TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells

Heo, S.K.,Noh, E.K.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland 2017 European journal of pharmacology Vol.804 No.-

<P>Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.</P>

Self-powered flexible touch sensors based on PZT thin films using laser lift-off

Noh, M.S.,Kim, S.,Hwang, D.K.,Kang, C.Y. Elsevier Sequoia 2017 Sensors and actuators. A Physical Vol.261 No.-

<P>Touch screens have become an inherent part of the user interface in many electronics applications such as smartphones. The two types of developed touch sensors, the resistive and capacitive sensing devices, may face several difficulties when applied to flexible device applications such as touch signals arising from bending motions. In this study, we assess the feasibility of flexible touch sensors based on piezoelectric PbZr0.52Ti0.48O3 (PZT) thin films. Piezoelectric ceramic based flexible touch sensors possess unique advantages including scalable fabrication, fast response time, durability, and being self-powered. A demonstration device has been fabricated with a sandwich structure consisting of Pt electrode/functional PZT/Pt electrode/flexible substrate structure using laser lift-off (LLO) method. In order to anneal the functional PZT layer at high temperature (600 degrees C), the device was first fabricated on the sapphire substrate and transferred via melting sacrificial PZT layer with an excimer laser. We demonstrate the detection of x- and y-axis touch location via piezoelectric materials and confirm that the flexible piezoelectric touch sensors can distinguish between touch-induced and bending-induced signals via signal location, signal shape, and duration time. A notable feature of this fabrication technique involves its possibility to be fabricated in high resolution. This device may potentially achieve high resolution with suitable fabrication techniques, thus, providing the possibility for the next generation touch sensors. (C) 2017 Elsevier B.V. All rights reserved.</P>

Genetic and functional analysis of TBK1 variants in Korean patients with sporadic amyotrophic lateral sclerosis

Kim, Y.E.,Oh, K.W.,Noh, M.Y.,Nahm, M.,Park, J.,Lim, S.M.,Jang, J.H.,Cho, E.H.,Ki, C.S.,Lee, S.,Kim, S.H. Elsevier Science Pub. Co 2017 Neurobiology of aging Vol.50 No.-

The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. One frameshift (c.1414delA) and 3 missense variants of uncertain significance in TBK1 were found in 4 patients each. In vitro functional studies revealed that the c.1414delA (p.Ile472Serfs*8) variant was associated with reduced mRNA expression of TBK1. Moreover, protein expression of this variant in patient-derived fibroblasts disrupted binding to autophagy adapter proteins and inhibited the function of TBK1 in HEK293T cells. In contrast, the 3 other missense variants of uncertain significance showed normal mRNA expression and no abnormalities in protein function. Based on these findings, the frequency of pathogenic TBK1 variants in Korean sALS patients was estimated to be 0.8% (1/129). In conclusion, pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients.

Metformin ameliorates acetaminophen hepatotoxicity via Gadd45β-dependent regulation of JNK signaling in mice

Kim, Y.H.,Hwang, J.H.,Kim, K.S.,Noh, J.R.,Choi, D.H.,Kim, D.K.,Tadi, S.,Yim, Y.H.,Choi, H.S.,Lee, C.H. Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.1

Background & Aims: Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure. Prolonged c-Jun N-terminal kinase (JNK) activation plays a central role in APAP-induced liver injury and growth arrest, and DNA damage-inducible 45 beta (Gadd45β) is known to inhibit JNK phosphorylation. Metformin has recently been shown to have hepatoprotective effects. The aim of the present study is to investigate whether metformin mitigates APAP-induced hepatotoxicity and to ascertain the molecular basis of this effect. Methods: We used APAP- and/or metformin-treated Gadd45β knockout (KO) mice and wild type (WT) C57BL/6J control mice. Primary mouse hepatocytes were isolated from WT and Gadd45β KO mice were used for in vitro study. Results: Metformin pretreatment protected against APAP toxicity with decreased liver damage, and inhibited APAP-induced prolonged hepatic JNK phosphorylation in WT mice. Gadd45β expression was increased after APAP treatment, and the expression of Gadd45β was further enhanced by metformin. The effects of metformin on APAP-induced liver injury and JNK phosphorylation were abolished in Gadd45β KO mice. Notably, subtoxic doses of APAP caused cell death and sustained JNK phosphorylation in Gadd45β-deficient primary hepatocytes. In parallel, APAP increased mortality, severe liver injury, and JNK activation in Gadd45β KO mice. Interestingly, metformin administered after APAP treatment protected against APAP-evoked hepatotoxicity in WT mice, but not in Gadd45β KO mice. Conclusions: This study is the first to demonstrate that metformin shows protective and therapeutic effects against APAP overdose-evoked hepatotoxicity via Gadd45β-dependent JNK regulation. Metformin would be a promising therapeutic strategy for treatment of APAP overdose.

Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes

Park, J.Y.,Rha, S.W.,Choi, B.,Choi, J.W.,Ryu, S.K.,Kim, S.,Noh, Y.K.,Choi, S.Y.,Akkala, R.G.,Li, H.,Ali, J.,Xu, S.,Ngow, H.A.,Lee, J.J.,Lee, G.N.,Kim, J.,Lee, S.,Na, J.O.,Choi, C.U.,Lim, H.E.,Kim, J.W Elsevier/North-Holland Biomedical Press 2015 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.184 No.-

Background: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. Methods: From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. Results: Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). Conclusions: In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion.

SUPPRESSION OF THE TETRAGONAL DISTORTION IN THIN Pb(Zr, Ti)$O_3$/MgO(100)

Kang, H.C.,Noh, D.Y.,Je, J.H. The Korean Vacuum Society 1997 Applied Science and Convergence Technology Vol.6 No.1

The paraelectric cubic-to-ferroelectric tetragonal phase transition of the thin Pb(Zr, Ti)$O_3$ (PZT) films grown on MgO(001) substrate was investigated in a series of synchrotron x-ray scattering experiments. As the thickness of the film decreases the transition temperature and the amount of the tetragonal distortion were decreased continuously Different from only the c-domains were existent in the thinnest 25nm thick film. Based on this we propose a model for the domain structure of the tetragonal PZT/MgO(100) film that is very different from the ones suggested in literature. We attribute the suppression of the transition to the substrate field that prefers the c-type domains near the interface and suppresses the tetragonal distortion to minimize the film-substrate lattice mismatch.

Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells

Kang, D.W.,Noh, Y.N.,Hwang, W.C.,Choi, K.Y.,Min, D.S. Pergamon Press 2016 Biochemical pharmacology Vol.113 No.-

<P>Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced beta-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-beta-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential. (C) 2016 Elsevier Inc. All rights reserved.</P>

Atomic layer deposition of Y2O3 films using heteroleptic liquid (iPrCp)2Y(iPr-amd) precursor

Park, I. S.,ChanJung, Y.,Seong, S.,Ahn, J.,Kang, J.,Noh, W.,Lansalot-Matras, C. Royal Society of Chemistry 2014 Journal of materials chemistry. C, Materials for o Vol.2 No.43

Novel Mn^II coordination compounds constructed from benzoate and various bipyridyl ligands: Magnetic property and catalytic activity

Hwang, I.H.,Jo, Y.D.,Kim, H.Y.,Kang, J.,Noh, J.Y.,Hyun, M.Y.,Kim, C.,Kim, Y.,Kim, S.J. Pergamon Press 2012 Polyhedron Vol.42 No.1

Three new Mn<SUP>II</SUP>-benzoates coordination polymers containing various bipyridyl ligands (3,3'-dipicoylamine (3), 3-methylisoquinoline (4), and 4,4'-dithiopyridine (5)) and a [Mn<SUB>6</SUB>(O<SUB>2</SUB>CPh)<SUB>10</SUB>(μ<SUB>4</SUB>-OH)<SUB>2</SUB>(CH<SUB>3</SUB>OH)<SUB>3</SUB>(H<SUB>2</SUB>O)].1.5(C<SUB>4</SUB>H<SUB>4</SUB>N<SUB>2</SUB>) cluster (1) have prepared and their structures were determined. The bipyridyl ligands can act as bridging ligands to produce 1-D or 2-D polymeric compounds. The pyrazine produced a Mn<SUB>6</SUB> cluster molecule, and 3-methylisoquinoline did a benzoate-bridged 1-D Mn<SUP>II</SUP> compound. The Mn<SUB>6</SUB> cluster (1) and 1-D Mn<SUP>II</SUP> compounds (3) and (4) show antiferromagnetic property. The compounds 1, 3, and 4 have catalyzed efficiently the transesterification of a variety of esters, while 5 has displayed a very slow conversion. The thermal stabilities of these complexes were also examined.