Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Yoo, Jung-Yoon,Choi, Kyung-Chul,Kang, HeeBum,Kim, Young Jun,Lee, Jeongmin,Jun, Woo Jin,Kim, Mi-Jeong,Lee, Yoo-Hyun,Lee, Ok-Hee,Yoon, Ho-Geun Elsevier 2010 FEBS letters Vol.584 No.11

<P><B>Abstract</B></P><P>This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression.</P><P><B>Structured summary</B></P><P>MINT-7719975: <I>L3MBTL2</I> (uniprotkb:Q969R5) and <I>HDAC3</I> (uniprotkb:O15379) <I>colocalize</I> (MI:0403) by <I>fluorescence microscopy</I> (MI:0416)</P><P>MINT-7719941, MINT-7719921: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>binds</I> (MI:0407) to <I>HDAC3</I> (uniprotkb:O15379) by <I>pull down</I> (MI:0096)</P><P>MINT-7719991: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>anti bait coimmunoprecipitation</I> (MI:0006)</P><P>MINT-7719958: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>physically interacts</I> (MI:0915) with <I>HDAC3</I> (uniprotkb:O15379) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7719897: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>two hybrid</I> (MI:0018)</P>

심근경색 모델 흰쥐에서 스트레스가 B-type Natriuretic Peptide 발현 및 심박변이율 변화에 미치는 영향

이삼윤(Sam Youn Lee),이미경(Mi Kyoung Lee),김남호(Nam-ho Kim),주민철(Min Cheol Joo),조항정(Hyang Jeong Jo),강지숙(Ji Sook Kang),김병숙(Byung Sook Kim),윤선식(Sun Sik Yoon),최을식(Eul Sig Choi),이문영(Moon Young Lee) 대한스트레스학회 2010 스트레스硏究 Vol.18 No.3

심박변이율의 감소는 심근 경색 환자에서 예후의 악화와 관련되어 있다. 심박변이율 중 very low frequency가 심부전환자의 예후를 판단할 수 있는 독립적 인자로서 사용이 가능하다고 보고된 바 있으며, 심실의 압력 증가에 반응해서 생성되는 B-type natriuretic peptide가 심근 경색의 예후 인자로서 사용할 수 있음 역시 보고된 바 있다. 본 연구에서는 심근경색 모델을 제작하여 일정의 회복 기간을 거친 다음 다시 일정 기간의 스트레스를 겪게 한 후 심박변이율의 변화 및 심실 조직에서의 BNP 발현 정도를 비교하여 스트레스에 의한 영향을 관찰하고자 하였다. Sprague-Dawley계 수컷 흰쥐 15마리를 대상으로 하였다. 실험동물은 인위적 스트레스 및 수술을 받지 않은 대조군(CON, n=5), 심근경색 수술을 받은 후 restraint stress를 받지 않은 군(MI+No Stress, n=5), 심근경색 수술을 받은 후 1주일 동안 restraint stress를 받은 군(MI+Stress, n=5)으로 분류하였다. 심근경색 모델 제작 직후 15분 이상 심전도의 변화를 기록하였으며, 2개월 정도 후 심근경색 수술을 받은 동물을 두 군으로 나누어 그 중 한 군에는 1주일 동안 restraint stress를 가한 후 restraint stress를 가하지 않은 동물과 심박변이율을 비교 분석하였다. 심실 조직은 좌심실 전벽 부위의 위축을 관찰할 수 있었고, 대식세포에 의하여 응고, 괴사된 심근세포의 탐식과 혈관이 풍부한 육아조직 및 섬유 변화를 볼 수 있었다. 심박변이율은 심근경색 수술을 받은 직후 심박수는 유의한 증가를 보였고, standard deviation of the normal to normal intervals (SDNN), very low frequency (VLF) 및 low frequency (LF)의 유의한 감소를 보였다. 심근경색 수술을 받았던 동물에서 두 달 정도의 회복 기간을 거친 후 스트레스를 받지 않은 군은 심박수 및 기타 심박변이율 분석에서 SDNN 값을 제외하고는 정상군과 유의한 차이를 관찰할 수 없었던 반면 1주일 동안 스트레스를 받은 군에서는 심박수가 다시 유의하게 증가했을 뿐만 아니라 SDNN, VLF 및 LF 역시 정상군과 유의한 차이를 보였다. 이상의 결과를 종합하면 심근경색 동물에 대해 1주일 동안 스트레스를 가한 결과 심박변이율이 감소하고 심실에서의 BNP 발현은 더욱 증가하여 악화함을 보여주고 있다. Diminished heart rate variability (HRV) is associated with less favorable prognosis after myocardial infarction (MI). It has been reported that very low frequency (VLF) power in HRV analysis is an independent risk predictor in patients with congestive heart failure and B-type natriuretic peptide (BNP) can be used as a prognostic factor of MI. The purpose of this study was to investigate whether stress has an effect to the changes of BNP expression and/or heart rate variability in MI model in rats. Male Sprague-Dawley rats were divided into 3 groups: control group (CON), MI group (MI+No Stress), and MI followed by stress group (MI+Stress). MI+Stress group rats were raised for a two month recovery period after the operation, followed by being exposed to restraint stress for 2 hours per day for 1 week. Electrocardiogram was recorded after the operation and the last day after 1 week of stress. The frequency components of HRV were calculated in the frequency domain such as VLF, low frequency (LF), high frequency (HF) and so on. In HRV analysis, standard deviation of the normal to normal intervals (SDNN) was significantly reduced in both groups compared to the control group. VLF and LF also were significantly reduced in MI+Stress group compared to the control groups. In addition, BNP expression in western blotting was shown the strongest bands in MI+ Stress group among experimental groups. These results suggest that BNP and HRV were aggravated by stress in MI rat model. (Korean J Str Res 2010;18:275∼285)

New Insight for Fluoroquinophenoxazine Derivatives as Possibly New Potent Topoisomerase Ⅰ Inhibitor

Kang, Da-Hye,Kim, Jung-Sook,Jung, Mi-Ja,Lee, Eung-Seok,Jahng, Yurngdong,Kwon, Youngjoo,Na, Younghwa 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18

Fluoroquinolones, represented by ciproxacin and norfloxacin, are well known clinical antimicrobial agents, and their phenyl ring expanded quinophenoxazines are reported as possible antitumor active compounds. These quinophenoxazines are known to inhibit DNA topoisomerase II essential for cell replication cycle. But there were no reports for topoisomerase I inhibition study for these compounds. In this report, we have prepared a few quinophenoxazine analogues and tested their topoisomerases I and II inhibitory activities and cytotoxicity. From the result, we found that qumophenoxazine analogues possessed strong topoisomerase I inhibitory capacity as well as topoisomerase II inhibition. Among the compounds prepared, A-62176 analogues showed strong topoisomerases I and II inhibitory activities. Interestingly, compound 8 missing the 3-aminopyrrolidine moiety at C2 position has similar potent inhibitory capacity against topoisomerases I & II at higher concentrations (20 and 10 uM, respectively). But compound 8 inhibited topoisomerase I function more selectively at lower concentration, 2 uM. Our observation mi&ht strongly implicate that fluoroquinophenoxazines can be developed as efficient topoisomerase I inhibitor with the elaborate modification.

Comparative AFLP Profiles among Strains of Korean Races of Xanthomonas oryzae pv. oryzae.

Kang,Mi-Hyung,Lee,Du-Ku,Noh,Tae-Hwan,Shim,Hyeong-Kwon,Na,Seung-Yong,Kim,Jae-Duk 한국자원식물학회 2004 Plant Resources Vol.7 No.1

We used an amplified fragment length polymorphism (AFLP) analysis, a novel PCR-based technique, to differentiate Xanthomonas oryzae pv. oryzae (Xoo) of Korean races. The 6 strains of Xoo K1, K2, K3 races were tested with 81 AFLP primer combinations to identify the best selective primers. The primer combinations were selected according to their reproducibility, number of polymorphic bands and polymorphism detected among Xoo strains. 18 strains of Xoo K1, K2 and K3 races were analyzed with the selected combinations of primer set. Some primer combinations (Eco R I +1 / Mse I+1) could differentiate Xoo of Korean races that were not distinguished by other fingerprinting analysis. Thus AFLP fingerprinting permitted very fine discrimination among different races.

언어 영재 교육을 위한 프로젝트 학습 프로그램 개발 연구

강미정(Kang Mi-jung) 한국어문교육학회 2008 어문학교육 Vol.36 No.-

  The purpose of this study is to construct and suggest project learning program suitable for the verbally gifted by searching its possibility as a method of learning program which enhances creative problem-solving ability of the verbally gifted.<BR>  To achieve the purpose of this study, the conception of the verbally gifted is established. The verbally gifted are defined as students who acquire language in their early life or are prominent in language domain(or have such possibility) with usually high lingual comprehension, production ability and lingual habits.<BR>  Learning program for the verbally gifted is mostly progressed with in-depth study, especially project learning program is shown as one of in-depth study programs which considerably correspond with cognitive and affective characteristics of the verbally gifted.<BR>  To construct actual project learning, I first selected learning themes, that is, content factors which can expect the educational effect of project learning among the educational contents for the verbally gifted. I analysed the former researches such as Choi, Jong-Oh(2004), Park Su-Ja(2004), Lee Sun-Young(2000), Lee Mi-Kyung(2005), Kwon Sun-hee(2006) et al, creative writing texts for the verbally gifted of educational districts in Busan, texts related to the verbally gifted published in KEDI and real teaching contents for the verbally gifted. As a result, four learning themes are selected; "Writing creatively", "Making ads.", "Researching authors", and "Dramatic role play".<BR>  To present selected themes to the verbally gifted easily, I made them concrete by the name of the following project; "Come here, Poet", "My own ads" "Searching for the authors", and "on the spot at that time". Such project themes make process project learning program through 5 steps; Finding out theme→ Planning project → Implementing project → Creating products → Presentation?exhibition & evaluation. This project learning program means somewhat different from the existing project learning programs. Considering cognitive and affective characteristics of the verbally gifted, it focuses on enhancing their creative problem-solving ability as much as possible.<BR>  Now gifted education of Korea is in the midst of transition periods. Besides visibly splendid results. there are many unexpected problems. That"s why deeper research should be conducted in various areas including the verbally gifted.<BR>  Finally, I want to raise interest towards the verbally gifted through this study and provide properly educational opportunities for them. I hope this study can be a tuning point which is of help to teachers in charge of gifted education.

Water-soluble Genistin Glycoside Isoflavones Upregulate Antioxidant Metallothionein Expression and Scavenge Free Radicals

Chung, Mi-Ja,Kang, Ah-Young,Jun, Hee-Jin,Kim Sang-Yeon,Moon, Tae-Hwa,Park, Kwan-Hwa,Lee, Sung-Joon 생명자원연구 2005 생명자원연구 Vol.13 No.-

Effects of dietary supplementation with probiotic CS-A on performance in broiler chickens

Seong Soo Kang1*, Se Eun Kim, Ara Go, Kyung Mi Shim, Chun Sik Bae, Chang Jong Moon, Sung-Ho Kim, Jong-Choon Kim, Jin-Cheol Yoo, Seung Sik Cho 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.3

Probiotics, enzymes, organic acids, oligosaccharides, antioxidants, and other functional materials are actively being explored as alternatives to antibiotics. Probiotics include live beneficial microorganisms that colonize the intestinal tract and competitively inhibit attachment and growth of harmful microbes. Probiotics also increase feed efficiency by assisting in nutrient absorption and digestion. The current study was conducted in order to evaluate the effect of a new probiotic, CS-A, as a dietary supplement of a fermented product on growth performance, feed intake, and feed conversion efficiency in broiler chickens, and to evaluate its value as an alternative for antibiotics used as a feed additive. Antibacterial and anti-inflammatory effects of CS-A were investigated in vitro and the in vivo effects of a constant concentration of supplemented CS-A on growth rate and feed efficiency were evaluated. In addition, the safety of CS-A was assessed by examination of common symptoms and mortality. Determination of minimal inhibitory concentration revealed an excellent antibacterial effect of CS-A. Cytotoxicity was low and anti-inflammatory effects were achieved at the effective concentration of CS-A. Supplementation with 0.1% CS-A resulted in a feed efficiency score of 1.84 in broilers, compared to 2.00 in the control group. There were no adverse clinical findings, necropsy findings, hematology, and altered serum biochemistry parameters, and no mortality. Thus, it is concluded that CS-A is safe and effective as a feed additive.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

Hepatic Cirrhosis Occurring in a Young Woodchuck(Marmota monax) Due to Vertical Transmission of Woodchuck Hepatitis Virus(WHV)

Kyu-shik Jeong,정원일,Jae-yong Chung,Mi-young An,Chae-yong Jung,Gyoung-jae Lee,Jong-soo Kang,Byeong-cheol Kang,Young-heun Jee,Bruce H Williams,Young-oh Kwon,Da-hee Jeong 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.2

Cirrhosis Occurring in a Young Woodchuck (Marmota monax) Due to Vertical Transmission of Woodchuck Hepatitis Virus (WHV)Da-hee Jeong, Won-il Jeong, Jae-yong Chung, Mi-young An, Chae-yong Jung, Gyoung-jae Lee1, Jong-soo Kang1, Byeong-cheol Kang2, Young-heun Jee3, Bruce H Williams4, Young-oh Kwon5 and Kyu-shik Jeong*College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea1Shinwon Scientific Co., LTD, Research Institute, Suwon, Korea2Clinical Research Institute, Seoul National University, Seoul 110-744, Korea3College of Veterinary Medicine, Jeju National University, Jeju 690-756, Korea

연부조직육종의 수술후 방사선 치료결과

김연실(Yeon Shil Kim),장홍석(Hong Seok Jang),윤세철(Sei Chul Yoon),유미령(Mi Ryeong Ryu),강기문(Ki Moon Kang),정수미(Su Mi Chung),김훈교(Hoon Kyo Kim),강용구(Yong Koo Kang) 대한방사선종양학회 1998 Radiation Oncology Journal Vol.16 No.4

목 적 : 최근들어 연부 조직 육종의 치료방법이 광범위 구획절제에서 사지기능을 보존하는 제한적 수술과 방사선/항암화학요법의 다병용치료로 변환되고 있으며 광범위 수술과 유사한 치료성적을 거두고 있다. 저자들은 수술후 방사선 치료를 시행한 연부 조직 육종 환자를 대상으로 치료 결과 및 실패 양상을 알아보고 관련된 예후 인자를 분석하여 수술 후 방사선치료의 역할을 알아보고자 하였다. 대상 및 방법 : 대상환자는 1983년부터 1994년까지 치료한 60명이었고 모두 추적관찰이 가능했으며 평균 추적기간은 50개월이었다. 원발병소는 상·하지가 35례(58%)로 가장 많았고 체간 12례(20%), 두경부 7례(12%)였으며 병리학적 유형에 따른 구분은 악성섬유구종 14례(23%),지방육종이 10례(17%), 악성신경섬유종 7례(12%) 등 이었다. 전체환자중 6례를 제외하고는 조직학적등급의 분석이 가능했고 grade I, II, III가 각각 27례(45%), 3례(5%), 24례(40%)였다. 수술적 절제는 19례(32%)에서 광범위절제, 36례(60%)에서 변연절제, 5례(8%)에서 국소절제를 시행하였다. 방사선치료선량은 28.8- 80Gy였고 25례에서 방사선치료와 함께 항암화학 요법을 병용하였다. 결 과 : 최종분석 시 실패 양상은 국소재발이 20례(25%), 원격전이 7례(12%), 국소재발과 원격전이를 동반한 경우가 14례(23%)였다. 원격전이한 환자는 구제치료와 상관 없이 모두 사망하였고 국소재발한 환자중 5명이 구제치료에 성공하여 무병생존하였다. 전체환자의 2년 및 5년 국소제어률은 68.0%와 48.7%로 비교적 저조한 결과를 보였다. 국소제어율에 영향을 미친 예후인자는 조직학적 유형, AJCC 병기, 조직학적 등급, 수술의 범위, 수술절연 침범 유무 및 잔존종양 정도, 림프절 전이 유무(p <0.05)였다. 전체 환자의 5년 생존률과 5년 무병생존률은 각각 60.4%, 36.6%였고 평균 생존기간은 89개월이었다. 단변량 분석에 의한 생존률에 영향을 미친 예후인자로는 조직학적 유형, AJCC 병기, 림프절 전이 유무, 조직학적 등급, 수술절연 침범 유무와 잔존 종양 정도 였다. 결 론 : 결론적으로 본 연구 결과 연부 조직 육종에서 제한적 수술과 수술 후 방사선치료로 비록 저조한 국소제어률을 보였으나 사지 절단 혹은 광범위 구획절제와 비교시 유사한 생존률을 얻었다. Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 60 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patints with median follow up duration 50 months (range 6 - 162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58%) was the most frequent site of occurrence followed by trunk (20%) and head and neck (12%). Histologically malignant fibrous histiocytoma (23%), liposarcoma (17%), malignant schwannoma (12%) constitute 52% of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42%) received chemotherapy with various regimen in the postoperative period. Results : Total 4 1 patients failed either with local recurrence or with distant metastasis. There were 29 patients(48%) of local recurrence. Four patients (7%) developed simultaneous local recurrence and distant metastasis and 8 patients (13%) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck prima ry. This feature is like ly explanation for the decreased loca l control rate . Five of 29 patients who fa iled only loca lly were salvaged by re- excis ion and/or re- irradiation and rema ined free of disease . Factors affecting loca l control include histologic type , grade, stage , extent of operation and surgica l ma rgin involvement, lymph node metastas is (p <0.05). All 21 patients who fa iled distantly are dead with progress ive disease at the time of this report. Our overall survival results are similar to those of larger series . Actuarial 5 year overall survival and disease fresurvival were 60.4 %, 36.6% respectively. Grade, stage (being close association with grade), residual disease (negative ma rgin, microscopic, gross) were significant as a predictor of survival in our series (p <0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.