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        S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

        Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

        S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

      • KCI등재

        저합금 고장력강 용접열영향부의 S . R . 귀열 발생 기구에 관한 연구

        이종섭,김태웅,장래웅,엄기원 대한금속재료학회(대한금속학회) 1989 대한금속·재료학회지 Vol.27 No.3

        This study was carried out to investigate the mechanism of S. R. cracking in HAZ of high strength low alloy steel. Among 3 commercial high strength steels, steel A (HT80), which is equivalent to ASTM A514 Gr.F. was most susceptible to S. R cracking whereas steel C(HT60) showed no crack in oblique Y-groove test even in high restraint. The cause of S. R cracking along the coarsened austenite grain boundary was secondary hardening phenomenon and impurity segregation to the prior austenite grain boundary. The crack susceptibility was reduced as increasing heat input due to the weakening of secondary hardening.

      • Inhibitory effects of Rumex japonicus Houtt. On the development of atopic dermatitis-like skin lesions in NC/Nga mice

        Lee, H-S.,Kim, S-K.,Han, J-B.,Choi, H-M.,Park, J-H.,Kim, E-C.,Choi, M-S.,An, H-J.,Um, J-Y.,Kim, H-M.,Min, B-I. 경희대학교 동서의학연구소 2006 東西醫學硏究所 論文集 Vol.2006 No.-

        Background Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an anti-oxidative effect in human skin disease. Objectives To examine whether RJH extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga mice, which are induced by the repeated application of picryl chloride (PC). Methods The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-γ. Results Oral administration of RJH-E to NC/Nga mice treated with PC inhibited the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and infiltration of inflammatory cells in the skin. The scratching behaviour and numbers of S. aureus, which are known to be exacerbated in AD, were also significantly reduced by RJH-E. No significant change was observed in the serum levels of IFN-γ, whereas IgE and IL-4 levels were significantly reduced by RJH-E. Conclusions These results suggest that RJH-E inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. Our results indicate that RJH treatment could provide an effective alternative therapy for the management of AD.

      • KCI등재

        열처리 단백질-광물질 복합제제 첨가가 In Vitro 발효성상과 착유우의 유량 및 유성분에 미치는 영향

        최낙진,배귀석,남경표,장문백,엄재상,고종렬,하종규 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.5

        본 연구의 in vitro 실험결과를 살펴보면, 배양액의 pH와 암모니아 생성량은 전 배양시간 동안 처리구간 통계적 유의차가 없었다. Total VFA, acetate, propionate, butyrate 생성량은 12 h에서 HPM을 0.2%, 1% 첨가한 시험구에서 대조구와 비교하여 증가하는 경향이 있었으나, 2% 첨가구에서는 오히려 감소되었고, 48 h 에서는 HPM 첨가한 세 처리구에서 대조구와 비교하여 모두 증가하는 경향을 보였다. 반면에, 다른 배양시간대에서는 처리구간 통계적 유의차는 발견되지 않았다. A/P ratio 경우에도 처리구간 유의차는 없었다. 총 gas 생성량은 배양시간 24 h과 48 h에 HPM 처리구에서 대조구와 비교하여 증가하였다 (P<0.05). 한편 사양실험은 열처리된 단백질 (대두박)과 광물질의 복합 제제 (HPM)가 젖소의 유생산량과 유성분에 끼치는 영향을 조사하기 위하여 수행되었는데 그 결과를 요약하면, 유생산량은 대조구와 비교하여 HPM 시험구에서 하루에 약 1㎏ 정도 더 높았고 (27. 7 vs 28.8 ㎏/d, P<0.001), 4% FCM 생성량 또한 대조구와 비교하여 볼 때 HPM 시험구에서 1.3㎏/d 이 더 높았다 (P<0.001). 유단백 (P<0.05)과 SNF (P<0.05)도 대조구와 비교하여 HPM 시험구에서 그 생산량이 증가되었다. 반면에, 유지방, MUN과 체세포수는 처리구간 통계적 유의차가 발견되지 않았다. 이상의 결과로 보아, HPM 첨가에 의한 반추위 발효 저해현상은 없었으며, HPM 내 함유되어 있는 열처리된 단백질과 광물질의 결합체와 잔여 광물질이 반추위 내 단백질과 결합하여 단백질 분해 속도를 지연시킴으로써, 단백질의 by-pass율을 증가시켜, 유생산량 증가와 유질을 개선 (유단백질, SNF 함량 증가 등) 하는 등 젖소의 생산성을 향상시킨 것으로 요약할 수 있다. This study, consisting of two experiments, was conducted to determine the effects of feeding heat treated protein and mineral complex (HPM) on milk production and composition, and ruminal fermentation of Holstein dairy cows. In in vitro experiment, HPM levels were 0, 0.2, 1 and 2%, and Timothy hay, which was substrate, was milled as 1 ㎜ size, and the effect of HPM on pH and ammonia and VFA were analyzed after incubation times of 0, 6, 12, 24 and 48 h, respectively. The pH and ammonia production were not significantly different between treatments during the incubation. In addition, generally, total VFA and individual VFA were not affected by HPM on 0, 6 and 24 h. While, total VFA and individual VFA were increased in 0.2% and 1% of HPM supplemented treatments, but decreased in 2% of HPM treatment compared with control on 12 h. On 48 h, total VFA and individual VFA were increased in HMP treatment compared to control(P<0.05). However, A/P ratio was not affected by HPM supplementation. Gas production was higher in HPM treatment compared to control on 24 h (P<0.05) and 48 h (P<0.05). In lactating experiment, fourteen lactating Holstein cows were used for 4 months in a cross over experimental design. There were two treatment; no added HPM as a control and 0.2% of HPM added as a test treatment. Daily milk yield (P<0.001), 4% FCM (P<0.001), milk protein (P<0.05) and SNF (solid not fat; P<0.05) were increased in HPM treatment compared to control. While, milk fat, MUN (milk urea nitrogen) and SCC (somatic cell count) were not significantly different between treatments.

      • KCI등재

        패스틴^� 첨가가 단백질 분해율과 반추위 발효 및 영양소 소화율에 미치는 영향

        최유지,최낙진,박성호,송재용,엄재상,고종렬,하종규 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.5

        본 시험은 패스틴^R을 첨가하였을 때, in vitro 상에서 단백질 fraction과 분해율에 미치는 영향과, in vivo 상에서 반추위 성상, 미생물 군집, 암모니아태 질소 농도 및 영양소 소화율에 미치는 영향을 규명하고자 실시하였다. In vitro 실험에서는 1㎜로 분쇄된 대두박을 기질로 하여 패스틴^R(㈜은진인터내셔날)을 첨가하여 borate-phosphate buffer와 중성세제에서의 조단백질 분해율을 측정하였으며, exogenous enzyme (Streptomyces griseus 유래 protease)를 이용하여 39℃에서 0, 2, 4, 8, 12, 48 시간동안 배양 후 조단백질 분해율을 측정하였다. 반추위 발효성상과 영양소 소화율은 반추위 fistula가 부착된 평균체중 300㎏의 홀스타인 수소 4두를 이용하여 무첨가구, 패스틴^R 첨가구의 두 개 처리구에 2마리씩 4마리를 배치하여 측정하였다. Buffer Soluble Protein fraction은 패스틴^R 첨가 수준별로 차이가 없었으나, 무첨가구에 비해 패스틴^R 첨가구에서 감소하는 경향을 보였다. 단백질 분해율은 배양 0 시간대에서 4시간대까지는 처리구간 유의성이 없었지만, 12 h과 48 h에서는 패스틴^R 첨가로 시험구에서 감소되었다. 용해 단백질 분해율 “a”는 패스틴^R 시험구에서 경미하게 높은 수치를 나타내었지만, 소화 가능한 단백질 분해율 “a+b”는 패스틴^R 시험구에서 낮은 경향을 보였다. 패스틴^R 첨가로 pH와 NH_3-N 농도는 증가하는 경향이었으며 휘발성지방산, 미생물 수 및 enzyme activity는 감소하였고 영양소 소화율은 높았으나 유의적인 차이는 없었다. This study, including two in vitro experiments and an invivo experiment were conducted to evaluate effects of Passtein^R on crude protein degradability, ruminal fermentation characteristics and nutrient digestibility. In in vitro experiment protein degradability was examined using borate-phosphate buffer and neutral detergent, and using protease from Stroptomyces griseus at 39℃ for 0, 2, 4, 8, 12 and 48 h. In addition, an in vivo experiment was conducted in a switch back design and ruminal fermentation and nutrient digestibility were determined. Four ruminal-fistulated Holstein cows weighing 300㎏ in mean body weight randomly allotted to 2 treatments (control and Passtein^R supplementation). Although there was no significant difference on protein fraction between treatments, it appears that Passtein^R supplementation decreased buffer soluble protein fraction compared to control. Protein degradability was not affected by Passtein^R from 0 h to 4 h, but decreased at 12 h and 48 h compared to control. Degradation of immediately degradable fraction was higher in Passtein^R treatment, but degradation of fermentable fraction was lower in Passtein^R treatment compared to control. The pH and NH_3-N concentration tended to increase in Passtein^R treatment, but VFA production, microbial counts and enzyme activity tended to decrease in Passtein^R treatment compared to control. In addition, nutrient digestibility in the total tract tended to increase in Passtein^R treatment compared to control.

      • SCISCIESCOPUS

        Kinase activity-independent suppression of p73α by AMP-activated kinase α (AMPKα)

        Lee, Y-G,Lee, S-W,Sin, H-S,Kim, E-J,Um, S-J Macmillan Publishers Limited 2009 Oncogene Vol.28 No.7

        Although p73α induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552–636 of p73α as bait. Among the clones that showed a specific interaction with p73α was AMP-activated protein kinase α (AMPKα). Additional yeast two-hybrid assays indicated that the βγ-binding domain of AMPKα is critical for the interaction with p73α. The interaction was further confirmed in vitro by glutathione S-transferase pull-down, and in vivo by immunoprecipitation and immunofluorescence microscopy. Transient coexpression of AMPKα resulted in downregulation of the effect of p73α, but not of p53, on various p53-responsive promoters. Chromatin immunoprecipitation indicated p73α-dependent recruitment of AMPKα to the p21WAF1 promoter. Treatment with 5-aminoimidazole-4-carboxamide ribonucleotide, an agonist of AMPKα, and expression of dominant-negative versions of AMPKα revealed that the repression of p73α was independent of AMPKα kinase activity. In addition, cisplatin-induced growth repression was impaired when AMPKα was overexpressed. Upon the knock down of AMPKα by siRNA, the induction of p21WAF1 by p73α was significantly increased. Taken together, these data indicate that AMPKα specifically regulates p73α by a direct interaction without affecting its phosphorylation status. From these data, we speculate that AMPKα may provide a molecular clue to understand the repressive role of the C-terminus of p73α in transcription and DNA damage response.Oncogene (2009) 28, 1040–1052; doi:10.1038/onc.2008.452; published online 15 December 2008

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