A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

Kim, I,Kang, E S,Yim, Y S,Ko, S J,Jeong, S-H,Rim, J H,Kim, Y S,Ahn, C W,Cha, B S,Lee, H C,Kim, C H Nature Publishing Group 2011 The pharmacogenomics journal Vol.11 No.3

SLC30A8 encodes the β-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.

단세포군 항체를 이용한 Shigella serotyping serum 개발(Ⅱ) : S. flexneri type Ⅰ,Ⅱ & type Ⅰ:6, group 6

정의범,이영희,김순남,박강수,이명숙,성원근,김종욱,홍승의,박정우 국립보건연구원 1994 국립보건원보 Vol.31 No.1

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

선형레이저로 계측한 모르타르소재기반 적층 비드 형상 안정성평가

박진수(J. S. Park),이상환(S. H. Lee),오지원(J. W. Oh),최한신(H. S. Choi) Korean Society for Precision Engineering 2020 한국정밀공학회 학술발표대회 논문집 Vol.2020 No.9월

산란계 개량에 관한 연구 1 . 순계의 생산능력 비교시험

상병찬,강만석,김동곤,한성욱 ( B . C . Sang,M . S . Kang,D . K . Kim,S . W . Han ) 한국축산학회 1980 한국축산학회지 Vol.22 No.5

This experiment was carried out to test performance of the domentic purebred fowl. The purpose of this experiment was to compare the productive performance of the purebred fowl to obtained basic materials for laying performance improvement by means of cross breeding. In this study, 1, 200 chickens was used-that is 6 purebred strains White Leghorns(720 chickens), 1 purebred strain Rhode Island Reds (120 chickens), 1 purebred strain New Hampshires (120 chickens). The results obtained in this study are as follows; 1. The average Viability of brooding, rearing and laying period was best for Rhode Island Reds and E. Strain among White Leghorns. 2. The average body weight at 8 weeks, first egg production days, 500days of age in W. L. was 546.86g. 1431.37g, 1738.34g, respectively, but there was no significant difference among. purebred strains of W. L. 3. The average Sexual maturity of 50% egg production was 170.58 days in W. L., but R. I. R. and S. N. H. were 189.94 days, 182.42days, respectively. There was significant difference at 1 % level among Strains. 4. The average hen-housed egg production was 214.16 eggs in W. L., but R. I. R. and S. N. H. were 214.22 eggs, 196.74 eggs, respectively. There was significant difference at 1% level among Strains, but the highest hen-housed egg production (231.84 eggs) was E. Strain among strains. 5. The average egg weight was 54. 48g in W. L, but R. I. R. and .S. N. H. were 56.12g, 54.90g, respectively, The highest egg weight (57.69g) was Coronial Strain of W. L. among strains. There was significant difference at 1 % Level among strains. 6. The average feed requirement was 3.01 in W. L. but R. I. R. and S. N. H. were 3.23, 3.52, respectively the highest feed requirement (2.79) was Coronial Strain of W. L. among strains. There was significant difference at 1 % level among strains. 7. On the basis of the results of this study, the productive performance was best for C. D. E. strains among W. L. and R. I. R.

중부 평야지에서 사일리지용 옥수수 품종 선발에 관한 연구 : 파종시기가 사일리지용 옥수수의 생육특성 및 수량에 미치는 영향 Effect of planting time on the growth and yield of silage corn

김준식,김원호,김원영,김영진,한학석,김맹중 한국축산학회 1998 한국축산학회지 Vol.40 No.1

This experiment was conducted at theForage Research Farm of the Beef and Dairy Cattle Division, National Livestock Research Institute, Songhwan in 1992 and 1995 to investigate the effects of planting time (April 15, May 11, June 5) on the growth and yield of silage com(Zea mat's L.). In the plant height, P3144W and DK729 were taller than the others, as 301.6, and 296.3cm, respectively, and P3282 was the shortest as 247.7㎝ at the first planting time. P3144W and DK729 were taller than the others, as 303.6㎝, 281.7㎝, respectively, and P3282 was the shortest as 249.6㎝ at the second planting time. P3144W was the tallest as 276.9㎝. DK689 was the shortest as 246.1㎝ at the third planting time. The ear heights of P3144W and P3282 were 137.3 and 132.7㎝, respectively, and Suweon 19 was the shortest as 116.4㎝ at the first planting time. Those of P3144W and P3282 were as 135.9, 134.4㎝, respectively, and Suwoen 19 was the shortest as 112.1㎝ at the second planting time. P3144W was the tallest as 111.0㎝ and Suweon 19 was the shortest as 94.2㎝ at the third planting time. In the dry matter yield per ha, P3352, DK729 and P3144W were higher than the others as 18,957, 18,840, 18,743㎏, respectively, and P3282 was the lowest as 13,863㎏ at the first planting time. 64743 and P3352 were 18,183 and 17,874㎏, respectively, and Suwoen 19 was the lowest as 15,007㎏ at the second planting time. P3144W was the highest as 19,112㎏ and Suwnen 19 was the lowest as 14,793㎏ at the third planting time. The TDN yield per ha, of P3352, P3144W and DK729 were 13,552, 13,281 and 13,252㎏, respectively, and P3282 was the lowest as 9,793㎏ at the first planting time. 64743 and P3352 were higher than the others as 13,149 and 13,009kg, respectively, and Suwoen 19 was the lowest as 10,872㎏ at the second planting time. P3144W was the highest as 13,521㎏ and Suwven 19 was the lowest as 10,392㎏ at the third planting time.

Pulse Shape Discrimination of Nuclear Recoil and Electron Recoil Events With a NaI(Tl) Crystal for Dark Matter Search

Kim, K. W.,Adhikari, G.,Adhikari, P.,Choi, S.,Ha, C.,Hahn, I. S.,Jeon, E. J.,Joo, H. W.,Kang, W. G.,Kim, H. J.,Kim, N. Y.,Kim, S. K.,Kim, Y. D.,Kim, Y. H.,Lee, H. S.,Lee, M. H.,Leonard, D. S.,Oh, S. Y IEEE 2016 IEEE transactions on nuclear science Vol.63 No.2

<P>In order to investigate discrimination between nuclear recoil and electron recoil events for the KIMS-NaI dark matter search experiment, we measured the pulse shapes produced by neutrons and gamma rays in a NaI(Tl) crystal. Relatively good pulse shape discrimination (PSD) power due to high light output of recently developed crystals makes it possible to test whether the annual modulation signal observed by the DAMA/LIBRA experiment is caused by nuclear recoil events. We applied the PSD to underground data taken with a 9.15 kg low-background and high-light-output NaI(Tl) crystal for 134 days. Good agreement between underground data and electron recoil events was observed.</P>

Salmonella Typhi, Salmonella Typhimurium 및 Salmonella Enteritidis의 항균제 감수성 (1997)

신영학,유정식,김기상,정동준,오경수,이점규,이상원,이근영,박미선,이복권,김호훈 국립보건연구원 1998 국립보건원보 Vol.35 No.-

수집형 감자 수확기 개발을 위한 굴취·이송 요인실험

이상희 ( S. H. Lee ),김영근 ( Y. K. Kim ),강태경 ( T. G. Kang ),김성우 ( S. W. Kim ),최용 ( Y. Choi ),전현종 ( H. J. Jun ),최일수 ( I. S. Choi ),현창식 ( C. S. Hyun ) 한국농업기계학회 2016 한국농업기계학회 학술발표논문집 Vol.21 No.2

감자는 국내에서 재배되는 주요 밭작물로 감자의 소비량은 증가하고 있지만, 재배면적은 2000년 29,400ha에서 2014년 22,000ha로 감소하고 있는 추세이며 생산량 또한 2000년 704,6000톤에서 2014년 590,000톤으로 감소하고 있다. 현재 감자의 수확작업은 굴취기를 이용하여 굴취한 후 인력으로 수집하는 형태로 감자 생산 총 노동시간 58.0hr/10a 중 수집 작업에 소요되는 시간이 17.1hr/10a에 달하며 농촌 노동력 감소와 고령화로 인해 수집형 감자 수확기 개발 요구가 높아지고 있다. 따라서 본 연구에서는 감자의 생력재배(Labor saving cultivation)를 높이기 위해 수집형 감자수확기개발을 위한 굴취날 각도 및 이송속도에 따른 요인실험을 수행 하였다. 수집형 감자 수확기는 트랙터 부착형으로 굴취날 각도 3수준(20, 23, 26°), 이송속도 3수준(0.3, 0.4, 0.5m/s)으로 조절할 수 있도록 제작하였다. 굴취날은 각도 별로 3개를 제작하여 날을 교체하는 방식으로 제작하였고, 시험은 평창 감자밭에서 이루어졌으며 시험포장의 토성은 양토였다. 굴취율은 3m구간 굴취 후 굴취된 개수와 미굴취 감자의 개수를 비교하였으며 3반복 측정 하였다. 이송속도는 모터 회전수를 제어할 수 있는 모터 컨트롤러를 따로 제작하여 기체는 정지시키고 이송부만 작동하며 실험하였다. 이송속도 별로 1회에 시료 50개를 투입하여 총 3반복 실험하였으며 표피손상과 형태가 파손된 것을 손상으로 간주하였다. 실험에 사용된 감자의 물성은 크기와 무게를 조사하였으며 평균 가로 75.4±6.26mm, 세로 62.5±5.3mm, 높이 81.7±7.67mm, 무게는 230.7±45.6g이었다. 수집형 감자 수확기의 굴취 및 이송 요인별로 시험하여 감자 굴취율, 이송손상 및 수집손상을 조사한 결과 굴취날 각도에 따른 굴취율은 감자수집에 미치는 영향이 적은 것으로 나타났다. 굴취날 각도 20, 23°에서는 약 99%로 수집되었으며, 26°의 굴취각에서는 모두 수집되었다. 또한 이송속도에 따른 이송부 및 수집부의 감자손상 및 손상률 시험결과 이송부손상률은 0.3m/s에서 2.67%, 0.4m/s에서 3.33%, 0.5m/s에서 6.67%로 0.5m/s의 이송속도에서 손상율 증가폭이 크게 상승하였다. 수집부 손상율 또한 0.3m/s에서 2%, 0.4m/s에서 2.67%, 0.5m/s에서 약 6.67%로 0.5m/s의 이송속도에서 증가폭이 크게 상승하였다. 따라서 본 연구의 수집형 감자 수확기는 작업속도, 감자손상 및 손상율을 고려할 때 0.4m/s의 이송속도에서 수확 시 가장 적절할것으로 판단하였다.

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

<P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>