S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study

Bae, S. J.,Lee, S. H.,Ahn, S. H.,Kim, H. M.,Kim, B. J.,Koh, J. M. Springer Science + Business Media 2016 Osteoporosis International Vol.27 No.8

<P>A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy. Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture. A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed. A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.</P>

Prediction of stone-free status and complication rates after tubeless percutaneous nephrolithotomy: a comparative and retrospective study using three stone-scoring systems and preoperative parameters

Choi, S. W.,Bae, W. J.,Ha, U. S.,Hong, S. H.,Lee, J. Y.,Kim, S. W.,Cho, H. J. Springer Science + Business Media 2017 World journal of urology Vol.35 No.3

<P>To investigate the factors predictive of surgical outcomes of tubeless percutaneous nephrolithotomy (TPCNL) and to compare the predictability and accuracy of the Guy's stone score, S.T.O.N.E. nephrolithometry, and CROES nomogram. We reviewed retrospectively the surgical outcomes recorded consecutively and imaging data of preoperative computed tomography scans of 141 patients who had undergone TPCNL from June 2012 to October 2015. Guy's, S.T.O.N.E., and CROES stone-scoring systems (SSSs) and other prognostic factors were assessed using univariate and multivariate statistical analyses. The initial stone-free and complication rates after TPCNL were 78.7 (111/141) and 17.0 % (24/141). On univariate analysis, all three scoring systems were identified as significant factors in terms of stone-free rate (SFR). The multivariate logistic regression analysis showed that the Guy's stone score and stone burden 385 mm(2) had significant correlations with stone-free status [odds ratios (OR) = 3.220, p = 0.001 and OR = 6.451, p = 0.002, respectively]. Guy's stone score (OR = 1.879, p = 0.013) was an independent risk factor for the development of complications. The area under the receiver operating characteristic (ROC) curves for the Guy's, S.T.O.N.E., and CROES SSSs and stone burden showed good results (0.821, 0.816, 0.820, and 0.800, respectively). Pairwise comparison of ROC curves showed that there was no significant difference between each final score and stone burden. Of the three scoring systems, Guy's stone score was the only significant predictive factor for SFR and complication rates after TPCNL in the multivariate logistic regression analysis. Stone burden was significantly associated with a postoperative stone-free status (SFS).</P>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J‐,S.,Park, J‐,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Bae, J.S.,Park, S.H.,Jamiyandorj, U.,Kim, K.M.,Noh, S.J.,Kim, J.R.,Park, H.J.,Kwon, K.S.,Jung, S.H.,Park, H.S.,Park, B.H.,Lee, H.,Moon, W.S.,Sylvester, K.G.,Jang, K.Y. American Association of Pathologists and Bacteriol 2016 The American journal of pathology Vol.186 No.12

<P>Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 alpha 1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, beta-catenin, cyclin D1, and NF-kappa B. Especially, SIRT6 expression was associated with the nuclear localization of B-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.</P>

인두편도염 환자와 보균자에서 분리한 Streptococcus pyogenes의 T-protein serotyping 및 항균제 감수성

이영희,황규잠,주영란,박강수,이광준,엄영길,배송미,차성호 국립보건연구원 1998 국립보건원보 Vol.35 No.-

Gd₂O₂S:Tb의 동시 계수 도플러 양전자 소멸법에 의한 결함 특성

이종용,배석환,김재홍,권준현,Lee, C.Y.,Bae, S.H.,Kim, J.H.,Kwon, J.H. 한국재료학회 2006 한국재료학회지 Vol.16 No.7

Coincidence Doppler Broadening (CDB) of positron annihilation spectroscopy was applied to analyze defects in the chemical state of Department of Physics, $Gd_2O_2S$:Tb intensifying screens. The screen samples were irradiated by 80 MV X-rays in hospital and were used for 0, 2, 4, and 6 years respectively. There was a positive relationship between the S-parameter values and time of exposure to X-rays. Most of the defects were indicated to have been generated by X-rays. A 1D CDB was developed in order to reduce the background noise, and the S-parameter values of the $Gd_2O_2S$:Tb intensifying screens, using the 1D CDB, varied between 0.4974 and 0.4991.

Various supercritical carbon dioxide cycle layouts study for molten carbonate fuel cell application

Bae, S.J.,Ahn, Y.,Lee, J.,Lee, J.I. Elsevier Sequoia 2014 Journal of Power Sources Vol.270 No.-

Various supercritical carbon dioxide (S-CO<SUB>2</SUB>) cycles for a power conversion system of a Molten Carbonate Fuel Cell (MCFC) hybrid system are studied in this paper. Re-Compressing Brayton (RCB) cycle, Simple Recuperated Brayton (SRB) cycle and Simple Recuperated Transcritical (SRT) cycle layouts were selected as candidates for this study. In addition, a novel concept of S-CO<SUB>2</SUB> cycle which combines Brayton cycle and Rankine cycle is proposed and intensively studied with other S-CO<SUB>2</SUB> layouts. A parametric study is performed to optimize the total system to be compact and to achieve wider operating range. Performances of each S-CO<SUB>2</SUB> cycle are compared in terms of the thermal efficiency, net electricity of the MCFC hybrid system and approximate total volumes of each S-CO<SUB>2</SUB> cycle. As a result, performance and total physical size of S-CO<SUB>2</SUB> cycle can be better understood for MCFC S-CO<SUB>2</SUB> hybrid system and especially, newly suggested S-CO<SUB>2</SUB> cycle shows some success.

Site-specific mutagenesis of yeast 2-Cys peroxiredoxin improves heat or oxidative stress tolerance by enhancing its chaperone or peroxidase function

Hong, S. H.,Lee, S. S.,Chung, J. M.,Jung, H. s.,Singh, S.,Mondal, S.,Jang, H. H.,Cho, J. Y.,Bae, H. J.,Chung, B. Y. Springer Science + Business Media 2017 Protoplasma Vol.254 No.1

<P>Yeast peroxiredoxin II (yPrxII) is an antioxidant enzyme that plays a protective role against the damage caused by reactive oxygen species (ROS) in Saccharomyces cerevisiae. This enzyme consists of 196 amino acids containing 2-Cys Prx with highly conserved two active cysteine residues at positions 48 and 171. The yPrxII has dual enzymatic functions as a peroxidase and molecular chaperone. To understand the effect of additional cysteine residues on dual functions of yPrxII, S79C-yPrxII and S109C-yPrxII, the substitution of Ser with Cys residue at 79 and 109 positions, respectively, was generated. S109C-yPrxII and S79C-yPrxII showed 3.7- and 2.7-fold higher chaperone and peroxidase activity, respectively, than the wild type (WT). The improvement in enzyme activity was found to be closely associated with structural changes in proteins. S109C-yPrxII had increased beta-sheet in its secondary structure and formed high-molecular-weight (HMW) as well as low-molecular-weight (LMW) complexes, but S79C-yPrxII formed only LMW complexes. HMW complexes predominantly exhibited a chaperone function, and LMW complexes showed a peroxidase function. In addition, transgenic yeast cells over-expressing Cys-substituted yPrxII showed greater tolerance against heat and oxidative stress compared to WT-yPrxII.</P>

Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation

Park, J.W.,Cho, J.W.,Joo, S.Y.,Kim, C.S.,Choi, J.S.,Bae, E.H.,Ma, S.K.,Kim, S.H.,Lee, J.,Kim, S.W. North-Holland ; Elsevier Science Ltd 2012 european journal of pharmacology Vol.683 No.1

The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague-Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2μg/kg/day, s.c.) for 4days. In another series of experiment, HK-2 cells were treated with cisplatin (50μM), with or without paricalcitol (0.2ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27<SUP>kip1</SUP> was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK½ and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27<SUP>kip1</SUP>, which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27<SUP>kip1</SUP>.