• Title/Summary/Keyword: ATF

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Cholic Acid Attenuates ER Stress-Induced Cell Death in Coxsackievirus-B3 Infection

  • Han, Jae-Young;Jeong, Hae In;Park, Cheol-Woo;Yoon, Jisoo;Ko, Jaeyoung;Nam, Sang-Jip;Lim, Byung-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.109-114
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    • 2018
  • Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the Picornaviridae and causes various diseases such as myocarditis and hand-foot-mouth disease. However, an effective antiviral drug is still not developed. In this study, we looked for potential inhibitors of CVB3 replication by examining the survival of CVB3-infected HeLa cells. We detected an antiviral effect by cholic acid and identified it as a candidate inhibitor of CVB3 replication. Cholic acid circulates in the liver and intestines, and it helps the digestion and absorption of lipids in the small intestine. HeLa cells were cultured in 12-well plates and treated with cholic acid (1 and $10{\mu}g/ml$) and $10^6PFU/ml$ of CVB3. After 16 h post-infection, the cells were lysed and subjected to western blot analysis and RT-PCR. The production of the viral capsid protein VP1 was dramatically decreased, and translation initiation factor eIF4G1 cleavage was significantly inhibited by treatment with $10{\mu}g/ml$ cholic acid. Moreover, cholic acid inhibited ERK signaling in CVB3-infected HeLa cells. RT-PCR showed that the amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription factor ATF4 were significantly reduced. These results showed that cholic acid strongly reduced ER stress and CVB3 proliferation. This compound can be developed as a safe natural therapeutic agent for enterovirus infections.

A New Calibration Method for the Characterization of Microwave Devices (마이크로파 소자 특성화를 위한 새로운 보정 방법)

  • 신헌철;유영길;정의붕;이종악
    • The Proceeding of the Korean Institute of Electromagnetic Engineering and Science
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    • v.2 no.3
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    • pp.10-16
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    • 1991
  • The error networks due to the measuring systems and the test fixture must be previously calibrated in order to characterize the microwave devices. In this paper, it is presented a new method to characterize the error networks in which only two different microstrip lines are used for the calibration. Once each length of two calibrat- ing microstrip lines is accurately defined, the calibrated data can be easily obtained without acknowledgement for the propagation constant. The end effect is not considered when fabricated the microstrip lines used to calibration. The ATF13736 GaAs MESFET is characterized by means of the calibrating procedure with this method. The range of measuring frequency is 2 to 18 GHz, and the bias voltage and current are $V_{DS}$ =2.5V, $I_{DS}$ =20mA, respectively. Compared the calibrated data with data sheet, it is showed that the magnitude is nearly agreed with each other and the phase is deviated by 0.1 to 12 degrees in lower frequencies.

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Regulation of the Gene Encoding Glutathione Synthetase from the Fission Yeast

  • Kim, Su-Jung;Shin, Youn-Hee;Kim, Kyung-Hoon;Park, Eun-Hee;Sa, Jae-Hoon;Lim, Chang-Jin
    • BMB Reports
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    • v.36 no.3
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    • pp.326-331
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    • 2003
  • The fission yeast cells that contained the cloned glutathione synthetase (GS) gene showed 1.4-fold higher glutathione (GSB) content and 1.9-fold higher GS activity than the cells without the cloned GS gene. Interestingly, $\gamma$-glutamylcysteine synthetase activity increased 2.1-fold in the S. pombe cells that contained the cloned GS gene. The S. pombe cells that harbored the multi copy-number plasmid pRGS49 (containing the cloned GS gene) showed a higher level of survival on solid media with cadmium chloride (1 mM) or mercuric chloride ($10\;{\mu}M$) than the cells that harbored the YEp357R vector. The 506 bp upstream sequence from the translational initiation point and N-terminal8 amino acid-coding region were fused into the promoteriess $\beta$-galactosidase gene of the shuttle vector YEp367R to generate the fusion plasmid pUGS39. Synthesis of $\beta$-galactosidase from the fusion plasmid pUGS39 was significantly enhanced by cadmium chloride and NO-generating S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SN). It was also induced by L-buthionine-(S,R)-sulfoximine, a specific inhibitor of $\gamma$-glutamylcysteine synthetase (GCS). We also found that the expression of the S. pombe GS gene is regulated by the Atf1-Spc1-Wis1 signal pathway.

Effect of Acer tegmentosum Maxim. extract on differentiation of osteoblastic Primary calvarial osteoblasts cells (조골세포의 분화에 산겨릅나무 추출물이 미치는 영향)

  • Oh, Tae Woo;Shim, Ki-Shuk;Kim, Kwang-Youn;Cho, Won-Kyung;Park, Kwang Il;Ma, Jin Yeul
    • Herbal Formula Science
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    • v.25 no.4
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    • pp.527-536
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    • 2017
  • Objectives : The present study, to confirm the osteoblast differentiation effects of Acer tegmentosum Maxim. (AT) extract. Methods : In this experiment, cell viability, Alizarin red S assay, and Alkaline phosphatase (ALP) activity with AT extract (50, $100{\mu}g/m{\ell}$). Also, we studied the expression of differentiation regulator with AT extract in primary calvarial osteoblasts cells (pOB). Results : As a result of AT treatment, we determined that AT extract stimulates ALP activity and alizarin red activities in the pOB cells for mineralization for 18 days. Moreover, these factors increasing osteogenic markers such as Runt-related transcription factor2 ($Run{\times}2$), osteocalcin (OC), osteopontin, osterix, smad1, smad5, activating transcription factor4 (ATF4) and collagen type I alpha 1. Conclusions : These results indicate that AT extract have effect on bone through the promotion of osteoblastic differentiation, suggesting that it could be used for the treatment of bone diseases.

Effect of Endoplasmic Reticulum (ER) Stress Inhibitor Treatment during Parthenogenetic Activation on the Apoptosis and In Vitro Development of Parthenogenetic Porcine Embryos

  • Park, Hye-Bin;Kim, Mi-Jeong;Jung, Bae-Dong;Lee, Seunghyung;Park, Choon-Keun;Yang, Boo-Keun;Cheong, Hee-Tae
    • Development and Reproduction
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    • v.22 no.3
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    • pp.235-244
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    • 2018
  • We investigate the effect of endoplasmic reticulum (ER) stress inhibitor treatment during parthenogenetic activation of oocytes on the ER stress generation, apoptosis, and in vitro development of parthenogenetic porcine embryos. Porcine in vitro matured oocytes were activated by 1) electric stimulus (E) or 2) $E+10{\mu}M$ Ca-ionophore (A23187) treatment (EC). Oocytes were then treated by ER stress inhibitors such as salubrinal (200 nM) and tauroursodeoxychloic acid (TUDCA, $100{\mu}M$) for 3 h prior to in vitro culture. Parthenogenetic embryos were sampled to analyze ER stress and apoptosis at the 1-cell and blastocyst stages. The x-box binding protein 1 (Xbp1) mRNA and ER stress-associated genes were analyzed by RT-PCR or RT-qPCR. Apoptotic gene expression was analyzed by RT-PCR. At the 1-cell stage, although no difference was observed in Xbp1 splicing among treatments, BiP transcription level in the E group was significantly reduced by salubrinal treatment, and GRP94 and ATF4 transcription levels in EC group were significantly reduced by all treatments (p<0.05) compared to control. In the EC group, both apoptotic genes were reduced by ER stress inhibitor treatments compared to control (p<0.05) except Caspase-3 gene by TUDCA treatment. These results suggest that the treatment of ER stress inhibitor during parthenogenetic activation can reduce ER stress, and thereby reduce apoptosis and promote in vitro development of porcine parthenogenetic embryos.

Effect of Exercise Intensity on Unfolded Protein Response in Skeletal Muscle of Rat

  • Kim, Kihoon;Kim, Yun-Hye;Lee, Sung-Hye;Jeon, Man-Joong;Park, So-Young;Doh, Kyung-Oh
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.3
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    • pp.211-216
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    • 2014
  • Endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and mitochondrial biogenesis were assessed following varying intensities of exercise training. The animals were randomly assigned to receive either low- (LIT, n=7) or high intensity training (HIT, n=7), or were assigned to a control group (n=7). Over 5 weeks, the animals in the LIT were exercised on a treadmill with a $10^{\circ}$ incline for 60 min at a speed of 20 m/min group, and in the HIT group at a speed of 34 m/min for 5 days a week. No statistically significant differences were found in the body weight, plasma triglyceride, and total cholesterol levels across the three groups, but fasting glucose and insulin levels were significantly lower in the exercise-trained groups. Additionally, no statistically significant differences were observed in the levels of PERK phosphorylation in skeletal muscles between the three groups. However, compared to the control and LIT groups, the level of BiP was lower in the HIT group. Compared to the control group, the levels of ATF4 in skeletal muscles and CHOP were significantly lower in the HIT group. The HIT group also showed increased PGC-$1{\alpha}$ mRNA expression in comparison with the control group. Furthermore, both of the trained groups showed higher levels of mitochondrial UCP3 than the control group. In summary, we found that a 5-week high-intensity exercise training routine resulted in increased mitochondrial biogenesis and decreased ER stress and apoptotic signaling in the skeletal muscle tissue of rats.

Investigation on effect of surface properties on droplet impact cooling of cladding surfaces

  • Wang, Zefeng;Qu, Wenhai;Xiong, Jinbiao;Zhong, Mingjun;Yang, Yanhua
    • Nuclear Engineering and Technology
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    • v.52 no.3
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    • pp.508-519
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    • 2020
  • During transients or accidents, the reactor core is uncovered, and droplets entrained above the quench front collides with the uncovered fuel rod surface. Droplet impact cooling can reduce the peak cladding temperature. Besides zirconium-based cladding, versatile accidental tolerant fuel (ATF) claddings, including FeCrAl, have been proposed to increase the accident coping time. In order to investigate the effect of surface properties on droplet impact cooling of cladding surfaces, the droplet impact phenomena are photographed on the FeCrAl and zircaloy-4 (Zr-4) surfaces under different conditions. On the oxidized FeCrAl surface, the Leidenfrost phenomenon is not observed even when the surface temperature is as high as 550 ℃ with We > 30. Comparison of the impact behaviors observed on different materials shows that nucleate and transition boiling is more intensive on surfaces with larger thermal conductivity. The Leidenfrost point temperature (LPT) decreases with the solid thermal effusivity (${\sqrt{k{\rho}C_p}}$). However, the CHF temperature is relatively insensitive to the surface oxidation and Weber number. Droplet spreading diameter is analyzed quantitatively in the film boiling stage. Based on the energy balance a correlation is proposed for droplet maximum spreading factor. A mechanistic model is also developed for the LPT based on homogeneous nucleation theory.

Effects of Daidzein on mRNA Expression of Gonadotropin Receptors and P450 Aromatase in Ovarian Follicles of White Silky Fowls

  • Liu, Hongyun;Zhang, Caiqiao;Ge, Chutian;Liu, Jianxin
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.12
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    • pp.1827-1831
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    • 2007
  • Effects of daidzein on expression of mRNAs of gonadotropin receptors (FSHR, LHR) and P450 aromatase (P450arom) were evaluated in ovarian follicles of white silky fowls. The hens were 13 months old in the post-peak period of egg laying and were randomly allocated as control and daidzein-treated groups, with daidzein supplemented to the basal diet at 10 mg/kg for 7 consecutive weeks. The mRNA expression of related genes was measured by semi-quantitative RT-PCR in the granulosa layers of the preovulatory follicle (PRF: F1, F2 ...) and follicular layers of the small yellow follicle (SYF), large white follicle (LWF) and atretic follicle (ATF). Results showed that daidzein supplementation significantly increased the number of SYF and LWF (p<0.05). The relative abundance of the FSHR mRNA decreased in the granulosa layers from F3 to F1, but LHR mRNA displayed opposite developmental changes. P450arom mRNA was highest in the SYF, but was very low in the granulosa layers after follicles finished selection. Treatment with daidzein resulted in increased mRNA expression of FSHR in F3 granulosa layer, LHR in granulosa layers of F3 to F1 and P450arom in LWF (p<0.05). These results indicated that dietary supplementation of daidzein up-regulated mRNA expression of gonadotropin receptors and P450arom to improve the development of preovulatory follicles in white silky fowls after the peak-laying period.

Synergistic Effects of Chios Gum Mastic Extract and Low Level Laser Therapy on Osteoblast Differentiation

  • Lee, Ki-Hyun;Kim, Young-Seok;Yu, Su-Bin;Kang, Hae-Mi;Kwak, Hyun-Ho;Kim, In-Ryoung;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.41 no.2
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    • pp.53-62
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    • 2016
  • In the present study, we evaluated the effect of CGM on osteogenic differentiation of cultured osteoblasts, and determined whether combination treatment with LLLT had synergistic effects on osteogenic differentiation. The results indicated that CGM promoted proliferation, differentiation, and mineralization of osteoblasts at the threshold concentration of $10{\mu}g/ml$; whereas, CGM showed cytotoxic properties at concentrations above $100{\mu}g/ml$. ALP activity and mineralization were increased at concentrations above $10{\mu}g/ml$. CGM in concentrations up to $10{\mu}g/ml$ also increased the expression of osteoblast-activated factors including type I collagen, BMP-2, RUNX2, and Osterix. The CGM ($50{\mu}g/ml$) and LLLT (80 mW for 15 sec) combination treatment group showed the highest proliferation levels, ALP activity, and mineralization ratios. The combination treatment also increased the levels of phosphorylated forms of p38, ATF2, PKD, ERK, and JNK. In addition, the osteoblast differentiation factors including type I collagen, BMP-2, RUNX2, and Osterix protein levels were clearly increased in the combination treatment group. These results suggested that the combination treatment of CGM and LLLT has synergistic effects on the differentiation and mineralization of osteoblastic cells.

Linkage and association scan for tanning ability in an isolated Mongolian population

  • Paik, Seung-Hwan;Kim, Hyun-Jin;Lee, Seung-Bok;Im, Sun-Wha;Ju, Young-Seok;Yeon, Je-Ho;Jo, Seong-Jin;Eun, Hee-Chul;Seo, Jeong-Sun;Kim, Jong-Il;Kwon, Oh-Sang
    • BMB Reports
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    • v.44 no.11
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    • pp.741-746
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    • 2011
  • Tanning ability is important, because it represents the ability of the skin to protect itself against ultraviolet (UV) radiation. Here, we sought to determine genetic regions associated with tanning ability. Skin pigmentation was measured at the outer forearm and buttock areas to represent facultative and constitutive skin color, respectively. In our study population consisting of isolated Mongolian subjects, with common histories of environmental UV exposure during their nomadic life, facultative skin color adjusted by constitutive skin color was used to indicate tanning ability. Through linkage analysis and family-based association tests of 345 Mongolian subjects, we identified 2 potential linkage regions regulating tanning ability on 5q35.3 and 12q13.2, having 6 and 7 significant single nucleotide polymorphisms (SNPs), respectively. Those significant SNPs were located in or adjacent to potential candidate genes related to tanning ability: GRM6, ATF1, WNT1, and SILV/Pmel17.