• 제목/요약/키워드: SH3 domain

검색결과 61건 처리시간 0.03초

Differential Gene Expression in Estradiol-3-Benzoate-Treated Liver and Chemically- Induced Hepatocellular Carcinoma

  • KIM , SEYL;KANG, JIN-SEOK;JANG, DONG-DEUK;LEE, KOOK-KYUNG;KIM, SOON-AE;HAN, BEOM-SEOK;PARK, YOUNG-IN
    • Journal of Microbiology and Biotechnology
    • /
    • 제14권6호
    • /
    • pp.1286-1294
    • /
    • 2004
  • In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

동적 무한요소를 이용한3차원 지반-구조물 상호작용계의 지진응답해석 (Seismic Response Analysis for Three Dimensional Soil-structure Interaction System using Dynamic Infinite Elements)

  • 서춘교;류정수;김재민
    • 한국지진공학회논문집
    • /
    • 제12권6호
    • /
    • pp.55-63
    • /
    • 2008
  • 본 연구에서는 지반-구조물 상호작용을 고려한3차원 지반-구조계의 지진응답 해석을 수행하고 그 기법의 적용성과 타당성을 검토한다. 이를 위해 구조물과 구조물 주변의 근역지반을3차원 유한요소로서 모델링하고 원역지반에 대해서는 기 개발한 3차원 동적 무한요소를 적용한다. 모든 입사 성분P, SV 그리고 SH파가 고려되었을 때, 등가 지진하중은 무한요소에 의해 구해진 무한 지반의 동적 강성과 자유장 해석을 통해 구해진 지반의 응력과 변위응답을 이용하여 구해진다. 검증 및 적용 예제는 적층 자유장의 지반응답해석과 전형적 원자로 격납건물의 지반-구조물 상호작용을 고려한 층응답 스펙트럼을 구하는 것으로 하였다. 해석 결과는 다른 기법에 의해 구해진 값들과 비교하였으며, 본 기법의 정확성과 정밀성을 확인할 수 있다.

시간-주파수 영역에서의 국지 미소지진과 지하인공폭발의 구별 (Discrimination of Local Microearthquakes and Artificial Underground Explosions on the Basis of Time-Frequency Domain)

  • 김소구;박용철
    • 지질공학
    • /
    • 제7권1호
    • /
    • pp.63-79
    • /
    • 1997
  • 본 연구의 목적은 시간-주파수 영역에서의 미소지진과 인공폭발을 구별하는 것으로 미소지진과 인공폭발의 주파수특성을 연구하기 위해서 3차원 스펙트로그램(주파수, 시간, 진폭)을 이용하였다. 3차원 스펙트로그램은 국지 및 광역 거리에서 관측된 자료에 대하여 각각의 위상에 대한 주파수대역의 연구에 매우 유용한 방법이다. 채석장 발파로부터 관측된 P파와 S파는 Hz 이상에서 큰 진폭을 가졌고 또한 가까운 거리에서는 뚜렷한 Rg파가 관측되었다. 미소 지진의 경우 P파와 S파는 넓은 주파수 대역에서 큰 진폭이나타났다. 인공 폭발과 미소지진의 구별을 위해서는 10Hz 이하에서 Pg/Lg 스펙트럼 비를 이용하였고 각각의 위상에서의 정확한 시간창(time window)을 구하기 위해서 다중 필터 방법(MFM)을 이용하여 군속도를 계산하였다. 또한 3 성분 자료에 관해서는 자료의 순수한 P, SV, SH 성질을 구하기 위해 자유 표면에서의 영향을 보정하고 각각의 위상에 대하여 FFT을 실시하여 7개의 주파수 대역(0.5-3, 2-4, 3-5, 4-6, 5-7, 6-8, 8-10Hz)에서 Pg/Lg 스펙트럼 비를 계산하였다. 위의 과정을 통해 6-8Hz 대역에서 미소지진과 인공폭발이 가장 잘 구별되었다.

  • PDF

인체 폐암조직에서 Phospholipase C 동위효소의 발현양상 (Expression of Phospholipase C Isozymes in Human Lung Cancer Tissues)

  • 황성철;마경애;최소연;오윤정;최영인;김덕기;이형노;최영화;박광주;이이형;이기범;하만준;배윤수
    • Tuberculosis and Respiratory Diseases
    • /
    • 제49권3호
    • /
    • pp.310-322
    • /
    • 2000
  • 배경 : Phospholipase C는 세포내 신호 전달과정의 초기 단계에 있어서, 매우 중요한 역할을 하는 효소로 알려져 있으며, 세포막에 존재하는 인지질 가운데 중요한 부분을 차지하는 $PIP_2$를 분해하여 제2전령물질인 DAG와 IP3를 생성한다. 이들 제2전령물질은 각각 PKC를 활성화시키고, 세포내의 $Ca^{2+}$농도를 증가 시켜서 세포내 여러 단백질 효소들을 활성화시키는 동시에, PLC 효소는 자체적으로 갖고 있는 고유의 SH2, SH3 및 PH domains 등의 기능 영역을 통해, 다른 신호 전달 인자들과 상호 작용하고, 세포막의 재구성이나, 세포분열, 발안과정에 관여 하게 된다. 이에 저자 등은 이전의 연구에서, 인체 정상 폐조직에서 PLC-${\beta}1$, -${\beta}3$, -${\gamma}1$ 및 -${\delta}1$ 동위효소가 존재함을 보고하였으며, bovine lung 내에서 PLC-${\gamma}1$ 동위 효소를 활성화 시키는 AHNAK 단백을 분리, 정제 및 클로닝 하였고, 이 AHNAK 단백이 인체 폐암조직내에서 정상조직에 비해 증가 되어 있음을 보고하여, 폐암의 발암과정에 있어서 칼슘-inositol 신호전달체계의 이상이 연관 되어있음을 제시하였다. 하지만 아직 인체 폐암조직이나 다른 종류의 폐질환에 대해서는, PLC 동위효소의 발현양상에 대한 보고가 없었으므로, 이에 저자 등은 수술로 적출한 인체 폐암 조직 내에서 PLC 동위 효소의 발현을 연구하여, 폐암의 발암과정에서 이들 효과가 갖는 역할을 규명하고자 하였다. 대상 및 방법 : 아주 대학교 병원에 내원하여 원발성 폐암으로 수술적 절제술을 받은 환자중에서, 신선냉동상태의 암조직과 동일환자의 정상폐조직이 확보가, 가능했던 37예의 환자를 대상으로 하였다. 이들조직을 대상으로 PLC-${\beta}1$, -${\beta}3$, -${\gamma}1$ 및 -${\delta}1$ 동위효소에 대해 Western blot 분석을 시행하였고, 대표적인 표본에 대해서는 PLC-${\gamma}1$에 대한 면역조직화학검사를 시행하였다. 결과 : 연구의 대상이었던 15예의 선암조직 모두에서, PLC-${\gamma}1$ 동위효소의 과발현을 관찰할 수 있었으며, 편평상피세포암 19예 중 16예에서 PLC-${\gamma}1$의 발현이 정상조직에 비해 증가하였음이 확인되었다. PLC-${\delta}1$ 동위효소의 경우, 대부분의 폐암조직에 감소되어 있었다. 하지만 이와는 반대로, 일부 선암 및 편평상피 암 조식(각3예)에서는, 현저한 증가를 보이기도 했다. 또한, 비록 그 증례수가 적기는 하였지만, 소세포 폐암 4예에서는, 모두에서 정상 폐조직보다, PLC-${\delta}1$ 효소의 발현이 현저히 감소되어 있음을 관찰하였다. 결론 : 이상의 결과로 미루어 폐암 조직 내에서 PLC-${\gamma}1$ 동위효소의 발현이 증가되어 있었는데, 이는 저자등이, 이미 보고한바 있는, PLC-${\gamma}1$의 활성화 AHNAK의 과발현과 함께, 폐암의 발암과정에, 칼슘-inositol 신호전달 채계의 이상이 관여할것이라는 실험적인 증거가 될수 있다고 하겠다. 하지만, PLC-${\delta}1$ 동위효소의 감소에 대해서는, 좀더 구체적인 기전의 규명 및 PLC-${\delta}1$ 효소의 역할에 대한 보다 많은 연구가 필요할것으로 사료된다.

  • PDF

Directional adjacency-score function for protein fold recognition

  • Heo, Mu-Young;Cheon, Moo-Kyung;Kim, Suhk-Mann;Chung, Kwang-Hoon;Chang, Ik-Soo
    • Interdisciplinary Bio Central
    • /
    • 제1권2호
    • /
    • pp.8.1-8.6
    • /
    • 2009
  • Introduction: It is a challenge to design a protein score function which stabilizes the native structures of many proteins simultaneously. The coarse-grained description of proteins to construct the pairwise-contact score function usually ignores the backbone directionality of protein structures. We propose a new two-body score function which stabilizes all native states of 1,006 proteins simultaneously. This two-body score function differs from the usual pairwise-contact functions in that it considers two adjacent amino acids at two ends of each peptide bond with the backbone directionality from the N-terminal to the C-terminal. The score is a corresponding propensity for a directional alignment of two adjacent amino acids with their local environments. Results and Discussion: We show that the construction of a directional adjacency-score function was achieved using 1,006 training proteins with the sequence homology less than 30%, which include all representatives of different protein classes. After parameterizing the local environments of amino acids into 9 categories depending on three secondary structures and three kinds of hydrophobicity of amino acids, the 32,400 adjacency-scores of amino acids could be determined by the perceptron learning and the protein threading. These could stabilize simultaneously all native folds of 1,006 training proteins. When these parameters are tested on the new distinct 382 proteins with the sequence homology less than 90%, 371 (97.1%) proteins could recognize their native folds. We also showed using these parameters that the retro sequence of the SH3 domain, the B domain of Staphylococcal protein A, and the B1 domain of Streptococcal protein G could not be stabilized to fold, which agrees with the experimental evidence.

Seismic motions in a non-homogeneous soil deposit with tunnels by a hybrid computational technique

  • Manolis, G.D.;Makra, Konstantia;Dineva, Petia S.;Rangelov, Tsviatko V.
    • Earthquakes and Structures
    • /
    • 제5권2호
    • /
    • pp.161-205
    • /
    • 2013
  • We study seismically induced, anti-plane strain wave motion in a non-homogeneous geological region containing tunnels. Two different scenarios are considered: (a) The first models two tunnels in a finite geological region embedded within a laterally inhomogeneous, layered geological profile containing a seismic source. For this case, labelled as the first boundary-value problem (BVP 1), an efficient hybrid technique comprising the finite difference method (FDM) and the boundary element method (BEM) is developed and applied. Since the later method is based on the frequency-dependent fundamental solution of elastodynamics, the hybrid technique is defined in the frequency domain. Then, an inverse fast Fourier transformation (FFT) is used to recover time histories; (b) The second models a finite region with two tunnels, is embedded in a homogeneous half-plane, and is subjected to incident, time-harmonic SH-waves. This case, labelled as the second boundary-value problem (BVP 2), considers complex soil properties such as anisotropy, continuous inhomogeneity and poroelasticity. The computational approach is now the BEM alone, since solution of the surrounding half plane by the FDM is unnecessary. In sum, the hybrid FDM-BEM technique is able to quantify dependence of the signals that develop at the free surface to the following key parameters: seismic source properties and heterogeneous structure of the wave path (the FDM component) and near-surface geological deposits containing discontinuities in the form of tunnels (the BEM component). Finally, the hybrid technique is used for evaluating the seismic wave field that develops within a key geological cross-section of the Metro construction project in Thessaloniki, Greece, which includes the important Roman-era historical monument of Rotunda dating from the 3rd century A.D.

Improvement of inspection system for common crossings by track side monitoring and prognostics

  • Sysyn, Mykola;Nabochenko, Olga;Kovalchuk, Vitalii;Gruen, Dimitri;Pentsak, Andriy
    • Structural Monitoring and Maintenance
    • /
    • 제6권3호
    • /
    • pp.219-235
    • /
    • 2019
  • Scheduled inspections of common crossings are one of the main cost drivers of railway maintenance. Prognostics and health management (PHM) approach and modern monitoring means offer many possibilities in the optimization of inspections and maintenance. The present paper deals with data driven prognosis of the common crossing remaining useful life (RUL) that is based on an inertial monitoring system. The problem of scheduled inspections system for common crossings is outlined and analysed. The proposed analysis of inertial signals with the maximal overlap discrete wavelet packet transform (MODWPT) and Shannon entropy (SE) estimates enable to extract the spectral features. The relevant features for the acceleration components are selected with application of Lasso (Least absolute shrinkage and selection operator) regularization. The features are fused with time domain information about the longitudinal position of wheels impact and train velocities by multivariate regression. The fused structural health (SH) indicator has a significant correlation to the lifetime of crossing. The RUL prognosis is performed on the linear degradation stochastic model with recursive Bayesian update. Prognosis testing metrics show the promising results for common crossing inspection scheduling improvement.

PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson's disease mouse model

  • Youn, Jong Kyu;Kim, Dae Won;Kim, Seung Tae;Park, Sung Yeon;Yeo, Eun Ji;Choi, Yeon Joo;Lee, Hae-Ran;Kim, Duk-Soo;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Hwang, Hyun Sook;Choi, Soo Young
    • BMB Reports
    • /
    • 제47권10호
    • /
    • pp.569-574
    • /
    • 2014
  • Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and $Fe^{2+}$, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson's disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion ($MPP^+$). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce $MPP^+$-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.

헬리코박터 파이로리의 병원성 단백질, CagA에 대한 분자 독성학적 측면에서의 고찰 (Overview on Molecular Toxicological Aspects of Helicobacter pylori Virulence Factor, Cytotoxin-associated Antigen A (CagA))

  • 김병주;정화진;황지나;강석하;오세진;서영록
    • Toxicological Research
    • /
    • 제20권3호
    • /
    • pp.179-185
    • /
    • 2004
  • Helicobacter pylori (H. pylori) infects more than half of the people in the world as a major microbe to cause most of gastric diseases. Recently, cytotoxin associated-antigen A (CagA) is believed as one of the most important virulence factors of H. pylori. Molecular toxicological pathway of CagA is necessary to investigate for understanding the pathological and toxicological aspects of H. pylori, since this virulence protein harasses intercellular processes of host cells to get profit for the survival of H. pylori. CagA is coded from cag pathogenicity island (cag PAI) and translocated into host cells by Type 4 secretion system (TFSS). Tyrosine phosphorylation of CagA targets Src homology 2-containing phosphotyrosine phosphatase (SHP-2) to form a CagA-SHP-2 complex. This complex depends on the similarity of sequence between EPIYA motif and Src homology 2 domain (SH2 domain) of CagA. The generation of growth factors is an essential role of CagA in protecting and healing gastric mucosa for the survival of H. pylori. On the other hand, the activation of IL-8 by CagA induces neutrophils generating inflammation and free radicals. Indeed, free radicals are well known carcinogen to induce DNA damage. In addition, the transduction of mitogen-activation signal by CagA is one of the interesting features to understand how to cause cancer. The relationship between cancer and inflammation with CagA was mainly discussed in this review.

DOBI is cleaved by caspases during TRAIL-induced apoptotic cell death

  • Park, Sun-Young;Shin, Jin-Na;Woo, Ha-Na;Piya, Su-Jan;Moon, Ae-Ran;Seo, Young-Woo;Seol, Dai-Wu;Kim, Tae-Hyoung
    • BMB Reports
    • /
    • 제42권8호
    • /
    • pp.511-515
    • /
    • 2009
  • Downstream of Bid (DOBI) known as Pus10, has been identified as a modulator of TRAIL-induced cell death using RNAi library screening. The crystal structure of DOBI has revealed that it is a crescent-shaped protein containing the pseudouridine synthase catalytic domain and a THUMP-containing domain. Here, we demonstrated that DOBI is expressed in various tissues such as heart and lung, and is also expressed in various tumor cells such as HeLa and A549. Although ectopic expression of DOBI does not promote TRAIL death signaling in HeLa cells, knock-down of DOBI expression using shRNA inhibited TRAIL death signaling. DOBI is cleaved into a 54 kD cleaved DOBI during cell death, and the recombinant DOBI protein can be directly cleaved by caspases-3, or -8 in vitro. Together, these data suggest that the cleaved DOBI may acquire a new function, possibly by cooperating with tBid in the mitochondrial event of cell death caused by TRAIL.