• Molecules and Cells
• /
• 제41권9호
• /
• pp.842-852
• /
• 2018

Notch signaling is an evolutionarily conserved pathway and involves in the regulation of various cellular and developmental processes. Ligand binding releases the intracellular domain of Notch receptor (NICD), which interacts with DNA-bound CSL [CBF1/Su(H)/Lag-1] to activate transcription of target genes. In the absence of NICD binding, CSL down-regulates target gene expression through the recruitment of various corepressor proteins including SMRT/NCoR (silencing mediator of retinoid and thyroid receptors/nuclear receptor corepressor), SHARP (SMRT/HDAC1-associated repressor protein), and KyoT2. Structural and functional studies revealed the molecular basis of these interactions, in which NICD coactivator and corepressor proteins competitively bind to ${\beta}-trefoil$ domain (BTD) of CSL using a conserved ${\varphi}W{\varphi}P$ motif (${\varphi}$ denotes any hydrophobic residues). To date, there are conflicting ideas regarding the molecular mechanism of SMRT-mediated repression of CSL as to whether CSL-SMRT interaction is direct or indirect (via the bridge factor SHARP). To solve this issue, we mapped the CSL-binding region of SMRT and employed a 'one- plus two-hybrid system' to obtain CSL interaction-defective mutants for this region. We identified the CSL-interaction module of SMRT (CIMS; amino acid 1816-1846) as the molecular determinant of its direct interaction with CSL. Notably, CIMS contains a canonical ${\varphi}W{\varphi}P$ sequence (APIWRP, amino acids 1832-1837) and directly interacts with CSL-BTD in a mode similar to other BTD-binding corepressors. Finally, we showed that CSL-interaction motif, rather than SHARP-interaction motif, of SMRT is involved in transcriptional repression of NICD in a cell-based assay. These results strongly suggest that SMRT participates in CSL-mediated repression via direct binding to CSL.

• Environmental Analysis Health and Toxicology
• /
• 제21권1호
• /
• pp.27-34
• /
• 2006

Numerous studies reported the significant association between genetic polymorphisms in the vitamin D receptor (VDR) gene and various bone phenotypes such as bone mineral density (BMD) and bone quality, although conflicting results were produced. The objective of this study was to investigate the association between a TaqI RFLP in the VDR gene and calcaneal BMD in Korean vegetarian men, and its interaction with nutrition status as an environmental factor. BUA (broadband ultrasound attenuation), SOS (sound of speed) and stiffness index of the calcaneus were measured using an ultrasound bone densitometer in 266 Korean men (age: $mean{\pm}SD;\;50.9{\pm}12.0$ year), and a TaqI RFLP in the VDR gene analysed by PCR-RFLP method. In total subjects, the distribution of TT, Tt and tt genotypes occurred with frequencies of 90.8%, 8.8% and 0.4%, respectively. There were no significant associations between this polymorphism and osteopenia-osteoporosis or several bone phenotypes in our subjects irrespectively of nutrition status (P>0.05). Therefore, our results suggest that a TaqI RFLP in the vitamin D receptor gene does not contribute to the susceptibility to the calcaneal BMD in Korean men.

• Archives of Pharmacal Research
• /
• 제29권8호
• /
• pp.691-698
• /
• 2006

Although glucocorticoids are known to affect osteoclast differentiation and function, there have been conflicting reports about the effect of glucocorticoids on osteoclast formation, leading to the assumption that microenvironment and cell type influence their action. We explored the effect of the synthetic glucocorticoid analog dexamethasone on the formation of osteoclasts. Dexamethasone inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts without affecting the formation of TRAP-positive mononuclear cells in a coculture of mouse osteoblasts and bone marrow cells. Dexamethasone did not inhibit mRNA expression levels of the receptor activator of nuclear factor-kB ligand and osteoprotegerin, the essential regulators of osteoclastogenesis. Dexamethasone down-regulated the expression of ${\beta}_3$ integrin mRNA and protein but did not alter expression of other osteoclast differentiation marker genes. Both dexamethasone and echistatin, a ${\beta}_3$ integrin function blocker, inhibited TRAP-positive multinucleated osteoclast formation but not TRAP-positive mononuclear cell formation. These results suggest that dexamethasone inhibits the formation of multinucleated osteoclasts, at least in part, through the down-regulation of ${\beta}_3$ integrin, which plays an important role in the formation of multinucleated osteoclasts.

• 문화기술의 융합
• /
• 제6권4호
• /
• pp.545-551
• /
• 2020

떡보와 중국 사신 민담은 흔히 외세에 무기력한 지배계층에 대한 민중의 비판의식이 담긴 이야기로 알려져 있다. 수문답으로 진행되는 의사소통을 기표 이론으로 설명한 연구결과가 있다. 중국 사신의 위치를 대타자로 간주하는 등의 라캉 이론을 이용하여 분석한 연구결과도 있다. 본 연구에서는 떡보와 사신의 욕망의 성격 차이를 분석하여 떡보의 담론 승리를 설명하는 것이 적절하다고 제안한다. 즉, 떡보의 욕망은 충동이며, 충동의 반복적이고 집요한 성격이 담론 승리의 주요 원인이라는 것이다. 또한 중국 사신은 대타자가 아니라 실재의 응답으로 보는 것이 타당하다. 충동의 형태로 반복되는 열등한 주체의 욕구에 대한 실재계의 응답으로 사신의 지위를 설정할 때 전통적인 민담 콘텐츠의 작동원리를 자연스럽게 이해할 수 있다.

• Molecules and Cells
• /
• 제37권11호
• /
• pp.767-776
• /
• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• Journal of Preventive Medicine and Public Health
• /
• 제49권3호
• /
• pp.153-164
• /
• 2016

Objectives: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined crosssectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. Methods: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Results: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ${\geq}25kg/m^2$). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Conclusions: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI.

• 한국ITS학회 논문지
• /
• 제14권1호
• /
• pp.13-21
• /
• 2015

본 연구에서는 두 가지 형태의 공용차로 운영 효율성에 초점을 맞추어 분석을 수행하였다. 직진 우회전 공용차로의 경우 인접한 직진차로에 비해 이용률이 현저히 떨어지는 것으로 나타났으며 그로 인해 신호운영의 효율성이 떨어지는 것으로 분석되었다. 이를 개선하기 위해서는 우선 차로별 교통량 수집을 통한 보다 정교한 신호최적화가 필요하다 할 수 있으며, 나아가 운전자 교육, 홍보를 통해 공용차로의 이용률을 제고하여야 할 것이다. 좌회전 유턴 공용차로에서는 유턴 교통량에 대한 대향 우회전 교통량 비율에 따라 포화교통류율이 감소한다는 것을 확인할 수 있었다. 하지만 유턴, 우회전 차량간 간섭에 따른 현실적인 포화교통류율 보정치를 개발하기 위해서는 차량간 간섭이 일어날 가능성에 대한 확률모형의 정립이 필요한 것으로 판단된다.

• 마케팅과학연구
• /
• 제19권2호
• /
• pp.40-52
• /
• 2009

Franchising is one of the fastest growing types of business. It is already popular and well-known in the U.S., and has been growing in many other countries including Korea. Furthermore, many Korean franchising companies have expanded their business overseas actively. According to the data by the Ministry of Industry and Resource, 82 companies out of a sample of 500 franchising companies are already operating in many foreign countries and 48% of them have started their foreign business since 2006. This clearly indicates the fast growing current trend of foreign operation by Korean franchising companies. In spite of the fast growing trend of foreign expansion in the industry, academic research on internationalization of franchising companies is extremely difficult to find. Accordingly, academic research on the issue is necessary and urgent in Korea. Among the various research questions on internationalization of franchising business, this study intends to investigate the difference in organizational factors between the franchising companies doing foreign operation and those doing business only domestically. More specifically, this research has the following purposes. First, considering the lack of theoretical basis of previous studies, resource-based theory and agency theory are employed as the theoretical bases. Second, this study explains the difference in internationalization based on organizational factors such as company size, history and growth rate. Third, the five hypotheses regarding the difference in organizational factors are presented and tested empirically, which is the first attempt in the area of this topic. Finally, the study attempts to clarify the conflicting implications among theories regarding some organizational factos such as growth rate. As the theoretical background, resource-based theory and agency theory are discussed. According to resource-based theory, a firm can grow continuously when it has competence and resource, and also the ability to develop them. The competence and resource can include capital, human resource, management skill, market information, ability to manage risk, etc. Meanwhile, agency theory views the relationship between franchisor and franchisee as an agency relationship. In agency theory, bonding capability and monitoring capability are the two key factors which promote internationalization of franchising companies. Based on the two theories, a conceptual model is designed. The model consists of two groups of variables. One is organizational factors including size, history, growth rate, price bonding and geographic dispersion. The other is whether a franchising company is operating overseas or not. We developed the following five research hypotheses basically describing the relationship between organizational factors and internationalization of franchising companies. H1: The size of franchising companies operating overseas is larger than that of franchising companies operating domestically. H2: The history of franchising companies operating overseas is longer than that of franchising companies operating domestically. H3: The growth rate of franchising companies operating overseas is higher than that of franchising companies operating domestically. H4: The price bonding of franchising companies operating overseas is higher than that of franchising companies operating domestically. H5: The geographic dispersion of franchising companies operating overseas is wider than that of franchising companies operating domestically. Data for the analyses are obtained from 2005 Korea Franchise Survey data co-generated by Ministry of Industry and Resource, GS1 Korea, and Korea Franchise Association. Out of 2,804 population companies, 2,489 companies are excluded for various reasons and 315 companies are selected as the final sample. Prior to hypotheses tests, validity and reliability of the measures of size, history, growth rate and price bonding are examined for further analyses. Geographic dispersion is not validated since it is measured using nominal data. A series of independent sample T-tests is used to find out whether there exists any significant difference between the companies internationalized and those operating only domestically for each organizational factor. Among the five factors, size and geographic dispersion show significant difference, growth rate and price bonding do not reveal any difference and, finally, history factor shows conflicting results in the difference depending on how to measure it.