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.

T_c and J_c distribution in in situ processed MgB₂ bulk superconductors with/without C doping

Kim, C.J.,Kim, Y.J.,Lim, C.Y.,Jun, B.H.,Park, S.D.,Choo, K.N. The Korea Institute of Applied Superconductivity a 2014 한국초전도저온공학회논문지 Vol.16 No.2

Temperature dependence of magnetic moment (m-T) and the magnetization (M-H) at 5 K and 20 K of the in situ processed $MgB_2$ bulk pellets with/without carbon (C) doping were examined. The superconducting critical temperature ($T_c$), the superconducting transition width (${\delta}T$) and the critical current density ($J_c$) were estimated for ten test samples taken from the $MgB_2$ bulk pellets. The reliable m-T characteristics associated with the uniform $MgB_2$ formation were obtained for both $MgB_2$ pellets. The $T_cs$ and ${\delta}Ts$ of all test samples of the undoped $MgB_2$ were the same each other as 37.5 K and 1.5 K, respectively. The $T_cs$ and ${\delta}Ts$ of the C-doped $MgB_2$ were 36.5 K and 2.5 K, respectively. Unlike the m-T characteristics, there existed the difference among the M-H curves of the test samples, which might be caused by the microstructure variation. In spite of the slight $T_c$ decrease, the C doping was effective in enhancing the $J_c$ at 5 K.

Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment

Jo, M.J.,Paek, A.R.,Choi, J.S.,Ok, C.Y.,Jeong, K.C.,Lim, J.H.,Kim, S.H.,You, H.J. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.769 No.-

<P>The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PAPP), were cleaved in C604-treated STF-cMyc cells. In addition, 5W620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway. (C) 2015 Elsevier B.V. All rights reserved.</P>

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Fatigue performance of deepwater SCR under short-term VIV considering various S-N curves

Kim, D.K.,Choi, H.S.,Shin, C.S.,Liew, M.S.,Yu, S.Y.,Park, K.S. Techno-Press 2015 Structural Engineering and Mechanics, An Int'l Jou Vol.53 No.5

In this study, a method for fatigue performance estimation of deepwater steel catenary riser (SCR) under short-term vortex-induced vibration was investigated for selected S-N curves. General tendency between S-N curve capacity and fatigue performance was analysed. SCRs are generally used to transport produced oil and gas or to export separated oil and gas, and are exposed to various environmental loads in terms of current, wave, wind and others. Current is closely related with VIV and it affects fatigue life of riser structures significantly. In this regards, the process of appropriate S-N curve selection was performed in the initial design stage based on the scale of fabrication-related initial imperfections such as welding, hot spot, crack, stress concentration factor, and others. To draw the general tendency, the effects of stress concentration factor (SCF), S-N curve type, current profile, and three different sizes of SCRs were considered, and the relationship between S-N curve capacity and short-term VIV fatigue performance of SCR was derived. In case of S-N curve selection, DNV (2012) guideline was adopted and four different current profiles of the Gulf of Mexico (normal condition and Hurricane condition) and Brazil (Amazon basin and Campos basin) were considered. The obtained results will be useful to select the S-N curve for deepwater SCRs and also to understand the relationship between S-N curve capacity and short-term VIV fatigue performance of deepwater SCRs.

Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

(S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

<P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

Measurements of surgeons’ exposure to ionizing radiation dose: comparison of conventional and mini C-arm fluoroscopy

Sung, K. H.,Min, E.,Chung, C. Y.,Jo, B. C.,Park, M. S.,Lee, K. SAGE Publications 2016 The journal of hand surgery. journal of the Britis Vol.41 No.3

<P>This study was performed to measure the equivalent scattered radiation dose delivered to susceptible organs while simulating orthopaedic surgery using conventional and mini C-arm fluoroscopy. In addition, shielding effects on the thyroid, thymus, and gonad, and the direct exposure delivered to the patient's hands were also compared. A conventional and mini C-arms were installed in an operating room, and a hand and an operator phantom were used to simulate a patient's hand and a surgeon. Photoluminescence dosimeters were used to measure the equivalent dose by scattered radiation arriving at the thyroid, thymus, and gonad on a whole-body phantom in the position of the surgeon. Equivalent scattered radiation doses were measured in four groups: (1) unshielded conventional C-arm group; (2) unshielded mini C-arm group; (3) lead-shielded conventional C-arm group; and (4) lead-shielded mini C-arm group. Equivalent scattered radiation doses to the unshielded group were significantly lower in the mini C-arm group than those in the conventional C-arm group for all organs. The gonad in the lead-shielded conventional C-arm group showed the highest equivalent dose among operator-susceptible organs, and radiation dose was reduced by approximately 96% compared with that in the unshielded group. Scattered radiation was not detected in any susceptible organ in the lead-shielded mini C-arm group. The direct radiation dose to the hand phantom measured from the mini C-arm was significantly lower than that measured from the conventional C-arm. The results show that the equivalent scattered radiation dose to the surgeon's susceptible organs and the direct radiation dose to a patient's hand can be decreased significantly by using a mini C-arm rather than a conventional C-arm. However, protective lead garments, such as a thyroid shield and apron, should be applied to minimize radiation exposure to susceptible organs, even during use of mini C-arm fluoroscopy.</P>

Relationship between Stress Gene Polymorphisms and Litter Size by AI in Pigs

Jin, H.J.,Kim, I.C.,Wee, M.S.,Yeon, S.H.,Kim, C.D.,Lee, S.S.,Cho, C.Y.,Cho, S.R.,Son, D.S.,Park, C.K. 韓國受精卵移植學會 2007 한국동물생명공학회지 Vol.22 No.4

This study was performed to investigate the relationship between PSS-HSP70 gene polymorphism and artificial insemination (AI) reproductivity in the pigs. The RFLP polymorphism of PSS and the SSCP polymorphisms of HSP70 K1, K3 and K4 PCR product were detected different patterns. In the experiment for AI of fresh semen, spring and fall season showed higher litter size born of 10.89 head than 10.47 head of summer season. Landrace was showed higher litter size of 9.96 head than that of Duroc and Yorkshire (p<0.05). Stress relating PSS and HSP70 polymorphism of PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showd a highest litter size born of 10.97 head and litter size born alive of 10.69 head than that of the other polymorphisms(p<0.05). In the experiment for AI of frozen semen, effects of season and pig breeds were not showed for litter size born. The stress relating polymorphism of PSS-Carrier, HSP70 K1-BB, K3-BB, K4-AB showed highest litter size born of 11.29 head and litter size born alive of 10.82 head and PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showed the lowest litter size born of 8.48 head and litter size born alive of 7.33 head than that of the other polymorphisms(p<0.05). These results suggest that AI litter size born for the stress of forzen thawed semen may be affected by PSS and HSP70 polymorphism in pigs.

Intravesical Instillation of c-MYC Inhibitor KSI-3716 Suppresses Orthotopic Bladder Tumor Growth

Jeong, K.C.,Kim, K.T.,Seo, H.H.,Shin, S.P.,Ahn, K.O.,Ji, M.J.,Park, W.S.,Kim, I.H.,Lee, S.J.,Seo, H.K. Williams and Wilkins Co 2014 The Journal of urology Vol.191 No.2

Purpose: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts. Materials and Methods: The small molecule KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an intravesical chemotherapy agent. KSI-3716 action was assessed by electrophoretic mobility shift assay, chromatin immunoprecipitation, transcription reporter assay and quantitative reverse transcriptase-polymerase chain reaction. Inhibition of cell proliferation and its mechanism was monitored by cell cytotoxicity assay, EdU incorporation assay and flow cytometry. The in vivo efficacy of KSI-3716 was examined by noninvasive luminescence imaging and histological analysis after intravesical instillation of KSI-3716 in murine orthotopic bladder xenografts. Results: KSI-3716 blocked c-MYC/MAX from forming a complex with target gene promoters. c-MYC mediated transcriptional activity was inhibited by KSI-3716 at concentrations as low as 1 μM. The expression of c-MYC target genes, such as cyclin D2, CDK4 and hTERT, was markedly decreased. KSI-3716 exerted cytotoxic effects on bladder cancer cells by inducing cell cycle arrest and apoptosis. Intravesical instillation of KSI-3716 at a dose of 5 mg/kg significantly suppressed tumor growth with minimal systemic toxicity. Conclusions: The c-MYC inhibitor KSI-3716 could be developed as an effective intravesical chemotherapy agent for bladder cancer.