• Title/Summary/Keyword: candidate role

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Quantitative and Comparative Analysis of Urinary Steroid Levels upon Treatment of an Anti-Diabetic Drug, CKD-501 using Gas Chromatography-Mass Spectrometry

  • Sadanala, Krishna Chaitanya;Jung, Byung-Hwa;Jang, In-Jin;Chung, Bong-Chul
    • Journal of Pharmaceutical Investigation
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    • v.41 no.1
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    • pp.37-43
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    • 2011
  • Urinary steroid levels were investigated in the treatment of CKD-501, a new anti-diabetic drug candidate. CKD-501 was administered orally at the dosage of 1, 2, 4 mg/day for 7 days to normal men (n=18). Urine was collected before, during and after stopping the drug administration and the urinary level of androgen, estrogen, progestin and corticoids were quantified using GC-MS (gas chromatography-mass spectrometry). Only urinary corticosteroid and an androgen, DHEA levels among all the analyzed steroids, have been found to increase progressively, reaching significant levels on the last day of drug treatment and later declined after the drug treatment is withdrawn. Therefore, it was thought that an increase in the urinary corticoid and DHEA levels could be a characteristic of CKD-501, since it prominently acts on the glucose sensitivity and suppresses the triglyceride levels. In conclusion, it was found that CKD-501, an anti-diabetic drug candidate, affects the glucocorticoid and DHEA levels and it plays a crucial role in glucose homeostasis.

Tusc2/Fus1 regulates osteoclast differentiation through NF-κB and NFATc1

  • Kim, Inyoung;Kim, Jung Ha;Kim, Kabsun;Seong, Semun;Kim, Nacksung
    • BMB Reports
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    • v.50 no.9
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    • pp.454-459
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    • 2017
  • Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and $Ca^{2+}$-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B ($NF-{\kappa}B$) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated $NF-{\kappa}B$ and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation.

Robust Online Object Tracking with a Structured Sparse Representation Model

  • Bo, Chunjuan;Wang, Dong
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.10 no.5
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    • pp.2346-2362
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    • 2016
  • As one of the most important issues in computer vision and image processing, online object tracking plays a key role in numerous areas of research and in many real applications. In this study, we present a novel tracking method based on the proposed structured sparse representation model, in which the tracked object is assumed to be sparsely represented by a set of object and background templates. The contributions of this work are threefold. First, the structure information of all the candidate samples is utilized by a joint sparse representation model, where the representation coefficients of these candidates are promoted to share the same sparse patterns. This representation model can be effectively solved by the simultaneous orthogonal matching pursuit method. In addition, we develop a tracking algorithm based on the proposed representation model, a discriminative candidate selection scheme, and a simple model updating method. Finally, we conduct numerous experiments on several challenging video clips to evaluate the proposed tracker in comparison with various state-of-the-art tracking algorithms. Both qualitative and quantitative evaluations on a number of challenging video clips show that our tracker achieves better performance than the other state-of-the-art methods.

Constructivism in Smart Tourism Research: Seoul Destination Image

  • Hwang, Jiyoung;Park, Hyo-Yeun;Hunter, William Cannon
    • Asia pacific journal of information systems
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    • v.25 no.1
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    • pp.163-178
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    • 2015
  • This paper specifically delineated the methodological application of constructivism in smart tourism studies. It explained what constructivism is and how this methodology could be applied in the study of smart tourism. In this study, residents of Seoul participated in constructivist research using the Q method to identify their subjectivities toward Seoul based on photographs most commonly found in tourism promotional material. Residents are concerned with good governance and cultural integrity, and they are aware of their role as stakeholders in tourism in their communities. However their potential contribution to destination image formation has been usually overlooked by researchers and marketers. Three clusters of subjectivities were revealed after 42 photographs of Seoul were sorted by 37 respondents. The results show how respondents perceived Seoul's destination image. The three clusters agreed that symbolic monuments were the key representations of Seoul. The paper recommends that tourism marketers and policy makers should focus on understanding and coordinating with residents' perceived image of Seoul as a destination when planning and decision making, especially in promoting Seoul as a destination market. This study, in conjunction with other constructivist research offers insight into how destination image is, especially with the rise of smart tourism, a complex social construction.

Genome-wide association study identifies 22 new loci for body dimension and body weight traits in a White Duroc×Erhualian F2 intercross population

  • Ji, Jiuxiu;Zhou, Lisheng;Guo, Yuanmei;Huang, Lusheng;Ma, Junwu
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.8
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    • pp.1066-1073
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    • 2017
  • Objective: Growth-related traits are important economic traits in the swine industry. However, the genetic mechanism of growth-related traits is little known. The aim of this study was to screen the candidate genes and molecular markers associated with body dimension and body weight traits in pigs. Methods: A genome-wide association study (GWAS) on body dimension and body weight traits was performed in a White $Duroc{\times}Erhualian$ $F_2$ intercross by the illumina PorcineSNP60K Beadchip. A mixed linear model was used to assess the association between single nucleotide polymorphisms (SNPs) and the phenotypes. Results: In total, 611 and 79 SNPs were identified significantly associated with body dimension traits and body weight respectively. All SNPs but 62 were located into 23 genomic regions (quantitative trait loci, QTLs) on 14 autosomal and X chromosomes in Sus scrofa Build 10.2 assembly. Out of the 23 QTLs with the suggestive significance level ($5{\times}10^{-4}$), three QTLs exceeded the genome-wide significance threshold ($1.15{\times}10^{-6}$). Except the one on Sus scrofa chromosome (SSC) 7 which was reported previously all the QTLs are novel. In addition, we identified 5 promising candidate genes, including cell division cycle 7 for abdominal circumference, pleiomorphic adenoma gene 1 and neuropeptides B/W receptor 1 for both body weight and cannon bone circumference on SSC4, phosphoenolpyruvate carboxykinase 1, and bone morphogenetic protein 7 for hip circumference on SSC17. Conclusion: The results have not only demonstrated a number of potential genes/loci associated with the growth-related traits in pigs, but also laid a foundation for studying the genes' role and further identifying causative variants underlying these loci.

Molecular Characterization and Chromosomal Mapping of the Porcine AMP-activated Protein Kinase ${\alpha}2$ (PRKAA2) Gene

  • Lee, Hae-Young;Choi, Bong-Hwan;Lee, Jung-Sim;Jang, Gul-Won;Lee, Kyung-Tai;Chung, Ho-Young;Jeon, Jin-Tea;Cho, Byung-Wook;Lee, Jun-Heon;Kim, Tae-Hun
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.5
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    • pp.615-621
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    • 2007
  • AMP-activated protein kinase alpha 2 (PRKAA2) plays a key role in regulation of fatty acid and cholesterol metabolism. This study investigated the porcine PRKAA2 gene as a positional candidate for intramuscular fat and backfat thickness traits in pig chromosome 6. A partial fragment of the porcine PRKAA2 gene, amplified by PCR, contained a putative intron 3 including a part of exon 3 and 4, comparable with that of human PRKAA2 gene. Within the fragment, several single nucleotide polymorphisms were identified using multiple sequence alignments. Of these, TaqI restriction enzyme polymorphism was used for genotyping various pig breeds including Korean reference family. Using linkage and physical mapping, the porcine PRKAA2 gene was mapped in the region between microsatellite markers SW1881 and SW1680 on chromosome 6. Allele frequencies were quite different among pig breeds. The full length cDNA of the porcine PRKAA2 (2,145 bp) obtained by RACE containing 1,656 bp open reading frame of deduced 552 amino acids, had sequence identities with PRKAA2 of human (98.2%), rat (97.8%), and mouse (97.5%). These results suggested that the porcine PRKAA2 is a positional candidate gene for fat deposition trait at near telomeric region of the long arm of SSC 6.

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.

New Evidences of Effect of Melanocortin-4 Receptor and Insulin-like Growth Factor 2 Genes on Fat Deposition and Carcass Traits in Different Pig Populations

  • Chen, J.F.;Xiong, Y.Z.;Zuo, B.;Zheng, R.;Li, F.E.;Lei, M.G.;Li, J.L.;Deng, C.Y.;Jiang, S.W.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.11
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    • pp.1542-1547
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    • 2005
  • The Melanocortin-4 Receptor (MC4R) and Insulin-like Growth Factor 2 (IGF2) are two important candidate genes related to fat deposition and carcass traits. MC4R was found on study on human obesity and then was studied as candidate gene affecting food intake and fat deposition traits in mice and pigs. Insulin-like Growth Factor 2 (IGF2) gene plays an important role on tumor cell proliferation and muscle growth. It also affects fat traits and live weight in pigs. In this paper, MC4R and IGF2 were studied as two candidate genes associated with important economic traits such as fat deposition and carcass traits in five different pig populations. Taq I-PCR-RFLP and Bcn I-PCR-RFLP were respectively used to detect the polymorphism of genotypes of MC4R and IGF2 genes. Different MC4R genotype frequencies were observed in four populations. IGF2 genotype frequencies were also different in two populations. The results of association analysis show both MC4R and IGF2 genes were significantly associated with fat deposition and carcass traits in about 300 pigs. This work will add new evidence of MC4R and IGF2 affecting fat deposition and carcass traits in pigs and show that two genes can be used as important candidate genes for marker assistant selection (MAS) of growth and lean meat percentage in pigs.

Genome-wide association study reveals genetic loci and candidate genes for average daily gain in Duroc pigs

  • Quan, Jianping;Ding, Rongrong;Wang, Xingwang;Yang, Ming;Yang, Yang;Zheng, Enqin;Gu, Ting;Cai, Gengyuan;Wu, Zhenfang;Liu, Dewu;Yang, Jie
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.4
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    • pp.480-488
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    • 2018
  • Objective: Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. Methods: We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. Results: After quality control, we detected 3,5971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs. We identified six quantitative trait loci (QTL) regions for ADG. These QTLs included four previously reported QTLs on Sus scrofa chromosome (SSC) 1, SSC5, SSC9, and SSC13, as well as two novel QTLs on SSC6 and SSC16. In addition, we selected six candidate genes (general transcription factor 3C polypeptide 5, high mobility group AT-hook 2, nicotinamide phosphoribosyltransferase, oligodendrocyte transcription factor 1, pleckstrin homology and RhoGEF domain containing G4B, and ENSSSCG00000031548) associated with ADG on the basis of their physiological roles and positional information. These candidate genes are involved in skeletal muscle cell differentiation, diet-induced obesity, and nervous system development. Conclusion: This study contributes to the identification of the casual mutation that underlies QTLs associated with ADG and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in ADG regulation.

Endogenous Proteolytic Systems and Meat Tenderness: Influence of Post-Mortem Storage and Processing

  • Kaur, Lovedeep;Hui, Seah Xin;Morton, James D.;Kaur, Ramandeep;Chian, Feng Ming;Boland, Mike
    • Food Science of Animal Resources
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    • v.41 no.4
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    • pp.589-607
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    • 2021
  • Meat proteolytic systems play a crucial role in meat tenderisation. Understanding the effects of processing technologies and post-mortem storage conditions on these systems is important due to their crucial role in determining the quality characteristics of meat and meat products. It has recently been proposed that tenderisation occurs due to the synergistic action of numerous endogenous proteolytic systems. There is strong evidence suggesting the importance of μ-calpain during the initial post-mortem aging phase, while m-calpain may have a role during long-term aging. The caspase proteolytic system is also a candidate for cell degradation in the initial stages of conversion of muscle to meat. The role of cathepsins, which are found in the lysosomes, in post-mortem aging is controversial. Lysosomes need to be ruptured, through aging, or other forms of processing to release cathepsins into the cytosol for participation in proteolysis. A combination of optimum storage conditions along with suitable processing may accelerate protease activity within meat, which can potentially lead to improved meat tenderness. Processing technologies such as high pressure, ultrasound, and shockwave processing have been reported to disrupt muscle structure, which can facilitate proteolysis and potentially enhance the aging process. This paper reviews the recent literature on the impacts of processing technologies along with post-mortem storage conditions on the activities of endogenous proteases in meat. The information provided in the review may be helpful in selecting optimum post-mortem meat storage and processing conditions to achieve improved muscle tenderness within shorter aging and cooking times.