Sun-Kyung Lee

Genetic variations in ATP2B1 , CSK , ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts

Blood pressure, one of the important vital signs, is affected by multiple genetic and environmental factors. Recently, several genome-wide association (GWA) studies have successfully identified genetic factors that influence blood pressure and hypertension risk. In this study, we report results of the Korean Association REsource (KARE, 8842 subjects) GWA study on blood pressure and hypertension risk. In all, 10 single-nucleotide polymorphisms (SNPs) that showed significant association with hypertension were further analysed for replication associations in the Health2 project (7861 subjects). Among these 10 SNPs, 3 were replicated in the Health2 cohort for an association with systolic or diastolic blood pressure. The most significant SNP (rs17249754 located in ATPase, Ca++ transporting, plasma membrane 1 (ATP2B1)) has been previously reported, and the other two SNPs are rs1378942 in the c-src tyrosine kinase (CSK) gene and rs12945290 in the arylsulphatase G (ARSG) gene. An additional hypertension case–control study confirmed that rs17249754 (in ATP2B1) increases hypertension risk in both the KARE and Health2 (meta-analysis, P-value=4.25 × 10−9) cohorts. One more SNP, rs995322, located in the CUB and Sushi multiple domains 1 (CSMD1), is also associated with increased risk of hypertension (meta-analysis, P-value=1.00 × 10−4). Despite the difficulty of obtaining replication results for a complex trait genetic association between blood pressure and hypertension, we were able to identify consistent genetic factors in both the Korean cohorts in ATP2B1, CSK, ARSG and CSMD1 genes.

Feasibility Analysis of the Positioning of Superconducting Fault Current Limiters for the Smart Grid Application Using Simulink and SimPowerSystem

One of the most important topics regarding the application of superconducting fault current limiters (SFCL) for upcoming smart grid is related to its possible effect on the reduction of abnormal fault current and the suitable location in the micro grids. Due to the grid connection of the micro grids with the current power grids, excessive fault current is a serious problem to be solved for successful implementation of micro grids. However, a shortage of research concerning the location of SFCL in micro grid is felt. In this work, a resistive type SFCL model was implemented by integrating Simulink and SimPowerSystem blocks in Matlab. The designed SFCL model could be easily utilized for determining an impedance level of SFCL according to the fault-current-limitation requirements of various kinds of the smart grid system. In addition, typical smart grid model including generation, transmission and distribution network with dispersed energy resource was modeled to determine the location and the performance of the SFCL. As for a dispersed energy resource, 10 MVA wind farm was considered for the simulation. Three phase faults have been simulated at different locations in smart grid and the effect of the SFCL and its location on the wind farm fault current was evaluated. Consequently, the optimum arrangement of the SFCL location in Smart Grid with renewable resources has been proposed and its remarkable performance has been suggested.

Characteristics of hydrogen co-doped ZnO : Al thin films

ZnO films co-doped with H and Al (HAZO) were prepared by sputtering ZnO targets containing 1 wt% Al2O3 on Corning glass at a substrate temperature of 150 °C with Ar and H2/Ar gas mixtures. The effects of hydrogen addition to Al-doped ZnO (AZO) films with low Al content on the electrical, the optical and the structural properties of the as-grown films as well as the vacuum- and air-annealed films were examined. Secondary ion mass spectroscopy analysis showed that the hydrogen concentration increased with increasing H2 in sputter gas. For the as-deposited films, the free carrier number increased with increasing H2. The Hall mobility increased at low hydrogen content, reaching a maximum before decreasing with a further increase of H2 content in sputter gas. Annealing at 300 °C resulted in the removal of hydrogen, causing a decrease in the carrier concentration. It was shown that hydrogen might exist as single isolated interstitial hydrogen bound with oxygen, thereby acting like an anionic dopant. Also, it was shown that the addition of hydrogen to ZnO films doped with low metallic dopant concentration could yield transparent conducting films with very low absorption loss as well as with proper electrical properties, which is suitable for thin film solar cell applications.

C. elegans behavior of preference choice on bacterial food

Caenorhabditis elegans is a free living soil nematode and thus in its natural habitat, C. elegans encounters many different species of soil bacteria. Although some soil bacteria may be excellent sources of nutrition for the worm, others may be pathogenic. Thus, we undertook a study to understand how C. elegans can identify their preferred food using a simple behavioral assay. We found that there are various species of soil bacteria that C. elegans prefers in comparison to the standard laboratory E. coli strain OP50. In particular, two bacterial strains, Bacillus mycoides and Bacillus soli, were preferred strains. Interestingly, the sole feeding of these bacteria to wild type animals results in extended lifespan through the activation of the autophagic process. Further studies will be required to understand the precise mechanism controlling the behavior of identification and selection of food in C. elegans.

Biarylpyrazolyl Oxadiazole as Potent, Selective, Orally Bioavailable Cannabinoid-1 Receptor Antagonists for the Treatment of Obesity

Since the CB1 cannabinoid receptor antagonist 1 (SR141716, rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In the present study, biarylpyrazole analogues based on a pyrazole core coupled with 1,3,4-oxadiazole were synthesized and tested for CB1 receptor binding affinity. Thorough SAR studies to optimize pyrazole substituents as well as 1,3,4-oxadiazole ring led to several novel CB1 antagonists with IC(50) approximately 1 nM for the CB1 receptor binding. Among these analogues, we identified 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1,3,4-oxadiazole 43c as a promising precandidate for the development as an antiobesity agent.

Interplay Between the Oxidoreductase PDIA6 and microRNA-322 Controls the Response to Disrupted Endoplasmic Reticulum Calcium Homeostasis

Depletion of Ca2+ in the endoplasmic reticulum favors activation of a stress response involving IRE1α. Responding the Right Way to Cellular Stress Some proteins must be folded correctly in the endoplasmic reticulum (ER) to function properly. Various stress conditions can cause the buildup of unfolded proteins in the ER, which can cause cell death. There are multiple ways in which cells can respond to deal with the buildup of unfolded proteins. Groenendyk et al. investigated how cells deal with the stress of depletion of calcium ions from the ER and identified a pathway involving a microRNA and an oxidoreductase in the ER. They found that depletion of calcium from the ER resulted in the decreased abundance of a microRNA, which enabled a target mRNA and the oxidoreductase it encoded to accumulate. The oxidoreductase then activated a specific stress response. The authors showed that this pathway could be present in mice and nematodes. The disruption of the energy or nutrient balance triggers endoplasmic reticulum (ER) stress, a process that mobilizes various strategies, collectively called the unfolded protein response (UPR), which reestablish homeostasis of the ER and cell. Activation of the UPR stress sensor IRE1α (inositol-requiring enzyme 1α) stimulates its endoribonuclease activity, leading to the generation of the mRNA encoding the transcription factor XBP1 (X-box binding protein 1), which regulates the transcription of genes encoding factors involved in controlling the quality and folding of proteins. We found that the activity of IRE1α was regulated by the ER oxidoreductase PDIA6 (protein disulfide isomerase A6) and the microRNA miR-322 in response to disruption of ER Ca2+ homeostasis. PDIA6 interacted with IRE1α and enhanced IRE1α activity as monitored by phosphorylation of IRE1α and XBP1 mRNA splicing, but PDIA6 did not substantially affect the activity of other pathways that mediate responses to ER stress. ER Ca2+ depletion and activation of store-operated Ca2+ entry reduced the abundance of the microRNA miR-322, which increased PDIA6 mRNA stability and, consequently, IRE1α activity during the ER stress response. In vivo experiments with mice and worms showed that the induction of ER stress correlated with decreased miR-322 abundance, increased PDIA6 mRNA abundance, or both. Together, these findings demonstrated that ER Ca2+, PDIA6, IRE1α, and miR-322 function in a dynamic feedback loop modulating the UPR under conditions of disrupted ER Ca2+ homeostasis.

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

We investigated the effects of an Na(+)/H(+) exchanger inhibitor, sabiporide, on excitotoxicity in cultured neuronal cells and in vivo. Sabiporide attenuated glutamate- or NMDA (N-methyl-d-aspartic acid)-induced neuronal cell death. Sabiporide also reduced glutamate or NMDA-induced increase in [Ca(2+)](i). In in vivo brain ischemia model, sabiporide produced protective effects, decreasing the infarct size and edema volume. Our results suggest that sabiporide elicits neuroprotective effect both in vitro and in vivo.

Large-scale synthesis of high-purity well-aligned carbon nanotubes using pyrolysis of iron(II) phthalocyanine and acetylene

Abstract Well-aligned carbon nanotubes (CNTs) with high purity have been produced by pyrolysis of iron(II) phthalocyanine and acetylene at 800 °C. The synthesized CNTs have a length of 75 μm and diameters ranging from 20 to 60 nm. The CNTs have a bamboo-like structure and exhibit good crystallinity of graphite sheets. The growth rate of the CNTs was rapidly increased with adding C2H2. Our results demonstrate that the proposed growth method is suitable to large-scale synthesis of high-purity well-aligned CNTs on various substrates.

Vacuolar (H + )-ATPases in Caenorhabditis elegans: What can we learn about giant H + pumps from tiny worms?

Vacuolar (H(+))-ATPases, also called V-ATPases, are ATP-driven proton pumps that are highly phylogenetically conserved. Early biochemical and cell biological studies have revealed many details of the molecular mechanism of proton pumping and of the structure of the multi-subunit membrane complex, including the stoichiometry of subunit composition. In addition, yeast and mouse genetics have broadened our understanding of the physiological consequences of defective vacuolar acidification and its related disease etiologies. Recently, phenotypic investigation of V-ATPase mutants in Caenorhabditis elegans has revealed unexpected new roles of V-ATPases in both cellular function and early development. In this review, we discuss the functions of the V-ATPases discovered in C. elegans.

Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on glutamate-induced neuronal cell death and ischemia-induced cerebral infarct

We investigated the effects of a novel Na(+)/H(+) exchanger-1 (NHE-1) inhibitor KR-33028 on glutamate excitotoxicity in cultured neuron cells in vitro and cerebral infarct in vivo by comparing its potency with that of zoniporide, a well-known, highly potent NHE-1 inhibitor. KR-33028 inhibited NHE-1 activation in a concentration-dependent manner (IC(50)=2.2 nM), with 18-fold greater potency than that of zoniporide (IC(50)=40.7 nM). KR-33028 significantly attenuated glutamate-induced LDH release with approximately 100 times lower EC(25) than that of zoniporide in cortical neurons in vitro (EC(25) of 0.007 and 0.81 microM, respectively), suggesting its 100-fold greater potency than zoniporide in producing anti-necrotic effect. In addition, the EC(50) of KR-33028 for anti-apoptotic effect was 100 times lower than that of zoniporide shown by TUNEL positivity (0.005 and 0.62 microM, respectively) and caspase-3 activity (0.01 and 2.64 microM, respectively). Furthermore, the EC(50) value of KR-33028 against glutamate-induced intracellular Ca(2+) overload was also 100 times lower than that of zoniporide (EC(50) of 0.004 and 0.65 microM, respectively). In the in vivo cerebral infarct model (60 min middle cerebral artery occlusion followed by 24 h reperfusion), KR-33028 reduced infarct size in a dose-dependent manner. Its ED(25) value, however, was quite similar to that of zoniporide (ED(25) of 0.072 and 0.097 mg/kg, respectively). Hence these results suggest that the novel NHE-1 inhibitor, KR-33028, could be an efficient therapeutic tool to protect neuronal cells against ischemic injury.