Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element.

Kim, M-J,Kang, J-H,Park, Y G,Ryu, G R,Ko, S H,Jeong, I-K,Koh, K-H,Rhie, D-J,Yoon, S H,Hahn, S J,Kim, M-S,Jo, Y-H Journal of Endocrinology, Ltd. [etc.] 2006 The Journal of endocrinology Vol.188 No.3

<P>Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and beta-cell proliferation. This study aimed to investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic beta-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position -48; 5'-TAACGTCA-3') of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying beta-cell proliferation by EX.</P>

IL-32γ inhibits cancer cell growth through inactivation of NF-κB and STAT3 signals

Oh, J H,Cho, M-C,Kim, J-H,Lee, S Y,Kim, H J,Park, E S,Ban, J O,Kang, J-W,Lee, D-H,Shim, J-H,Han, S B,Moon, D C,Park, Y H,Yu, D-Y,Kim, J-M,Kim, S H,Yoon, D-Y,Hong, J T Nature Publishing Group 2011 Oncogene Vol.30 No.30

<P>Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (<I>bcl-2</I>, <I>X-chromosome inhibitor of apoptosis protein</I> (<I>IAP</I>), <I>cellular IAP</I> and <I>cellular FADD-like IL-1β-converting enzyme-inhibitory protein</I>, <I>cyclin D</I>), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (<I>caspase-3</I> and <I>-9</I>, <I>bax</I>) increased. In tumor, spleen and blood, the number of cytotoxic CD8<SUP>+</SUP> T cells and CD57<SUP>+</SUP> natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 <I>in vitro</I>. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.</P>

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior

Yang, Y R,Jung, J H,Kim, S-J,Hamada, K,Suzuki, A,Kim, H J,Lee, J H,Kwon, O-B,Lee, Y K,Kim, J,Kim, E-K,Jang, H-J,Kang, D-S,Choi, J-S,Lee, C J,Marshall, J,Koh, H-Y,Kim, C-J,Seok, H,Kim, S H,Choi, J H,Ch Macmillan Publishers Limited, part of Springer Nat 2017 Molecular psychiatry Vol.22 No.10

<P>Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase C gamma 1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase C gamma 1 (PLC gamma 1) in the forebrain (Plcg1(f/f); CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of gamma-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1(f/f); CaMKII mice. These findings provide evidence that PLC gamma 1 is critical for synaptic function and plasticity and that the loss of PLC gamma 1 from the forebrain results in manic-like behavior.</P>

Optimal operation strategy development for fuel cell hybrid vehicle

D. J. Xuan,J. W. Kim,Y. B. Kim 대한기계학회 2011 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.25 No.1

An overall simulation model for fuel cell hybrid vehicle (FCHV) power train in parallel configuration using MATLAB/Simulink programming is constructed in this study. The model runs on power control strategy by using logic-threshold approach, achieved by the hybrid control unit (HCU) and fuel cell stack number. Using accelerator and decelerator pedal positions deduced from the driving schedule as the primary input, the simulation implements power flow and distribution under different vehicle operating modes. The HCU control strategy also incorporates regenerative braking and recharge for battery capacity recovery. Using the D-optimality method for experiment points selection and sequential quadratic programming (SQP) algorithm for obtaining the optimal operational parameters, three control threshold variables of HCU and optimal stack cell number are selected for hydrogen fuel economy under certain driving cycles. The proposed method provides optimized configurations of the FCHV model and the fuel cell stack, which has the capability in satisfying drive power request while satisfying vehicle driving schedule and battery state of charge (SOC) recovery with lower fuel consumption.

Effects of Cryoprotectants and Post-storage Priming on Seed Germination of Sugi (Cryptomeria japonica D. Don)

Kim, D.H.,Han, S.H.,Ku, J.J.,Lee, K.Y. J.D. SAUERLAENDER'S VERLAG 2009 Silvae genetica Vol.58 No.4

Facile chemical bath deposition of CuS nano peas like structure as a high efficient counter electrode for quantum-dot sensitized solar cells

Kim, H.J.,Kim, J.H.,Pavan Kumar, CH.S.S.,Punnoose, D.,Kim, S.K.,Gopi, C.V.V.M.,Srinivasa Rao, S. Elsevier Sequoia 2015 Journal of Electroanalytical Chemistry Vol.739 No.-

In this paper, highly efficient nano peas like structure CuS film has been successfully employed in quantum dot sensitized solar cells (QDSSCs) for its highest catalytic activity at minimal cost. The CuS thin film electrode was deposited on fluorine-doped tin oxide (FTO) substrate by chemical bath deposition technique using urea at low deposition temperatures. This electrode elevated the short circuit current and fill factor in comparison to the frequently used Pt electrode. Moreover, electrochemical measurement data disclosed higher electrocatalytic activity toward polysulfide reduction. The CuS film exhibited an average particle size of 180-270nm and film thickness of 825nm. It also revealed superior J<SUB>sc</SUB> (13.87mA/cm<SUP>2</SUP>) and conversion efficiency of 4.01% which is remarkably higher than that of the Pt-based cell (1.07%). In addition, stability test conducted for both CuS and Pt-based cells for about 900min at working conditions affirmed that the long-term stability of the CuS film decreased by 16.66% (4.02-3.35%), while that of the Pt based cell got elevated by 24.29% until 700min, and consequently diminished by 8.27% from 700 to 900min.

Fully subthreshold current-based characterization of interface traps and surface potential in III-V-on-insulator MOSFETs

Kim, S.K.,Lee, J.,Geum, D.M.,Park, M.S.,Choi, W.J.,Choi, S.J.,Kim, D.H.,Kim, S.,Kim, D.M. Pergamon Press ; Elsevier Science Ltd 2016 Solid-state electronics Vol.122 No.-

We report characterization of the interface trap distribution (D<SUB>it</SUB>(E)) over the bandgap in III-V metal-oxide-semiconductor field-effect transistors (MOSFETs) on insulator. Based only on the experimental subthreshold current data and differential coupling factor, we simultaneously obtained D<SUB>it</SUB>(E) and a nonlinear mapping of the gate bias (V<SUB>GS</SUB>) to the trap level (E<SUB>t</SUB>) via the effective surface potential (ψ<SUB>S,eff</SUB>). The proposed technique allows direct extraction of the interface traps at the In<SUB>0.53</SUB>Ga<SUB>0.47</SUB>As-on insulator (-OI) MOSFETs only from the experimental subthreshold current data. Applying the technique to the In<SUB>0.53</SUB>Ga<SUB>0.47</SUB>As channel III-V-OI MOSFETs with the gate width/length W/L=100/50, 100/25, and 100/10μm/μm, we obtained D<SUB>it</SUB>(E)@?10<SUP>11</SUP>-10<SUP>12</SUP>eV<SUP>-1</SUP>cm<SUP>-2</SUP> over the bandgap without the dimension dependence.

T_c and J_c distribution in in situ processed MgB₂ bulk superconductors with/without C doping

Kim, C.J.,Kim, Y.J.,Lim, C.Y.,Jun, B.H.,Park, S.D.,Choo, K.N. The Korea Institute of Applied Superconductivity a 2014 한국초전도저온공학회논문지 Vol.16 No.2

Temperature dependence of magnetic moment (m-T) and the magnetization (M-H) at 5 K and 20 K of the in situ processed $MgB_2$ bulk pellets with/without carbon (C) doping were examined. The superconducting critical temperature ($T_c$), the superconducting transition width (${\delta}T$) and the critical current density ($J_c$) were estimated for ten test samples taken from the $MgB_2$ bulk pellets. The reliable m-T characteristics associated with the uniform $MgB_2$ formation were obtained for both $MgB_2$ pellets. The $T_cs$ and ${\delta}Ts$ of all test samples of the undoped $MgB_2$ were the same each other as 37.5 K and 1.5 K, respectively. The $T_cs$ and ${\delta}Ts$ of the C-doped $MgB_2$ were 36.5 K and 2.5 K, respectively. Unlike the m-T characteristics, there existed the difference among the M-H curves of the test samples, which might be caused by the microstructure variation. In spite of the slight $T_c$ decrease, the C doping was effective in enhancing the $J_c$ at 5 K.

Reference stress based J and COD estimation of circumferential through-wall cracked elbows under in-plane bending

Kim, C.G.,Bae, K.D.,Kim, Y.J.,Oh, Y.J.,Budden, P.J. Pergamon Press 2015 Engineering fracture mechanics Vol.142 No.-

This paper proposes J-integral and crack opening displacement (COD) estimation equations based on the reference stress method for circumferential through-wall cracked elbows under in-plane bending. For best estimates of J and COD, an optimized reference load, used to define the reference stress, is given. The proposed equations are compared with detailed finite element results. They are further validated against eight published full-scale pipe test data. Comparison of crack initiation and maximum loads shows good agreement.

15-Deoxy-Δ^12,14-prostaglandin J₂ induces p53 expression through Nrf2-mediated upregulation of heme oxygenase-1 in human breast cancer cells

Kim, D. H.,Song, N. Y.,Kim, E. H.,Na, H. K.,Joe, Y.,Chung, H. T.,Surh, Y. J. Informa Healthcare 2014 Free radical research Vol.48 No.9

<P>Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and cytoprotective functions. However, HO-1 has oncogenic functions in cancerous or transformed cells. In the present work, we investigated the effects of HO-1 on the expression of p53 induced by 15-deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> (15d-PGJ<SUB>2</SUB>) in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d-PGJ<SUB>2</SUB> led to time-dependent increases in the expression of p53 as well as HO-1. Upregulation of p53 expression by 15d-PGJ<SUB>2</SUB> was abrogated by si-RNA knock-down of HO-1. In MCF-7 cells transfected with HO-1 si-RNA, 15d-PGJ<SUB>2</SUB> failed to induce expression of p53 as well as HO-1. In addition, HO-1 inducers enhanced the p53 expression. We speculated that iron, a by-product of HO-1-catalyzed reactions, could mediate 15d-PGJ<SUB>2</SUB>-induced p53 expression. Upregulation of p53 expression by 15d-PGJ<SUB>2</SUB> was abrogated by the iron chelator desferrioxamine in MCF-7 cells. Iron released from heme by HO-1 activity is mostly in the Fe<SUP>2+</SUP> form. When MCF-7 cells were treated with the Fe<SUP>2+</SUP>-specific chelator phenanthroline, 15d-PGJ<SUB>2</SUB>-induced p53 expression was attenuated. In addition, levels of the Fe-sequestering protein H-ferritin were elevated in 15d-PGJ<SUB>2</SUB>-treated MCF-7 cells. In conclusion, upregulation of p53 and p21 via HO-1 induction and subsequent release of iron with accumulation of H-ferritin may confer resistance to oxidative damage in cancer cells frequently challenged by redox-cycling anticancer drugs.</P>