Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells

( Hee Jun Cho ),( Byung Moo Oh ),( Jong-tae Kim ),( Jeewon Lim ),( Sang Yoon Park ),( Yo Sep Hwang ),( Kyoung Eun Baek ),( Bo-yeon Kim ),( Inpyo Choi ),( Hee Gu Lee ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.2

Interleukin-21 is a common γ-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted IFN-γ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

쑥가루 첨가량에 따른 쑥개떡의 기호성 및 텍스쳐에 관한 연구

서연희,이춘자,조후종 동아시아식생활학회 1996 동아시아식생활학회지 Vol.6 No.1

This study examined the distinctive character and level of preference of SsookGae-Dduck which was produced with making 2, 3, 4, 5% of difference, adding 30% mugwort. In the sensory evaluation for SsookGae-Dduck, the bitterness, hardness and flavor were highly evaluated as the amount of mugwort powder was increasing. The sweetness and color showed the highest number in the adding group of 2% mugwort powder. In the being moistness degree, the 30% adding group of mugwort was the highest one, and 3% adding group in the mugwort powder. And the chewiness was highly marked in the adding group of 30% mugwort, and 5% adding group was highly marked in the mugwort powder. In the mechanical evaluation of SsookGae-Dduck, the hardness and adhesiveness were highly marked in the adding group of 5% mugwort powder, the adding group of 4% showed the highest number in the springiness, cohesiveness, gumminess and chewiness. Through these all studies, the mugwort powder should be used in the multi way of our food life and it was really necessary to be studies and to be taken interest in this area constantly.

구동 전동기 입력 전류 및 전력신호에 의한 전동 게이트밸브 진단연구

박종호,이성노,성게용,조두연 충남대학교 산업기술연구소 1999 산업기술연구논문집 Vol.14 No.2

The motor-operated valves are used extensively within nuclear power plants in safety-related and balance-of-plant systems and located in almost all plant fluid systems. Their failures have resulted in significant plant maintenance efforts. More important, the operational readiness of nuclear plant safety-related systems has often been affected by MOV degradation and failure. The performance of motor-operated valves should be evaluated to ensure the nuclear safety. It will be accomplished by understanding the state of the art of the diagnostic method and developing the appropriate new methodology to evaluate the measuring parameters to predict the valve performance Measured and evaluated were the changes of the motor current signature taken by simulating the abnormal conditions on the gate MOVs used extensively in the nuclear power plants. Based on the evaluation results, the conclusion can be as follows: 1.The DC signature of motor power shows more sensitive than the current. Both of them have similar behavior during the simulation. 2.The changes of the valve stroke and magnitude with appropriate management of the signature occured during the stroke can be used as an index showing the valve failure and degradation. 3.The diagnosis of valve by simultaneous use of the valve current and power is more useful than the method using the motor current only.

인터넷상에서 페트리 넷을 이용한 하이퍼-프리젠테이션의 명시 표현 및 불일치성을 검증하기 위한 방법 연구

우시연,조종근,임영환,임기욱 한국정보처리학회 2002 정보처리논문지 Vol.9-b No.5

하이퍼-프리젠테이션 개념은 하이퍼-미디어 개념을 확장한 것으로, 동적으로 연출되고 있는 상황에서 링크개념을 설정하여 특정시점이나 지점에서 원하는 다음 정보를 보기 위해서 비순차적으로 연출할 수 있도록 하는 연출이다. 이러한 비순차적인 연출방법인 하이퍼-프리젠테이션 개념을 도입함으로써, 자유로운 멀티미디어 연출이 가능하게 되었지만, 이러한 동기화 방법에 의해서 혼합된 여러 프레젠테이션들간에는 일관성 문제가 발생할 수 있다. 본 논문에서는 하이퍼-프리젠테이션 명시 프로그램의 일관성 검증을 위해서 Petri Net을 이용한 하이퍼-프리젠테이션 명시 방법을 제시하고, 그것을 이용한 명시 프로그램의 일관성을 검증하는 방법을 제안한다. The concept of a hyperpresentation, as an extension of a hypermedia, is the presentation in which time-varying multimedia presentations are dynamically linked together and a hyperlink's context can be changed over time at any time during a continuous presentation. While this concept provides users with a flexible and powerful tool for their descriptions of the multimedia presentation, inconsistency problems in the synchronized presentations connected by hyper links can be introduced. This paper introduces a method of describing the hyperpresentation using Petri Net and proposes a methods of detecting inconsistent hyper link loop in the hyperpresentation description.

급성 호흡곤란으로 내원한 성대기능이상 1례

함초롬,박경일,박혜연,황철웅,김종연,김태년,진재용,이성순 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Vocal cord dysfunction (VCD) is a respiratory disorder characterized by the abnormal adduction of the vocal cords upon inspiration, expiration, or both, leading to a diverse array of acute obstructive airway signs and symptoms (wheezing, chest tightness, shortness of breath, and cough). VCD frequently mimics or confounds asthma. Misdiagnosis as asthma has led to inappropriate treatment, most notably with high-dose corticosteroids. Mistaken for anaphylaxis or angioedema, VCD has led to intubation and tracheostomy. VCD should be suspected in patients who are treated aggressively for asthma but continue to experience dyspnea. The diagnosis of VCD is made from direct visualization of the vocal cords during an attack. Inspiratory, anterior vocal cord closure with a posterior glottic chink is seen. On pulmonary function testing, a pattern of "saw-toothing", or fluttering of the inspiratory limb, representing fluctuations in the abnormal cord motion is seen in VCD patient. Treatment includes discussion of the diagnosis with the patients, discontinuing unnecessary medications, using of a helium-oxygen mixture in acute attack. Speech therapy and psychotherapy are the mainstays of long-term treatment. Here in we report a case of VCD in company with asthma.

백서 해마에서 카이닌산 유도 경련에 의한 JNK 경유 신호전달경로 활성화의 발달 단계에 따른 변화

김종흔,정희연,노명선,안용민,강웅구,김용식,조수철 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.5

연구목적 : 어린 백서의 해마에서 전기경련충격(electroconvulsive shock, ECS) 후 활성화되는 것으로 알려져 있는 MAPK계 신호전달경로가 카이닌산(Kainic acid, KA)에 의한 경련 후 어떤 양상으로 활성화되는 지를 초기 발달 단계에 따라서 관찰하고자 하였다. 방 법 : 생후 7일, 14일, 21일 된 어린 백서와 성년 백서의 해마에서 면역블롯 방법으로 MAPK계 효소의 인산화 효소 중 하나인 SAPK/ERK kinase-1(SEK-1), MAPK계 효소인 c-Jun N terminal protein kinase(JNK), 전사인자 c-Jun 및 조기유전자 단백질 Fos의 단백질 양과 기저 인산화를 측정하였고, 백서에게 KA를 주사하여 경련을 유발한 후 위 단백질들의 인산화 변화의 양상을 같은 방법으로 관찰하였다. 결 과 : SEK-1, JNK, c-Jun 모두 연령 증가에 따른 단백질 양 자체에는 변화가 없었다. JNK와 c-Jun은 기저 인산화의 양적 변화도 없었으나 SEK-1의 경우 기저 인산화 양이 생후 7일에 가장 높고 이후 연령이 높아짐에 따라 감소하였다. JNK의 경우 KA 주사 후 인산화 변화 양상이 관찰되지 않았으나 SEK-1과 c-Jun은 생후 14일부터 연령의 증가와 함께 인산화 양도 증가하였다. Fos 역시 생후 7일부터 발현되어 연령의 증가와 함께 발현양이 증가하였다. 결 론 : 백서 해마에서의 MAPK계 신호전달계의 성숙은 연령의 증가에 따라, 또 신호전달 물질에 따라 차이를 보였다. KA 유도 경련 후 JNK는 생후 21일까지도 활성화가 되지 않는 것으로 보아, 세포주에서 알려진 SEK-1 - JNK-c-Jun - Fos로 연결되는 신호전달 경로가 어린 백서의 해마에서는 적용될 수 없음을 시사한다. Objective : We observed the developmental pattern of activation of MAPK signal transduction pathways known to be activated by eletroconvulsive shock(ECS) in young rat hippocampus after kainic acid(KA)-induced seizure. Methods : We used the method of immunoblotting for examining the basal protein amount and basal level of phosphorylation of MAPK kinase(SAPK/ERK kinase -1, SEK-1), MAPK(c-Jun N terminal protein kinase, JNK), transcription factor(c-Jun) and immediate early gene proteins(Fos) in rat hippocampus at postnatal day 7, 14 and 21, respectively. We also examined the changes of phosphorylation of those proteins after kainic acid-induced seizure in the same way. Results : The basal protein amounts of SEK-1, JNK, and c-Jun did not show age-dependent changes and basal level of phosphorylation of JNK and c-Jun remains unchanged throughout the early developmental period. The basal level of phosphorylation of SEK-1 was peaked at postnatal 7 days and then decreased with aging. After kainic acid-induced seizure, the change of phosphorylation of JNK was not observed but those of SEK-1 and c-Jun increased after postnatal day 14. The expression of Fos was observed at postnatal day 7 and also increased with aging. Conclusion : These results show that the MAPK signal transduction system in rat hippocampus matures in accordance with aging, but the process of maturation differs depending specific proteins. This study suggests the signal transduction cascade(SEK-1 - JNK - c-Jun - Fos) which is well established in cell line studies may not be applied to rat hipposcampus because we could not observe the activation of JNK after KA-induced seizure in young rat hippocampus.

약이성 음료(藥餌性飮料)에 관한 고찰

서연희,조후종,오성천 명지대학교 자연과학연구소 1996 자연과학논문집 Vol.14 No.-

우리나라 약이성 음료의 재료와 종류 및 효능의 다양성 등을 알아본 결과 약이성 음료의 종류에는 차혼성차류 4종, 꽃잎차 3종, 과일차 5종, 곡재차 3종, 약재차 7종외에 탕류 21종, 장류 7종 등이 있고, 이들을 효능별로 보면 간에 유효한 것이 17종, 소화기에 유효한 것이 25종, 호흡기에 유효한 것이 18종, 신경안정에 유효한 것이 13종, 그리고 양기에 효능이 있는 것이 3종 이었다. After Chosum periods, the culture of Suncha (green tea) was declined, but medicine beverage was developed with medicine foods. Among the traditional beverage which was seen to reports and treatises, Yusacha (tea analog with /without green tea), Tang (boiled herb extract), Jang(lactic acid fermented rice beverage), had distinguished variable medical effects. The effect of medicine beverage were related with protecting stomach, strengthening stomach, promoting digestion, robusting internal organs, and stablizing mind.

정신분열병과 Neuregulin 1 유전자의 연합연구

박동연,이유상,조은영,조승희,장용이,전현옥,장수연,윤세창,김종원,홍경수 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.3

Objectives : The authors recently found a suggestive evidence of linkage of chromosome 8p21-12 to schizophrenia in Korean multiplex families. Neuregutin 1 (NRGI) was identified in this locus as a positional and functional candidate gene for Schizo-phrenia, through several independent studies with European and Chinese populations. The purpose of this study is to determine whether NRGl is associated with schizophrenia in Korean population. Methods : Three SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177) and two microsatellites markers (478B14-848,420M9-1395) located at the 5' end of NRGI were genotyped for 242 unrelated schizophrenia patients and the same num-ber of normal controls. Genetic association was tested by χ²-test (df=1). Not only for the whole patients group but also for asubgroup of patients with auditory hallucination. This subtype showed stronger linkage with chromosome 8p12 in the prior study of the authors with multiplex families. Results : G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with auditory hallucination compared to the control group (p=0.03, 0R=1.76). We also found that 3 SNPs haplotype TTC (p=0.04, 0R=0.58) and five markers haplotype TTC53 (p=0.01,0R=0.49) were associated with schziophrenia with a protective effect. Three SNPs haplotype CGT which is a part of the at-risk haplotype of the Icelandic schizophrenia families was found in excess in the patients group but no significant association was observed. Conclusion : NRGI might either play a mle in the predisposition to schizophrenia or be in linkage disequilibrium with a causal locus of this illness.

육군 병사들의 복무기간에 따른 불안, 우울 및 충동성에 대한 연구

이종훈,조주연 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

연구목적과 방법 : 저자는 군복무기간에 따른 우울, 불안, 충동성향을 평가하기 위하여 548명의 병사들에게 Beck의 우울척도(BDI), Zung이 개발한 자가평정 불안척도(SAS), Barratt이 개발한 충동성 검사(BIS)를 실시하였다. 일반 병사들은 다음과 같이 3군으로 나뉘어졌다. 제1군 : 군복무기간이 8개월이하인 병사 제2군 : 군복무기간이 9개월에서 16개월인 병사 제3군 : 군복무기간이 17개월이상인 병사 결 과 : 1) 제1군의 우울척도 총점(F value=3.60, p<.05)과 부정적 자기상/정신운동지연의 하부척도 점수(F value=5.82, p<.01)가 제2군의 것보다 의미있게 더 높았다. 2) 제1군의 자가평정 불안척도 점수가 다른 두 군에 비해서 의미있게 높았다(R value=5.80, p<.01). 3) 제1군의 총충동점수(F value=3.42, p<.05)와 운동충동점수(F value=3.29, p<.05)가 제3군에 비해 의미있게 높았다. 결 론 : 비록 병사들의 각 척도별 측정평균점수는 정상범위에 속할지라도, 이번 연구의 결과는 제1군의 경우 다른 두 군에 비해 더 우울하고, 불안하고, 충동적이라는 것을 말한다. 따라서 군복무기간중 사고를 방지하기 위해서, 우리는 군복무기간이 8개월 이하인 사병의 경우 더 많은 주의와 관심을 가지고 관리해야 되겠다. Objectives & Methods : The authors applied Beck's Depression Inventory(BDI), Self-rating Anxiety Scale(SAS) and Barratt Impulsiveness Scale(BIS) to 548 enlisted men to evaluate the differences of anxious, depressive and impulsive trends according to the duration of the military service. The enlisted men were divided into 3 groups as follows : Group 1 : those who had served under 8 months. Group 1 : those who had served from 9 to 16 months. Group 1 : those who had served over 17 months. Results : 1) The scores of BDI(F=3.60, p<.05) and negative self image and psychomotor retardation subscale(F=5.8, p<.01) of group 1 were significantly higher than those of group 2, respectively. 2) The SAS score of group 1 was significantly higher than that of others(F=5.80, p<.05). 3) The scores of total BIS(F=3.42, p<.05) and impulsiveness-motor subscale(F=3.29, p<.05) of group 1 were significantly higher than those of group 3, respectively. Conclusion : In spite of their scores were in normal range, these results suggest that the enlisted men of group 1 are more anxious, depressive and impulsive than those of the others. So we should give more attention to them and offer more concerns for them to protect the military accident.

백서 해마에서 카이닌산에 의한 조기유전자의 발현과 p42, p44 MAPK 및 EIK-1 인산화의 발달 단계에 따른 변화

정희연,김수진,김종흔,정선주,박주배,김용식,조수철 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.4

연구목적 : 어린 백서에게 카이닌산(kainic acid, KA)을 주사하여 발작을 일으킨 후, 해마에서 조기유전자 -c-fos, junB, 및 TIS1의 발현 유도 양상을 발달 단계별로 조사하여 전기경련충격(electroconvulsive shock, ECS)에서의 결과와 비교함으로써 백서 뇌 신호전달계의 성숙과정을 파악하고자 하였다. 그리고 KA 주사후 p42, p44 mitogen activated protein kinase(MAPK)의 인산화 및 그에 의해 활성화되는 것으로 알려진 전사인자 Elk-1의 인산화를 관찰하여, KA 주사후 MAPK 신호절달계를 통한 c-fos의 발현로 알려진 전사인자 Elk-1의 인산화를 관찰하여, KA 주사후 MAPK 신호전달계를 통한 c-fos의 발현 경로를 발달 단계별로 밝히고자 하였다. 방 법 : 생후 7, 14 21일 된 수컷 백서에서 KA를 복강내 주사한 후, 백서 해마에서 조기유전자의 발현 양상은 northern blot analysis로, p42, p44 MAPK와 Elk-1의 인산화는 immunoblotting으로 관찰하였다. 결 론 : 생후 7일된 백서의 해마에서는 ECS와는 달리, KA에 의한 세 가지 조기유전자의 발현이 관찰되지 않았다. 그러나 생후 14일부터 이들 조기유전자의 뚜렷한 발현을 관찰할 수 있었고 생후 21일에는 성숙한 백서와 같은 수준의 발현 양상을 볼 수 있었다. 세 가지 유전자 모두 백서의 연령과 KA 주사 후 시간에 따른 발현 유도 양상은 비슷하였다. p42, p44 MAPK는 생후 7일부터 상당한 수준의 기저치 인산화가 관찰되었으나, KA에 의한 인산화 증가는 생후 14일부터 관찰되었다. Elk-1의 인상화 역시 생후 7일부터 높은 수준으로 관찰되었으나 KA 주사 후 시간에 따른 Elk-1 인산화의 변화는 관찰할 수 없었다. 결 론 : ECS와 KA가 조기유전자 발현 양상에 차이를 보이는 것은 이들 유전자의 발현과 관련되어 활성화되는 신호전달경로의 차이 때문으로 생각된다. 백서 해마에서 KA에 의한 MAPK 활성화에 관여하는 신호 전달 기구는 연령이 높아짐에 따라 점차 성숙하고, MAPK의 활성화로 전달된 신호는 Elk-1 이외의 다른 경로를 통해 c-fos 발현을 조절하는 것으로 추측된다. Objectives : In order to investigate the maturational process of intracellular signal transduction system in rat brain, we studied the induction of the immediate early genes(IEGs)-c-fos, iunB, and TIS1 in each developmental stage after kainic acid(KA)-induced seizure in young rat hippocampus and then compared these with the results after electroconvulsive shock(ECS) And to elucidate the induction mechanism of c-fos via mitogen-activated protein kinase(MAPK) by KA in each developmental stage, we investigated the phosphorylation of p42, p44 MAPK and Elk-1 after KA treatment in young rat hippocampus. Methods : We examined the induction patterns of IEGs by northern blot analysis, and the phosphorylation of p42, p44 MAPK and Elk-1 by immunoblotting in rat hippocampus at post-natal day 7, 14, and 21(P7, P14 & P21), respectively after intraperitoneal injection of KA. Results : Unlike ECS, KA did not induce c-fos, junB, and TIS1 in P7 hippocampus. But these genes were apparently induced at P14 and to an adult level at P21. These three IEGs showed similar temporal patterns of induction in each developmental stage. Although the basal level of phosphorylated 42p, 44p MAPK was considerable in P7 rat hippocampus, the increase or phosphorylation after KA treatment was observed at P14. While the phosphorylation of Elk-1 was detected with high basal level in P7 rat, the amount of phosphorylated Elk-1 was not changed after KA treatment. Conclusion : Our results suggest that the differences in IEGs induction patterns between KA and ECS may be due to the differences in the activated signal transduction pathways. And our results also implicate that the signal transduction system involved in MAPK phosphorylation after KA treatment mature with aging and c-fos induction via MAPK activation may be regulated through some pathways other than Elk-1 in rat hippocampus.