• Journal of Microbiology and Biotechnology
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• 제27권9호
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• pp.1701-1710
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• 2017

Classical swine fever virus (CSFV) is the etiologic agent of classical swine fever, a highly contagious disease that causes significant economic losses to the swine industry. The lapinized C-strain, a widely used vaccine strain against CSFV, has low growth efficiency in cell culture, which limits the productivity in the vaccine industry. In this study, a recombinant virus derived from C-strain was constructed and subjected to continuous passaging in PK-15 cells with the goal of acquiring a high progeny virus yield. A cell-adapted virus variant, RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC variants indicated that at least six nucleotide changes were fixed in RecCpp80. Further adaption of RecCpp80 variant in swine testicle cells led to a higher virus yield without additional mutations. Introduction of each of these residues into the wild-type RecC backbone showed that one mutation, M979R (T3310G), located in the C-terminal region of E2 might be closely related to the cell-adapted phenotype. Rabbit inoculation revealed that $RecCpp40_{+10}$ failed to induce fever in rabbits, whereas $RecCpp80_{+10}$ caused a fever response similar to the commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell culture by introducing specific mutations in its E2 protein. The mutations in RecCpp80 that led to the loss of fever response in rabbits require further investigation. Continuous passaging of the C-strain-based recombinant viruses in PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at 3310 and 3531 might play major roles in the enhanced capacity of general virus reproduction. Such findings may help design a modified C-strain for improved productivity of commercial vaccines at reduced production cost.

• 대한약리학회지
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• 제31권2호
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• pp.241-250
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• 1995

Protein B23 is one of the major nucleolar phosphoproteins associated with pre-ribosomal particles, and is localized in the granular region of the nucleolus. Recent studies suggest that protein B23 shuttles between nucleus and cytoplasm and also interacts with HIV Rev. These findings indicate that protein B23 is important in nucleocytoplasmic relationship and viral replication. However, the exact function of protein B23 is not clear yet. In acute nucleolar hypertrophy of rat liver, treated with thioacetamide, there was observed an increase of not only protein B23 but also B23-like protein p45 when anti-B23 monoclonal antibody (MAb) was used for identification. On the basis of the large B23 specific epitope structure composed of 68 amino acids, a hypothesis was formulated to examine that p45 is the pre-B23 resulting from excessive production of B23. In an attempt to investigate the precursor of B23, we analyzed the subcellular fractions and microsomal subfractions. Subsequently, we analyzed the finger printings of B23-like proteins using the tryptic peptide mapping. The results are summarized: 1) Using B23 MAb, we observed the presence of B23-like proteins in nucleolar fraction, nucleoplasmic fraction and microsomal fraction. 2) In the further microsomal subfractionation, we could partially purify B23-like protein in 2M layer of sucrose gradient. 3) When ion exchange chromatography was employed, there were protein species 80kDa(p80), 65kDa(p65) and 60kDa(p60). 4) Based on the tryptic map analysis of $^{125}I$ labeled proteins, the similarity between B23 and p80 was found only in 9 out of 14(B23) and 21(p80) peptides, and difference was found in the remaining peptides. p80 and p60 had 18 common peptides, and all the peptides of p60 were similar to those of p80. From these results, it is proposed that p45 is an abnormal metabolite resulting from carcinogenesis by thioacetamide, and it is not the precursor of B23. In addition, we suggest that p80 may be a precursor of p45.

• Nutrition Research and Practice
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• 제10권1호
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• pp.115-124
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• 2016

BACKGROUND/OBJECTIVES: This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. SUBJECTS/METHODS: The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > $23kg/m^2$) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < $1{\times}10^{-4}$). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. RESULTS: We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; $P=8.0{\times}10^{-7}$, rs1040675; $2.3{\times}10^{-6}$) and BMI (rs10786764; $P=2.5{\times}10^{-5}$, rs10786764; $6.57{\times}10^{-5}$). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P < $10{\times}10^{-4}$. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < $1{\times}10^{-4}$). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. CONCLUSION: We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

• 벤처창업연구
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• 제16권3호
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• pp.121-143
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• 2021

사회적경제가 사회문제 해결의 대안 중 하나로 부상하면서 사회적경제의 규모화 방법론인 소셜 프랜차이즈에 대한 관심과 실험도 계속 증가하고 있다. 소셜 프랜차이즈의 성패는 가맹본부, 가맹점 구성원은 물론 서비스 대상인 수혜자나 지역 주민, 그리고 지역 내 이해관계자에게 미치는 파급력이 크지만 성공가능성을 높일 수 있는 방안에 대한 연구는 아직 미흡하다. 본 연구는 선행연구를 기반으로 소셜 프랜차이즈의 특성이 경영성과에 미치는 영향 분석을 통해 성공요인을 도출하고, 소셜 프랜차이즈의 차별점인 가맹점 자율성이 특성요인과 경영성과 사이에서 갖는 매개효과를 파악하고자 하였다. 사회적가치지향성, 사회적경제 경험, 지역 네트워크 활용, 고객지향성을 소셜 프랜차이즈의 경영성과에 영향을 미치는 특성 요인으로 도출하였으며, 가맹점 자율성을 매개변수로 설정하고 가맹점 구성원 대상 설문조사를 실시하여 영향력을 분석하였다. 연구를 통해 사회적경제 경험과 지역 네트워크 활용은 경제적 성과에 정(+)의 영향을 미치며, 사회가치지향성, 지역 네트워크 활용, 고객 지향성은 사회적 성과에 정(+)의 영향이 있음을 규명하였다. 또한 가맹점 자율성이 사회적경제 경험, 지역 네트워크 활용과 경제적 성과 사이에서, 지역 네크워크 활용과 사회적 성과 사이에서 매개 역할을 하는 결과를 제시하였다. 본 연구는 소셜 프랜차이즈를 대상으로 본격적인 실증연구를 진행한 첫 연구로서의 의미를 갖는다. 연구를 통해 향후 소셜 프랜차이즈에 대한 이론적 연구가 더욱 활성화 되고 소셜 프랜차이즈를 모색하거나 이미 운영중인 조직에게는 성과 창출을 위한 유용한 참고자료로 활용될 수 있기를 기대한다.

• 생명과학회지
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• 제32권2호
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• pp.94-100
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• 2022

B형간염바이러스(HBV)의 만성 감염은 간경화와 간세포암 발생 빈도를 현저히 높인다. HBV 감염의 임상적 결과는 숙주 유전적 요인과 바이러스의 유전자 변이, 그리고 환경적 요인 등에 결정된다. HBV 복제를 위한 HBV의 pre-genomic RNA 전사는 바이러스의 core promoter 활성화에 의해 조절된다. Core promoter 돌연변이는 급성간 질환과 간세포암 발생에 연관되어 있다. 본 연구팀은 미얀마의 HBV 감염 환자들로부터 바이러스 유전자를 획득하여 core promoter 부위의 유전자 변이들을 파악하였다. Core promoter의 상대적 유전자 활성 차이를 분석하기 위해서 core promoter를 luciferase reporter에 재조합한 시스템을 제작하였다. 분석한 core promoter의 유전자 변이들 중에서 C1731T와 G1806A 돌연변이가 HBV core promoter의 전사 활성화를 증가에 관여하였다. 돌연변이 부위를 중심으로 전사 인자들의 가능한 결합 부위 변화를 컴퓨터 프로그램 분석을 통해 조사한 결과, C/EBPβ와 XBP1 반응 부위가 새롭게 생성되었음을 도출하였다. C/EBPβ의 세포 내 발현은 C1713T 돌연변이를 가진 core promoter의 전사 활성을 증가시켰으며, XBP1 발현은 G1806A 돌연변이를 함유한 M95 promoter를 활성을 증가시켰다. HBV 감염의 치료는 약제 내성과 백신 회피 돌연변이 발생으로 문제점을 가지고 있는 상황에서, 이 연구 결과는 HBV core promoter 돌연변이의 분자생물학적 그리고 임상학적 중요성을 제공한다.

• IMMUNE NETWORK
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• 제20권5호
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• pp.41.1-41.11
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• 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense single-stranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor - angiotensin converting enzyme 2 (ACE2) - on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene. The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

• 대한치과보철학회지
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• 제53권4호
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• pp.345-351
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• 2015

목적: 이 실험의 목적은 전치부 임플란트에 적용되는 지르코니아 지대주의 적절한 축벽의 두께를 평가하는 것이었다. 재료 및 방법: 시편들은 4가지의 서로 다른 두께로 제작되었으며, 일정하게 제작하고자 CAD/CAM 시스템을 이용하여 소결전 지르코니아 블록을 가공한 후 소결하였다. 가공된 시편들은 두께에 따라 Group 1 (0.5 mm), Group 2 (0.8 mm), Group 3 (1.0 mm), Group 4 (1.2 mm)의 4가지 그룹으로 분류되었다. 임플란트 시스템은 외부연결형(US, Osstem, Pussan, Korea) 을 이용하였다. 지대주 시편들은 시멘트 유지형 지대주를 복제하여 제작되었다. 크라운은 1.5 mm 의 두께로 CAD/CAM을 이용하여 제작되었다. 제작된 지대주 시편들을 임플란트에 고정시킨 후 레진시멘트(RelyXTM UniCem, 3M ESPE AG, Seefeld, Germany)를 이용하여 크라운을 합착하였다. 지르코니아 지대주의 파절을 측정하기 위해 만능시험기로 임플란트 장축에 30도의 각도로 힘을 가하였다. 결과: Group 1, Group 2, Group 3와 Group 4의 파절강도는 각각 $236.00{\pm}67.55N$, $599.00{\pm}15.80N$, $588.20{\pm}33.18N$, $97.83{\pm}98.13N$이었다. Group 1이 다른 그룹에 비해 통계학적으로 유의성 있게 낮은 강도를 보여주었다(independent Mann-Whitney U-test, P<.05). 나머지 Group 2, Group 3와 Group 4는 서로 통계학적으로 유의성을 보여주지 않았다(independent Mann-Whitney U-test, P>.05). 결론: 지르코니아 지대주는 파절에 저항하기 위해 적절한 두께를 필요로 한다. 이 실험의 결과로 판단할 때, 지르코니아 지대주가 전치부 임플란트에 적용되기 위해서는 0.8 mm 이상의 두께를 가져야 된다고 추천된다.

• Genomics & Informatics
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• 제9권2호
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• pp.52-58
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• 2011

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genome-wide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=$1.27{\times}10^{-6}$) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.

• Molecules and Cells
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• 제45권12호
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.