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        The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance insulin-induced AP-1 activity and cellular transformation

        Lee, N. Y.,Choi, H.-K.,Shim, J.-H.,Kang, K.-W.,Dong, Z.,Choi, H. S. Oxford University Press 2009 Carcinogenesis Vol.30 No.4

        <P>Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase Pin1 and is a central signaling mechanism in cell proliferation and transformation. Although Pin1 is frequently overexpressed in hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not been completely elucidated. Here, we show that Pin1 interacts with p70S6K in vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-) mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin-induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1 enhanced the insulin-induced extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2 phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1 activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly, Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation promoted by insulin much more than green fluorescent protein-overexpressing JB6 Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1 plays an important role in insulin-induced tumorigenesis and is a potential therapeutic target in hepatocarcinoma.</P>

      • Monitoring and determination of Cabarmate resistance in field strain of Myzus persicae (Hemiptera: Aphidaidae)

        Jung Hun Oh,Deok Ho Kwon,Ju Il Kim,Jae Dong Shim,Si Hyeock Lee 한국응용곤충학회 2011 한국응용곤충학회 학술대회논문집 Vol.2011 No.10

        The green peach aphid (Myzus persicae) is a serious pest of agricultural and horticultural crops all over the world. M. persica has rapidly developed resistance to a wide variety of insecticides, including carbamates. The E4/FE4 carboxylesterase is known to be involved in carbamate resistance. To compare the E4/FE4 carboxylesterase gene copy number, as a genetic resistance marker, between seven field strains, quantitative real-time PCR (qPCR) was performed. In addition, quantitative sequencing (QS) was employed to predict the frequencies of acetylcholinesterase (AChE) mutations (A301S and S431F) that are associated with target site insensitivity. All M. persica strains examined possessed the S431F mutation in the heterozygous state except for a susceptible strain, implying the possibility of AChE duplication. In contrast, no A301S mutation was found. Frequency prediction equation was generated from the plots of signal ratios and amplification critical time, which showed a high correlation (r2>0.996). QS analysis of M. persicae populations revealed that the allele frequency of S431F ranged 4% to 63%. Taken together, the AChE resistance allele frequencies determined by QS and the E4/FE4 gene copy number by qPCR should facilitate the detection and monitoring of carbamate resistance in M. persicae in the field.

      • Epigallocatechin gallate suppresses lung cancer cell growth through Ras-GTPase-activating protein SH3 domain-binding protein 1.

        Shim, Jung-Hyun,Su, Zheng-Yuan,Chae, Jung-Il,Kim, Dong Joon,Zhu, Feng,Ma, Wei-Ya,Bode, Ann M,Yang, Chung S,Dong, Zigang American Association for Cancer Research, Inc 2010 Cancer prevention research Vol.3 No.5

        <P>Green tea is a highly popular beverage globally. Green tea contains a number of polyphenol compounds referred to as catechins, and (-)-epigallocatechin gallate (EGCG) is believed to be the major biologically active compound found in green tea. EGCG has been reported to suppress lung cancer, but the molecular mechanisms of the inhibitory effects of EGCG are not clear. We found that EGCG interacted with the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) with high binding affinity (K(d) = 0.4 micromol/L). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells, which express much lower levels of G3BP1. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1 H1299 cells were resistant to the inhibitory effects of EGCG on growth and colony formation compared with shMock-transfected H1299 cells. EGCG interfered with the interaction of G3BP1 and the Ras-GTPase-activating protein and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1 downstream signaling, including extracellular signal-regulated kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, in wild-type H1299 and shMock H1299 cells but had little effect on H460 or shG3BP1 H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1.</P>

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        Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain–caspase and apoptosis signaling kinase 1–p38 mitogen-activated protein kinase activation cascades

        Shim, Hye-Young,Park, Jong-Hwa,Paik, Hyun-Dong,Nah, Seung-Yeol,Kim, Darrick S.H.L.,Han, Ye Sun Lippincott Williams Wilkins, Inc. 2007 ANTICANCER DRUGS Vol.18 No.6

        The molecular mechanisms of genistein-induced apoptosis of human breast cancer MCF-7 cells were investigated. Genistein showed 50% cell growth inhibition at IC50=27.5±0.8 μmol/l in 24 h incubation under 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay conditions. Genistein is known to express both cell growth activity at nanomolar concentrations and anti-cell growth activity at micromolar concentrations. It was found that genistein at 100 μmol/l concentration effectively induced apoptosis of MCF-7 cells in 24 h. Genistein-induced apoptosis involved activation of calpain, caspase 7 and poly(ADP ribose) polymerase. Dantrolene, an inhibitor of Ca release from the endoplasmic reticulum, inhibited genistein-induced activation of calpain and caspase 7, in addition to effectively negating genistein-induced apoptosis. MCF-7 cells treated with genistein also showed increased phosphorylation of p38 mitogen-activated protein kinase, whereas no effect was observed for extracellular signal-regulating kinase 1/2. Phosphorylation of apoptosis signaling kinase 1, an upstream regulator of p38 mitogen-activated protein kinase, was also increased by genistein treatment. Genistein-induced phosphorylation of apoptosis signaling kinase 1 and p38 mitogen-activated protein kinase was diminished by the presence of dantrolene. These results suggest that genistein-induced apoptosis in MCF-7 cells is mediated through calpain–caspase 7 and apoptosis signaling kinase 1–p38 mitogen-activated protein kinase activation cascades that involve Ca release from the endoplasmic reticulum.

      • KCI등재SCISCIE
      • KCI등재

        질소시용수준이 수도 분얼경의 소유관속 발육에 미치는 영향

        Dong Jin Lee,Benito S. Vergara,Oscar B. Zamora,Ie Sung Shim,Bong Ku Kim,Je Cheon Chae 韓國作物學會 1994 Korean journal of crop science Vol.39 No.4

        본 실험은 질소시용 수준이 수도의 이삭줄기, 엽신 및 엽초의 소유관속 발육에 미치는 영향을 구명 하여 수량을 증대시킬 수 있는 방안을 모색하기 위하여 '89∼'90년에 국제벼연구소 (IRRI)에서 인도형인 IR 58과 일본형인 운봉 7을 공시하여 수행하였다. 1. 분얼경의 수수절간에 발달된 소유관속수는 질소시용 수준이 증가할수록 유의하게 증가되는 경향이었으며, 주간의 경우 질소 무시용구에 비하여 질소시용구에서 IR 58은 39% 및 운봉 7은 24% 증가하였다. 2. 주간 및 일찍 출현된 1, 2차 분얼경의 발육 순서로 소유관속수가 많이 발육되어 있었으며, 분얼경의 출현이 늦을수록 유관속의 발육이 저하 되었다. 3. 주간의 수수절간, 엽신 및 엽초의 소유관속발육은 질소 무비구 및 소비구에 비하여 질소 증시구에서 다소 증가하는 경향이었다. 4. 수수절간의 소유관속수는 이삭당 영화수 및 입중과 밀접한 정의 상관관계를 나타냈으며, 이는 줄기에 발달된 소유관속이 영화수의 분화와 깊은 연관성을 가지고 있으며, 발달된 유관속을 통해 양수분 전류가 원할히 이루어져서 결국 이삭당 입중도 증가되는 결과를 보였다. The experiments were conducted to evaluate the effect of nitrogen application on the development of small vascular bundle in the rice plants. Two cultivars, IR58, an indica type and Unbong 7, a japonica type were used in this study. The number of small vascular bundles in peduncle of different tillers was increased with the increase of nitrogen level. In the main culm, number of small vascular bundles at higher nitrogen level was increased by 39% in IR58 and 24% in Unbong 7 compared with nitrogen free plot. The main culm had more small vascular bundles in the peduncle and number of small vascular bundle was decreased with later tiller order and tiller development. The number and cross sectional area of small vascular bundles in flag leaf blade and sheath of main culm were increased with increasing levels of nitrogen. The number of small vascular bundles in peduncle was highly correlated with the number of spikelets and grain weight per panicle.

      • SCOPUSKCI등재

        Photohysical Properties of New Psoralen Derivatives:Psoralens Linked to Adenine through Polymethylene Chains

        Yoo, Dong-Jin,Park, Hyung-Du,Kim, Ae-Rhan,Rho, Young S.,Shim, Sang-Chul Korean Chemical Society 2002 Bulletin of the Korean Chemical Society Vol.23 No.9

        The model compounds, 8-methoxypsoralen-CH2O(CH2)n-adenine (MOPCH2OCnAd, n=2, 3, 5, 6, 8, and 10) in which 5 position of 8-methoxypsoralen (8-MOP) is linked by various lengths of polymethylene bridge to N9 of adenine. UV absorption spectra are identical with the sum of MOPCH2OC3 and adenine absorption spectra. Solvent effects on the UV absorption and fluorescence emission spectra indicate that the lowest excited singlet state is the $(\pi${\rightarrow}$\pi*)$ state. The spectral characteristics of the fluorescence of MOPCH2OCnAd are strongly dependent upon the nature of the solvents. The fluorescence emission spectra in aprotic solvents are broad and structureless due to the excimer formation through the folded conformation accelerated by hydrophobic ${\pi}-{\pi}$ stacking interaction. Increasing polarity of the protic solvents leads to higher population of unfolded conformation stabilized through favorable solvation and H-bonding, and consequently to an increase in the fluorescence intensity, fluorescence lifetime, and a shift of fluorescence maximum to longer wavelengths. The decay characteristics of the fluorescence in polar protic solvents shows two exponential decays with the lifetimes of 0.6-0.8 and 1.6-1.9 ns in 5% ethanol/water, while MOPCH2OC3 shows 0.5 and 1.7 ns fluorescence lifetimes. The long-lived component of fluorescence can be attributed to the relaxed species (i.e., the species for which the solvent reorientation (or relaxation) has occurred), while the short-lived components can be associated with the unrelaxed, or only partially relaxed, species.

      • SCISCIESCOPUS

        A Non-Contact-Type RF MEMS Switch for 24-GHz Radar Applications

        Jaehong Park,Shim, E.S.,Wooyeol Choi,Youngmin Kim,Youngwoo Kwon,Dong-il Cho IEEE 2009 Journal of microelectromechanical systems Vol.18 No.1

        <P>This paper presents the design, fabrication, and measurement results for a novel non-contact-type radio-frequency (RF) microelectromechanical systems switch for 24-GHz radar applications. The proposed switches are free from unavoidable microwelding and stiction problems in other contact types, which in turn guarantee high reliability and long lifetime. The developed switch is a capacitive shunt type using a variation of the capacitance between the signal line and ground lines. The capacitance is precisely regulated by comb-drive actuators. This concept is simple, but the design requires a large and precise mechanical motion. In addition, for a low-loss switch structure, an air bridge with a large air gap is required. Therefore, the selective silicon-on-insulator process, based on the sacrificial bulk micromachining process, is designed for this switch fabrication. First, large insulating supports are fabricated 60 ¿m below the wafer surface, and then, the RF switch is fabricated on these insulating supports. The measured actuation voltage is 25 V, and the actuation stroke is 25 ¿m. The switching times are 8 ms in the off to the on state and 200 ¿s in the on to the off state. In the RF characteristic measurements, the insertion loss without the long coplanar waveguide line loss is 0.29 dB and the isolation is 30.1 dB at 24 GHz. The bandwidth is relatively narrow, and the isolation is 25 dB or better in the range of 23.5-29 GHz. The reliability test for the switch was performed 10<SUP>9</SUP> times with 18-mW RF power. We observed no mechanical failure or RF performance degradation. A power handling capacity of 0.9 W with a hot-switch condition was achieved.</P>

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