• Title/Summary/Keyword: Role Identification

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Identification and Functional Characterization of P159L Mutation in HNF1B in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5)

  • Kim, Eun Ky;Lee, Ji Seon;Cheong, Hae Il;Chung, Sung Soo;Kwak, Soo Heon;Park, Kyong Soo
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.240-246
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    • 2014
  • Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

Identification of Genes Modulated by High Extracellular Calcium in Coculture of Mouse Osteoblasts and Bone Marrow Cells by Oligo Chip Assay

  • Kim, Hyung-Keun;Song, Mi-Na;Jun, Ji-Hae;Woo, Kyung-Mi;Kim, Gwan-Shik;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.31 no.2
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    • pp.53-65
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    • 2006
  • Calcium concentration in the bone resorption lacunae is high and is in the mM concentration range. Both osteoblast and osteoclast have calcium sensing receptor in the cell surface, suggesting the regulatory role of high extracellular calcium in bone metabolism. In vitro, high extracellular calcium stimulated osteoclastogenesis in coculture of mouse osteoblasts and bone marrow cells. Therefore we examined the genes that were commonly regulated by both high extracellular calcium and $1,25(OH)_2vitaminD_3(VD3)$ by using mouse oligo 11 K gene chip. In the presence of 10 mM $[Ca^{2+}]e$ or 10 nM VD3, mouse calvarial osteoblasts and bone marrow cells were co-cultured for 4 days when tartrate resistant acid phosphatase-positive multinucleated cells start to appear. Of 11,000 genes examined, the genes commonly regulated both by high extracellular calcium and by VD3 were as follows; 1) the expression of genes which were osteoclast differentiation markers or were associated with osteoclastogenesis were up-regulated both by high extracellular calcium and by VD3; trap, mmp9, car2, ctsk, ckb, atp6b2, tm7sf4, rab7, 2) several chemokine and chemokine receptor genes such as sdf1, scya2, scyb5, scya6, scya8, scya9, and ccr1 were up-regulated both by high extracellular calcium and by VD3, 3) the genes such as mmp1b, mmp3 and c3 which possibly stimulate bone resorption by osteoclast, were commonly up-regulated, 4) the gene such as c1q and msr2 which were related with macrophage function, were commonly down-regulated, 5) the genes which possibly stimulate osteoblast differentiation and/or mineralization of extracellular matrix, were commonly down-regulated; slc8a1, admr, plod2, lox, fosb, 6) the genes which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were commonly up-regulated; s100a4, npr3, mme, 7) the genes such as calponin 1 and tgfbi which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were up-regulated by high extracellular calcium but were down-regulated by VD3. These results suggest that in coculture condition, both high extracellular calcium and VD3 commonly induce osteoclastogenesis but suppress osteoblast differentiation/mineralization by regulating the expression of related genes.

The Effects of Fan Citizenship behavior to Sports team value and Local Community value on Spectator Sports (관람스포츠에서의 팬시민행동이 구단가치와 지역사회가치에 미치는 영향)

  • Lee, Jong-Ho;Yun, Dae-Hong;Kang, Min-Seok
    • Management & Information Systems Review
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    • v.30 no.4
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    • pp.385-414
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    • 2011
  • Fans' role and influence is becoming more extensive in these days' complex and competitive sports market. This research considers fans as internal members of sports team, employee and confirms active and voluntary fan citizenship behavior's effects on team, community, and social exchange among community residents, so that an enterprise can increase accessibility from many-sided perspectives when establishing sports marketing strategy in the future. The concept of fan citizenship behavior is set up considering characteristic of sports industry based on employee's organizational citizenship behavior discussed from the internal marketing and organization theory and preliminary studies about client citizenship behavior mentioned from service industry area. Although the sixteen research hypothesis are not fully supported. The results are summarized as follows. These findings give theoretical and marketing implication to future researcher and marketer. First, fan's positive aspect is confirmed which is different from general consumer by examining fan citizenship behavior's effect on teal value in the sports industry. Second, it was confirmed that the team needs marketing strategies about not only relationship between each individual fan, but also interaction between fans in the future. Third, it was confirmed that direct fan's behavior as well as individual fan's cognitive area have effects on team's and social value.

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Endophytic fungi harbored in Panax notoginseng: diversity and potential as biological control agents against host plant pathogens of root-rot disease

  • Zheng, You-Kun;Miao, Cui-Ping;Chen, Hua-Hong;Huang, Fang-Fang;Xia, Yu-Mei;Chen, You-Wei;Zhao, Li-Xing
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.353-360
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    • 2017
  • Background: Endophytic fungi play an important role in balancing the ecosystem and boosting host growth. In the present study, we investigated the endophytic fungal diversity of healthy Panax notoginseng and evaluated its potential antimicrobial activity against five major phytopathogens causing root-rot of P. notoginseng. Methods: A culture-dependent technique, combining morphological and molecular methods, was used to analyze endophytic fungal diversity. A double-layer agar technique was used to challenge the phytopathogens of P. notoginseng. Results: A total of 89 fungi were obtained from the roots, stems, leaves, and seeds of P. notoginseng, and 41 isolates representing different morphotypes were selected for taxonomic characterization. The fungal isolates belonged to Ascomycota (96.6%) and Zygomycota (3.4%). All isolates were classified to 23 genera and an unknown taxon belonging to Sordariomycetes. The number of isolates obtained from different tissues ranged from 12 to 42 for leaves and roots, respectively. The selected endophytic fungal isolates were challenged by the root-rot pathogens Alternaria panax, Fusarium oxysporum, Fusarium solani, Phoma herbarum, and Mycocentrospora acerina. Twenty-six of the 41 isolates (63.4%) exhibited activity against at least one of the pathogens tested. Conclusion: Our results suggested that P. notoginseng harbors diversified endophytic fungi that would provide a basis for the identification of new bioactive compounds, and for effective biocontrol of notoginseng root rot.

Identification and phylogenetic analysis of the human endogenous retrovirus HERV-W pol in cDNA library of human fetal brain (인간태아의 뇌로부터 유래된 cDNA liberary에서 내생레트로바이러스 HERV-W pol 유전자의 동정과 계통)

  • Kim, Heui-Soo;Jeon, Seung-Heui;Yi, Joo-Mi;Kim, Tae-Hyung;Lee, Won-Ho
    • Journal of Life Science
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    • v.13 no.3
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    • pp.291-297
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    • 2003
  • A human endogenous retroviral family (HERV-W) has recently been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Two pol fragments (HWP-FB10 and HWP-FBl2) of HERV-W family were identified and analysed by the PCR approach with cDNA library of human fetal brain. They showed 89 percent nucleotide sequence similarity with that of the HERV-W (accession no. AF009668). Deletion/insertion or point mutation in the coding region of the pol fragments from human fetal brain resulted in amino acid frameshift that induced a mutated protein. Phylogenetic analysis of the HERV-W family from GenBank database indicates that the HWP-FB10 is very closely related to the AC000064 derived from human chromosome 7q21-q22. Further studies on the genetic relationship with neighbouring genes and functional role of these new HERV-W pol sequences are indicated.

Identification of cis-Regulatory Region Controlling Semaphorin-1a Expression in the Drosophila Embryonic Nervous System

  • Hong, Young Gi;Kang, Bongsu;Lee, Seongsoo;Lee, Youngseok;Ju, Bong-Gun;Jeong, Sangyun
    • Molecules and Cells
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    • v.43 no.3
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    • pp.228-235
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    • 2020
  • The Drosophila transmembrane semaphorin Sema-1a mediates forward and reverse signaling that plays an essential role in motor and central nervous system (CNS) axon pathfinding during embryonic neural development. Previous immunohistochemical analysis revealed that Sema-1a is expressed on most commissural and longitudinal axons in the CNS and five motor nerve branches in the peripheral nervous system (PNS). However, Sema-1a-mediated axon guidance function contributes significantly to both intersegmental nerve b (ISNb) and segmental nerve a (SNa), and slightly to ISNd and SNc, but not to ISN motor axon pathfinding. Here, we uncover three cis-regulatory elements (CREs), R34A03, R32H10, and R33F06, that robustly drove reporter expression in a large subset of neurons in the CNS. In the transgenic lines R34A03 and R32H10 reporter expression was consistently observed on both ISNb and SNa nerve branches, whereas in the line R33F06 reporter expression was irregularly detected on ISNb or SNa nerve branches in small subsets of abdominal hemisegments. Through complementation test with a Sema-1a loss-of-function allele, we found that neuronal expression of Sema-1a driven by each of R34A03 and R32H10 restores robustly the CNS and PNS motor axon guidance defects observed in Sema-1a homozygous mutants. However, when wild-type Sema-1a is expressed by R33F06 in Sema-1a mutants, the Sema-1a PNS axon guidance phenotypes are partially rescued while the Sema-1a CNS axon guidance defects are completely rescued. These results suggest that in a redundant manner, the CREs, R34A03, R32H10, and R33F06 govern the Sema-1a expression required for the axon guidance function of Sema-1a during embryonic neural development.

Knowledge of Cervical Cancer Screening among Health Care Workers Providing Services Across Different Socio-economic Regions of China

  • Di, Jiang-Li;Rutherford, Shannon;Wu, Jiu-Ling;Song, Bo;Ma, Lan;Chen, Jing-Yi;Chu, Cordia
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2965-2972
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    • 2016
  • Background: China carries a heavy burden of cervical cancer (CC) and substantial disparities exist across regions within the country. In order to reduce regional disparities in CC, the government of China launched the National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 2009. Critical to the success of the program are the health care workers who play a pivotal role in preventing and managing CC by encouraging and motivating women to use screening services and by providing identification and treatment services. This study aimed to assess cervical cancer knowledge among these health care workers at the county level in maternal and child health (MCH) hospitals across different socio-economic regions of China. Materials and Methods: A cross-sectional survey was conducted and self-administered questionnaires were sent to all health care workers (a total of 66) providing cervical cancer screening services in 6 county level MCH hospitals in Liaoning, Hubei and Shaanxi provinces, representing eastern, central and western regions of China; 64 (97.0%, 64/66) of the workers responded. ANOVA and Chi-square test were used to compare the knowledge rate and scores in subgroups. Results: The knowledge level of the respondents was generally low. The overall combined knowledge rate was 46.9%. The knowledge rates for risk factors, prevention, clinical symptoms, screening and diagnostic tests and understanding of positive results were 31.3%, 37.5%, 18.1%, 56.3% and 84.4%, respectively. Statistically significant differences in scores or rates of CC knowledge were seen across the different regions. The total and sectional scores in the less developed regions were statistically significantly lower than in the other regions. Conclusions: The majority of the health care workers who provide CC screening service in NCCSPRA at county level MCH hospitals do not have adequately equipped with knowledge about CC. Given the importance of knowledge to the program's success in reducing CC burden in rural women in China, efforts are needed to improve the knowledge of health care workers, especially in less developed regions.

Anti-Diabetic and Anti-Obese Effects of Ginseng: from Root to Berry

  • Yuan Chun-Su
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.129-144
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    • 2002
  • We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.

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The role of geophysics in understanding salinisation in Southwestern Queensland (호주 Queensland 남서부 지역의 염분작용 조사)

  • Wilkinson Kate;Chamberlain Tessa;Grundy Mike
    • Geophysics and Geophysical Exploration
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    • v.8 no.1
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    • pp.78-85
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    • 2005
  • This study, combining geophysical and environmental approaches, was undertaken to investigate the causes of secondary salinity in the Goondoola basin, in southwestern Queensland. Airborne radiometric, electromagnetic and ground electromagnetic datasets were acquired, along with data on soils and subsurface materials and groundwater. Relationships established between radiometric, elevation data, and measured material properties allowed us to generate predictive maps of surface materials and recharge potential. Greatest recharge to the groundwater is predicted to occur on the weathered bedrock rises surrounding the basin. Electromagnetic data (airborne, ground, and downhote), used in conjunction with soil and drillhole measurements, were used to quantify regolith salt store and to define the subsurface architecture. Conductivity measurements reflect soil salt distribution. However, deeper in the regolith, where the salt content is relatively constant, the AEM signal is influenced by changes in porosity or material type. This allowed the lateral distribution of bedrock weathering zones to be mapped. Salinisation in this area occurs because of local-andintermediate-scale processes, controlled strongly by regolith architecture. The present surface outbreak is the result of evaporative concentration above shallow saline groundwater, discharging at break of slope. The integration of surficial and subsurface datasets allowed the identification of similar landscape settings that are most at risk of developing salinity with groundwater rise. This information is now being used by local land managers to refine management choices that prevent excess recharge and further salt mobilisation.

Novel reassortant 2.3.4.4B H5N6 highly pathogenic avian influenza viruses circulating among wild, domestic birds in Xinjiang, Northwest China

  • Zhang, Qian;Mei, Xindi;Zhang, Cheng;Li, Juan;Chang, Nana;Aji, Dilihuma;Shi, Weifeng;Bi, Yuhai;Ma, Zhenghai
    • Journal of Veterinary Science
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    • v.22 no.4
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    • pp.43.1-43.10
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    • 2021
  • Background: The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. Objectives: This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. Methods: AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. Results: Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016-2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. Conclusions: These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.