• Title/Summary/Keyword: Regulatory Science

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Inhibitory Effects of Functional Sujeonggwa Drinks on Hepatic Lipid Accumulation in Hypercholesterolemic ApoE Knockout Mice (고콜레스테롤혈증 ApoE Knockout Mice에서 기능성 수정과의 간지질 축적 억제 효과)

  • Baek, Aran;Kim, Mijeong;Jung, Koeun;Kim, Seulki;Lee, Jeehyun;Song, Yeong Ok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.11
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    • pp.1648-1657
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    • 2014
  • In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.

Effects of Lipopolysaccride-induced Stressor on the Expression of Stress-related Genes in Two Breeds of Chickens (Lipopolysaccride 감염처리가 닭의 품종간 스트레스연관 유전자 발현에 미치는 영향)

  • Jang, In Surk;Sohn, Sea Hwan;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.44 no.1
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    • pp.1-9
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    • 2017
  • The objective of the present study was to determine the expression of genes associated with lipopolysaccharide (LPS)-induced stressor in two breeds of chickens: the Korean native chicken (KNC) and the White Leghorn chicken (WLH). Forty chickens per breed, aged 40 weeks, were randomly allotted to the control (CON, administered the saline vehicle) and LPS-injected stress groups. Samples were collected at 0 and 48 h post-LPS injection, and total RNA was extracted from the chicken livers for RNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In response to LPS, 1,044 and 1,193 genes were upregulated, and 1,000 and 1,072 genes were downregulated in the KNC and WLH, respectively, using a ${\geq}2$-fold cutoff change. A functional network analysis revealed that stress-related genes were downregulated in both KNC and WLH after LPS infection. The results obtained from the qRT-PCR analysis of mRNA expression of heat shock 90 (HSP90), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), activating transcription factor 4 (ATF4), sterol regulatory element-binding protein 1 (SREBP1), and X-box binding protein 1 (XBP1) were confirmed by the results of the microarray analysis. There was a significant difference in the expression of stress-associated genes between the control and LPS-injected KNC and WLH groups. The qRT-PCR analysis revealed that the stress-related $HSP90{\alpha}$ and HMGCR genes were downregulated in both LPS-injected KNC and WLH groups. However, the HSP70 and $HSP90{\beta}$ genes were upregulated only in the LPS-injected KNC group. The results suggest that the mRNA expression of stress-related genes is differentially affected by LPS stimulation, and some of the responses varied with the chicken breed. A better understanding of the LPS-induced infective stressors in chicken using the qRT-PCR and RNA microarray analyses may contribute to improving animal welfare and husbandry practices.

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.

Risk Assessment of As, Cd, Cu and Pb in Different Rice Varieties Grown on the Contaminated Paddy Soil (중금속 오염 논토양에서 재배된 벼 품종간 위해성평가 비교)

  • Kim, Won-Il;Kim, Jin-Kyoung;Yoo, Ji-Hyock;Paik, Min-Kyoung;Park, Sang-Won;Kwon, Oh-Kyung;Hong, Moo-Ki;Yang, Jay-E;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.42 no.1
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    • pp.53-57
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    • 2009
  • Heavy metal pollution may be one of the most serious challenges confront crop production and human health. Therefore, the selection of heavy metal tolerance cultivars which adapted to the contaminated fields will introduced a suitable solution for management this critical environmental risk. The objectives of this research is to assess human health risk using geochemical analyses and exposure assessment of heavy metals in rice cultivars. Risk for inhabitants in the closed mine area was comparatively assessed for As, Cd, Cu and Pb in 10 rice varieties as a major exposure pathway. The average daily dose (ADD) of each heavy metal was estimated by analyzing the exposure pathways to rice and soil. For the non-carcinogenic risk characterization, Hazard Quotient (HQ) and Hazard Index (HI) were calculated using toxicity indices provided by US-EPA IRIS. The different rice varieties revealed a wide range of HI values from 23.6 to 34.3, indicating that all rice varieties have a high potential toxic risk. The DA rice variety showed the lowest HI value while the TB rice variety the highest. The probabilities of cancer risk for As via rice consumption were varied with rice varieties ranging from 2.0E-03 to 3.5E-03 which exceeded the regulatory acceptable risk of 1 in 10,000 set by US-EPA. The DA rice variety also showed the lowest value while the TB rice variety gave the highest value. Our results indicate that risk assessment can be contribute to screen the pollution safe rice cultivars in paddy fields affected by the mining activity.

Shopping Value, Shopping Goal and WOM - Focused on Electronic-goods Buyers (쇼핑 가치 추구 성향에 따른 쇼핑 목표와 공유 의도 차이에 관한 연구 - 전자제품 구매고객을 중심으로)

  • Park, Kyoung-Won;Park, Ju-Young
    • Journal of Global Scholars of Marketing Science
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    • v.19 no.2
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    • pp.68-79
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    • 2009
  • The interplay between hedonic and utilitarian attributes has assumed special significance in recent years; it has been proposed that consumption offerings should be viewed as experiences that stimulate both cognitions and feelings rather than as mere products or services. This research builds on previous work on hedonic versus utilitarian benefits, regulatory focus theory, customer satisfaction to address two question: (1) Is the shopping goal at the point of purchase different from the shopping value? and (2) Is the customer loyalty after the use different from the shopping value and shopping goal? We surveyed 345 peoples those who have bought the electronic-goods within 6 months. This research dealt with the shopping value which is consisted of 2 types, hedonic and utilitarian. Those who pursue the hedonic shopping value may prefer the pleasure of purchasing experience to the product itself. They tend to prefer atmosphere, arousal of the shopping experience. Consistent with previous research, we use the term "hedonic" to refer to their aesthetic, experiential and enjoyment-related value. On the contrary, Those who pursue the utilitarian shopping value may prefer the reasonable buying. It may be more functional. Consistent with previous research, we use the term "utilitarian" to refer to the functional, instrumental, and practical value of consumption offerings. Holbrook(1999) notes that consumer value is an experience that results from the consumption of such benefits. In the context of cell phones for example, the phone's battery life and sound volume are utilitarian benefits, whereas aesthetic appeal from its shape and color are hedonic benefits. Likewise, in the case of a car, fuel economics and safety are utilitarian benefits whereas the sunroof and the luxurious interior are hedonic benefits. The shopping goals are consisted of the promotion focus goal and the prevention focus goal, based on the self-regulatory focus theory. The promotion focus is characterized into focusing ideal self because they are oriented to wishes and vision. The promotion focused individuals are tend to be more risk taking. They are more sensitive to hope and achievement. On the contrary, the prevention focused individuals are characterized into focusing the responsibilities because they are oriented to safety. The prevention focused individuals are tend to be more risk avoiding. We wanted to test the relation among the shopping value, shopping goal and customer loyalty. Customers show the positive or negative feelings comparing with the expectation level which customers have at the point of the purchase. If the result were bigger than the expectation, customers may feel positive feeling such as delight or satisfaction and they would want to share their feelings with other people. And they want to buy those products again in the future time. There is converging evidence that the types of goals consumers expect to be fulfilled by the utilitarian dimension of a product are different from those they seek from the hedonic dimension (Chernev 2004). Specifically, whereas consumers expect the fulfillment of product prevention goals on the utilitarian dimension, they expect the fulfillment of promotion goals on the hedonic dimension (Chernev 2004; Chitturi, Raghunathan, and Majahan 2007; Higgins 1997, 2001) According to the regulatory focus theory, prevention goals are those that ought to be met. Fulfillment of prevention goals in the context of product consumption eliminates or significantly reduces the probability of a painful experience, thus making consumers experience emotions that result from fulfillment of prevention goals such as confidence and securities. On the contrary, fulfillment of promotion goals are those that a person aspires to meet, such as "looking cool" or "being sophisticated." Fulfillment of promotion goals in the context of product consumption significantly increases the probability of a pleasurable experience, thus enabling consumers to experience emotions that result from the fulfillment of promotion goals. The proposed conceptual framework captures that the relationships among hedonic versus utilitarian shopping values and promotion versus prevention shopping goals respectively. An analysis of the consequence of the fulfillment and frustration of utilitarian and hedonic value is theoretically worthwhile. It is also substantively relevant because it helps predict post-consumption behavior such as the promotion versus prevention shopping goals orientation. Because our primary goal is to understand how the post consumption feelings influence the variable customer loyalty: word of mouth (Jacoby and Chestnut 1978). This research result is that the utilitarian shopping value gives the positive influence to both of the promotion and prevention goal. However the influence to the prevention goal is stronger. On the contrary, hedonic shopping value gives influence to the promotion focus goal only. Additionally, both of the promotion and prevention goal show the positive relation with customer loyalty. However, the positive relation with promotion goal and customer loyalty is much stronger. The promotion focus goal gives the influence to the customer loyalty. On the contrary, the prevention focus goal relates at the low level of relation with customer loyalty than that of the promotion goal. It could be explained that it is apt to get framed the compliment of people into 'gain-non gain' situation. As the result, for those who have the promotion focus are motivated to deliver their own feeling to other people eagerly. Conversely the prevention focused individual are more sensitive to the 'loss-non loss' situation. The research result is consistent with pre-existent researches. There is a conceptual parallel between necessities-needs-utilitarian benefits and luxuries-wants-hedonic benefits (Chernev 2004; Chitturi, Raghunathan and Majaha 2007; Higginns 1997; Kivetz and Simonson 2002b). In addition, Maslow's hierarchy of needs and the precedence principle contends luxuries-wants-hedonic benefits higher than necessities-needs-utilitarian benefits. Chitturi, Raghunathan and Majaha (2007) show that consumers are focused more on the utilitarian benefits than on the hedonic benefits of a product until their minimum expectation of fulfilling prevention goals are met. Furthermore, a utilitarian benefit is a promise of a certain level of functionality by the manufacturer or the retailer. When the promise is not fulfilled, customers blame the retailer and/or the manufacturer. When negative feelings are attributable to an entity, customers feel angry. However in the case of hedonic benefit, the customer, not the manufacturer, determines at the time of purchase whether the product is stylish and attractive. Under such circumstances, customers are more likely to blame themselves than the manufacturer if their friends do not find the product stylish and attractive. Therefore, not meeting minimum utilitarian expectations of functionality generates a much more intense negative feelings, such as anger than a less intense feeling such as disappointment or dissatisfactions. The additional multi group analysis of this research shows the same result. Those who are unsatisfactory customers who have the prevention focused goal shows higher relation with WOM, comparing with satisfactory customers. The research findings in this article could have significant implication for the personal selling fields to increase the effectiveness and the efficiency of the sales such that they can develop the sales presentation strategy for the customers. For those who are the hedonic customers may be apt to show more interest to the promotion goal. Therefore it may work to strengthen the design, style or new technology of the products to the hedonic customers. On the contrary for the utilitarian customers, it may work to strengthen the price competitiveness. On the basis of the result from our studies, we demonstrated a correspondence among hedonic versus utilitarian and promotion versus prevention goal, WOM. Similarly, we also found evidence of the moderator effects of satisfaction after use, between the prevention goal and WOM. Even though the prevention goal has the low level of relation to WOM, those who are not satisfied show higher relation to WOM. The relation between the prevention goal and WOM is significantly different according to the satisfaction versus unsatisfaction. In addition, improving the promotion emotions of cheerfulness and excitement and the prevention emotion of confidence and security will further improve customer loyalty. A related potential further research could be to examine whether hedonic versus utilitarian, promotion versus prevention goals improve customer loyalty for services as well. Under the budget and time constraints, designers and managers are often compelling to choose among various attributes. If there is no budget or time constraints, perhaps the best solution is to maximize both hedonic and utilitarian dimension of benefits. However, they have to make trad-off process between various attributes. For the designers and managers have to keep in mind that without hedonic benefit satisfaction of the product it may hard to lead the customers to the customer loyalty.

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Metabolites profiling and hypolipidemic/hypocholesterolemic effects of persimmon (Diosyros kaki Thumb.) by different processing procedures: in vitro and in vivo studies (제조방법에 따른 떫은감 (Diosyros kaki Thumb.)의 대사체 프로파일링과 중성지질/콜레스테롤 대사 관련 유전자발현 연구 : in vitro 및 in vivo 연구)

  • Park, Soo-Yeon;Oh, Eun-Kyung;Lim, Yeni;Shin, Ji-Yoon;Jung, Hee-Ah;Park, Song-Yi;Lee, Jin Hee;Choe, Jeong-Sook;Kwon, Oran
    • Journal of Nutrition and Health
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    • v.51 no.4
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    • pp.275-286
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    • 2018
  • Purpose: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). Methods: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. Results: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. Conclusion: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

Collection, Identification and Hepatic Effect of Native Cordyceps militaris (새로운 번데기 동충하초의 수집, 동정 및 간기능에 미치는 효과)

  • Lee, Ki-Won;Nam, Byung-Hyouk;Jo, Wool-Soon;Oh, Su-Jung;Kang, Eun-Young;Cui, Yong;Lee, Jae-Yun;Cheon, Sang-Cheol;Jeong, Min-Ho;Lee, Jae-Dong
    • The Korean Journal of Mycology
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    • v.34 no.1
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    • pp.7-14
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    • 2006
  • Entomopathogenic fungus Cordyceps militaris is famous for its medicinal efficacies. It has been reported to have various pharmacological activities such as anti-tumour, insecticidal, antibacterial, immunomodulatory and antioxidant. In this study, we investigated the effect of the extract of C. militaris (MPUN8501), which was identified by the analysis of the nucleotide sequences of 5.8S ribosomal RNA, on the function of liver. C. militaris powder was extracted using hot water extracts method as time, volume and temperature and using method as differential polarity of organic solvent. Each fraction was tested for the improvement of hepatic enzyme alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. The BuOH extracts (CME) had highest activity which was used for the test of toxicity and efficacy of C. militaris. The enhancing effect of CME on the activity of ADH and ALDH was much more than medicine, drink, natural tea etc. Thus CME promoted the resolution of alcohol and acetaldehyde in rats, inducing recovery to normal condition rapidly. Furthermore, oral administration of CME effectively protected the carbon tetrachloride-induced acute hepatic injury as revealed by the hematological parameters (levels of sGOT and sGPT) and histological observation. CME was ascertained to be safe by regulatory toxicity studies of single dose toxicity and genotoxicity. These results suggest that CME would be useful for the maintaining normal hepatic activity as a functional health food.

Extract of Rubus coreanus Fruits Increases Expression and Activity of Endothelial Nitric Oxide Synthase in the Human Umbilical Vein Endothelial Cells (복분자 추출물에 의한 내피세포 NO 합성효소의 활성과 발현 증가)

  • Yoon, Hyun-Joong;Park, Soo-Young;Oh, Sung-Tack;Lee, Kee-Young;Yang, Sung-Yeul
    • Journal of Life Science
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    • v.21 no.1
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    • pp.44-55
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    • 2011
  • This study aimed to investigate the effects of water extract of Rubus coreanus (RCE) on the expression and activity of endothelial nitric oxide synthase (eNOS), as well as its signal transduction pathways in human umbilical vein endothelial cells (HUVECs). The specific inhibitors of NOS show RCE treatment increases NO production in HUVECs due to the up-regulation of eNOS rather than iNOS. The real-time expression level of eNOS mRNA was also increased upon RCE treatment in HUVECs. While a PKC-specific inhibitor, RO-317549, did not alter RCE-induced NO production in HUVECs, tamoxifen (estrogen receptor-specific inhibitor), PD98059 (ERK-specific inhibitor) and LY-294002 (PI3K/Akt-specific inhibitor) did have suppressive effects. Increased NO production by RCE seems to result from a higher level of active eNOS (pSer1177). Specifically, inhibition of ERK not only decreased the level of active eNOS, but also increased the inactive form of the enzyme (pThr495) in HUVECs. This study suggests that RCE treatment increases NO production in HUVECs due to the increased expression and activity of eNOS. It is also shown that RCE-induced eNOS activation occurs partly through the binding of RCE to the estrogen receptor, along with ERK and PI3K/Akt-dependent signal transduction pathways. In addition, the regulatory binding proteins of eNOS including Hsp90 and caveolin-1 were related to these effects of RCE on eNOS activity in HUVECs.

Operator exposure risk assessment of benzimidazole fungicides on Korean agricultural condition (Benzimidazole계 살균제의 농작업자 위해성평가)

  • Lee, Je-Bong;Shin, Jin-Sup;Jeong, Mi-Hye;Park, Yeon-Ki;Im, Geon-Jae;Kang, Kyu-Young
    • The Korean Journal of Pesticide Science
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    • v.9 no.4
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    • pp.347-353
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    • 2005
  • Pesticide risk assessment for pesticide operators as well as for consumers has become one of the pesticide regulatory tools to reduce any unreasonable adverse health effects from pesticide use. The risk for pesticide operators can be quantified by comparing the acceptable operator exposure level(AOEL) with exposure level during pesticide application. This study is to evaluate the risk of benzimidazole fungicides application worker. The exposure level of pesticide applicators were calculated using Japanese operator exposure study tested with EPN 45% EC. The AOELs for pesticides were obtained dividing relevant lowest no observed abuse effect levels(NOAELs) for the exposure scenario into uncertainty factor, 100. For the non-cancer and cancer occupational risk assessment, $Q_1^*$ produced by US/EPA and life time average daily dose(LADD) calculated from average daily dose(ADD), treatment days per year, worked years for life time were used. Operator exposure for benzimidazole fungicides application were benomyl 0.2, carbendazim 0.36 and thiophanate-methyl 0.42 mg/kg/day. Short-term AOELs for benomyl, carbendazim and thiophanate-methyl were 0.3, 0.1, and 0.2 mg/kg/day, and long-term AOEL were 0.025, 0.025, 0.08 mg/kg/day, respectively. LADDs were benomyl 0.0038, carbendazim 0.0067, thiophanate-methyl 0.0081 mg/kg/day. The ratios of exposure to AOEL were $0.28{\sim}1.5$ for short-term and $3.73{\sim}9.88$ for long-term. Cancer risk for operator were $9.12{\times}10^{-6}$ for benomyl, $1.61{\times}10^{-5}$ for carbendazim and $1.13{\times}10^{-4}$ for thiophanate-methyl by the standard application scenario. The result showed 3 fungicides exceed the risk criteria, $1.0{\times}10^{-6}$. The above risk assessments were based upon conservative assumptions and therefore are believed to be protective of the applicator. To refine the risk at the more actual conditions, further risk assessment with more realistic data would be needed.

Discovery of UBE2I as a Novel Binding Protein of a Premature Ovarian Failure-Related Protein, FOXL2 (조기 난소 부전증 유발 관련 단백질인 FOXL2의 새로운 결합 단백질 UBE2I의 발견)

  • Park, Mira;Jung, Hyun Sook;Kim, Hyun-Lee;Pisarska, Margareta D.;Ha, Hye-Jeong;Lee, Kangseok;Bae, Jeehyeon;Ko, Jeong-Jae
    • Development and Reproduction
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    • v.12 no.3
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    • pp.289-296
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    • 2008
  • BPES (Blepharophimosis/Ptosis/Epicanthus inversus Syndrome) is an autosomal dominant disorder caused by mutations in FOXL2. Affected individuals have premature ovarian failure (POF) in addition to small palpebral fissures, drooping eyelids, and broad nasal bridge. FOXL2 is a member of the forkhead family transcription factors. In FOXL2-deficient ovaries, granulosa cell differentiation dose not progress, leading to arrest of folliculogenesis and oocytes atresia. Using yeast two-hybrid screening of rat ovarian cDNA library with FOXL2 as bait, we found that small ubiquitin-related modifier (SUMO)-conjugating E2 enzyme UBE2I protein interacted with FOXL2 protein. UBE2I also known as UBC9 is an essential protein for processing SUMO modification. Sumoylation is a form of post-translational modification involved in diverse signaling pathways including the regulation of transcriptional activities of many transcriptional factors. In the present study, we confirmed the protein-protein interaction between FOXL2 and UBE2I in human cells, 293T, by in vivo immunoprecipitation. In addition, we generated truncated FOXL2 mutants and identified the region of FOXL2 required for its association with UBE2I using yeast-two hybrid system. Therefore, the identification of UBE2I as an interacting protein of FOXL2 further suggests a presence of novel regulatory mechanism of FOXL2 by sumoylation.

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