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>

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.

Individually carbon-coated and electrostatic-force-derived graphene-oxide-wrapped lithium titanium oxide nanofibers as anode material for lithium-ion batteries

Kim, J.,Kim, J.Y.,Pham-Cong, D.,Jeong, S.Y.,Chang, J.,Choi, J.H.,Braun, P.V.,Cho, C.R. Pergamon Press 2016 ELECTROCHIMICA ACTA Vol.199 No.-

The as-electrospun polymeric lithium titanate nanofibers are crystallized into Li<SUB>4</SUB>Ti<SUB>5</SUB>O<SUB>12</SUB> nanofibers (denoted as LTO NFs) via post-annealing. The LTO NFs are coated with a carbon layer using a glucose polymer via hydrothermal synthesis. The GO layer electrostatically attracts to the positively charged LTO NFs, resulting in the uniform wrapping of individual LTO NFs without aggregation. The introduction of uniformly coated carbon and GO double layers led to an enhanced rate capability (110mAhg<SUP>-1</SUP>at 20C) and over two orders of magnitude higher diffusion coefficient (D<SUB>Li</SUB>=~1.04x10<SUP>-11</SUP>cm<SUP>2</SUP>s<SUP>-1</SUP>) of the tailored LTO NFs with carbon and GO network compared with those of the pristine LTO NFs. Extended testing for over 100 cycles demonstrates the cyclic stability and Coulombic efficiency of over 99% of this system. These results indicate that the interconnection and networks of LTO NFs through carbon coating and the individual GO wrapping, which facilitates the lithium ion and electron transportation, may show excellent electrochemical performance.

Conjugated polymers containing pyrimidine with electron withdrawing substituents for organic photovoltaics with high open-circuit voltage

Kim, J.,Lee, J.,Chae, S.,Shim, J.Y.,Lee, D.Y.,Kim, I.,Kim, H.J.,Park, S.H.,Suh, H. IPC Science and Technology Press 2016 Polymer Vol.83 No.-

Polymers using 6-(2-thienyl)-4H-thieno[3,2-b]indole (TTI) with high planarity were synthesized and utilized for the photovoltaics. Push-pull types of conjugated polymers (PTTICN, PTTICNR and PTTIFR) containing TTI as electron pushing unit and 2-pyriminecarbonitrile or 2-fluoropyrimidine as electron pulling unit were synthesized. We designed pyrimidine derivatives with strong electron-withdrawing group (C?N or fluorine) for the generation of strong electron pulling property. By the combination with the electron pushing unit, the pyrimidines with strong electron pulling units will provide low highest occupied molecular orbital (HOMO) energy levels for higher open-circuit voltages (V<SUB>OC</SUB>). For the syntheses of the polymers, the electron pushing and the electron pulling units were combined by Stille coupling reaction with Pd(0)-catalyst. The polymers of PTTICN and PTTICNR with CN unit show higher V<SUB>OC</SUB> than the polymer with fluorine unit. The device comprising PTTICNR and PCBM (1:4) with diiodooctane (DIO) additive showed a V<SUB>OC</SUB> of 0.82 V, a J<SUB>SC</SUB> of 6.38 mA/cm<SUP>2</SUP>, and a fill factor (FF) of 0.53, giving a power conversion efficiency of 2.81%.

Influence of surface texturing conditions on crystalline silicon solar cell performance

Kim, H.,Park, S.,Kim, S.M.,Kim, S.,Kim, Y.D.,Tark, S.J.,Kim, D. Elsevier 2013 Current Applied Physics Vol.13 No.suppl2

We carried out the surface texturing of crystalline silicon in alkaline solutions via anisotropic etching. We achieved random pyramids of about 10 μm in size. The size of these pyramids was then gradually reduced using a new solution. In this paper, we investigate the impact of the size of the pyramids on the emitter properties and the front electrode (Ag) contact. To make small (~3.5 μm) and large (~9.0 μm) pyramids, we controlled the texturing time and performed one-sided texturing using a silicon nitride film. We compared the formation and quality of a POCl<SUB>3</SUB>-diffused n<SUP>+</SUP> emitter in a furnace for small and large pyramids by using SEM images and emitter saturation current density (J<SUB>0e</SUB>) measured Quasi-Steady-State Photo-Conductance (QSSPC). For a comparison, we carried out to simulated using TCAD simulator software (SILVACO, the Athena module). After metallization, we measured the Ag contact resistance via the transfer length method (TLM). We observed the surface distributions of the Ag crystallites using SEM images. We used light I-V to measure the performance of screen-printed solar cells. The efficiency of the solar cell in the case of the small and that in the case of the large pyramids improved by about 17.4% and 17.0%, respectively. We believe that differences in the emitter uniformity and the front Ag contact resistance resulted from this difference in the cell performance. Solar cells perform better when the pyramids are small.

Identification of Novel SNPs in Bovine Insulin-like Growth Factor Binding Protein-3 (IGFBP3) Gene

Kim, J.Y.,Yoon, D.H.,Park, B.L.,Kim, L.H.,Na, K.J.,Choi, J.G.,Cho, C.Y.,Lee, H.K.,Chung, E.R.,Sang, B.C.,Cheong, I.J.,Oh, S.J.,Shin, Hyoung Doo Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.1

The insulin-like growth factors (IGFs), their receptors, and their binding proteins play key roles in regulating cell proliferation and apoptosis. Insulin-like growth factor binding protein-3 (IGFBP3, OMIM #146732) is one of the proteins that bind to the IGFs. IGFBP3 is a modulator of IGF bioactivity, and direct growth inhibitor in the extravascular tissue compartment. We identified twenty-two novel single nucleotide polymorphisms (SNPs) in IGFBP3 gene in Korean cattle (Hanwoo, Bos taurus coreanae) by direct sequencing of full gene including -1,500 bp promoter region. Among the identified SNPs, five common SNPs were screened in 650 Korean cattle; one SNP in promoter (IGFBP3 G-854C), one in 5'UTR region (IGFBP3 G-100A), two in intron 1 (IGFBP3 G+421T, IGFBP3 T+1636A), and one in intron 2 (IGFBP3 C+3863A). The frequencies of each SNP were 0.357 (IGFBP3 G-854C), 0.472 (IGFBP3 G-100A), 0.418 (IGFBP3 G+421T), 0.363 (IGFBP3 T+1636A) and 0.226 (IGFBP3 C+3863A), respectively. Haplotypes and their frequencies were estimated by EM algorithm. Six haplotypes were constructed with five SNPs and linkage disequilibrium coefficients (|D'|) between SNP pairs were also calculated. The information on SNPs and haplotypes in IGFBP3 gene could be useful for genetic studies of this gene.

Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs

Kim, K.R.,Kim, H.Y.,Lee, Y.D.,Ha, J.S.,Kang, J.H.,Jeong, H.,Bang, D.,Ko, Y.T.,Kim, S.,Lee, H.,Ahn, D.R. Elsevier Science Publishers 2016 Journal of controlled release Vol.243 No.-

<P>Nanoparticle delivery systems have been extensively investigated for targeted delivery of anticancer drugs over the past decades. However, it is still a great challenge to overcome the drawbacks of conventional nanoparticle systems such as liposomes and micelles. Various novel nanomaterials consist of natural polymers are proposed to enhance the therapeutic efficacy of anticancer drugs. Among them, deoxyribonucleic acid (DNA) has received much attention as an emerging material for preparation of self-assembled nanostructures with precise control of size and shape for tailored uses. In this study, self-assembled mirror DNA tetrahedron nanostructures is developed for tumor-specific delivery of anticancer drugs. L-DNA, a mirror form of natural D-DNA, is utilized for resolving a poor serum stability of natural D-DNA. The mirror DNA nanostructures show identical thermodynamic properties to that of natural D-DNA, while possessing far enhanced serum stability. This unique characteristic results in a significant effect on the pharmacokinetics and biodistribution of DNA nanostructures. It is demonstrated that the mirror DNA nanostructures can deliver anticancer drugs selectively to tumors with enhanced cellular and tissue penetration. Furthermore, the mirror DNA nanostructures show greater anticancer effects as compared to that of conventional PEGylated liposomes. Our new approach provides an alternative strategy for tumor-specific delivery of anticancer drugs and highlights the promising potential of the mirror DNA nanostructures as a novel drug delivery platform. (C) 2016 Elsevier B.V. All rights reserved.</P>

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%.