• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• 동의생리병리학회지
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• 제17권3호
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• pp.633-642
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• 2003

A pain is the symptom which defends against noxious stimulus about a human body, it is known that if the periphery of perceptive nerve were stimulated by a physical or chemical factors, the stimulation is induced by transmission to pain center in the cerebral cortex according to pain conduction tract. The treatment of pain is to decrease a stimulus that causes a pain or block off a nerve transmitting a stimulus or puts on a way to calm down pain center, but It is for adjustment of a pain to be the most representative in acupuncture among various ways to cure a pain in Oriental medicine. However, the analgesic effect of an individual response to acupuncture stimulation shows marked individual variations, so these days genetic a few approach is attempted. On this the author determined that the responding group was appointed those whose tail flick latency (TFL) responding time delayed the minimum of 30 % comparing with basal reaction time. For those whose TFL time had shorter than 30 % was grouped as a non-responding group. And then the hypothalamus of each group was dissected and RNA was further purified. After synthesizing cDNA using oligo dT primer, products were finally applied to the PCR. The results were as follows; The ratio of responding group to non-responding group was 6:4. Ach T (acetylcholinesterase T subunit), BF-I (Brain factor-I), DBH (Dopamine β-hydroxylase) and PNM (Phosphotidylethanolamine N-Methyltransferase) were revealed significantly in the responding group. Cathepsin B and Tau were revealed significantly in the non-responding group. The PCR results show that Ach T, BF-I, DBH and PNM are expressed abundantly in the responding group, where as cathepsin B and tau are abundant in the non-responding group. These results suggest that the analgesic effect on acupuncture stimulation is related to regulation of neurotransmitter as well as neurodegeration of cerebrum.

• 생명과학회지
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• 제30권10호
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• pp.844-850
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• 2020

본 연구는 지구온난화와 태풍에 의해 수확기의 손실을 막기 위해 벼의 출수기를 당기는 유전자를 찾는 것을 목표로 한다. 청청/낙동 배가반수체(CNDH)와 모본인 청청, 부본인 낙동을 재료로 사용하여 QTL을 이용해 출수기 관련 유전자의 위치를 조사하고 gene을 cloning하여 염기서열을 분석하였다. 분석결과 염색체 8번에 13개의 contig가 있었고 그 중 출수기와 관련된 1개의 ORF가 존재했다. 단백질 서열을 분석한 결과 벼의 Os08g0341700, 그리고 AtSFH13, AtSFH7 단백질과 유사한 것으로 보인다. 신호전달과 관계가 있는 Os08g0341700은 phosphatidylinositol transfer-like protein II와 유사하며 아직 완전한 information은 밝혀지지 않았다. 하지만 Sec14P와 연관이 있으며 세포 생장 등에 관여하는 phosphatidylinositol 특이적 신호전달 경로의 역할을 할 것으로 추정 중이다.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.93-93
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• 2017

To develop rice cultivars with increased biomass and grain yield, superior lodging resistance is an essential trait. The new breeding approach can be adopted for the improvement of stem lodging resistance by enhancing culm strength. The resistance to breaking type lodging is attributed to bending moment of basal culm (M), which is composed of the section modulus (SM) and bending stress (BS). The resistance to the bending type lodging is attributed to flexural rigidity (FR) of stem, which is composed of the secondary moment of inertia (SMI) and Young's modulus (YM). Starch and cell wall components such as cellulose, hemicellulose and lignin also play a significant role in physical strength of culm, and thus affect lodging. Leaf Star has a superior lodging resistance due to its thick and stiff culm because of its high M and FR compared with Koshihikari. Furthermore, Leaf Star contains high densities of hemicellulose, cellulose and low lignin density in culm compared with Koshihikari. In this study, we performed QTL analysis for these traits associated with culm strength, using 94 recombinant inbred lines (RILs, $F_8$), derived from a cross between Leaf Star and Koshihikari. The SM in the RILs showed a continuous distribution. QTLs for SM were detected on chrs.2, 3 and 10. Leaf Star alleles increased SM on chrs. 2 and 3, but Koshihikari allele increased on chr.10. These QTLs overlapped with those QTLs identified using backcrossed inbred line derived from a cross between Chugoku 117 and Koshihikari, the parents of Leaf Star. The FR in Leaf Star was higher than that in Koshihikari due to the larger SMI and YM. 3 QTLs for SMI were detected on chrs.2, 3 and 10. Leaf Star alleles increased SMI on chrs.2 and 3, and Koshihikari alleles increased on chr.10. One QTL on chr.3 and two QTLs on chr.5 for hollocelulose content were detected with Leaf Star alleles contribution. Moreover, two QTLs were detected for hemicellulose density on chrs.3 and 5. Leaf Star allele increased hemicellulose density on chr.5, and Koshihikari allele increased on chr.3. Furthermore, two QTLs for cellulose density were detected on chr.5, and one QTL on chr.2. For starch content, one QTL on chr.3 and two QTLs on chr.5 with Leaf Star alleles contribution were detected. TULK-6 carrying a chromosome segment of Leaf Star on chr.5 in the Koshihikari genetic background showed higher densities of starch and hemicellulose than those in Koshihikari. These results suggest that the detected QTLs for culm strength could be utilized for the improvement of lodging resistance in rice by marker-assisted selection.

• BMB Reports
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• 제42권5호
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• pp.286-292
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• 2009

Arginine deiminase (ADI), an arginine-degrading enzyme, has anti-proliferative and anti-tumor activities and is capable of inhibiting the production of nitric oxide (NO). Modulation of nitric oxide (NO) production is considered a promising approach for the treatment of various diseases including cancer, inflammation and neuronal disorders. In this study, an ADI gene was fused with an HIV-1 Tat peptide in a bacterial expression vector to produce an genetic in-frame Tat-ADI fusion protein. When added exogenously to the culture media, the expressed and purified Tat-ADI fusion proteins were efficiently transduced into macrophage Raw 264.7 cells in a time- and dose-dependent manner. Furthermore, transduced Tat-ADI fusion proteins markedly increased cell viability in cells treated with lipopolysaccharide (LPS). This increase in viability was mediated by an inhibition of NO production. These results suggest that this Tat-ADI fusion protein can be used in protein therapies of NO-related disorders such as cancer, inflammation and neuronal diseases.

• Asian-Australasian Journal of Animal Sciences
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• 제31권4호
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• pp.473-479
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• 2018

Objective: The study was designed to perform a genome-wide association (GWA) and partitioning of genome using Illumina's PorcineSNP60 Beadchip in order to identify variants and determine the explained heritability for the total number of teats in Yorkshire pig. Methods: After screening with the following criteria: minor allele frequency, $MAF{\leq}0.01$; Hardy-Weinberg equilibrium, $HWE{\leq}0.000001$, a pair-wise genomic relationship matrix was produced using 42,953 single nucleotide polymorphisms (SNPs). A genome-wide mixed linear model-based association analysis (MLMA) was conducted. And for estimating the explained heritability with genome- or chromosome-wide SNPs the genetic relatedness estimation through maximum likelihood approach was used in our study. Results: The MLMA analysis and false discovery rate p-values identified three significant SNPs on two different chromosomes (rs81476910 and rs81405825 on SSC8; rs81332615 on SSC13) for total number of teats. Besides, we estimated that 30% of variance could be explained by all of the common SNPs on the autosomal chromosomes for the trait. The maximum amount of heritability obtained by partitioning the genome were $0.22{\pm}0.05$, $0.16{\pm}0.05$, $0.10{\pm}0.03$ and $0.08{\pm}0.03$ on SSC7, SSC13, SSC1, and SSC8, respectively. Of them, SSC7 explained the amount of estimated heritability along with a SNP (rs80805264) identified by genome-wide association studies at the empirical p value significance level of 2.35E-05 in our study. Interestingly, rs80805264 was found in a nearby quantitative trait loci (QTL) on SSC7 for the teat number trait as identified in a recent study. Moreover, all other significant SNPs were found within and/or close to some QTLs related to ovary weight, total number of born alive and age at puberty in pigs. Conclusion: The SNPs we identified unquestionably represent some of the important QTL regions as well as genes of interest in the genome for various physiological functions responsible for reproduction in pigs.

• 한국가축번식학회지
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• 제24권4호
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• pp.451-455
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• 2000

본 연구는 TT2 embryonic stem(ES) cell을 이용하여 chimeric mouse를 생산하는데 있어서 더욱 간편한 공배양방법 개발하기 위하여 수행되었다. 유전자 적중 생쥐의 개발은 유전자의 기능을 연구하는데 매우 중요한 수단으로 이용되고 있다. 이러한 생쥐의 개발에 있어서 chimeric mouse를 생산하는 과정은 ES cell의 종류의 차이는 있지만 주로 배반포기의 수정란에 ES cell을 주입하고 있다. 이 기술은 고가의 미세조작장치 뿐만 아니라 고도의 기술을 요하고 있다. 그러므로 본 연구에서는 TT2 ES cell를 8세포기 수정란과 공배양할 때의 필요로 하는 적절한 ES cell의 수를 검증함으로써 chimeric mouse의 생산 효율을 높일 수 있었다. 각각 0.5$\times$$10^{6}$, 1$\times$$10^{6}$과 2$\times$$10^{6}$$m\ell$의 ES cell을 8 세포기의 수정란과 공배양하였을때 0.5$\times$$10^{6}$과 1$\times$$10^{6}$$m\ell$에서 높은 배반포기로의 발달율을 나타내었다. 또한 가임신된 생쥐에 이들 배반포기를 이식한 결과 1$\times$$10^{6}$$m\ell$에서 높은 chimeric mouse 생산 효율을 나타내었다. 이러한 결과는 적절한 수의 ES cell과 수정란을 공배양함으로써 매우 간단하게 효율 좋은 chimeric mouse을 얻을 수 있음을 제시하고 있다.

• 한국강구조학회 논문집
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• 제19권1호
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• pp.29-41
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• 2007

다른 복잡한 의사 결정 문제와 같이 구조설계는 많은 다른 기준들 사이의 상반관계에서 이루어지는 의사 결정 문제이다 . 다양하게수학적으로 프로그래밍 된 설계 기법이 점차 현실적인 요소를 감안하여 현실화되고 있으나 여전히 많은 설계의 제한, 즉 수학적으로 모델화 되지 못하는 많은 설계요소들과 관련되어 있다. 본 연구는 이러한 제한을 인식하고 강 프레임 구조물의 최적 설계에 관하여 다루어 지지 않은 설계요소를 감안하여 실무 설계자들에게 하나의 유일한 설계해가 아닌 다른 몇 가지 유용한 설계 대안을 제시할 수 있는 설 계 시스템을 개발 하였다. 본 연구의 알고리즘에 의해 얻어진 설계 대안들은 모델화된 목적함수에 관해 최적의 해는 아니지만 매우 적합한 해들이 며, 동시에 유일한 최적해와 비교 시 다른 설계 해로써 때로는 임의 모델화 되지 않은 설계요소에 관해서는 오히려 더 나은 결과를 나타내 줍 중에 효과적으로 저항하도록 보와 기둥이 모멘트 연결된 강 프레임 구조물을 대상으로 안정성에 문제가 없이 경비절감에 효과적인 설계를 위해 재료비뿐만 아니라 가설 시 부재연결에 소요되는 경비를 포함하는 최소 경비 설계를 위한 의사 결정 지원 시스템을 개 발하고자 한다. 본 시스템은 최적 설계해에 대한 설계대안을 생성하기 위한 변형된 최적화 문제형식으로, 이때 최적 설계해는 하중저항계수설계법 에 따른 비선형 해석과정과 유전알고리즘을 바탕으로 한 최적화 알고리즘을 결합한 알고리즘을 반복 수행하여 얻은 모멘트 연결의 수와 총 경비 와의 상반관계로부터 결정된다. 유용성 평가를 위해 생성된 각 설계대안을 다양한 설계요소에 관해 고찰하였다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권6호
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• pp.558-566
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• 2020

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion: The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

• 미생물학회지
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• 제43권3호
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• pp.159-165
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• 2007

C형 간염바이러스(hepatitis C virus; HCV)증식을 효과적이며 특이적으로 제어할 수 있는 유전산물을 개발하기 위하여 HCV 중식조절이자인 NS5B RNA replicase 존재에 의해 allosteric하게 그 활성 이 조절될 수 있는 HCV internal ribosome entry site (IRES) 표적 hammerhead 리보자임을 개발하였다. 우선 HCV IRES 염기서열 중+382 nucleotide(nt) 부위가 리보자임에 의해 가장 잘 인식되었음을 관찰하였다. 이러한 allosteric 리보자임은 NS5B RNA replicase와 특이적으로 결합하는 RNA aptamer 부위, aptamer와 NS5B와의 결합에 의해 리보자임 활성을 유도할 수 있도록 구조적 변이를 전달할 수 있는 communication module부위 및 HCV IRES의 +382 nt를 인지하는 hammerhead 리보자임 등으로 구성되도록 설계하였다. 특히 in vitro selection기법을 활용하여 NS5B 의존적으로 리보자임 활성을 증가시킬 수 있는 communication module 염기서열을 밝혀내었다. 이러한 리보자임은 단백질이 없거나 대조 단백질인 bovine serum albumin이 존재할 때에는 절단반응을 유도하지 못하였으나 HCV NS5B 단백질이 존재할 매에만 효과적으로 NS5B 농도 의존적으로 절단 반응을 유도할 수 있음을 관찰하였다. 이러한 allosteric 리보자임은 HCV중식의 효과적인 증식 억제 선도물질 뿐만 아니라 HCV 치료선도물질의 스크리닝용 도구 및 HCV 조절 인자를 탐색할 수 있는 HCV 진단용 리간드로서도 활용될 수 있을 것이다.