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Role of STAT3 as a Molecular Adaptor in Cell Growth Signaling: Interaction with Ras and other STAT Proteins

  • Song, Ji-Hyon;Park, Hyon-Hee;Park, Hee-Jeong;Han, Mi-Young;Kim, Sung-Hoon;Lee, Choong-Eun
    • BMB Reports
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    • v.34 no.5
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    • pp.484-488
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    • 2001
  • STATs are proteins with a dual function: signal transducers in the cytoplasm and transcriptional activators in the nucleus. Among the six known major STATs (STAT1-6), STAT3 has been implicated in the widest range of signaling pathways that regulate cell growth and differentiation. As a part of our on-going investigation on the pleiotropic functions of STAT proteins, we examined the role of STAT3 as a molecular adaptor that links diverse cell growth signaling pathways. We observed that STAT3 can be specifically activated by multiple cytokines, such as IL-3, in transformed fibroblasts and IL-4 or IFN-$\gamma$ in primary immune cells, respectively. The selective activation of STAT3 in H-ras-transformed NIH3T3 cells is associated with an increased expression of phosphoserioe STAT3 in these cells, compared to the parental cells. Notably phosphoresine-STAT3 interacts with oncogenic ras, shown by immunoprecipitation and Western blots. The results suggest the role of STAT3 in rasinduced cellular transformation as a molecular adaptor linking the Jak/STAT and Ras/MAPK pathways. In primary immune cells, IL-4 and IFN-$\gamma$ each induced (in addition to the characteristic STAT6 and STAT1 homodimers) the formation of STAT3-containing complexes that bind to GAS probes, which correspond to the $Fe{\varepsilon}$ Rll and $Fe{\gamma}$ RI promoter sequences, respectively. Since IL-4 and IFN-$\gamma$ are known to counter-regulate the expression of these genes, the ability of STAT3 to form heterodimeric complexes with STAT6 or STAT1 implies its role in the fine-tuned control of genes that are regulated by IL-4 and IFN-$\gamma$.

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A STUDY OF SASIN-ANIMAL SKY MAP ON CHONMUNRYUCHO (천문유초(天文類初)에 기록된 사신동물천문도(四神動物天文圖) 연구)

  • 양홍진;박명구
    • Journal of Astronomy and Space Sciences
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    • v.20 no.1
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    • pp.83-94
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    • 2003
  • Chon-Mun-Ryu-Cho (天文類抄), written (edited) by Lee Sun-Ji (李純之) during the period of King Se-Jong, is a representative astronomy book of Cho-Sun (朝鮮: A.D. 1392-1910) Dynasty. We find and study in the first page of the book; the description of 28 oriental constellations as a Sasin (four mythical oriental animals)-animal sky map which is not widely known yet. The map consists of four groups of constellations, each of which represents the Sasin: Chang-Ryong (蒼龍: dragon), Baek-Ho (白虎: tige.s with Ki-Rin [離隣: Oriental giraffe]), Ju-Jak (朱崔: Chinese phoenix), Hyun-Mu (玄武: a tortoise interwined with a snake). Each group (animals) spans 2 ~ 7 of 28 oriental constellations (宿). As we know from the illustration (論說) of the Chon-Sang-Yol-Cha-Bun-Ya-Ji-Do (天象列次分野之圖), a representative sky map of Cho-Sun Dynasty, astronomy in Cho-Sun Dynasty is closely related to that in Go- Gu-Rye. (高句麗: B.C. 37 -A.D. 668) Dynasty. Since these Sasin-animals appear in most mural paintings of Go-Gu-Rye. (高句麗) tombs, visualization of sky with these animal constellations could have been established as early as in Go-Gu-Ryer Dynasty. We also reconstruct this ”A Sasin-animal Korean sky map” based on the shapes of the Sasin and Ki-Rin from Go-Gu-Ryer paintings and 28 oriental constellations in Chon- S an g- Yol- C h a- B un- Ya- J i- Do.

Incorporation of Winter Rapeseed (Brassica napus) as Green Manure on Mineralization and Uptake of Nitrogen to Succeeding Corn (Zea mays L.) (유채의 녹비 환원에 의한 질소무기화 및 옥수수의 질소 흡수)

  • Choi, Bong-Su;Hong, Ki-Chan;Sung, Jwa-Kyung;Nam, Jae-Jak;Lim, Jung-Eun;Lee, Hyeon-Yong;Yang, Jae-E.;Ok, Yong-Sik
    • Korean Journal of Organic Agriculture
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    • v.17 no.3
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    • pp.381-391
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    • 2009
  • Crop production can be secured by the cycle of green manure crops as an alternative of the chemical fertilizer. Recently, rapeseed (Brassica napus L.) has been cultivated in the south part of Korea for the production of biodiesel. In this research, we focused on recycling rapeseed residue, which is produced after harvesting the rapeseed for biodiesel, as a potential source of nitrogen to the succeeding crop. Pot experiment was conducted to evaluate the effects of winter rapeseed as green manure on mineralization and uptake of nitrogen to the succeeding corn (Zea mays L.). Result showed that total nitrogen and C/N ratio of rapeseed at the harvesting stage was 0.54% and 63, respectively. The incorporation of rapeseed without decomposition period slightly inhibited nitrogen uptake to the succeeding corn compared to those with 30 days decomposition period. The pH and EC values of soils increased by increasing the period of decomposition of rapeseed from 5.2 to 6.4 and from 0.05 dS/m to 0.21 dS/m, respectively. Significant amounts of $NH_4^+$ and $NO_3^-$ are released by incorporation of rapeseed. The succeeding corn took up 86% and 88% of inorganic nitrogen released from the rapeseed with and without decomposition period, respectively. The overall results suggested that the utilization of rapeseed residue as green manure can be an alternative source of nitrogen in corn-rapeseed double cropping system.

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Gene expression microarray analysis of Paeoniae radix on IL-$1{\beta}$-stimulated primary human gingival fibroblast (Microarray를 이용한 작약(芍藥)의 인간치은섬유모세포 유전자 발현 조절 연구)

  • Kim, Kyung-Ho;Choi, Yeong-Gon;Hong, Yeon-Mi;Yeo, Su-Jung;Choi, Ji-Hoon;Kim, Young-Hong;Lee, Je-Hyun;Lim, Sa-Bi-Na
    • The Journal of Korean Medicine
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    • v.31 no.2
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    • pp.91-108
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    • 2010
  • Background & Objective: The aim of this study was to investigate the effect of P. radix on the inflammatory related gene expression in IL-$1{\beta}$-stimulated primary human gingival fibroblast using Whole Transcript Sense Target (WT-ST). Method: Human gingival fibroblast was incubated with P. radix [100 or $200\;{\mu}g/ml$], and IL-$1{\beta}$ [$1ng/m{\ell}$] added an hour later. After 24h, total RNA was extracted using RNeasy Mini Kit and the whole gene expression patterns were performed using WT-ST Labeling $Assay^{(R)}$. Result: In the DEG results, 782 genes were up-regulated in the IL-$1{\beta}$-treated group as compared to control and among those, 43 genes were associated with inflammation. 981 genes were down-regulated after treatment with IL-$1{\beta}$ and of those 7 genes were associated with inflammation. 1439 genes were up-regulated after treatment with P. radix plus IL-$1{\beta}$-treated when compared to IL-$1{\beta}$-treated alone group and 1225 genes were down-regulated in the same condition. Among the down-regulated genes, 5 were associated with inflammation- and inhibitor genes such as GDF15 and LIF. In the analysis of the P. radix plus IL-$1{\beta}$-treated group, the most significant pathways were the cytokine-cytokine receptor interaction, toll-like receptor signaling, JAK-STAT signaling and tyrosine metabolism. The gene expression patterns in the P. radix $200{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group appear to be more involved in the metabolism-related pathways than in the $100{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group. Conclusion & Discussion: By microarray analysis of gene expression data, we are able to identify gene expression patterns associated with not only anti-inflammation effect but also transcription function of P. radix.

Opto-mechanical Analysis for Primary Mirror of Earth Observation Camera of the MIRIS (MIRIS EOC 주경의 광기계 해석)

  • Park, Kwi-Jong;Moon, Bong-Kon;Park, Sung-Jun;Park, Young-Sik;Lee, Dae-Hee;Ree, Chang-Hee;Nah, Jak-Young;Jeong, Woog-Seob;Pyo, Jeong-Hyun;Lee, Duk-Hang;Nam, Uk-Won;Rhee, Seung-Wu;Yang, Sun-Choel;Han, Won-Yong
    • Korean Journal of Optics and Photonics
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    • v.22 no.6
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    • pp.262-268
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    • 2011
  • MIRIS(Multi-purpose Infra-Red Imaging System) is the main payload of the STSAT-3(Korea Science and Technology Satellite. 3), which is being developed by KASI(Korea Astronomy & Space Institute). EOC(Earth Observation Camera), which is one of two infrared cameras in MIRIS, is the camera for observing infrared rays from the Earth in the range of $3{\sim}5{\mu}m$. The optical system of the EOC is a Cassegrain prescription with aspheric primary and secondary mirrors, and its aperture is 100mm. A ring type flexure supports the EOC primary mirror with pre-loading in order to withstand expected load due to the shock and vibration from the launcher. Here we attempt to use the same mechanism by which a retainer supports the lens. Through opto-mechanical analysis it was confirmed that the EOC primary mirror is effectively supported.

Quantitation of n-Hexane Extractable Material (HEM) and Estimation of Annual Pollutant Loading Rate by Sewage Sludge Applicated to Land (하수슬러지 중 노말헥산추출물질 (HEM) 함량 분석 및 토양 시용시 연간 오염부하량 추정)

  • Nam, Jae-Jak;Park, Woo-Kyun;Lim, Dong-Kyu;Lee, Sang-Hak
    • Korean Journal of Environmental Agriculture
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    • v.21 no.1
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    • pp.45-49
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    • 2002
  • To estimate annual pollutant loading rate of n-hexane extractable material (HEM) to soil 84 sewage sludge samples were analyzed. The average content of HEM was 27.7$\pm$26.5 g/kg, and ranged from 1.05 to maximum 194 g/kg. According to the number of population of the city the areas were classified as five regions, i.e. big, large, middle, small, and rural area in which the waste water treated plants were grown. The contents of HEM were 22.7$\pm$16.7, 33.3$\pm$25.8, 22.0$\pm$8.7, 31.0$\pm$38.8, 27.7$\pm$25.1 g/kg, in big, large, middle, small, and rural area, respectively. The applicated areas with sewage sludge to land also were divided as 4 sites by US EPA criteria such as agricultural, forest, public contact sites, and reclamation site. The quantitation of annual pollutant loading rate was estimated using a function (99 percentile concentration = $\bar{X}$ + 3$\sigma$) when the application amounts were in dosages of 7,000, 26,000, 18,000, 74,000 kg/ha in 5 regions, respectively. The annual pollutant loading rate of HEM to soil by sewage sludge application was maximum 1,032, 3,832, 2,653, and 10,908 kg/ha in agricultural, forest, public contact sites, and reclamation site, respectively.

Toxicity Assessment of the Soil by Bioassay Following a Long-Term Application of Sewage Sludge (생물검정법을 이용한 하수슬러지 장기연용 토양의 독성평가)

  • Nam, Jae-Jak;Lee, Seung-Hwan;Kwon, Soon-Ik;Hong, Suk-Young;Lim, Dong-Kyu;Koh, Mun-Hwan;Song, Beom-Hun
    • Korean Journal of Environmental Agriculture
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    • v.23 no.4
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    • pp.258-263
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    • 2004
  • Bioassay was employed to assess toxicity of soil which had been treated with sewage sludges for seven years. The $Microtox^{(R)}$ and root elongation test of lettuce (Lactuca Sativa.) elucidated that the intensity of soil toxicity was closely related with the types and amount of sewage sludges applied. Both bioassay methods proved to be useful in an assessment of soil toxicity and were consistent to some extent with the conventional chemical analysis methods. $EC_{50}$ values resulted from $Microtox^{(R)}$ were highly correlated with concentration of heavy metals in soils amended with sewage sludges : Cu ($r^2=\;0.86^{**}$), Cr ($r^2\;=\;0.84^{**}$), Ni ($r^2\;=\;0.83^{**}$), and Zn ($r^2\;=\;0.69^{**}$). This demonstrated that both bioassay techniques could be employed as tools for soil toxicity assessment when the soil was exposed to solid wastes such as sewage sludge.

Establishment of Database and Distribution Maps for Biomass Resources (바이오매스 자원 DB 구축과 분포도 작성)

  • Kim, Yi-Hyun;Nam, Jae-Jak;Hong, S. Young;Choe, Eun-Young;Hong, Seung-Gil;So, Kyu-Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.42 no.5
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    • pp.379-384
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    • 2009
  • This study was carried out to understand the national and regional distribution of the biomass resources produced in Korea annually via establishing database (DB) and distribution maps of biomass resources data including as livestock manures, food wastes and agricultural by-product. The information of the annual production of each biomass resources was obtained from Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF), Ministry of Environment (MOE) and National Statistical Office (NSO). Based on biomass resources data, we established database architecture table about livestock manures and food wastes. The distribution maps for the total amount of manures produced from each livestock animal were built up in both national and regional scales and used for analysis of the space-based and time-based distribution of the manure resources. Distribution maps for food wastes and agricultural by-product were also produced, respectively. It was shown that the analysis through resource mapping can be used to identify the sources of collectable biomass feasibly determining suitable region for establishment of a biomass-energy production. The biomass distribution maps graphically provide the information regarding biomass resources to policy-makers, farmers, general users and it was expected to be utilized for policy-making of environmental-friendly agriculture and bio-energy.

Novel Isoquinolinamine and Isoindoloquinazolinone Compounds Exhibit Antiproliferative Activity in Acute Lymphoblastic Leukemia Cells

  • Roolf, Catrin;Saleweski, Jan-Niklas;Stein, Arno;Richter, Anna;Maletzki, Claudia;Sekora, Anett;Escobar, Hugo Murua;Wu, Xiao-Feng;Beller, Matthias;Junghanss, Christian
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.492-501
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    • 2019
  • Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of major histocompatibility complex class I genes and signaling pathways

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Tran, Ha Thi Thanh;Dang, Hoang Vu;Nguyen, Viet Khong;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.5
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    • pp.614-628
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    • 2019
  • Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.