• Title/Summary/Keyword: Potential Functions

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Selection signature reveals genes associated with susceptibility loci affecting respiratory disease due to pleiotropic and hitchhiking effect in Chinese indigenous pigs

  • Xu, Zhong;Sun, Hao;Zhang, Zhe;Zhang, Cheng-Yue;Zhao, Qing-bo;Xiao, Qian;Olasege, Babatunde Shittu;Ma, Pei-Pei;Zhang, Xiang-Zhe;Wang, Qi-Shan;Pan, Yu-Chun
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.2
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    • pp.187-196
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    • 2020
  • Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (FST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r2 = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r2 = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8+ T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

  • Yuan, Chun-Hui;Yang, Xue-Qin;Zhu, Cheng-Liang;Liu, Shao-Ping;Wang, Bi-Cheng;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.265-271
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    • 2014
  • Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

  • Li, Ping;Xie, Xiao-Bing;Chen, Qian;Pang, Guo-Lian;Luo, Wan;Tu, Jian-Cheng;Zheng, Fang;Liu, Song-Mei;Han, Lu;Zhang, Jian-Kun;Luo, Xian-Yong;Zhou, Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6949-6954
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    • 2014
  • Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

D99 Type I Signal Peptidase Implicated Stabilizing the Protein Structure (Type I 신호펩디드 가수분해효소에 존재하는 D99 아미노산 잔기의 구조적 역할 가능성)

  • Sung, Meesook;Eunyoung Han;Lee, Hoyoung
    • Microbiology and Biotechnology Letters
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    • v.31 no.2
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    • pp.140-144
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    • 2003
  • Type Ⅰ signal peptidase is an integral membrane protein that functions to cleave signal peptides from secreted and membrane proteins. The enzyme serves as a potential target for the development of novel antibacterial agents due to its unique physiological properties. Despite being one of the best characterized enzymes, the catalysis of Type Ⅰ signal peptidase still remains controversy over the catalytic serine/lysine dyad mechanism. It appears that the dyad proteases are generally less efficient than the prototypical serine/histidine/aspartic acid triad found in most enzymes, although Type Ⅰ signal peptidase is an exception to this rule. In this paper, we have proposed that Type Ⅰ signal peptidase may act as the serine/lysine/aspartic acid triad cataltytic mechanism. Therefore, the aspartic acid 99 residue in the E. coli signal peptidase was chosen and mutated to an alanine to see if there is any possible role of the aspartic acid in the catalytic function. Type Ⅰ signal peptidase D99A protein was inactive in vitro assay using the procoat synthesized by in vitro transcription translation. However, the mutant was active using a highly sensitive in vivo assay. Pulse-chase experiments show that the replacement of aspartic acid 99 with alanine results in a very unstable signal peptidase molecule. Therefore, we conclude that it is unlikely that the residue is directly involved in catalysis, but rather plays an important role in stabilizing the protein structure.

Functional Characterization of Phosphorylation of the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nucleocapsid Protein (PRRS 바이러스 Nucleocapsid 단백질 인산화의 기능학적 연구)

  • Lee, Chang-Hee
    • Microbiology and Biotechnology Letters
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    • v.37 no.3
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    • pp.287-292
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    • 2009
  • The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is a basic multifunctional protein which has been reported to be a serine phosphoprotein with yet-identified functions. As a first step towards understanding the general role of N protein phosphorylation during virus replication, the non-phosphorylated mutant N gene was constructed by mutating all serine residues to alanine. This recombinant N protein was identified to be unphosphorylated, confirming that serine residues truly function as core amino acids responsible for N protein phosphorylation. The PRRSV N protein has been shown to possess the biological features of nuclear localization and N-N homodimerization which individually play critical roles in virus infection. In the present study, therefore, it was attempted to investigate whether these two properties of the N protein are modulated by its phosphorylation status. However, experimental results showed that the non-phosphorylated N protein was still present in the nucleus and nucleolus, and was able to associate with itself by non-covalent interactions. Taken together, the data suggest phosphorylation-independent regulation of N protein nuclear transport or oligomerization, thereby implying the potential involvement of phosphorylation in regulating the activities of the N protein at other levels including RNA-binding capacity.

The Relationships between Inhibitory Control and Action Monitoring; Event-related Potential Study (억제적 통제 및 행동 감시간의 관계: 사건관련전위 연구)

  • 강승석;박성근;하태현;노규식;김명선;권준수
    • Korean Journal of Cognitive Science
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    • v.14 no.4
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    • pp.1-7
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    • 2003
  • The common features of the behavioral inhibition and the action monitoring that are considered as one of the executive functions were investigated using event-related brain potentials (ERPs) and source localization analysis. The electrophysiological correlates of behavioral inhibition and action monitoring ate analyzed when the subjects performed the Go/NoGo task. Two ERP components of behavioral inhibition termed as N200 and P300 in NoGo condition were differ from those of Go condition, that is the amplitudes of NoGo N200 and P300 are largest on the fronto-central region, which may reflect the inhibitory control of frontal lobe required in NoGo condition. The error-related negativity (ERN) observed on the fronto-central region when the subjects committed error was much larger in amplitude and faster in latency than those of the correct-related negativity (CRN), which may indicate that the signal of action monitoring is much more required for the error response. The correlation analysis for the ERP components of behavioral inhibition and action monitoring revealed the significant negative correlation among the latencies of NoGo N200 and P300 and the amplitude of ERN, which may reflects that the faster subjects inhibit response, the more monitor their own action. The close relationship between behavioral inhibition and action monitoring was also supported by the results of source localization analysis, which showed the common neural sources of NoGo N200 and ERN was anterior cingulate cortex.

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Function of Global Regulator CodY in Bacillus thuringiensis BMB171 by Comparative Proteomic Analysis

  • Qi, Mingxia;Mei, Fei;Wang, Hui;Sun, Ming;Wang, Gejiao;Yu, Ziniu;Je, Yeonho;Li, Mingshun
    • Journal of Microbiology and Biotechnology
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    • v.25 no.2
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    • pp.152-161
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    • 2015
  • CodY is a highly conserved protein in low G+C gram-positive bacteria that regulates genes involved in sporulation and stationary-phase adaptation. Bacillus thuringiensis is a grampositive bacterium that forms spores and parasporal crystals during the stationary phase. To our knowledge, the regulatory mechanism of CodY in B. thuringiensis is unknown. To study the function of CodY protein in B. thuringiensis, BMB171codY- was constructed in a BMB171 strain. A shuttle vector containing the ORF of cry1Ac10 was transformed into BMB171 and BMB171codY-, named BMB171cry1Ac and BMB171codY-cry1Ac, respectively. Some morphological and physiological changes of codY mutant BMB171codY-cry1Ac were observed. A comparative proteomic analysis was conducted for both BMB171codY-cry1Ac and BMB171cry1Ac through two-dimensional gel electrophoresis and MALDI-TOF-MS/MS analysis. The results showed that the proteins regulated by CodY are involved in microbial metabolism, including branched-chain amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, and energy metabolism. Furthermore, we found CodY to be involved in sporulation, biosynthesis of poly-β-hydroxybutyrate, growth, genetic competence, and translation. According to the analysis of differentially expressed proteins, and physiological characterization of the codY mutant, we performed bacterial one-hybrid and electrophoretic mobility shift assay experiments and confirmed the direct regulation of genes by CodY, specifically those involved in metabolism of branched-chain amino acids, ribosomal recycling factor FRR, and the late competence protein ComER. Our data establish the foundation for in-depth study of the regulation of CodY in B. thuringiensis, and also offer a potential biocatalyst for functions of CodY in other bacteria.

Development of a Method to Analyze Powering Performance of a Ship and its Application to Optimum Hull Form Design (선박(船舶)의 정수중(靜水中) 추진성능(推進性能) 해석(解析) 및 최적선형설계(最適船型設計)에의 응용(應用))

  • Seung-Il,Yang
    • Bulletin of the Society of Naval Architects of Korea
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    • v.22 no.2
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    • pp.35-48
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    • 1985
  • The present work develops a method of evaluating thrust deduction and wake for different loads of the propeller using the concerted application of the theoretical tools and experimental techniques. It also shows the applicability of the new method to the design of optimum hull form. Firstly, the problem of hull-propeller interaction was analyzed in terms of inviscid as well as viscous components of the thrust deduction and wake. The wavemaking resistance of a hull and propeller were mathematically represented by sources on the hull surface and sink on the propeller plane, respectively. The strength of sink was determined by utilizing the radial distributions of propeller load and nominal wake. The resistance increment due to a propeller and the axial perturbation flow induced by the hull in the propeller plane were calculated. Especially, the inviscid component of the thrust deduction was calculated by subtraction the wavemaking resistance of a bare hull, the wavemaking resistance of a free-running propeller and the augmentation of propeller resistance due to hull action from the wavemaking resistance of the hull with a propeller. The viscous components of the thrust deduction and wake were estimated as functions of propeller load which were established by the propeller load varying test after deduction the calculated inviscid components. Secondly, an analysis method of powering performance was developed based on the potential theory and the propeller load varying test. The hybrid method estimates the thrust deduction, wake and propeller open-water efficiency for different propeller load. This method can be utilized in the analysis of powering performance for the propeller load variation such as the added resistance due to hull surface roughness, the added resistance due to wind, etc. Finally, the hybrid method was applied to the optimum design of hull form. A series of afterbody shapes was obtained by systematically varying the waterplane and section shapes of a parent afterbody without changing the principal dimensions, block coefficient and prismatic coefficient. From the comparison of the predicted results such as wavemaking resistance, thrust deduction, wake and delivered power, an optimum hull form was obtained. The delivered power of the optimized hull form was reduced by 5.7% which was confirmed by model tests. Also the predicted delivered power by the hybrid method shows fairly good agreement with the test result. It is therefore considered that the new analysis method of powering performance can be utilized as a practical tool for the design of optimum hull form as for the analysis of powering performance for the propeller load variation in the preliminary design stage.

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The Effects of Interactive Metronome on Short-term Memory and Attention for Children With Mental Retardation (상호작용식 메트로놈(Interactive Metronome: IM) 훈련이 지적장애 아동의 집중력과 단기기억력에 미치는 영향)

  • Bak, Ah-Ream;Yoo, Doo-Han
    • The Journal of Korean Academy of Sensory Integration
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    • v.14 no.1
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    • pp.19-30
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    • 2016
  • Objective : The purpose of this study was to identify the effects of Interactive Metronome (IM) training on short-term memory and attention for children with mental retardation. Methods : For this study, single-subject experimental research was conducted using an ABA design. We observed two children, twice a week for 9 weeks, which was 18 sessions in total. We evaluated the children's brain waves without intervention and the child's pseudo randomly selected sample of one short-term memory task as assessed in the baseline A phase for three sessions. In the intervention phase the children received 40-50 minutes of Interactive Metronome training twice a week, a total of 12 sessions. The short-term memory test and long form test as assessed after treatment, without brain wave in short form test measuring. During the baseline A phase, data were collected using the same procedure as the baseline A phase. Results : After the interactive metronome training, positive changes was observed in brain waves, attentions and short-term memory. Conclusion : The results of this study expect that IM training has a potential for improving cognitive functions of children with mental retardation. In addition, the results of this study can be used as basic data in attention and short-term memory of occupational therapy intervention for children with mental retardation.

Effect of Ssanghwa-tang Extract on Antioxidant and Anti-aging Enzyme Activities (쌍화탕 추출물이 항산화효소 및 항노화관련 효소 활성에 미치는 영향)

  • Park, Ji-Young;Hwang, Jae-Gyu;Yun, Jong-Kuk;Han, Kil-Hwan;Do, Eun-Ju;Kim, Sung-Ok;Kim, Mi-Ryeo
    • The Korea Journal of Herbology
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    • v.27 no.3
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    • pp.67-74
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    • 2012
  • Objectives : The present study was designed to investigate effects of Ssanghwa-tang (Shu$\bar{a}$nghu$\bar{a}$-g$\bar{e}$ng) on oxidation/reduction reaction-related and aging-related enzymes $in$ $vitro$. Methods : We performed MTT assay, collagenase inhibition assay, elastase inhibition assay, tyrosinase inhibition assay, DPPH free radical scavenging assay, SOD-like activity and xanthine oxidase (XO) inhibition assay. Results : The 50% ethanol (EtOH) extract of Ssanghwa-tang (SHT) showed 55% inhibition of collagenase activity, and 42% inhibition of elastase activity at 1 mg/ml concentration. Also it's treatment showed 18% inhibition of tyrosinase activity, to relate whitening effect, at the same dose of 50% ethanol extract of SHT. Antioxidant activities were determined by DPPH radical scavenging, XO inhibiting activity and SOD-like activity. These scavenging, XO-inhibiting and SOD-like activities were measured in 80%, 75%, and 28% inhibitions, respectively, at a 1 mg/ml treated dose, compared to those of control. The inhibitory effects of 50% EtOH extract on aging and oxidation-related enzyme activities were higher than those of water extract and 95% EtOH extract. Conclusions : Taken together, our findings suggest that the SHT has potential and applicable benefits for development of cosmetics to have anti-aging (anti-wrinkle and whitening) and anti-oxidation functions.