness, mutual reciprocity, self enhancement, normative compliance, and security. Each of them exerted differential impact on SNS usage motives, social capital, ad response, and word-of-mouth, among others. The five values were used as an input for segmenting SNS users and clustering method produced four value segments; experience seeker, interdependent sympathizer, self enhancer, and norm-bound. Each value group not only influenced SNS perceptions and behavioral responses differently, but also showed a systematic relationship with SNS service types. The study findings demonstrate that Schwartz's value system provides a very useful theoretical basis for understanding the psychological mechanism underlying SNS usage.

Nucleophilic Substitution Reactions of Phenyl Y-Substituted-Phenyl Carbonates with Butane-2,3-dione Monoximate and 4-Chlorophenoxide: Origin of the α-Effect

  • Kim, Min-Young;Min, Se-Won;Um, Ik-Hwan
    • Bulletin of the Korean Chemical Society
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    • v.34 no.1
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    • pp.49-53
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    • 2013
  • Second-order rate constants have been measured spectrophotometrically for the reactions of phenyl Y-substituted-phenyl carbonates 7a-g with butane-2,3-dione monoximate ($Ox^-$) in 80 mol % $H_2O$/20 mol % DMSO at $25.0{\pm}0.1^{\circ}C$. The ${\alpha}$-nucleophile $Ox^-$ is 53-95 times more reactive than the corresponding normal-nucleophile 4-$ClPhO^-$ toward 7a-g, indicating that the ${\alpha}$-effect is operative. The magnitude of the ${\alpha}$-effect (e.g., the $k_{Ox^-}/k_{4-ClPhO^-}$ ratio) is independent of the electronic nature of the substituent Y. The cause of the ${\alpha}$-effect for the reactions of 7a-g has been suggested to be ground-state (GS) effect rather than transition-state (TS) stabilization through a six-membered cyclic TS, in which $Ox^-$ behaves a general acid/base catalyst. This idea is further supported by the result that $OH^-$ exhibits negative deviation from the linear Br${\o}$nsted-type plot composed of a series of aryloxides, while $Ox^-$ deviates positively from the linearity. Differential solvation of the GS of $Ox^-$ and 4-$ClPhO^-$ has been suggested to be responsible for the ${\alpha}$-effect exerted by $Ox^-$.

Apolipoprotein E in Synaptic Plasticity and Alzheimer's Disease: Potential Cellular and Molecular Mechanisms

  • Kim, Jaekwang;Yoon, Hyejin;Basak, Jacob;Kim, Jungsu
    • Molecules and Cells
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    • v.37 no.11
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    • pp.767-776
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    • 2014
  • Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

Evaluation of Lateral Earth Pressure on Buried Pipes in Soft Ground Undergoing Lateral Movement (측방유동지반속 지중매설관에 작용하는 토압식 산정)

  • 홍원표;한중근;배태수
    • Journal of the Korean Geotechnical Society
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    • v.18 no.5
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    • pp.55-65
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    • 2002
  • Model tests were performed to investigate the mechanism of lateral earth pressure on a buried pipe, which was installed in a plastic flowing soil mass undergoing lateral movement. On the basis of failure mode tests, the equation of lateral earth pressure to apply Maxwell's visco-elastic model was proposed to consider the soil deformation velocity. Through a series of model tests of differential soil deformation velocity, lateral earth pressure of theoretical equation was compared with experimental results. When lateral soil movement was raised, the lateral earth pressure acting on buried pipe increases linearly with the soil deformation velocity. It shows that the lateral earth pressure on buried pipe is largely affected by soil deformation velocity. When plastic soil movement was raised, lateral earth pressure predicted by theoretical equation showed good agreement with experimental results. Also, coefficient of viscosity by theoretical equation had a good agreement with direct shear test results.

Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on Gene Expression in Mouse Skin Carcinogenesis (마우스 피부암 발생과정에 있어서 2,3,7,8-Tetrachlorodibenzo-p­Dioxin (TCDD) 처리에 의한 유전자발현 변화 연구)

  • Ryeom Tai Kyung;Kim Ok Hee;Kong Mi Kyung;Park Mi Sun;Jee Seung Wan;Eom Mi Ok;Kang Ho Il
    • Environmental Mutagens and Carcinogens
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    • v.25 no.1
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    • pp.40-46
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    • 2005
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic compound and tumor promoter. In our experiment, we investigated the effects of TCDD on gene expression in mouse skin carcinogenesis. We used cDNA microarray to detect the differential gene expression in tumors induced in hairless mouse skin by MNNG plus TCDD protocol. We found that erb-2, c-ets2 and p27$^{kip1}$ were significantly up-regulated, but TNFR2, AKT-l, integrin $\beta$l, maspin, IGF-l, c-raf-l, Rb were significantly down-regulated, in tumor region, respectively. We also found that the expression of 53 genes involved in cen cycle, signal transduction, apoptosis, adhesion molecule, angiogenesis, and invasion, were changed two fold more, in tumor surrounding region. These data suggest that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis in mouse skin carcinogenesis.

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