Youngha Kim
KAIST
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Featured researches published by Youngha Kim.
Biochemical and Biophysical Research Communications | 2013
Min-Young Noh; Kwangwoo Chun; Byung Yong Kang; Heejaung Kim; Ji-Seon Park; Han-Chang Lee; Youngha Kim; Sae-Kwang Ku; Seung Hyun Kim
Glycogen synthase kinase-3 (GSK-3) is emerging as a prominent therapeutic target of Alzheimers disease (AD). A number of studies have been undertaken to develop GSK-3 inhibitors for clinical use. We report two novel GSK-3 inhibitors (C-7a and C-7b) showing good activity and pharmacokinetic (PK) profiles. IC50 of new GSK-3 inhibitors were in the range of 120-130 nM, and they effectively reduced the Aβ-oligomers induced neuronal toxicity. Also, new GSK-3 inhibitors decreased the phosphorylated tau at pThr231, pSer396, pThr181, and pSer202, and inhibited the GSK-3 activity against Aβ-oligomers induced neuronal cell toxicity. In B6;129-Psen1(tm1Mpm) Tg(APPSwe, tauP301L)1Lfa/Mmjax model of AD, oral administration of C-7a (20 mg/kg, 50 mg/kg) showed increased total arm entries and spontaneous alteration of Y-maze which was regarded as short-term memory. In particular, 50 mg/kg C-7a treated mice significantly decreased the level of phosphorylated tau (Ser396) in brain hippocampus. We suggest that new GSK-3 inhibitor (C-7a) is potential candidates for the treatment of AD.
Genes & Genomics | 2011
Mi-Hee Park; Seok-Rae Park; Mi-Ra Lee; Youngha Kim; Pyeung-Hyeun Kim
Retinoic acid (RA) is considered to possess an activity of IgA isotype switching. Thus far, TGF-β1 is known to be the most powerful IgA isotype switch factor. To elucidate the molecular mechanisms underlying the Ig germ line (GL) α transcriptional regulation by RA, we constructed three different sizes of mouse GLα promoter reporters; short-GLα(−130/+14), middle-GLα(−448/+72) and long-GLα(−3028/+72). Based on luciferase assay, RA increased the activity of all three GLα promoter reporters by approximately 2-fold and the effect was further enhanced by TGF-β1. Overexpression of Smad3/4 increased TGF-β1-induced GLα promoter activities but had no effect on RA-induced GLα promoter activities. In order to analyze the characteristics of the RA-inducible GLα promoter region, we also constructed two mutant reporters: Smad3 binding elements (SBEs)-substituted short-GLα (short-GLα mSBE) and Runx3 binding elements (RBEs)-substituted short-GLα (short-GLα mRBE) promoter reporters. Promoter activities of the two mutant reporters to RA were comparable to that of wild type reporter, while those of the two mutant reporters to TGF-β1 were markedly diminished as compared to that of WT short-GLα. Finally, RA-induced GLα transcription was virtually disappeared by LE540, an antagonist of RA receptor (RAR). Taken together, these results suggest that RA induces GLα transcription mainly through RAR pathway, where neither Smad3/4 nor Runx3 is involved.
Bioorganic & Medicinal Chemistry Letters | 2013
Kwangwoo Chun; Ji-Seon Park; Han-Chang Lee; Youngha Kim; In-Hea Ye; Kang-Jeon Kim; Il-Whea Ku; Min-Young Noh; Goang-Won Cho; Heejaung Kim; Seung Hyun Kim; Jeong-Min Kim
New potent glycogen synthase kinase-3 (GSK-3) inhibitors, 8-amino-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives, were designed by modeling, synthesized and evaluated in vitro. Compound 17c showed good potency in enzyme and cell-based assays (IC50=111 nM, EC50=1.78 μM). Moreover, it has demonstrated desirable water solubility, PK profile, and moderate brain penetration.
Immune Network | 2012
Youngha Kim; Sang-Hoon Lee; Yung-Choon Yoo; Junglim Lee; Jong-Hwan Park; Seok-Rae Park
Immune cells express toll-like receptors (TLRs) and respond to molecular patterns of various pathogens. CpG motif in bacterial DNA activates innate and acquired immune systems through binding to TLR9 of immune cells. Several studies reported that CpG can directly regulate B cell activation, differentiation, and Ig production. However, the role of CpG in B cell growth and Ig production is not fully understood. In this study, we analyzed the effect of CpG on the kinetics of mouse B cell viability, proliferation, and Igs production. Overall, CpG enhanced mouse B cell growth and production of Igs in a dose-dependent manner. Unlike LPS, 100 nM CpG (high dose) did not support TGF-β1-induced IgA and IgG2b production. Moreover, 100 nM CpG treatment abrogated either LPS-induced IgM or LPS/TGF-β1-induced IgA and IgG2b production, although B cell growth was enhanced by CpG under the same culture conditions. We subsequently found that 10 nM CpG (low dose) is sufficient for B cell growth. Again, 10 nM CpG did not support TGF-β1-induced IgA production but, interestingly enough, supported RA-induced IgA production. Further, 10 nM CpG, unlike 100 nM, neither abrogated the LPS/TGF-β1-nor the LPS/RA-induced IgA production. Taken together, these results suggest that dose of CpG is critical in B cell growth and Igs production and the optimal dose of CpG cooperates with LPS in B cell activation and differentiation toward Igs production.
IEEE Transactions on Applied Superconductivity | 2007
Youngha Kim; Tae-Hyun Sung; Sang-Chul Han; Y.H. Han; Nyeon-Ho Jeong; Kwangsoo No
YBa2Cu3OX (YBCO) coated conductors have been fabricated on cube textured Cu or Cu-based alloy substrates using various buffer layers such as CeO2, ZrO2, etc. Fabrication of buffer layers on Cu substrates using surface-oxidation epitaxy (SOE) has the potential to reduce the process complexibility and make the coated conductor more cost effective. In this work, we fabricated cube textured Cu2O as a component buffer layer by thermal oxidation of cube textured Cu(200) substrates. A biaxially-aligned textured Cu2O layer was obtained for 1 min oxidation in air at 1000degC. Texture analysis was performed using X-ray Diffraction (XRD) analysis. Microstructural characteristics of the layer were determined by scanning electron microscopy (SEM). The experimental results suggested that the Cu2O can be a promising buffer layer for YBCO coated conductors from the viewpoint of the simplification of the process.
Integrated Ferroelectrics | 2005
Hanjong Paik; Jongin Hong; Young-Ah Jeon; Sung Kwan Kim; Yunseok Kim; Youngha Kim; Yang Soo Kim; Kwangsoo No
ABSTRACT In this study, we report on the (100) cube-textured Pb(Zr0.4,Ti0.6)O3 (PZT) thin films using a conducting perovskite CaRuO3 (CRO) bottom electrode, and which was compared to the (111) textured PZT on Pt electrode. X-ray diffraction (XRD) reveals that the CRO bottom electrode has a pseudo-cubic nature on Si, and the PZT thin films prepared on CRO/Si shows a (100) textured growth. PZT films on CRO electrode have a well-saturated ferroelectricity with a remanent polarization (Pr) and coercive field (Ec) of 25 μ C/cm2 and 75 kV/cm, respectively. These PZT films are more fatigue resistive character than that on Pt bottom electrode.
Journal of Physics D | 2007
Hanjong Paik; Youngha Kim; Han-Wook Song; Kwangsoo No
The transport properties, chemical composition and energy band structure of directly integrated CaRuO3−δ thin films on a Si substrate were investigated by resistance–temperature (R–T) measurement, x-ray photoelectron spectroscopy (XPS) and near edge x-ray absorption fine structure (NEXAFS) spectroscopy of oxygen K-edge. At high deposition temperatures, the metallic characteristic of CaRuO3−δ thin film is susceptible, with a clear preference for (1 1 0) crystallite formation, which induces delocalized charge carrier migration. At low deposition temperatures, CaRuO3−δ thin film takes on semiconductor behaviour responsible for current path localization causing weakening of Ru 4d-O 2p-Ca 3d orbital overlapping due to the imperfect crystalline growth. Even though there was different crystallite formation according to deposition temperature, the relative compositional difference of each element was negligible, which was supported by XPS and wavelength dispersive x-ray spectroscopy (WDXS) analysis. Thus, the change in conductivity from semiconducting to metallic is caused by the fine crystallite nature of CaRuO3−δ at low deposition temperature which induces charge carrier localization by utilizing the incorporation of Ca–O bonding weakening, reducing the conduction energy bandwidth W and expansion of the local conduction energy band separation Δ.
Materials Letters | 2012
Sunghwan Lee; Seung-Hyun Kim; Youngha Kim; Angus I. Kingon; David C. Paine; Kwangsoo No
Superconductor Science and Technology | 2009
Tae Gyoung Lee; Mahipal Ranot; Won Kyung Seong; Soon-Gil Jung; Wonseok Kang; Jinho Joo; C.-J. Kim; Byung-Hyuk Jun; Youngha Kim; Yue Zhao; Shi Xue Dou
Physica C-superconductivity and Its Applications | 2009
Youngha Kim; C.-J. Kim; Byung-Hyuk Jun; Tae-Hyun Sung; Y.H. Han; Sang-Chul Han; Hanjong Paik; J.S. Youn; Kwangsoo No