• Title/Summary/Keyword: Signaling system

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Parkin Interacts with the PDZ Domain of Multi-PDZ Domain Protein MUPP1 (Parkin과 Multi-PDZ Domain Protein (MUPP1) 단백질 간의 PDZ 결합)

  • Jang, Won Hee;Jeong, Young Joo;Choi, Sun Hee;Lee, Won Hee;Kim, Mooseong;Kim, Sang-Jin;Urm, Sang-Hwa;Moon, Il Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.820-826
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    • 2014
  • The localization to specific subcellular sites and the regulation of cell surface receptors and channels are crucial for proper functioning. Postsynaptic density-95/Disks large/Zonula occludens-1 (PDZ)-domain is involved in recognition of and interaction between various proteins, by which the localization and the regulation are mediated. Multi-PDZ domain protein 1 (MUPP1) contains 13 PDZ domains. MUPP1 serves a scaffolding function for structure proteins and signaling proteins, but the mechanism how MUPP1 is stabilized and signalized has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and Parkin. Parkin is an E3 ubiquitin ligase. Loss-of-function mutations of Parkin gene are known to cause an autosomal recessive juvenile parkinsonism. Parkin bound to the $12^{th}$ PDZ domain, but not to other PDZ domains of MUPP1. The C-terminal end of Parkin has a type II PDZ-association motif, which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, Parkin co-localized with MUPP1. When co-expressed with ubiquitin in HEK-293T cells, MUPP1 has been strongly ubiquitinated by Parkin. These findings collectively suggest that MUPP1 is a novel substrate of Parkin and its function or stability could be modulated by Parkin-mediated ubiquitination.

Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

An Analysis into the Characteristics of the High-pass Transportation Data and Information Processing Measures on Urban Roads (도시부도로에서의 하이패스 교통자료 특성분석 및 정보가공방안)

  • Jung, Min-Chul;Kim, Young-Chan;Kim, Dong-Hyo
    • The Journal of The Korea Institute of Intelligent Transport Systems
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    • v.10 no.6
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    • pp.74-83
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    • 2011
  • The high-pass transportation information system directly collects section information by using probe cars and therefore can offer more reliable information to drivers. However, because the running condition and features of probe cars and statistical processing methods affect the reliability of the information and particularly because the section travel time is greatly influenced by whether there has been delay by signals on urban roads or not, there can be much deviation among the collected individual probe data. Accordingly, researches in multilateral directions are necessary in order to enhance the credibility of the section information. Yet, the precedent studies related to high-pass information provision have been conducted on the highway sections with the feature of continuous flow, which has a limit to be applied to the urban roads with the transportational feature of an interrupted flow. Therefore, this research aims at analyzing the features of high-pass transportation data on urban roads and finding a proper processing method. When the characteristics of the high-pass data on urban roads collected from RSE were analyzed by using a time-space diagram, the collected data was proved to have a certain pattern according to the arriving cars' waiting for signals with the period of the signaling cycle of the finish node. Moreover, the number of waiting for signals and the time of waiting caused the deviation in the collected data, and it was bigger in traffic jam. The analysis result showed that it was because the increased number of waiting for signals in traffic jam caused the deviation to be offset partially. The analysis result shows that it is appropriate to use the mean of this collected data of high-pass on urban roads as its representative value to reflect the transportational features by waiting for signals, and the standard of judgment of delay and congestion needs to be changed depending on the features of signals and roads. The results of this research are expected to be the foundation stone to improve the reliability of high-pass information on urban roads.

Relationship between Reactive Oxygen Species and Adenosine Monophosphate-activated Protein Kinase Signaling in Apoptosis Induction of Human Breast Adenocarcinoma MDA-MB-231 Cells by Ethanol Extract of Citrus unshiu Peel (진피 추출물에 의한 인간유방암 MDA-MB-231 세포의 apoptosis 유도에서 ROS 및 AMPK의 역할)

  • Kim, Min Yeong;HwangBo, Hyun;Ji, Seon Yeong;Hong, Su-Hyun;Choi, Sung Hyun;Kim, Sung Ok;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.29 no.4
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    • pp.410-420
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    • 2019
  • Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

A Study on the Prediction Model of Stock Price Index Trend based on GA-MSVM that Simultaneously Optimizes Feature and Instance Selection (입력변수 및 학습사례 선정을 동시에 최적화하는 GA-MSVM 기반 주가지수 추세 예측 모형에 관한 연구)

  • Lee, Jong-sik;Ahn, Hyunchul
    • Journal of Intelligence and Information Systems
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    • v.23 no.4
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    • pp.147-168
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    • 2017
  • There have been many studies on accurate stock market forecasting in academia for a long time, and now there are also various forecasting models using various techniques. Recently, many attempts have been made to predict the stock index using various machine learning methods including Deep Learning. Although the fundamental analysis and the technical analysis method are used for the analysis of the traditional stock investment transaction, the technical analysis method is more useful for the application of the short-term transaction prediction or statistical and mathematical techniques. Most of the studies that have been conducted using these technical indicators have studied the model of predicting stock prices by binary classification - rising or falling - of stock market fluctuations in the future market (usually next trading day). However, it is also true that this binary classification has many unfavorable aspects in predicting trends, identifying trading signals, or signaling portfolio rebalancing. In this study, we try to predict the stock index by expanding the stock index trend (upward trend, boxed, downward trend) to the multiple classification system in the existing binary index method. In order to solve this multi-classification problem, a technique such as Multinomial Logistic Regression Analysis (MLOGIT), Multiple Discriminant Analysis (MDA) or Artificial Neural Networks (ANN) we propose an optimization model using Genetic Algorithm as a wrapper for improving the performance of this model using Multi-classification Support Vector Machines (MSVM), which has proved to be superior in prediction performance. In particular, the proposed model named GA-MSVM is designed to maximize model performance by optimizing not only the kernel function parameters of MSVM, but also the optimal selection of input variables (feature selection) as well as instance selection. In order to verify the performance of the proposed model, we applied the proposed method to the real data. The results show that the proposed method is more effective than the conventional multivariate SVM, which has been known to show the best prediction performance up to now, as well as existing artificial intelligence / data mining techniques such as MDA, MLOGIT, CBR, and it is confirmed that the prediction performance is better than this. Especially, it has been confirmed that the 'instance selection' plays a very important role in predicting the stock index trend, and it is confirmed that the improvement effect of the model is more important than other factors. To verify the usefulness of GA-MSVM, we applied it to Korea's real KOSPI200 stock index trend forecast. Our research is primarily aimed at predicting trend segments to capture signal acquisition or short-term trend transition points. The experimental data set includes technical indicators such as the price and volatility index (2004 ~ 2017) and macroeconomic data (interest rate, exchange rate, S&P 500, etc.) of KOSPI200 stock index in Korea. Using a variety of statistical methods including one-way ANOVA and stepwise MDA, 15 indicators were selected as candidate independent variables. The dependent variable, trend classification, was classified into three states: 1 (upward trend), 0 (boxed), and -1 (downward trend). 70% of the total data for each class was used for training and the remaining 30% was used for verifying. To verify the performance of the proposed model, several comparative model experiments such as MDA, MLOGIT, CBR, ANN and MSVM were conducted. MSVM has adopted the One-Against-One (OAO) approach, which is known as the most accurate approach among the various MSVM approaches. Although there are some limitations, the final experimental results demonstrate that the proposed model, GA-MSVM, performs at a significantly higher level than all comparative models.

An Analysis on the Conditions for Successful Economic Sanctions on North Korea : Focusing on the Maritime Aspects of Economic Sanctions (대북경제제재의 효과성과 미래 발전 방향에 대한 고찰: 해상대북제재를 중심으로)

  • Kim, Sang-Hoon
    • Strategy21
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    • s.46
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    • pp.239-276
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    • 2020
  • The failure of early economic sanctions aimed at hurting the overall economies of targeted states called for a more sophisticated design of economic sanctions. This paved way for the advent of 'smart sanctions,' which target the supporters of the regime instead of the public mass. Despite controversies over the effectiveness of economic sanctions as a coercive tool to change the behavior of a targeted state, the transformation from 'comprehensive sanctions' to 'smart sanctions' is gaining the status of a legitimate method to impose punishment on states that do not conform to international norms, the nonproliferation of weapons of mass destruction in this particular context of the paper. The five permanent members of the United Nations Security Council proved that it can come to an accord on imposing economic sanctions over adopting resolutions on waging military war with targeted states. The North Korean nuclear issue has been the biggest security threat to countries in the region, even for China out of fear that further developments of nuclear weapons in North Korea might lead to a 'domino-effect,' leading to nuclear proliferation in the Northeast Asia region. Economic sanctions had been adopted by the UNSC as early as 2006 after the first North Korean nuclear test and has continually strengthened sanctions measures at each stage of North Korean weapons development. While dubious of the effectiveness of early sanctions on North Korea, recent sanctions that limit North Korea's exports of coal and imports of oil seem to have an impact on the regime, inducing Kim Jong-un to commit to peaceful talks since 2018. The purpose of this paper is to add a variable to the factors determining the success of economic sanctions on North Korea: preventing North Korea's evasion efforts by conducting illegal transshipments at sea. I first analyze the cause of recent success in the economic sanctions that led Kim Jong-un to engage in talks and add the maritime element to the argument. There are three conditions for the success of the sanctions regime, and they are: (1) smart sanctions, targeting commodities and support groups (elites) vital to regime survival., (2) China's faithful participation in the sanctions regime, and finally, (3) preventing North Korea's maritime evasion efforts.

Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK (담배 연기에 의한 Muc5ac 유전자 발현에 관여하는 세포 내 신호 전달 경로로서의 ERK1/2와 p38 MAPK)

  • Kim, Yong Hyun;Yoon, Hyoung Kyu;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup;Cho, Kyung Sook
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.6
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    • pp.590-599
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    • 2005
  • Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.