• Title/Summary/Keyword: Activating function

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Development of Natural Killer Cells from Hematopoietic Stem Cells

  • Yoon, Suk Ran;Chung, Jin Woong;Choi, Inpyo
    • Molecules and Cells
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    • v.24 no.1
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    • pp.1-8
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    • 2007
  • Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

Alternatives for Activating Development Finance in the Regional Development Projects (지역개발사업을 위한 개발금융 활성화 방안)

  • 박원석
    • Journal of the Economic Geographical Society of Korea
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    • v.2 no.1_2
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    • pp.63-81
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    • 1999
  • The aims of this study are to analyze the current states and problems of development finance in the regional development projects, and to examine new sources and techniques of development finance for activating regional development projects. Analyzing the current states of development finance in regional development project, the problems such as the poorness of development function, the low accessibility to formal financial market, especially capital market, and the dominant use of corporate financing can be seen. In these context, four alternatives are proposed in order to activate development finance. First alternative is to use the funds which invest the equity of real estate, such as REITs. The second is to activate project financing. The third is to use asset backed securities. The forth is using mezzanine capitals as the means of protecting investors.

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Construction of Comprehensive Metabolic Network for Glycolysis with Regulation Mechanisms and Effectors

  • JIN, JONG-HWA;JUNG, UI-SUB;JAE, WOOK-NAM;IN, YONG-HO;LEE, SANG-YUP;LEE, DOHE-ON;LEE, JIN-WON
    • Journal of Microbiology and Biotechnology
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    • v.15 no.1
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    • pp.161-174
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    • 2005
  • Abstract Glycolysis has a main function to provide ATP and precursor metabolites for biomass production. Although glycolysis is one of the most important pathways in cellular metabolism, the details of its regulation mechanism and regulating chemicals are not well known yet. The regulation of the glycolytic pathway is very robust to allow for large fluxes at almost constant metabolite levels in spite of changing environmental conditions and many reaction effectors like inhibitors, activating compounds, cofactors, and related metal ions. These changing environmental conditions and metabolic reaction effectors were focused on to understand their roles in the metabolic networks. In this study, we have investigated for construction of the regulatory map of the glycolytic metabolic network and tried to collect all the effectors as much as possible which might affect the glycolysis metabolic pathway. Using the results of this study, it is expected that a complex metabolic situation can be more precisely analyzed and simulated by using available programs and appropriate kinetic data.

Characterization of Constitutively Activating Eel Follicle-Stimulating Hormone Receptor

  • Kim, Jeong-Soo;Byambaragchaa, Munkhzaya;Min, Kwan-Sik
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.4
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    • pp.267-271
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    • 2019
  • This study aimed to investigate the function of the constitutively activating mutation D540G on eel FSHR activity by in vitro functional studies. Site-directed mutagenesis was carried out to generate the D-to-G mutation at position 540 of the pcDNA3-eel FSHR construct. Vectors expressing either wild type or mutant receptor were transfected into Chinese hamster ovary (CHO-K1) cells. The functional characteristics of both the wild type and mutant receptors were analyzed by a cAMP assay. cAMP accumulation was highly increased in cells transfected with the D540G mutant receptor in a dose-dependent manner. Of note, basal cAMP levels were remarkably increased (~13.1-fold) with expression of this mutant when compared to wild type receptor. These findings suggest that the D540G mutation in the eel FSHR may contribute to ovulation during eel sex maturation as well as play a pivotal role in inducing FSHR activity.

Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

  • Byung Chul Jung;Hyun-Kyung Kim;Sung Hoon Kim;Yoon Suk Kim
    • BMB Reports
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    • v.56 no.3
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    • pp.166-171
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    • 2023
  • Monocytes are peripheral leukocytes that function in innate immunity. Excessive triglyceride (TG) accumulation causes monocyte death and thus can compromise innate immunity. However, the mechanisms by which TG mediates monocyte death remain unclear to date. Thus, this study aimed to elucidate the mechanisms by which TG induces monocyte death. Results showed that TG induced monocyte death by activating caspase-3/7 and promoting poly (ADP-ribose) polymerase (PARP) cleavage. In addition, TG induced DNA damage and activated the ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 and ATM-and Rad3-related (ATR)/checkpoint kinase 1 pathways, leading to the cell death. Furthermore, TG-induced DNA damage and monocyte death were mediated by caspase-2 and -8, and caspase-8 acted as an upstream molecule of caspase-2. Taken together, these results suggest that TG-induced monocyte death is mediated via the caspase-8/caspase-2/DNA damage/executioner caspase/PARP pathways.

Depletion of Cytoplasmic Tail of UL18 Enhances and Stabilizes the Surface Expression of UL18

  • Kim, Jung-Sik;Kim, Bon-Gi;Yoon, Il-Hee;Kim, Sang-Joon;Park, Chung-Gyu
    • IMMUNE NETWORK
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    • v.8 no.4
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    • pp.130-136
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    • 2008
  • Background: Human cytomegalovirus UL18, a MHC class I homologue, has been considered a natural killer (NK) cell decoy. It ligates LIR-1/ILT2 (CD85j), an NK inhibitory receptor, to prevent lysis of infected target cells. However, precise role of UL18 to NK cell cytotoxicity is yet elusive. Difficulty in clarifying the function of UL18 lies in complication in detecting UL18 mainly due to low level expression of UL18 on the surface and gradual loss of its expression. Methods: To overcome this hurdle, cDNA of cytoplasmic tail-less UL18 was constructed and expressed in swine endothelial cell (SEC). The expression level and its stability in the cell surface were monitored with FACS analysis. Results: Surface expression of UL18 is up-regulated by removing cytoplasmic tail portion from UL18F (a full sequence of UL18). SECs transfected with a cDNA of UL18CY (a cytoplasmic tail-less UL18) stably expressed UL18 molecule on the surface without gradual loss of its expression during 6 week continuous cultures. In the NK cytotoxicity assay, UL18 functions either inhibiting or activating NK cell cytotoxicity according to the source of NK cells. We found that there is individual susceptibility in determining whether the engagement of NK cell and UL18 results in overall inhibiting or activating NK cell cytotoxicity. Conclusion: In this study, we found that cytoplasmic tail is closely related to the regulatory function for controlling surface expression of UL18. Furthermore, by constructing stable cell line in which UL18 expression is up-regulated and stable, we provided a useful tool to clarify exact functions of UL18 on various immune cells having ILT2 receptor.

IQGAP1, a signaling scaffold protein, as a molecular target of a small molecule inhibitor to interfere with T cell receptor-mediated integrin activation

  • Li, Lin-Ying;Nguyen, Thi Minh Nguyet;Woo, Eui Jeon;Park, Jongtae;Hwang, Inkyu
    • Korean Journal of Agricultural Science
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    • v.47 no.2
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    • pp.361-373
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    • 2020
  • Integrins such as lymphocyte function-associated antigen -1 (LFA-1) have an essential role in T cell immunity. Integrin activation, namely, the transition from the inactive conformation to the active one, takes place when an intracellular signal is generated by specific receptors such as T cell receptors (TCRs) and chemokine receptors in T cells. In an effort to explore the molecular mechanisms underlying the TCR-mediated LFA-1 activation, we had previously established a high-throughput cell-based assay and screened a chemical library deposited in the National Institute of Health in the United States. As a result, several hits had been isolated including HIKS-1 (Benzo[b]thiophene-3-carboxylic acid, 2-[3-[(2-carboxyphenyl) thio]-2,5-dioxo-1-pyrrolinyl]-4,5,6,7-tetrahydro-,3-ethyl ester). In an attempt to reveal the mode of action of HIKS-1, in this study, we did drug affinity responsive target stability (DARTS) assay finding that HIKS-1 interacted with the IQ motif containing GTPase activating protein 1 (IQGAP1), a 189 kDa multidomain scaffold protein critically involved in various signaling mechanisms. Furthermore, the cellular thermal shift assay (CETSA) provided compelling evidence that HIKS-1 also interacted with IQGAP1 in vivo. Taken together, it can be concluded that HIKS-1 interferes with the TCR-mediated LFA-1 activation by interacting with IQGAP1 and thereby disrupting the signaling pathway for LFA-1 activation.

The Design of Extensible Transport Protocol (확장 가능한 전송 프로토콜의 설계)

  • Park, Kihyun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2014.05a
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    • pp.142-146
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    • 2014
  • The mobile computing has been a main mean of computing, because of recent development of smartphone and mobile communication network. The new service technologies, such as cloud computing, big data, SDN (Software Defined Network), and NFV (Network Function Virtualization), are appearing due to activating of the data center. These changes have brought various requirements for transport layer protocol. In addition, the transport protocol should have a extensible function to adapt additional technologies. This paper proposed that transport layer divide into three layer structure for extensible function, and designed the ETP(Extensible Transport Protocol) which is located in the bottom layer.

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Prediction of Parathyroid Hormone Signalling Potency Using SVMs

  • Yoo, Ahrim;Ko, Sunggeon;Lim, Sung-Kil;Lee, Weontae;Yang, Dae Ryook
    • Molecules and Cells
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    • v.27 no.5
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    • pp.547-556
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    • 2009
  • Parathyroid hormone is the most important endocrine regulator of calcium concentration. Its N-terminal fragment (1-34) has sufficient activity for biological function. Recently, site-directed mutagenesis studies demonstrated that substitutions at several positions within shorter analogues (1-14) can enhance the bioactivity to greater than that of PTH (1-34). However, designing the optimal sequence combination is not simple due to complex combinatorial problems. In this study, support vector machines were introduced to predict the biological activity of modified PTH (1-14) analogues using mono-substituted experimental data and to analyze the key physicochemical properties at each position that correlated with bioactivity. This systematic approach can reduce the time and effort needed to obtain desirable molecules by bench experiments and provide useful information in the design of simpler activating molecules.

Functional Electrical Stimulation : A Review of Clinical Application (기능적 전기자극의 임상 적용에 관한 고찰)

  • Cho, Mi-Suk;Lee, In-Hak;Kim, In-Sup
    • Journal of the Korean Academy of Clinical Electrophysiology
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    • v.4 no.1
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    • pp.39-47
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    • 2006
  • Functional Electrical Stimulation(FES) cause paralysed muscles to contract in some clinical circumstances. Generally, FES has been thought of as a valuable tool in activating any skeletal muscle paralysed as a result of upper motor neuron damage. But, the function of cardiac and smooth muscle is also affected by upper motor neuron damage. Today, various applications of FES are investigated, including conditioning cardiovascular exercise, caugh and breathing assistant, improving bowel and bladder control, hand grasp, standing and walking etc. This review will focus on the literature reporting application of FES to control respiratory capabilities and internal organ function as well as increase muscular strength, hand grasp, standing and walking in patients with upper motor diseases.

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