• 제목/요약/키워드: Pathway analysis model

검색결과 237건 처리시간 0.026초

척추동물 망막의 신호 전달 경로 시뮬레이터 개발 및 분석 (Simulator Development and Analysis for Signal Flow Pathway in Vertebrate Retina)

  • 백승범;장영조;조경록
    • 한국콘텐츠학회논문지
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    • 제18권11호
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    • pp.655-664
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    • 2018
  • 망막은 눈을 통해 입력되는 빛을 수용하여, 이를 전기신호로 변환한 후 뇌의 시각 피질에 전달하는 역할을 수행한다. 망막을 하드웨어로 구현하기 위해서는 망막의 구조와 동작에 대한 이해가 필요하며, 이를 위해 망막의 모델링이 유용할 수 있다. 본 논문에서는 척추동물의 망막을 구성하는 신경세포와 시냅스의 신호 전달 경로를 포함하는 2-D 망막 네트워크 모델을 소개한다. 또한 수치해석을 기반으로 다양한 조건에서 망막 모델을 해석하기 위해 시뮬레이터를 개발하였다. 이를 통해 다양한 세기의 빛이 망막에서 흡수되었을 때, 기존의 연구와 대비하여, 각 세포와 시냅스 노드 단위로 입출력 반응을 정밀하게 검증하여 인공망막 장치 개발에 기여하였다.

Metabolic Flux Distribution for $\gamma$-Linolenic Acid Synthetic Pathways in Spirulina platensis

  • Meechai Asawin;Pongakarakun Siriluk;Deshnium Patcharaporn;Cheevadhanarak Supapon;Bhumiratana Sakarindr
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제9권6호
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    • pp.506-513
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    • 2004
  • Spirulina produces $\gamma$-linolenic acid (GLA), an important pharmaceutical substance, in a relatively low level compared with fungi and plants, prompting more research to improve its GLA yield. In this study, metabolic flux analysis was applied to determine the cellular metabolic flux distributions in the GLA synthetic pathways of two Spiru/ina strains, wild type BP and a high­GLA producing mutant Z19/2. Simplified pathways involving the GLA synthesis of S. platensis formulated comprise of photosynthesis, gluconeogenesis, the pentose phosphate pathway, the anaplerotic pathway, the tricarboxylic cycle, the GLA synthesis pathway, and the biomass syn­thesis pathway. A stoichiometric model reflecting these pathways contains 17 intermediates and 22 reactions. Three fluxes - the bicarbonate (C-source) uptake rate, the specific growth rate, and the GLA synthesis rate - were measured and the remaining fluxes were calculated using lin­ear optimization. The calculation showed that the flux through the reaction converting acetyl­CoA into malonyl-CoA in the mutant strain was nearly three times higher than that in the wild­type strain. This finding implies that this reaction is rate controlling. This suggestion was sup­ported by experiments, in which the stimulating factors for this reaction $(NADPH\;and\;MgCl_{2})$ were added into the culture medium, resulting in an increased GLA-synthesis rate in the wild type strain.

Identification of Genetic Variations in CBL, SORBS1, CRK, and RHOQ, Key Modulators in the CAP/TC10 Pathway of Insulin Signal Transduction, and Their Association with Type 2 Diabetes Mellitus in the Korean Population

  • Hong, Kyung-Won;Jin, Hyun-Seok;Lim, Ji-Eun;Go, Min-Jin;Lee, Jong-Young;Hwang, Sue-Yun;Park, Hun-Kuk;Oh, Berm-Seok
    • Genomics & Informatics
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    • 제7권2호
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    • pp.53-56
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    • 2009
  • Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

Molecular characterization of a novel rice(Oryza sativa L.) MAP kinase, OsEDRl, its role in defense signaling pathway.

  • Kim, Jung-A;Jwa, Nam-Soo
    • 한국식물병리학회:학술대회논문집
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    • 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
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    • pp.82-83
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    • 2003
  • Plants have evolved differently from animals having mobile activities. Thus, plants should have developed unique defense mechanisms against biotic/abiotic stresses to which plants are differently exposed, according to seasons. Most organisms have an conserved signaling network using mitogen-activated protein kinase (MAPK) cascade(s). The phenomenon implied that they are functionally very important in all organisms. In fact, they constitute one of the major components of signaling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. Recently, complete MAPK cascade was first characterized in Arabidopsis from the receptor kinase (FLS2) through fellowing MEKKI -MKK4/MKK5-MPK3/MPK6-WRKY22/MRKY29 pathway. Whereas, MAPK cascade signaling pathway in monocot plant including rice (0ryza sativa L.), the most important of all food crops and an established monocot plant research model, MAPKinase kinase kinases (MAPKKK) of rice are the first upstream component of the MAPK cascade, but MAPKKK has been first identified and characterized in our lab and designated as, OsEDRl based on its homology with the Arabidopsis EDRI. The Arabidopsis EDRl was regarded as a negative regulator of defense response and the role of rice OsEDRl was analyzed. Transcriptional regulation of OsEDRl was detected under various stresses and immunoblotting analysis is going on to detect the level of OsEDRl protein in the mutants showing unique phenotype. We also introduced the constitutively active and the dominant negative forms of the OsEDRl for characterizing biological function.

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Fangchinoline Has an Anti-Arthritic Effect in Two Animal Models and in IL-1β-Stimulated Human FLS Cells

  • Villa, Thea;Kim, Mijin;Oh, Seikwan
    • Biomolecules & Therapeutics
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    • 제28권5호
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    • pp.414-422
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    • 2020
  • Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 µM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.

다매체/다경로 노출을 고려한 benzo(a)pyrene의 총 인체 노출량 예측 (Estimating Human Exposure to Benzo(a)pyrene through Multimedia/Multiroute Exposure Scenario)

  • 문지영;양지연;임영욱;박성은;신동천
    • Environmental Analysis Health and Toxicology
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    • 제18권4호
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    • pp.255-269
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    • 2003
  • The objective of this study was to estimate human exposure to benzo (a)pyrene through multimedia/multi-pathway exposure scenario. The human exposure scenario for benzo(a)pyrene was consisted of 12 multiple exposure pathways, and the multipathway human exposure model based on this scenario constituted. In this study, the multipathway human exposure model was used to estimate the concentrations in the exposure contact media, human intake factors and lifetime average daily dose (LAD $D_{model}$) of benzo(a)pyrene in the environment. Sensitivity analysis was performed to identify the important parameters and Monte-Carlo simulation was undertaken to examine the uncertainty of the model. The total LAD $D_{model}$ was estimated to be 5.52${\times}$10$^{-7}$ mg/kg-day (2.06${\times}$10$^{-7}$ -8.65${\times}$10$^{-7}$ mg/kg-day) using the multipathway human exposure model. The inhalation dose accounted for 78% of the total LADD, whereas ingestion and dermal contact intake accounted for 20.2% and 1.8% of the total exposure, respectively. Based on the sensitivity analysis, the most significant contributing input parameter was benzo (a)pyrene concentration of ambient air. Consequently, exposure via inhalation in outdoor/indoor air was the highest compared with the exposure via other medium/pathways.

Prediction of Maximum Yields of Metabolites and Optimal Pathways for Their Production by Metabolic Flux Analysis

  • Hong, Soon-Ho;Moon, Soo-Yun;Lee, Sang-Yup
    • Journal of Microbiology and Biotechnology
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    • 제13권4호
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    • pp.571-577
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    • 2003
  • The intracellular metabolic fluxes can be calculated by metabolic flux analysis, which uses a stoichiometric model for the intracellulal reactions along with mass balances around the intracellular metabolites. In this study, metabolic flux analyses were carried out to estimate flux distributions for the maximum in silico yields of various metabolites in Escherichia coli. The maximum in silico yields of acetic acid and lactic acid were identical to their theoretical yields. On the other hand, the in silico yields of succinic acid and ethanol were only 83% and 6.5% of their theoretical yields, respectively. The lower in silico yield of succinic acid was found to be due to the insufficient reducing power. but this lower yield could be increased to its theoretical yield by supplying more reducing power. The maximum theoretical yield of ethanol could be achieved, when a reaction catalyzed by pyruvate decarboxylase was added in the metabolic network. Futhermore, optimal metabolic pathways for the production of various metabolites could be proposed, based on the results of metabolic flux analyses. In the case of succinic acid production, it was found that the pyruvate carboxylation pathway should be used for its optimal production in E. coli rather than the phosphoenolpyruvate carboxylation pathway.

방선균 항생제 고생산 산업균주를 기반으로 한 모델 폴리케타이드의 이종숙주 발현 (Heterologous Expression of a Model Polyketide Pathway in Doxorubicin-overproducing Streptomyces Industrial Mutants)

  • 김혜진;이한나;김응수
    • 한국미생물·생명공학회지
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    • 제40권1호
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    • pp.10-16
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    • 2012
  • 방선균 Streptomyces peucetius OIM ($\underline{O}$verproducing $\underline{I}$ndustrial $\underline{M}$utant)은 반복적인 돌연변이를 통하여 폴리케타이드 항생제인 독소루비신(DXR)의 생산성이 최적화 된 고생산성 산업균주이다. 이 S. peucetius OIM 변이종을 대리의 숙주로 이용하여, 생합경로 크기가 작은 모델 폴리케타이드인 알로에사포나린 II(액티노로딘의 합성경로 유도체)의 생합성 유전자군을 고복제수 플라스미드에 클로닝하여 알로에사포나린 II의 기능적 발현을 확인하여 정량분석을 수행하였다. OIM 균주의 알로에사포나린 II의 생산량은 조절 네트워크가 극대화된 S. coelicolor 변이종 뿐만 아니라 야생형S. peucetius 보다 매우 높은 수준으로 생산되는 것으로 확인되었다. 또한 알로에사포나린 II의 생산 수준은 다운-조절자 $wblA_{spe}$가 제거된 S. peucetius OIM 균주에서 가장 높은것으로 측정되었으며, 이는 합리적으로 유전체를 재설계한 S. peucetius OIM 변이종 균주가 이종의 폴리케타이드 생합성을 높은 수준으로 발현할 수 있는 대리의 숙주로서 충분히 활용 가능함을 보여준다.

미래 기후변화 시나리오와 수문모형 매개변수에 따른 미래 유량예측 불확실성 (Uncertainty of future runoff projection according to SSP scenarios and hydrologic model parameters)

  • 김진혁;송영훈;정은성
    • 한국수자원학회논문집
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    • 제56권1호
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    • pp.35-43
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    • 2023
  • 미래 유량분석은 기후변화 시나리오와 수문모형의 매개변수에 영향을 받고 이에 따른 불확실성이 존재한다. 본 연구에서는 Shared Socioeconomic Pathway (SSP) 시나리오와 수문모형 매개변수에 따른 미래 유량 분석의 불확실성을 분석하고자 하였다. SSP 시나리오 중, 대표적으로 사용되는 SSP2-4.5와 SSP5-8.5시나리오를 사용하였으며, 수문모형으로는 Soil and Water Assessment Tool (SWAT) 모형을 사용하였다. SWAT 모형의 매개변수는 SWAT-CUP을 이용해 관측된 유량 데이터에 따라 총 11개의 기간에 대해 매개변수 최적화를 각각 수행하였다. 그 후 분포의 차이를 계산 할 수 있는 Jensen-Shannon Divergence (JS-D)를 이용해 과거 유량 대비 미래 추정된 유량의 불확실성 분석을 수행하였다. 분석결과 미래 유량의 불확실성은 SSP5-8.5에서 SSP2-4.5보다 더 크게 분석되었으며, 가까운 미래(2021-2060년) 보다 먼 미래(2061-2100년)에서 더 크게 분석되었다. 강우-유출 분석은 수문모형 매개변수에 따라 88.5%-108.5%까지 차이가 발생하였으며, 이에 따라 미래 유량을 추정하는데 불확실성이 발생하였다. 본 연구에서의 수문 모형의 매개변수에 따른 미래 유량 추정의 불확실성은 평년 대비 유량이 적은 연도의 관측 유량 데이터를 이용한 매개변수를 이용할 시 불확실성이 크게 분석되었다. 또한 평년 대비 유량 변화가 큰 기간의 매개 변수일수록 미래 유량 추정의 불확실성이 크게 분석되었다.

Mangiferin ameliorates cardiac fibrosis in D-galactose-induced aging rats by inhibiting TGF-β/p38/MK2 signaling pathway

  • Cheng, Jing;Ren, Chaoyang;Cheng, Renli;Li, Yunning;Liu, Ping;Wang, Wei;Liu, Li
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권2호
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    • pp.131-137
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    • 2021
  • Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.