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Ape1/Ref-1 Stimulates GDNF/GFR ${\alpha}$ 1-mediated Downstream Signaling and Neuroblastoma Proliferation

  • Kang, Mi-Young;Kim, Kweon-Young;Yoon, Young;Kang, Yoon-Sung;Kim, Hong-Beum;Youn, Cha-Kyung;Kim, Dong-Hui;Kim, Mi-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.349-356
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    • 2009
  • We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

Effects of Benzyl Isothiocyanate and Its N-Acetylcysteine Conjugate on Induction of Detoxification Enzymes in Hepa1c1c7 Mouse Hepatoma Cells

  • Hwang, Eun-Sun
    • Preventive Nutrition and Food Science
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    • v.19 no.4
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    • pp.268-273
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    • 2014
  • The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

Screening of Zero-Valent Metal for the Removal of High Concentration PCE and 1,1,1 TCA (고농도 PCE 및 1,1,1 TCA 제거를 위한 영가금속 선정)

  • Kwon, Soo-Youl;Kim, Young
    • Journal of Wetlands Research
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    • v.12 no.1
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    • pp.23-31
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    • 2010
  • Chlorinated aliphatic hydrocarbons (CAHs) such as tetrachloroethylene (PCE), 1,1,1-trichloroethane (1,1,1-TCA) are the contaminants most frequently found in soil and groundwater. They have a potential to be toxic to and persistent in environment. This study is focused on selection of zero-valent metal and ores for the removal of high concentration PCE or 1,1,1-TCA and mixture of two compound. For the screening of suitable metals, we measured dechlorination rate, removal capacities and economics by using batch reactor test. This results suggest that removal rate and dechlorination of high quality iron and zinc are higher than slag and nature ores like zinc and manganese. Among nature ores, zinc ores(64% purity) have highest removal capacities. And in economics zinc ores is 10 times better than high quality metal tested. We conclude zinc ore is most suitable metal for the removal of PCE or 1,1,1-TCA.

Meta-analysis of Association Studies of CYP1A1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese

  • Liu, Chang;Jiang, Zheng;Deng, Qian-xi;Zhao, Ya-nan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4689-4695
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    • 2014
  • Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

(1-3, 1-4)-$\beta$-Glucan and Starch Contents and Their Hydrolytic Enzyme Activities in Developing Barley Kernels (등숙 중인 보리 종실중 (1-3, 1-4)-$\beta$-Glucan과 전분 함량 및 이들의 가수분해효소 활성)

  • 윤성중;박상래;유남희
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.4
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    • pp.403-409
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    • 1997
  • To obtain information on the accumulation of (1-3, 1-4)-$\beta$-glucans during kernel maturation, (1-3, 1-4)-$\beta$-glucan contents and (1-3, 1-4)-$\beta$-glucanase activities were determined in developing kernels of the two Korean cooking barley varieties, Neulssalbori and Saessalbori. (1-3, 1-4)-$\beta$-Glucan contents in kernels at 5 and 10 days after anthesis(DAA) were very low and the contents increased rapidly in kernels at 15 to 25 DAA. (1-3, 1-4)-$\beta$-Glucan content in kernels at harvest was about 3.5 to 4% of kernel dry matter. (1-3, 1-4)-$\beta$-Glucanase activities were relatively higher in younger kernels but the levels of the activity were very low compared with those in germinating kernels. A significant negative correlation was observed between (1-3, 1-4)-$\beta$-glucan contents and (1-3, 1-4)-$\beta$-glucanase activities. Low levels of (1-3, 1-4)-$\beta$-glucanase activites in kernels at 15 to 30 DAA, however, may indicate that (1-3, 1-4)-$\beta$-glucanases have little effect on the final content of (1-3, 1-4)-$\beta$-glucans in barley kernels. Starch contents and $\alpha$-amylase activities were also determined in developing barley kernels. Starch contents increased rapidly as kernels matured and the content at harvest was about 60% of kernel dry matter. Relativley higher levels of $\alpha$-amylase activities in kernels at the earlier developmental stage decreased rapidly as kernels matured.

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Water Requirement of Potato According to Growth Stage (노지재배 감자의 생육시기별 물 요구량 구명)

  • Eom, Ki-Cheol;Park, So-Hyun;Yoo, Sung-Yung
    • Korean Journal of Soil Science and Fertilizer
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    • v.45 no.6
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    • pp.861-866
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    • 2012
  • Water is the most important resource for the potato cultivation, especially to get the maximum water use efficiency and yield of potato, Water has to be applied moderately based on the water requirement of the potato. Crop water requirement (WR) is a function of the Potential evapo-transpiration(PET) and Crop coefficient (Kc). PET can be estimated by the climate data measured at the weather station in the production region. Kc was measured by the NIAST (RDA) through Lysimeter experiments. In this study, the growth stage of potato was divided as four (G-1 : Apr. 1~Apr. 15, G-2 : Apr. 16~May. 10, G-3 : May. 11~May. 31, G4 : Jun. 1~Jun. 15). The average PET during potato growing season of the 45 areas was $2.95mm\;day^{-1}$. The most water requirement was the G-3 stage among the potato growth stage. The MWR (Mean water requirement) according to growth stage was 1.0~1.2 (average 1.1), 1.5~1.8 (average 1.6), 1.9~2.2 (average 2.0) and 1.7~2.1 (average 1.8) mm $day^{-1}$, in the G-1, G-2, G-3 and G-4 stage, respectively. The TWR (Total water requirement) according to growth stage was 18.0~22.1 (average 19.3), 50.6~66.6 (average 56.3), 63.5~88.2 (average 72.4) and 38.3~54.5 (average 44) mm, in the G-1, G-2, G-3 and G-4 stage, respectively.

The Roles of Amino and Carboxyl Domains in the Mouse Wee1 Kinases (생쥐 Wee1 인산화효소들의 각 도메인의 역할에 관한 연구)

  • Han, Seung-Jin
    • Journal of Life Science
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    • v.18 no.1
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    • pp.114-119
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    • 2008
  • The molecular machinery controlling cell cycle is centered around the regulation of the activity of maturation-promoting factor (MPF), a complex composed of a catalytic Cdc2 and the cyclinB regulatory subunit. Cdc2 kinase is inactivated by phosphorylation of inhibitory kinase, Wee1. It has been known that there are three different Wee1 kinases in the mammalian cell, Wee1A, Wee1B and Myt1. To investigate the regulatory mechanism of Wee1 kinases, the phosphorylation and degradation of Wee1A and Wee1B were checked in the Xenopus oocyte cell cycle. When Wee1 kinases were injected into frog oocyte, Wee1B was more stable than Wee1A. Wee1A and Wee1B kinase were phosphorylated by many kinases such as PKA and Akt. The roles of amino or carboxyl terminal in mouse Wee1A or Wee1B kinase were investigated using chimeric constructs. The degree of protein phosphorylation, degradation and cell cycle progression were different between chimeric constructs. The amino domain of Wee1A was implicated in the protein phosphorylation and degradation while amino domain of Wee1B and carboxyl domain of Wee1A were involved in the activity regulation. These results suggested that the domains of Wee1 kinase have different and significant roles in regulating the Wee1 kinases in the cell cycle progression.

S1P1 Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia

  • Gaire, Bhakta Prasad;Bae, Young Joo;Choi, Ji Woong
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.522-529
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    • 2019
  • M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

MOMENT CONVERGENCE RATES OF LIL FOR NEGATIVELY ASSOCIATED SEQUENCES

  • Fu, Ke-Ang;Hu, Li-Hua
    • Journal of the Korean Mathematical Society
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    • v.47 no.2
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    • pp.263-275
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    • 2010
  • Let {$X_n;n\;\geq\;1$} be a strictly stationary sequence of negatively associated random variables with mean zero and finite variance. Set $S_n\;=\;{\sum}^n_{k=1}X_k$, $M_n\;=\;max_{k{\leq}n}|S_k|$, $n\;{\geq}\;1$. Suppose $\sigma^2\;=\;EX^2_1+2{\sum}^\infty_{k=2}EX_1X_k$ (0 < $\sigma$ < $\infty$). We prove that for any b > -1/2, if $E|X|^{2+\delta}$(0<$\delta$$\leq$1), then $$lim\limits_{\varepsilon\searrow0}\varepsilon^{2b+1}\sum^{\infty}_{n=1}\frac{(loglogn)^{b-1/2}}{n^{3/2}logn}E\{M_n-\sigma\varepsilon\sqrt{2nloglogn}\}_+=\frac{2^{-1/2-b}{\sigma}E|N|^{2(b+1)}}{(b+1)(2b+1)}\sum^{\infty}_{k=0}\frac{(-1)^k}{(2k+1)^{2(b+1)}}$$ and for any b > -1/2, $$lim\limits_{\varepsilon\nearrow\infty}\varepsilon^{-2(b+1)}\sum^{\infty}_{n=1}\frac{(loglogn)^b}{n^{3/2}logn}E\{\sigma\varepsilon\sqrt{\frac{\pi^2n}{8loglogn}}-M_n\}_+=\frac{\Gamma(b+1/2)}{\sqrt{2}(b+1)}\sum^{\infty}_{k=0}\frac{(-1)^k}{(2k+1)^{2b+2'}}$$, where $\Gamma(\cdot)$ is the Gamma function and N stands for the standard normal random variable.

Introduction to nondestructive testing

  • 정용무
    • Journal of Welding and Joining
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    • v.12 no.4
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    • pp.1-10
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    • 1994
  • 이 글에서는 비파괴검사개론에 관하여 알아보았다. 1. 비파괴검사의 의의 1.1 비파괴검사의 역사 1.2 비파괴검사의 원리 1.3 비파괴검사의 목적과 역할 1.3.1 품질관리 1.3.2 생산원가의 절감 1.3.3 품질의 평가 1.3.4 점검 1.4 비파괴검사자의 역할 2. 비파괴검사자의 방법 2.1 방사선투과시험 2.1.1 직접촬영법 2.1.2 투시법 2.1.3 전자사진법 2.1.4 계기법 2.2 초음파탐상시험 2.2.1 음향검사와 초음파탐상 2.2.2 초음파의 성질과 종류 2.2.3 접촉매질 2.2.4 초음파 탐상 방법 2.2.5 초음파 탐촉자 2.3 자기탐상시험 2.3.1 자기탐상 원리 2.3.2 자기탐상 방법 1) 자장측정 탐상법 2) 자기기록 탐상법 3) 탐사 코일법 4) 자분탐상시험 2.3.3 자분탐상시험 2.4 침투탐상시험 2.4.1 침투탐상시험의 원리 2.4.2 침투탐상시험법의 기본 1) 침투탐상시험의 종류 2) 현상체의 종류 2.4.3 침투탐상시험의 장단점 2.5 전자유도시험 (와전류탐상법) 2.5.1 와전류의 발생과 탐지 2.5.2 와전류의 탐지 2.5.3 와전류 탐촉자 2.5.4 와전류 탐상시험의 적용과 장단점.

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