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>

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.

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>

Reply to ''Comment on ''Facile chemical bath deposition of CuS nano peas like structure as a high efficient counter electrode for quantum-dot-sensitized solar cells'' by H.-J. Kim, J.-H. Kim, CH. S. S. Pavan Kumar, D. Punnoose, S.-K. Kim, C. V. V. M. Gop

Kim, H.J.,Kim, J.H.,Pavan Kumar, C.H.S.S.,Punnoose, D.,Kim, S.K.,Gopi, C.V.V.M.,Rao, S.S. Elsevier Sequoia 2015 Journal of Electroanalytical Chemistry Vol.756 No.-

Structure-property relationship of D-A type copolymers based on thienylenevinylene for organic electronics

Kim, Y.A.,Jeon, Y.J.,Kang, M.,Jang, S.Y.,Kim, I.B.,Lim, D.H.,Heo, Y.J.,Kim, D.Y. Elsevier Science 2017 Organic electronics Vol.46 No.-

A series of D-A type conjugated polymers based on (E)-1,2-bis(3-dodecyllthiophen-2-yl)ethene (TV) as electron donor unit and with different repeating subunits, PTVBO8, PTVBT8, PTVTBO12, and PTVTBT12 were synthesized for use in organic field effect transistors and bulk heterojunction organic photovoltaics. Upon incorporation of alkoxy substituents in acceptor units, benzooxadiazole (BO) and benzothiadiazole (BT), polymer solubility improved and higher molecular weight polymers were obtained. In addition, all copolymers showed favorable thermal stability (T<SUB>d</SUB> > 300 <SUP>o</SUP>C), and low band gap properties (1.49-1.67 eV). The thiophene-flanked TV-TBX copolymers, PTVTBO12 and PTVTBT12, exhibited higher molecular weight and superior device performance in both OFETs and OPVs compared with the TV-BX copolymers. The electronic energy levels of copolymers were strongly influenced by the nature of acceptor units, while optical band gaps and shape of molecular orientation of polymer chains were affected by the presence or absence of thiophene spacer. Charge carrier mobilities in TV-TBX copolymers were 1 order of magnitude greater than in TV-BX copolymers. OFETs based on a PTVTBT12 with TG/BC configuration displayed the highest hole mobility of 0.48 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP>. The photovoltaic device containing a PTVTBO12:PC<SUB>71</SUB>BM (1:2 w/w) blend system exhibited best performance with a V<SUB>oc</SUB> of 0.56 V, a short-circuit current density (Jsc) of 13.1 mA cm<SUP>-2</SUP>, a fill factor (FF) of 69%, and a power conversion efficiency (PCE) of 5.0%.

Optical subthreshold current method for extracting the interface states in MOS systems

Kim, M.S.,Nam, I.C.,Kim, H.T.,Shin, H.T.,Kim, T.E.,Park, H.S.,Kim, K.S.,Kim, K.H.,Choi, J.B.,Min, K.S.,Kim, D.J.,Kang, D.W.,Kim, D.M. IEEE 2004 IEEE electron device letters Vol.25 No.2

Optical subthreshold current method (OSCM) is proposed for characterizing the interface states in MOS systems using the current-voltage characteristics under a photonic excitation. An optical source with a subbandgap (E<SUB>ph</SUB>>E<SUB>g</SUB>) photonic energy (E<SUB>ph</SUB>=0.943 eV, P<SUB>opt</SUB>=+5 dBm), which is less than the silicon bandgap (E<SUB>g</SUB>=1.12;eV), is employed for the optical subthreshold current characterization of interface states in the photoresponsive energy band. We applied the OSCM method under a subbandgap photonic excitation to MOS systems with a poly-Si gate and verified a U-shaped distribution of interface trap density D<SUB>it</SUB>=10<SUP>10</SUP>∼10<SUP>12</SUP> eV<SUP>-1</SUP>cm<SUP>-2</SUP> for n- and p-type MOSFETs with W/L=30 μm/1.2 μm.

Nocardioides basaltis sp. nov., isolated from black beach sand

Kim, K.-H.,Roh, S. W.,Chang, H.-W.,Nam, Y.-D.,Yoon, J.-H.,Jeon, C. O.,Oh, H.-M.,Bae, J.-W. Microbiology Society 2009 International journal of systematic and evolutiona Vol.59 No.1

<P>A novel Gram-positive, aerobic, short-rod-shaped bacterium, designated strain J112T, was isolated from black sand collected from Soesoggak, Jeju Island, Korea. The strain was found to be oxidase-negative and catalase-positive. Cells grew at 10-37 degrees C, at pH 5.5-8.0 and with 1-10 % NaCl. Growth occurred on marine agar but not on R2A or trypticase soy agar. A phylogenetic analysis based on 16S rRNA gene sequences showed that the strain belongs to the radiation of the genus Nocardioides. Strain J112T shared the highest 16S rRNA gene sequence similarities with Nocardioides marinisabuli SBS-12T (99.2 %), Nocardioides terrigena DS-17T (97.3 %), Nocardioides kribbensis KCTC 19038T (97.1 %) and type strains of other Nocardioides species with validly published names (<97 %). The DNA-DNA hybridization values between strain J112T and the three most closely related strains were low enough to justify the assignment of this strain to a novel species. On the basis of these phenotypic, phylogenetic and chemotaxonomic data, strain J112T represents a novel species of the genus Nocardioides, for which the name Nocardioides basaltis sp. nov. is proposed. The type strain is J112T (=KCTC 19365T=JCM 14945T).</P>

Observation of a d-wave gap in electron-doped Sr₂IrO₄

Kim, Y. K.,Sung, N. H.,Denlinger, J. D.,Kim, B. J. NATURE PUBLISHING GROUP 2016 NATURE PHYSICS Vol.12 No.1

<P>High-temperature superconductivity in cuprates emerges out of a highly enigmatic 'pseudogap' metal phase. The mechanism of high-temperature superconductivity is probably encrypted in the elusive relationship between the two phases, which spectroscopically is manifested as Fermi arcs-disconnected segments of zero-energy states-collapsing into d-wave point nodes upon entering the superconducting phase. Here, we reproduce this distinct cuprate phenomenology in the 5d transition-metal oxide Sr2IrO4. Using angle-resolved photo-emission, we show that the clean, low-temperature phase of 6-8% electron-doped Sr2IrO4 has gapless excitations only at four isolated points in the Brillouin zone, with a predominant d-wave symmetry of the gap. Our work thus establishes a connection between the low-temperature d-wave instability and the previously reported high-temperature Fermi arcs in electron-doped Sr2IrO4 (ref. 1). Although the physical origin of the d-wave gap remains to be understood, Sr2IrO4 is the first non-cuprate material to spectroscopically reproduce the complete phenomenology of the cuprates, thus offering a new material platform to investigate the relationship between the pseudogap and the d-wave gap.</P>