Polymorphisms of <i>KCNJ11</i> (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population

Koo, B. K.,Cho, Y. M.,Park, B. L.,Cheong, H. S.,Shin, H. D.,Jang, H. C.,Kim, S. Y.,Lee, H. K.,Park, K. S. Blackwell Publishing Ltd 2007 Diabetic medicine Vol.24 No.2

<P>Abstract</P><P>Aims </P><P>Kir6.2 is found in the pancreatic B-cell, cardiac and skeletal muscle and non-vascular smooth muscle. <I>KCNJ11</I>, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in <I>KCNJ11</I> are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.</P><P><B>Methods </B></P><P>We sequenced <I>KCNJ11</I> to identify common polymorphisms using 24 Korean DNA samples. Of the 14 polymorphisms found in <I>KCNJ11</I>, six common ones [genomic sequence (g.)−1709A>T, g.−1525T>C, g.67G>A (E23K), g.570C>T (A190A), g.1009A>G (I337V), and g.1388C>T] were genotyped in 761 Type 2 diabetic patients and in 630 non-diabetic subjects.</P><P><B>Results</B> </P><P>All the polymorphic loci in <I>KCNJ11</I> are in strong linkage disequilibrium in the Korean population and act as one haplotype block. g.67G>A and g.1009A>G were associated with an increased risk of Type 2 diabetes [age, sex, and body mass index (BMI)-adjusted odds ratios (OR) = 1.376 (1.085–1.745), <I>P</I> = 0.008 and 1.411 (1.111–1.791), <I>P</I> = 0.005, respectively], as was one haplotype (A-T-A-C-G-C in the order of polymorphisms as shown above) containing g.67A and g.1009G [OR = 1.359 (1.080–1.709), <I>P</I> = 0.009]. The haplotype (A-T-A-C-G-C) was also strongly associated with hypertension [OR = 1.655 (1.288–2.126), <I>P</I> < 0.001].</P><P><B>Conclusions </B></P><P>Polymorphisms in <I>KCNJ11</I> are associated with Type 2 diabetes and also with hypertension in the Korean population.</P>

Conduritol F, the discriminant marker between C. wilfordii and C. auriculatum by ¹H NMR spectroscopy

Jang, H.S.,Jeong, B.,Choi, S.Y.,Jang, G.H.,Park, K.C.,Kwon, Y.S.,Yang, H. Academic Press 2017 Microchemical Journal Vol. No.

<P>Quantitative H-1 nuclear magnetic resonance (qNMR) spectroscopy is a powerful and versatile technique to enable the absolute quantification of specific components in a mixture with excellent reproducibility and robustness. In the present study, qNMR analysis was applied to conduritol F, a chemical marker with the potential to distinguish between C wilfordii and C auriculatum. We found that the signals of H-5 and H-6 of conduritol F were well-separated from others with purities sufficient to be used to distinguish between C wilfordii and C. auriculatum. This simple methodology can be applied to identify one or two species in products or powdered herbs widely distributed in the markets. (C) 2017 Elsevier B.V. All rights reserved.</P>

Microstructural evolution and tensile properties of oxide dispersion strengthened Alloy 617 at elevated temperatures

Chun, Y.B.,Mao, X.,Han, C.H.,Jang, J. Elsevier Sequoia 2017 Materials science & engineering Structural materia Vol.706 No.-

<P><B>Abstract</B></P> <P>This study investigated evolution of the microstructure of oxide dispersion strengthened Alloy 617 with annealing temperature. A mixture of prealloyed Alloy 617 and Y<SUB>2</SUB>O<SUB>3</SUB> powders was mechanically alloyed and consolidated by hot-extrusion at 1100°C. Hot extrusion developed a submicron-sized grain structure with M<SUB>23</SUB>C<SUB>6</SUB> carbides and finely dispersed Al<SUB>2</SUB>O<SUB>3</SUB> and Y<SUB>2</SUB>Ti<SUB>2</SUB>O<SUB>7</SUB> oxides. The fine-grained structure was stable during subsequent annealing at temperatures up to 1250°C. Further increase of annealing temperature to 1300°C resulted in a significantly coarsened grain structure, which was coincident with the abrupt coarsening of oxides. M<SUB>23</SUB>C<SUB>6</SUB> carbides in the as-extruded conditions were transformed to M<SUB>7</SUB>C<SUB>3</SUB> carbides with complex shapes when annealed at 1200°C, and their shapes changed to very coarse hexagonal prisms at 1250°C, which was followed by the formation of eutectic M<SUB>2</SUB>C carbides at grain boundaries at 1300°C. Tensile tests of the as-extruded ODS Alloy 617 showed that the yield strength decreased steeply at a transition temperature of around 600°C, which can be attributed to diffusional creep along the grain boundaries.</P>

200 GeV/핵자 유황이온과 핵건판핵의 충돌에 의해 생성된 헬륨 파쇄핵의 극한파쇄 연구

김동철,송진섭,윤천실,정성헌,박인곤,김종오,김철수,김태연,이승희,조재희,천병구,김재률,김준원,김태익,박명렬,장한일,임인택 慶尙大學校 기초과학연구소 1992 基礎科學硏究所報 Vol.8 No.-

고에너지 중이온 원자핵과 핵건판의 충돌에서, 200GeV/핵자 유황이온에 의해 생성된 파쇄 헬륨핵(Z=2)의 실험실계의 방출각 분포는 표적핵에 무관한 회귀공식. dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)]로 잘 표현된다. 여기에서 의사신속도 η=-ln[tan(θ/2)]이고, y_b는 실험실계의 입사입자(^32S)의 신속도이다. 이 공식에 의한 적합에서 k=-0.057±0.008로 얻어진다. 즉, 핵건판과 고에너지 중이온의 충돌에서 파쇄 헬륨핵의 exp(η-y_b)의 분포는 "극한파쇄" 현상을 잘 설명하고 있다. The angular distribution of emission angle θ of helium (Z=2) produced in the collisions of incident particles of 200 GeV/nucleon ^32S in nuclear emulsion is well expressed by dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)] where the pseudorapidity is η=-ln[tan(θ/2)], the laboratory system primary rapidity is y_b, and k=-0.057+0.008. The shape of this frequency of occurrence distributions in terms of exp(η-y_b) attests to the validity of the concept of "limiting fragmentation" for helium projectile fragments produced in the projectile fragmentation regions of heavy ion collisions in nuclear emulsion.

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder

Jung, W. H.,Kang, D.‐,H.,Han, J. Y.,Jang, J. H.,Gu, B.‐,M.,Choi, J.‐,S.,Jung, M. H.,Choi, C.‐,H.,Kwon, J. S. Blackwell Publishing Ltd 2011 Acta psychiatrica Scandinavica Vol.123 No.5

<P>Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder.</P><P><B>Objective: </B> Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD.</P><P><B>Method: </B> Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task.</P><P><B>Results: </B> Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation.</P><P><B>Conclusion: </B> These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.</P>

Ni-Co 합금강의 기계적 특성에 대한 탄소함량의 영향

장경천,국중민,정장만,권택용,최병기 한국공작기계학회 2004 한국공작기계학회 춘계학술대회논문집 Vol.2004 No.-

This study was to evaluate the effect of carbon content on metallic change and fatigue characteristics with Fe-29%Ni-17%Co, low heat expansion alloy, widely using electronic components, precision machines, and sealing with glass and metal etc. The steels were fabricated with variation of carbon content, 0, 0.03, 0.06, 0.1, and 0.20% with VIM and tensile test and fatigue test were performed to achieve the above purpose. The more carbon content, the higher hardness value and yield strength. But elongation of 0.03%C, 0.06%C, and 0.10%C specimen decreased about 2.2%, 1.5% and 0.8% respectively more than that of the base metal. Especially the strength and elongation of 0.20%C specimen increased simultaneously about 14.4% and 7.5%. Fatigue life of 0.03%C specimen decreased but the more carbon content, the higher fatigue life over 0.06% carbon content more than that of base metal.

Myelin Basic Protein Citrullination, a Hallmark of Central Nervous System Demyelination, Assessed by Novel Monoclonal Antibodies in Prion Diseases

Jang, B.,Jeon, Y. C.,Shin, H. Y.,Lee, Y. J.,Kim, H.,Kondo, Y.,Ishigami, A.,Kim, Y. S.,Choi, E. K. HUMANA PRESS INC 2018 Molecular Neurobiology Vol.55 No.4

<P>Myelin basic protein (MBP) citrullination by peptidylarginine deiminase (PAD) enzymes leads to incomplete protein-lipid bilayer interactions and vulnerability to proteolytic enzymes, resulting in disorganization of the myelin sheath in the central nervous system. Therefore, citrullinated MBP (citMBP) has been suggested as a hallmark of demyelination, but how citMBP is implicated in prion diseases remains unknown. For the first time, we developed mouse monoclonal anti-citMBP IgG1 (clones 1B8, 1H1, and 3C6) and IgM (clone 3G5) antibodies that recognize human citMBP at its R25, R122, and R130 residues and at its C-terminal region (or the corresponding sites in mouse MBP), respectively. Using a biochemical, immunohistochemical, and immunogold-silver staining for electron microscopy techniques, we found that MBP residue R23 (corresponding to human R25) was specifically citrullinated, was stained as intense punctae in the corpus callosum, the striatum, and the cerebellar white matter, and was predominantly localized in disorganized myelin in the brains of scrapie-infected mice. In the brains of Creutzfeldt-Jakob disease (CJD) patients, MBP residues R25, R122, and R130 were markedly citrullinated and were stained as fibrils and punctae. In particular, white matter regions, such as the midbrain and the medulla, exhibited high levels of citMBP compared to other regions. However, the high levels of citMBP were not correlated with PAD2 expression. The clone 3G5 recognized significantly increased expression of the 18.5 kDa and/or 21.5 kDa variants of MBP in prion disease. Our findings suggest that significantly increased levels of citMBP may reflect demyelinating neuropathology, and that these newly developed antibodies may be useful for identifying demyelination.</P>

NMR Solution Structure of HP0827 (O25501_HELPY) from Helicobacter pylori: Model of the Possible RNA-binding Site

Jang, S.-B.,Ma, C.,Lee, J.-Y.,Kim, J.-H.,Park, S. J.,Kwon, A.-R.,Lee, B.-J. Oxford University Press 2009 The Journal of biochemistry Vol.146 No.5

<P>The HP0827 protein is an 82-residue protein identified as a putative ss-DNA-binding protein 12RNP2 Precursor from Helicobacter pylori. Here, we have determined 3D structure of HP0827 using Nuclear Magnetic Resonance. It has a ferredoxin-like fold, beta1-alpha1-beta2-beta3-alpha2-beta4 (alpha; alpha-helix and beta; beta-sheet) and ribonucleoprotein (RNP) motifs which are thought to be important in RNA binding. By using structural homologues search and analyzing electrostatic potential of surface, we could compared HP0827 with other RNA-binding proteins (sex-lethal, T-cell restricted intracellular antigen-1, U1A) to predict RNA-binding sites of HP0827. We could predict that beta sheets of HP0827, especially beta1 and beta3, are primary region for RNA binding. Consequently, similar to other RNA-binding proteins, RNP motifs (Y5, F45, F47), positively charged and hydrophobic regions (K32, R37, K40, K41, K43, R70, R73) are proposed as a putative RNA-binding sites. In addition, differences in amino acids composition of RNP motifs, N, C-terminal residues, loop-region fold and the orientation of alpha1-helix with other RNA recognition motif proteins could give specific biological functions to HP0827. Finally, the study on natural RNA target is also important to completely understand the biological function of HP0827.</P>

Far upstream element-binding protein-1, a novel caspase substrate, acts as a cross-talker between apoptosis and the c-myc oncogene

Jang, M,Park, B C,Kang, S,Chi, S-W,Cho, S,Chung, S J,Lee, S C,Bae, K-H,Park, S G Macmillan Publishers Limited 2009 Oncogene Vol.28 No.12

Far upstream element-binding protein-1 (FBP-1) binds to an upstream element of the c-myc promoter and regulates the c-myc mRNA level. Earlier, FBP-1 was identified as a candidate substrate of caspase-7. Here, we report that FBP-1 is cleaved by executor caspases, both in vitro and during apoptosis. Cleavage occurs at the caspase consensus site (DQPD<SUP>74</SUP>) located within the classical bipartite nuclear localization signal sequence. In cells subjected to apoptotic stimuli, the caspase-mediated cleavage of FBP-1 leads to its decreased presence in the nucleus, concomitant with the marked downregulation of c-Myc and its various target proteins. By contrast, cells transfected with a non-cleavable mutant of FBP-1 (D74A) maintain higher levels of c-Myc and are protected from apoptosis. On the basis of these results, we suggest that the oncogenic potential of c-Myc is ‘switched off’ after apoptosis induction as a consequence of the caspase-mediated cleavage of FBP-1.Oncogene (2009) 28, 1529–1536; doi:10.1038/onc.2009.11; published online 16 February 2009

Antiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins

Jang, Y.,Lee, H.W.,Shin, J.S.,Go, Y.Y.,Kim, C.,Shin, D.,Malpani, Y.,Han, S.B.,Jung, Y.S.,Kim, M. Elsevier/North-Holland 2016 ANTIVIRAL RESEARCH Vol.134 No.-

<P>The spiro compound 5,6-dimethyl-3H,3'H-spiro(benzofuran-2,1'-isobenzofuran)-3,3'-dione (KR-23502) has antiviral activity against influenza A and more potently B viruses. The aim of this study is to elucidate its mechanism of action. Subcellular localization and time-course expression of influenza B viral proteins, nucleoprotein (NP) and matrix protein 1 (M1), showed that KR-23502 reduced their amounts within 5 h post-infection. Early steps of virus life cycle, including virus entry, nuclear localization of NP and viral RNA-dependent RNA replication, were not affected by KR-23502. Instead it interrupted a later event corresponding to nuclear export of NP and M1 proteins. Delivery of viral ribonucleoprotein (vRNP)-M1 complex has been known to be mediated by the viral nuclear export protein (NEP) through interaction with cellular chromosomal maintenance 1 (CRM1) protein. In this study, we experimentally demonstrated that the compound targets the nuclear export of vRNP. Moreover, a single mutation (aspartate to glycine) at amino acid position 54 in M1 [M1(D54G)] was detected after 18 passages in the presence of KR-23502 with a 2-fold increase in 50% effective concentration indicating that this compound has a relatively high genetic barrier to resistance. Interestingly, it was observed that proteasome-mediated degradation of M1 (D54G) was attenuated by KR-23502. In conclusion, we suggest that KR-23502 shows its anti-influenza activity by downregulating NEP/CRM1-mediated nuclear export of influenza vRNP and M1. KR-23502 provides a core chemical skeleton for further structure-based design of novel antivirals against influenza viruses. (C) 2016 Elsevier B.V. All rights reserved.</P>