• Title/Summary/Keyword: Correlation Function

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Synaptic Organization of Vibrissa Afferent Terminals in the Trigeminal Interpolar Nucleus (삼차신경중간핵에서 저역치기계자극수용기 유래 들신경섬유 종말의 연접양상)

  • Ahn, Hyoung-Joon;Paik, Sang-Kyoo;Bae, Yong-Chul;Choi, Jong-Hoon;Kim, Chong-Youl
    • Journal of Oral Medicine and Pain
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    • v.30 no.1
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    • pp.87-106
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    • 2005
  • In order to evaluate the mechanism of transmission as well as processing of sensory information originating from low-threshold mechanoreceptor in oral and maxillofacial region at primary synaptic region of trigeminal nervous system, vibrissa afferent fibers of adult cat were labeled with intra-axonal HRP injection. Serial sections containing labeled boutons were obtained from the piece of trigeminal interpolar nucleus. Under electron microscope, total 30 labeled boutons were observed, and ultrastructural characteristics, frequency of occurence, synaptic organizations of vibrissa afferent terminals were analysed. The results were as follows: 1. Labeled boutons contained clear, spherical synaptic vesicles with diameter of 45$\sim$55nm. They formed asymmetrical synapse with dendrites showing definite postsynaptic density, larger synaptic cleft, multiple synaptic structures at various regions. With unlabeled axon terminals(p-ending) containing polymorphic synaptic vesicles, they formed symmetrical synapse showing indefinite postsynaptic density and narrower synaptic area. 2. Each labeled bouton formed 1 to 15 synapses, the average of 4.77$\pm$3.37 contacts per labeled bouton, with adjacent neuronal profiles. Relatively complex synaptic organization, which formed synapses with more than 5 neuronal profiles, was observed in a large number(46.7%, n=14) of labeled boutons. 3. Axo-somatic synapse was not observed. The number of axo-dendritic synapse was 1.83$\pm$1.37 per labeled bouton. Majority(85.0%) of axo-dendritic synapses were formed with dendritic shafts, nonprimary dendrites(n=47, 1.57$\pm$1.38/1 bouton), however, synapses formed with primary dendrites(n=6, 0.20$\pm$0.41/1 bouton) or dendritic spines(n=2, 0.07$\pm$0.25/1 bouton) were rare. 4. 76.7%(n=23) of labeled boutons formed axo-axonic synapse (2.93$\pm$2.36/1 bouton) with p-endings containing pleomorphic vesicles. Synaptic triad, in which p-endings formed synapses with labeled boutons and dendrites adjacent to the labeled boutons simultaneoulsy, were also observed in 60.0%(n=18) of labeled boutons. From the above results, vibrissa afferent terminals of adult cat showed distinctive synaptic organization in the trigeminal interpolar nucleus, thus, suggests their correlation with the function of the trigeminal interpolaris nucleus, which participates in processing of complex sensory information such as two-point discrimination and motivational-affective action. Further studies on physiologic functions such as quantitative analysis on ultrastructures of afferent terminals and nerve transmitters participating in presynaptic inhibition are required.

The Normal Predicted Value of Peak Expiratory Flow(PEF) Measured by the Peak Flow Meter and Correlation Between PEF and Other Ventilatory Parameters (Peak Flow Meter로 측정한 최대호기류속도(PEF)의 추정정상치 및 가타 환기기능검사와의 상관관계)

  • Kim, Min-Chul;Kwon, Kee-Buem;Yim, Dong-Hyun;Song, Chang-Seuk;Jung, Yong-Seuk;Jang, Tae-Won;Yeu, Ho-Dae;Jung, Maan-Hong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.1000-1011
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    • 1998
  • Background: For the diagnosis or evaluation of airway obstruction in bronchial asthma and chronic obstructive lung disorders, various parameters derived from the forced expiratory volume curve and maximal expiratory flow volume curve have been used. Recently the peak expiratory flow(PEF) measured by the peak flow meter is widely used because of its simplicity and convenience. But there were still no data of the predicted normal values measured by the peak flow meter in Korea. This study was to obtain the predicted normal value of PEF and to know the accuracy of this value to predict $FEV_1$. Method: The measurements of PEF by the MiniWright peak flow meter and several parameters derived from the forced expiratory volume and maximal expiratory flow volume curves by the Microspiro HI 501(Chest Co.) were done in 129 men and 125 women without previous history of the respiratory diseases. The predicted normal values of parameters according to the age and the height were obtained, and the regression equation of $FEV_1$ by PEF was calculated. Results: The predicted normal values of PEF(L/min) were -2.45$\times$Age(year) +1.36 $\times$ Height(cm)+427 in men, and -0.96 $\times$ Age (year) + 2.01 $\times$ Height (cm) + 129 in women. FEFmax derived from the maximal expiratory flow volume curve was less than by 125 L/min in men and 118 L/min in women respectively compared to PEF. $FEV_1$(ml) predicted by PEF was 5.98 $\times$ PEF(L/min) + 303 in men, and 4.61 $\times$ PEF(L/min) + 291 in women respectively. Conclusion : The predicted normal value of PEF measured by the peak flow meter was calculated and it could be used as a standard value of PEF while taking care of patients with airway obstruction. $FEV_1$, the gold standard of ventilatory function, could be predicted by PEF to a certain extent.

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Purification of Human HtrA1 Expressed in E. coli and Characterization of Its Serine Protease Activity (E. coli에서 발현된 human HtrA1 단백질의 정제와 HtrA1의 serine protease 활성 조건에 관한 연구)

  • Kim, Kyung-Hee;Kim, Sang-Soo;Kim, Goo-Young;Rhim, Hyang-Shuk
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1133-1140
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    • 2006
  • Human HtrA1 (High temperature requirement protein A1) is a homologue of the E. coli periplasmic serine protease HtrA. A recent study has demonstrated that HtrA1 is a serine protease involved in processing of insulin like growth factor binding protein (ICFBP), indicating that it serves as an important regulator of IGF activity. Additionally, several lines of evidence suggest a striking correlation between proteolytic activity of HtrA1 serine protease and the pathogenesis of several diseases; however, physiological roles of HtrA1 remain to be elucidated. We used the pGEX bacterial expression system to develop a simple and rapid method for purifying HtrA1, and the recombinant HtrA1 protein was utilized to investigate the optimal conditions in executing its proteolytic activity. The proteolytically active HtrA1 was purified to approximately 85% purity, although the yield of the recombinant HtrA1 protein was slightly low $460{\mu}g$ for 1 liter E. coli culture). Using in vitro endoproteolytic cleavage assay, we identified that the HtrA1 serine protease activity was dependent on the enzyme concentration and the incubation time and that the best reaction temperature was $42^{\circ}C$ instead of $37^{\circ}C$. We arbitrary defined one unit of proteolytic activity of the HtrA1 serine protease as 200nM of HtrA1 that cleaves half of $5{\mu}M\;of\;{\beta}-casein$ during 3 hr incubation at $37^{\circ}C$. Our study provides a method for generating useful reagents to investigate the molecular mechanisms by which HtrA1 serine protease activity contributes in regulating its physiological function and to identify natural substrates of HtrA1.

Method Validation for the Determination of Eleutherosides and β-Glucan in Acanthopanax koreanum (탐라오가피의 Eleutheroside B, E 및 β-Glucan 함량 분석 및 분석법 검증)

  • Kim, Young-Hyun;Bae, Da-Bin;Park, Sun-Ok;Lee, Sang-Jong;Cho, Ok-Hyun;Lee, Ok-Hwan
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.9
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    • pp.1419-1425
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    • 2013
  • The aim of this study was to investigate the method validation for the determination of eleutherosides (B and E) and ${\beta}$-glucan in Acanthopanax (A.) koreanum. This medicinal plant reportedly mainly included eleutherosides which exhibit the pharmacological effects, and ${\beta}$-glucan substantially enhances the function of the immune system by activating macrophages. The specificity, linearity, precision, accuracy, limit of detection (LOD, S/N=3), and limit of quantification (LOQ, S/N=10) were measured by HPLC and enzymatic methods. Our results showed that the coefficient of calibration correlation ($R^2$) for eleutheroside B and E were 0.9997 and 0.9999, respectively. The limits of detection (LOD) for eleutheroside B and E were $0.050{\mu}g/mL$ and $0.025{\mu}g/mL$, respectively. The recovery rate of eleutheroside B and E were revealed in the high range of 100.66~110.04% and 94.26~111.62%, respectively. The inter-day precision of eleutheroside B and E in the root and stem in A. koreanum were 1.4~5.0% and 1.1~2.5%, respectively. The intra-day precision of eleutheroside B and E in the root and stem in A. koreanum were 2.8~2.9% and 0.4~1.1%, respectively. Furthermore, the inter-day and intra-day precision of ${\beta}$-glucan in the stem, leaf, and fruit of A. koreanum were 1.32~5.67% and 8.01~11.76%, respectively. In conclusion, the methods were validated for the detection of eleutherosides and ${\beta}$-glucan in A. koreanum.

Estimate on the Crustal Thickness from Using Multi-geophysical Data Sets and Its Comparison to Heat Flow Distribution of Korean Peninsula (다양한 지구물리 자료를 통해 얻은 한반도의 지각두께 예측과 지열류량과의 비교)

  • Choi, Soon-Young;Kim, Hyung-Rae;Kim, Chang-Hwan;Park, Chan-Hong;Suh, Man-Chul
    • Economic and Environmental Geology
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    • v.44 no.6
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    • pp.493-502
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    • 2011
  • We study the deep structure of Korean Peninsula by estimating Moho depth and crustal thickness from using land and oceanic topography and free-air gravity anomaly data. Based on Airy-Heiskanen isostatic hypothesis, the correlated components between the terrain gravity effects and free-air gravity anomalies by wavenumber correlation analysis(WCA) are extracted to estimate the gravity effects that will be resulted from isostatic compensation for the area. With the resulting compensated gravity estimates, Moho depth that is a subsurface between the crust and mantle is estimated by the inversion in an iterative method with the constraints of 20 seismic depth estimates by the receiver function analysis, to minimize the uncertainty of non-uniqueness. Consequently, the average of the resulting crustal thickness estimate of Korean Peninsula is 32.15 km and the standard deviation is 3.12 km. Moho depth of South Korea estimated from this study is compared with the ones from the previous studies, showing they are approximately consistent. And the aspects of Moho undulation from the respective study are in common deep along Taebaek Mountains and Sobaek Mountains and low depth in Gyeongsang Basin relatively. Also, it is discussed that the terrain decorrelated free-air gravity anomalies inferring from the intracrustal characteristics of the crust are compared to the heat flow distributions of South Korea. The low-frequency components of terrain decorrelated Free-air gravity anomalies are highly correlated with the heat flow data, especially in the area of Gyeongsang basin where high heat flow causes to decrease the density of the rocks in the lower crust resulting in lowering the Moho depth by compensation. This result confirms that the high heat sources in this area coming from the upper mantle by Kim et al. (2008).

Utility-Based Video Adaptation in MPEG-21 for Universal Multimedia Access (UMA를 위한 유틸리티 기반 MPEG-21 비디오 적응)

  • 김재곤;김형명;강경옥;김진웅
    • Journal of Broadcast Engineering
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    • v.8 no.4
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    • pp.325-338
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    • 2003
  • Video adaptation in response to dynamic resource conditions and user preferences is required as a key technology to enable universal multimedia access (UMA) through heterogeneous networks by a multitude of devices In a seamless way. Although many adaptation techniques exist, selections of appropriate adaptations among multiple choices that would satisfy given constraints are often ad hoc. To provide a systematic solution, we present a general conceptual framework to model video entity, adaptation, resource, utility, and relations among them. It allows for formulation of various adaptation problems as resource-constrained utility maximization. We apply the framework to a practical case of dynamic bit rate adaptation of MPEG-4 video streams by employing combination of frame dropping and DCT coefficient dropping. Furthermore, we present a descriptor, which has been accepted as a part of MPEG-21 Digital Item Adaptation (DIA), for supporting terminal and network quality of service (QoS) in an interoperable manner. Experiments are presented to demonstrate the feasibility of the presented framework using the descriptor.

Analysis of the Correlation between Human Sensibility and Physical Property of luminous Sources -Focused on Response according to Character of Color Temperature by luminous Sources- (건축조명광원의 광학적 특성에 따른 인간의 감성반응 분석 -조명광원별 색온도 특성에 따른 반응을 중심으로-)

  • Lee, Jin-Sook;Oh, Do-Suk
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.19 no.5
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    • pp.9-16
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    • 2005
  • The purpose of this research is to acquire emotional data on luminous source by measuring and evaluating human emotional response to the change of the optical feature of luminous environment Luminous sources used in actual architectural space were selected with the optical feature of luminous soured then to measure and analysis human emotional response on Luminous Source. As a result of that 1) In the result of performance measurement by the item of the clear vision of an optic function the fluorescent lamp of daylight indicated the most excellent Performance. 2) In the item of fatigue and stress, the metal halide lamp and mercury lamp showed the most 3) In $\ulcorner$ suitable in light$\lrcorner$, $\ulcorner$a similar with daylight$\lrcorner$ adjective of the amenity item the fluorescent lamp of daylight which color temperature was high turned up to be high also, in $\ulcorner$brilliant$\lrcorner$, adjective, the metal halide lamp and mercury lamp turned up to be low. 4) In the result of factor analysis, three factors $\ulcorner$activity$\lrcorner$, $\ulcorner$potency$\lrcorner$, $\ulcorner$evaluation$\lrcorner$ were abstracted and $\ulcorner$activity$\lrcorner$ factor has the most influential on evaluating the mood of interior space. 5) For the affection in the mood evaluation by each luminous sources, $\ulcorner$activity$\lrcorner$ factor was the most influential by metal halide lamp and fluorescent lamp of daylight, $\ulcorner$potency$\lrcorner$ factor was most influential by kind of incandescent lamp, $\ulcorner$evaluation$\lrcorner$ factor was most influential by fluorescent lamp of low color temperature.

An Analysis of IT Trends Using Tweet Data (트윗 데이터를 활용한 IT 트렌드 분석)

  • Yi, Jin Baek;Lee, Choong Kwon;Cha, Kyung Jin
    • Journal of Intelligence and Information Systems
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    • v.21 no.1
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    • pp.143-159
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    • 2015
  • Predicting IT trends has been a long and important subject for information systems research. IT trend prediction makes it possible to acknowledge emerging eras of innovation and allocate budgets to prepare against rapidly changing technological trends. Towards the end of each year, various domestic and global organizations predict and announce IT trends for the following year. For example, Gartner Predicts 10 top IT trend during the next year, and these predictions affect IT and industry leaders and organization's basic assumptions about technology and the future of IT, but the accuracy of these reports are difficult to verify. Social media data can be useful tool to verify the accuracy. As social media services have gained in popularity, it is used in a variety of ways, from posting about personal daily life to keeping up to date with news and trends. In the recent years, rates of social media activity in Korea have reached unprecedented levels. Hundreds of millions of users now participate in online social networks and communicate with colleague and friends their opinions and thoughts. In particular, Twitter is currently the major micro blog service, it has an important function named 'tweets' which is to report their current thoughts and actions, comments on news and engage in discussions. For an analysis on IT trends, we chose Tweet data because not only it produces massive unstructured textual data in real time but also it serves as an influential channel for opinion leading on technology. Previous studies found that the tweet data provides useful information and detects the trend of society effectively, these studies also identifies that Twitter can track the issue faster than the other media, newspapers. Therefore, this study investigates how frequently the predicted IT trends for the following year announced by public organizations are mentioned on social network services like Twitter. IT trend predictions for 2013, announced near the end of 2012 from two domestic organizations, the National IT Industry Promotion Agency (NIPA) and the National Information Society Agency (NIA), were used as a basis for this research. The present study analyzes the Twitter data generated from Seoul (Korea) compared with the predictions of the two organizations to analyze the differences. Thus, Twitter data analysis requires various natural language processing techniques, including the removal of stop words, and noun extraction for processing various unrefined forms of unstructured data. To overcome these challenges, we used SAS IRS (Information Retrieval Studio) developed by SAS to capture the trend in real-time processing big stream datasets of Twitter. The system offers a framework for crawling, normalizing, analyzing, indexing and searching tweet data. As a result, we have crawled the entire Twitter sphere in Seoul area and obtained 21,589 tweets in 2013 to review how frequently the IT trend topics announced by the two organizations were mentioned by the people in Seoul. The results shows that most IT trend predicted by NIPA and NIA were all frequently mentioned in Twitter except some topics such as 'new types of security threat', 'green IT', 'next generation semiconductor' since these topics non generalized compound words so they can be mentioned in Twitter with other words. To answer whether the IT trend tweets from Korea is related to the following year's IT trends in real world, we compared Twitter's trending topics with those in Nara Market, Korea's online e-Procurement system which is a nationwide web-based procurement system, dealing with whole procurement process of all public organizations in Korea. The correlation analysis show that Tweet frequencies on IT trending topics predicted by NIPA and NIA are significantly correlated with frequencies on IT topics mentioned in project announcements by Nara market in 2012 and 2013. The main contribution of our research can be found in the following aspects: i) the IT topic predictions announced by NIPA and NIA can provide an effective guideline to IT professionals and researchers in Korea who are looking for verified IT topic trends in the following topic, ii) researchers can use Twitter to get some useful ideas to detect and predict dynamic trends of technological and social issues.

The Way of Expression of Wangreungdo(王陵圖: A Kind of A Royal Mausoleum Map) Reflected on Sanhyoungdo(山形圖: A Kind of A Mountain Map) in the Late Nineteenth Century - Centering the Drawings Relevant to Jogyoungdan(肇慶壇) of Lee Han, the Founder of Jeonju Lee Family - (19세기 후반 산형도(山形圖)로 본 왕릉도(王陵圖)의 표현방법(表現方法) -전주이씨(全州李氏) 시조(始祖) 이한(李翰)의 조경단(肇慶檀) 관련 그림을 중심으로-)

  • Kim, Jeong-Moon
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.30 no.1
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    • pp.57-65
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    • 2012
  • This work attempted to study the properties of expression of ground, the composition of outlook and the implications of the connotative symbolic scenery throughout investigating the properties of expression content and method of the scenery, outlook, viewpoint, natural features for each drawing and intention of making 4 old maps, which had been made in the period of the Great Korean Empire and had been called 'Wansan-dohyoung(完山圖形),' 'Jogyeongdan- bigak-jaesil-dohyoung(肇慶壇碑閣齋室圖形),' 'Jeonju-geonjisan-dohyoung(全州乾止山圖形)' and 'Jogyeongmyo-gyounggijeon-dohyoung(肇慶廟慶基殿圖形),' and analyzing the correlation between their drawings. For this aim, observatory investigation by using a map, on-spot investigation, analysis involving the satellite images and internet were carried out with literature review simultaneously. The result of investigation could be sum up as follows. Gyounggijeon(1410), Jogyeongmyo(1771) and Jogyeongdan(1899), where are the core space to lay the historically firm foundation for securing the fact Jeonju is the home of the Royal Family of Joseon, had been built, fixed and extended for giving legitimacy to the Joseon Dynasty and a part of strengthening of royal authority. And these had played an important role of spiritual mainstay from early in the Joseon Dynasty to the era of the Great Korean Empire and had been managed and maintained continuously. It is grasped that the 4 maps consist of Sanhyuoungdo(山形圖; a kind of a mountain map), which is the map for showing a burial place of Lee Han(李翰), the founder of the Joseon Dynasty, and its auxiliary drawings and these had been drawn intensively to justify dignity and authority of the Imperial Family and the Emperor after the name of country was renamed the Great Korean Empire as a part of national undertaking. In detail, Wansan-doghyoung is the key map for announcing the existence of Jogyeong-myo, Gyounggijeon and Jogyeongdan in Jeonju and informing their locations and Geonjisan-dohyoung is the map of divination based on topography for highlighting the geomantic justification of the founder's mausoleum. Jogyeongdan-bigak-jaesil-dohyooung is the partial map detailing for Geonjisan-dohyoung. Jeonju-geonjisan-dohyoung and Jogyeongmyo-gyounggijeon-dohyoung had employed the binary reduced scale and the bird-eye view method and in the above maps, Geonji Mountain is the main mountain and these maps make an exaggeration of the main geographical features, centering Wangjabong and Euimyoso, unlike the real geographical features. Also, the other main geographical features, which are found in the burial place, are expressed in detail by changing the view. In the point of view of 1 set being consisted of 4 maps, 'Wansan-dohyoung' has the property not only as Gunhyoundo, which Gun and Hyoun mean a unit of the administrative district, respectively and Gynhyoundo is a kind of the map for recording their locations, but also as the map of showing their locations. On the other side, 'Jogyoungmyogyounggijeondohyoung' is a kind of lay-out drawing as a partially detailed map. In addition, it has been found out that 'Jeonju-geonjisan-dohyoung' and 'Jogyeongdan-bigak-jaesil-dohyoung' is not only Pungsu- hyounggukdo having the function of Sanhyoungdo but also a detail drawing. On the base of these properties, it is considered that the functionality as a serial map had been strengthened, unlike the existing old maps.

Development of Natural Antioxidants and Whitening Agents for Cosmeceuticals

  • Kim, Jong-Pyung
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.79-92
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    • 2007
  • Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

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