• Title/Summary/Keyword: regulatory networks

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Delineating Transcription Factor Networks Governing Virulence of a Global Human Meningitis Fungal Pathogen, Cryptococcus neoformans

  • Jung, Kwang-Woo;Yang, Dong-Hoon;Maeng, Shinae;Lee, Kyung-Tae;So, Yee-Seul;Hong, Joohyeon;Choi, Jaeyoung;Byun, Hyo-Jeong;Kim, Hyelim;Bang, Soohyun;Song, Min-Hee;Lee, Jang-Won;Kim, Min Su;Kim, Seo-Young;Ji, Je-Hyun;Park, Goun;Kwon, Hyojeong;Cha, Sooyeon;Meyers, Gena Lee;Wang, Li Li;Jang, Jooyoung;Janbon, Guilhem;Adedoyin, Gloria;Kim, Taeyup;Averette, Anna K.;Heitman, Joseph;Cheong, Eunji;Lee, Yong-Hwan;Lee, Yin-Won;Bahn, Yong-Sun
    • 한국균학회소식:학술대회논문집
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    • 2015.05a
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    • pp.59-59
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    • 2015
  • Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but the treatment of cryptococcosis remains challenging. To develop novel therapeutic targets and approaches, signaling cascades controlling pathogenicity of C. neoformans have been extensively studied but the underlying biological regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs) in this basidiomycetous fungus. In this study, we constructed a high-quality of 322 signature-tagged gene deletion strains for 155 putative TF genes, which were previously predicted using the DNA-binding domain TF database (http://www.transcriptionfactor.org/). We tested in vivo and in vitro phenotypic traits under 32 distinct growth conditions using 322 TF gene deletion strains. At least one phenotypic trait was exhibited by 145 out of 155 TF mutants (93%) and approximately 85% of the TFs (132/155) have been functionally characterized for the first time in this study. Through high-coverage phenome analysis, we discovered myriad novel TFs that play critical roles in growth, differentiation, virulence-factor (melanin, capsule, and urease) formation, stress responses, antifungal drug resistance, and virulence. Large-scale virulence and infectivity assays in insect (Galleria mellonella) and mouse host models identified 34 novel TFs that are critical for pathogenicity. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and ubiquitous human fungal pathogens.

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Construction of Gene Network System Associated with Economic Traits in Cattle (소의 경제형질 관련 유전자 네트워크 분석 시스템 구축)

  • Lim, Dajeong;Kim, Hyung-Yong;Cho, Yong-Min;Chai, Han-Ha;Park, Jong-Eun;Lim, Kyu-Sang;Lee, Seung-Su
    • Journal of Life Science
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    • v.26 no.8
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    • pp.904-910
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    • 2016
  • Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The gene network analysis has been performed by diverse types of methods such as gene co-expression, gene regulatory relationships, protein-protein interaction (PPI) and genetic networks. Moreover, the network-based methods were described for predicting gene functions such as graph theoretic method, neighborhood counting based methods and weighted function. However, there are a limited number of researches in livestock. The present study systemically analyzed genes associated with 102 types of economic traits based on the Animal Trait Ontology (ATO) and identified their relationships based on the gene co-expression network and PPI network in cattle. Then, we constructed the two types of gene network databases and network visualization system (http://www.nabc.go.kr/cg). We used a gene co-expression network analysis from the bovine expression value of bovine genes to generate gene co-expression network. PPI network was constructed from Human protein reference database based on the orthologous relationship between human and cattle. Finally, candidate genes and their network relationships were identified in each trait. They were typologically centered with large degree and betweenness centrality (BC) value in the gene network. The ontle program was applied to generate the database and to visualize the gene network results. This information would serve as valuable resources for exploiting genomic functions that influence economically and agriculturally important traits in cattle.

Correlates of Subjective Well-being in Korean Culture (한국문화에서 주관안녕에 영향을 미치는 사회심리 요인들)

  • Hahn, Doug-Woong
    • Korean Journal of Culture and Social Issue
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    • v.12 no.5_spc
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    • pp.45-79
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    • 2006
  • The purpose of this paper was to review the results of the subjective well-being(swb) studies performed by Hahn and coworkers in Korean culture. As the correlates of swb, we dealt with demographic/individual difference variables, intrapersonal variables, interpersonal process variables, and Korean cultural variables. We proposed that the components of swb were consisted of quality of life(cognitive swb) and overall happy feelings about one's own life(emotional swb). It was also assumed that a measure of total swb could be calculated by summated mean of cognitive swb and emotional swb measures. The data of the swb studies were analyzed and interpreted according to the above three measures of swb. The results of a nationwide survey(Hahn, 2004) from age of 19 to 75 years ald(n=2,230) showed significant simple correlation coefficients between the following demographic/individual difference variables and swb: Gender difference in swb was found(total swb r=.08, p<.001; life satisfaction r=.10, p<.001; overall emotional swb r=.05, p<.05). Men were happier than women in terms of all three measures of swb. It was also found that women appeared to experience greater positive and negative emotions. Correlation between age and emotional swb(r=.09, p<.001) was significant, but life satisfaction was not significant(r=.04, n.s). Correlations between economic status and swb were also significant(total swb r =.23, p<.001; life satisfaction r=.15 p<.001; overall emotional swb r=.15, p<.001l). Although existence of father was negatively related to emotional swb(r=-.05, p<.05), the existence of mother was not related to any of swb measures. Similarly existence of brothers was related positively to overall emotional swb, but existence of sisters was not. Though existence of son was not related to swb, daughter contributed negatively to swb(total swb -.12, p<.01; life satisfaction -.09, p<.05; emotional swb r=-.12, p<.01). We assumed that family member-in-Iaw also contributed to swb because the extended dose social networks were important in Korean culture. The results showed that the following family member-in-law variables were related to swb: Parents-in-law(total swb r=.11, p<.01; life satisfaction r=.10, p<.01; emotional swb r=.10, p<.01), father-in-law(total swb r=.11, p<.01; life satisfaction r=.11, p<.01; emotional swb r=.06, n.s). The result suggested that especially father-in-law contributed to swb through financial and social support. Correlations between emotional experiences in everyday life and swb were also presented. The range of correlation coefficients between the positive emotion measures and swb were r=.30~.48(p<.001) when the above two measures obtained at same time. But the range decreased to r=.19~32(p<.001) when the swb measure was obtained 9 month later longitudinally. Intercorrelations between positive emotional experience; and life satisfaction were r=.37~58(p<.001) when two measures were obtained at same time. We also examined the effects of the intrapersonal cognitive responses to the most stressful life event upon swb. The results of nationwide survey(n=1,021) showed that self-disclosure(total swb r=.09, p<.010; life satisfaction r=.10, p<.01; emotional swb r=.07, p<.01), rumination(total swb r=-.17, p<.001), thought avoidance(total swb r=.12, p<.001; life satisfaction r=-.08; emotional swb r=-.12, p<.001) and suppression(total swb r=-.13, p<.001; life satisfaction r=-.08, p<.05: emotional swb r=-.13, p<.001) contributed to swb. It was also suggested that mismatch between self-guide and regulatory focus contributed negatively to emotional swb. It was also found that social comparison motives and fulfillment of the motives contributed to swb. The results of a survey research(n=363 college students) revealed that the higher the general social comparison motive, the lower the swb(total swb r=-.15, P<.01: life satisfaction r=-.17. p<.01; emotional swb r=-.10, p<.05). It was also found that satisfaction level of self-evalution motive contributed positively to swb(total swb r=-.14. p<.01: life satisfaction r=-.12, p<.05; emotional swb r=.15, p<.001). Both of self-improvement motive(r=.13, p<.05) and satisfaction level of self-improvement motive(r=.12, p<.05) contributed positively to emotional swb, respectively. The above results suggested that swb was depended upon the interaction effect of social comparison motive; and level of fulfillment of the motives. We also reported the significant multiple predictors of swb in a sample of age from 60years to 89years olds. The results of multiple regression analysis showed that the significant multiple predictors of swb were past illness(β=.174, p<.001), economic status(β=.418, p<.001), marital satisfaction(β=.0841, p<.001), satisfaction of offsprins(β=.065, p<.01), expectation level of social support from offsprings(β=-.049, p<.001), and negative emotions(β=-.454. p<.001) among 16 social psychological factors. It was also found that swb was an important multiple predictors of physical health. This finding was replicated in a longitudinal study. Both of positive and negative emotional experiences were significant multiple predictors of physical health one year later. The results of the discriminant analysis showed both of total swb and positive emotional experiences contributed to discriminate the happy and healthy olds from unhappy and unhealthy olds. We paper also examined the effects of the nonnative social behaviors upon swb in Korean culture. The main hypotheses of the study(Hahn, 2006, in press) was that the important nonnative behaviors would influence on swb through both of the mediation processes of adjustment to social relationships and psychological stress. The survey data were collected from 2,129 adults age of 19 to 75, from 7 regional areas in Korea. The results of the study revealed that almost all of correlation coefficients between 15 normative social behaviors and the above three criteria w-ere significant. The fitness test results of the covariance structural equation model showed that all of the fitness indices were satisfactory (GFI=.974, AGFI=.909, NNFI=.922, NFI=.973, CFI=.974. RMR=.049, RMSEA=.073). The results of the analysis revealed that the following five path coeffi6ents from behaviors to social adjustment were significant; behavior tor family and family members(t=5.87, p<.001), courteous behavior(t=4.39, p<.001), faithful behavior (t=2.15. p<.05). collectivistic behavior(t=8.31, p<.001). Seven path coefficients from the normative behaviors to psychological stress were significant; behavior for family and family members (t=-4.63, p<.001), faithful behavior(t=-3.86, p<.001). suppression of emotional expression(t=3.99, p<.001), trustworthy and dependable behavior(t=-2.21, p<.05), collectivistic behavior(t=3.72, p<.001), effortful and diligent behavior(t=2.94, p<.001), husbandry and saving behavior(t=3.40, p<.001). The above results suggested that four normative behaviors among seven behaviors contributed negatively to psychological stress in current Korean society. The results abo confirmed the hypothesized paths from social adjustment (t=10.40, p<.001) to swb and from psychological stress(t=-19.74, p<.001) to swb. The important results of the study were discussed in terms of the Confucian traditions and recent social changes in Korean culture. Finally limitations of this review paper were discussed and the suggestions for the future study were also proposed.