• Title/Summary/Keyword: mechanistic model

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Purification and preliminary analysis of the ATP-dependent unfoldase HslU from the gram-positive bacterium Staphylococcus aureus

  • Jeong, Soyeon;Ha, Nam-Chul;Kwon, Ae-Ran
    • Biodesign
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    • v.6 no.4
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    • pp.96-99
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    • 2018
  • The gram-positive bacterium Staphylococcus aureus is a common cause of abscesses, sinusitis and food poisoning. The emergence of antibiotic-resistant strains has caused significant clinical issues worldwide. The HslU-HslV complex was first identified as a prokaryotic homolog of eukaryotic proteasomes. HslU is an unfoldase that mediates the unfolding of the substrate proteins, and it works with the protease HslV in the complex. To date, the protein complex has been mostly studied in gram-negative bacteria. In this study, we report the purification and crystallization of the full-length HslU from S. aureus. The crystal diffracted X-rays to a $3.5{\AA}$ resolution, revealing that the crystals belong to space group $P2_1$, with unit cell parameters of a = 166.5, b = 189.6, $c=226.6{\AA}$, and ${\beta}=108.1^{\circ}$. We solved the phage problem by molecular replacement using the structure of HslU from Haemophilus influenzae as a search model. The cell content analysis with this molecular replacement solution revealed that 24 molecules are contained in the asymmetric unit. This structure provides insight into the structural and mechanistic difference of the HslUV complex of gram-positive bacteria.

Emerging role of Hippo pathway in the regulation of hematopoiesis

  • Inyoung Kim;Taeho Park;Ji-Yoon Noh;Wantae Kim
    • BMB Reports
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    • v.56 no.8
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    • pp.417-425
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    • 2023
  • In various organisms, the Hippo signaling pathway has been identified as a master regulator of organ size determination and tissue homeostasis. The Hippo signaling coordinates embryonic development, tissue regeneration and differentiation, through regulating cell proliferation and survival. The YAP and TAZ (YAP/TAZ) act as core transducers of the Hippo pathway, and they are tightly and exquisitely regulated in response to various intrinsic and extrinsic stimuli. Abnormal regulation or genetic variation of the Hippo pathway causes a wide range of human diseases, including cancer. Recent studies have revealed that Hippo signaling plays a pivotal role in the immune system and cancer immunity. Due to pathophysiological importance, the emerging role of Hippo signaling in blood cell differentiation, known as hematopoiesis, is receiving much attention. A number of elegant studies using a genetically engineered mouse (GEM) model have shed light on the mechanistic and physiological insights into the Hippo pathway in the regulation of hematopoiesis. Here, we briefly review the function of Hippo signaling in the regulation of hematopoiesis and immune cell differentiation.

Regorafenib prevents the development of emphysema in a murine elastase model

  • Kwangseok Oh;Gun-Wu Lee;Han-Byeol Kim;Jin-Hee Park;Eun-Young Shin;Eung-Gook Kim
    • BMB Reports
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    • v.56 no.8
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    • pp.439-444
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    • 2023
  • Emphysema is a chronic obstructive lung disease characterized by inflammation and enlargement of the air spaces. Regorafenib, a potential senomorphic drug, exhibited a therapeutic effect in porcine pancreatic elastase (PPE)-induced emphysema in mice. In the current study we examined the preventive role of regorafenib in development of emphysema. Lung function tests and morphometry showed that oral administration of regorafenib (5 mg/kg/day) for seven days after instillation of PPE resulted in attenuation of emphysema. Mechanistically, regorafenib reduced the recruitment of inflammatory cells, particularly macrophages and neutrophils, in bronchoalveolar lavage fluid. In agreement with these findings, measurements using a cytokine array and ELISA showed that expression of inflammatory mediators including interleukin (IL)-1β, IL-6, and CXCL1/KC, and tissue inhibitor of matrix metalloprotease-1 (TIMP-1), was downregulated. The results of immunohistochemical analysis confirmed that expression of IL-6, CXCL1/KC, and TIMP-1 was reduced in the lung parenchyma. Collectively, the results support the preventive role of regorafenib in development of emphysema in mice and provide mechanistic insights into prevention strategies.

Evaluation of Traffic Load and Moisture-Induced Nonlinear In-situ Stress on Pavement Foundation Layers (도로기초에서 교통 및 환경하중에 의한 비선형 현장응력 평가)

  • Park, Seong-Wan;Hwang, Kyu-Young;Jeong, Mun-Kyoung;Seo, Young-Guk
    • Journal of the Korean Geotechnical Society
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    • v.25 no.7
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    • pp.47-54
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    • 2009
  • Better understanding of in-situ mechanical behavior of pavement foundations is very important to predict long-term effects on the system performance of transport infrastructure. For this purpose resilient stiffness characterization of geomaterials is needed to properly adopt such mechanistic analysis under both traffic and environmental loadings. In this paper in-situ monitoring data from KHC test road were used to analyze the non-linear response using finite element method for a selected constitutive model of foundation geomaterials, and the results were compared with the field data.

Development of FEMAXI-ATF for analyzing PCMI behavior of SiC cladded fuel under power ramp conditions

  • Yoshihiro Kubo;Akifumi Yamaji
    • Nuclear Engineering and Technology
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    • v.56 no.3
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    • pp.846-854
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    • 2024
  • FEMAXI-ATF is being developed for fuel performance modeling of SiC cladded UO2 fuel with focuses on modeling pellet-cladding mechanical interactions (PCMI). The code considers probability distributions of mechanical strengths of monolithic SiC (mSiC) and SiC fiber reinforced SiC matrix composite (SiC/SiC), while it models pseudo-ductility of SiC/SiC and propagation of cladding failures across the wall thickness direction in deterministic manner without explicitly modeling cracks based on finite element method in one-dimensional geometry. Some hypothetical BWR power ramp conditions were used to test sensitivities of different model parameters on the analyzed PCMI behavior. The results showed that propagation of the cladding failure could be modeled by appropriately reducing modulus of elasticities of the failed wall element, so that the mechanical load of the failed element could be re-distributed to other intact elements. The probability threshold for determination of the wall element failure did not have large influence on the predicted power at failure when the threshold was varied between 25 % and 75 %. The current study is still limited with respect to mechanistic modeling of SiC failure as it only models the propagation of the cladding wall element failure across the homogeneous continuum wall without considering generations and propagations of cracks.

Technical Reviews on Ecosystem Modeling Approach and its Applicability in Ecosystem-Based Coastal Management in Saemangeum Offshore and Geum River Estuary (생태계기반 연안관리를 위한 생태모델 개발방향에 대한 기술적 검토 - 새만금 외해역 및 금강 하구역 사례)

  • Kim, Hae-Cheol;Kim, Yong Hoon;Chang, Won-Keun;Ryu, Jongseong
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.18 no.3
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    • pp.233-244
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    • 2015
  • Marine ecosystem modelling has become a more widely used decision-making tool in coastal ecosystem-based management. However, it is not trivial to develop a well calibrated/validated model with potential applicability and practicality because understanding ecological processes with complexities is a pre-requisite for developing robust ecosystem models and this accompanies a great deal of well coordinated efforts among field-going ecologists, laboratory scientists, modelers, stake-holders and managers. This report aims to provide a brief introduction on two different approaches in marine ecological models: deterministic (mechanistic) and stochastic (statistical) approach. We also included definitions, historical overview of past researches, case studies, and contextual suggestions for coastal management in Korea. A long list of references this report included in this study might be used as an introductory material for those who wish to enter ecosystem modelling field.

Effects of Perilla frutescens L. on anti-oxidant and anti-inflammation activity (자소엽 및 자소자의 염증조절 활성 비교)

  • Son, Hyeong-U;Heo, Jin-Chul;Seo, Myung-Sun;Lee, Sang-Han
    • Food Science and Preservation
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    • v.17 no.5
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    • pp.757-761
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    • 2010
  • It is recognized that Perilla frutescens L. (PfL) are useful for various diseases, including allergic disorders. To evaluate whether the PfL extract have potential in alleviating oxidant and inflammatory process, some in vitro antioxidant assays and in vivo DNFB-induced atopic assay were investigated. Extracts of PfL have potent anti-oxidant activity by DPPH or FRAP assay. By treatment of high temperature / high pressure extraction process of PfL seed, the activity was increased. Using a mouse animal model, we found that PfL extract reduces ear thickness and epithelial thickening and infiltration of immune cells inhibition. Collectively, the present results suggest that PfL can be used as an antioxidant and/or anti-inflammatory biomaterial, that should be proved to evaluate on mechanistic study and development of functional food.

Ginsenoside Rg3 attenuates skin disorders via down-regulation of MDM2/HIF1α signaling pathway

  • Han, Na-Ra;Ko, Seong-Gyu;Moon, Phil-Dong;Park, Hi-Joon
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.610-616
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    • 2021
  • Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

Development of a Forecasting Model for Bacterial Wilt in Hot Pepper (고추 풋마름병 예찰 모형 개발)

  • Kim, Ji-Hoon;Kim, Sung-Taek;Yun, Sung-Chul
    • Research in Plant Disease
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    • v.18 no.4
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    • pp.361-369
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    • 2012
  • A population density model for bacterial wilt, which is caused by Ralstonia solanacearum, in hot pepper was developed to estimate the primary infection date after overwintering in the field. We developed the model mechansitically to predict reproduction of the pathogen and pathogensis on seedlings of the host. The model estimates the pathogen's populations both in the soil and in the host. In order to quantify environmental infection factors, various temperatures and initial population densities were determined for wilt symptoms on the seedlings of hot pepper in a chamber. Once, the pathogens living in soil multiply up to 400 cells/g of soil, they can infect successfully in the host. Primary infection in a host was supposed to be started when the population of the pathogen were over $10^9$ cells/g of root tissue. The estimated primary infection dates of bacterial wilt in 2011 in Korea were mostly mid-July or late-July which were 10-15 days earlier than those in 2010. Two kinds of meterological data, synoptic observation and field measurements from paddy field and orchard in Kyunggi, were operated the model for comparing the result dates. About 1-3 days were earlier from field data than from synoptic observation.

Proposal Strategy and Establishment Process of a New Scientific Theory Examined through the Theory of Continental Drift (대륙이동설을 통해 살펴본 새로운 과학이론의 제안전략과 확립과정)

  • Jun-Young Oh;Eun-Ju Lee
    • Journal of the Korean Society of Earth Science Education
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    • v.17 no.1
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    • pp.20-33
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    • 2024
  • The purpose of this study is to examine the scientific activities of scientists justifying Wegener's continental drift in the 20th century, which is explained as a revolutionary process in earth science, and methodologically analyze the strategy of proposing new scientific theories and how the process of theory selection is carried out. Previously, the Earth was a static model and only the vertical movement of the crust was considered. However, the theory of continental drift proposed horizontal movement of the crust as a dynamic model of the Earth, eliminating numerous problems. Therefore, this study seeks to explore the rational activities of numerous scientists until the current plate tectonics theory was formed. Additionally, the theory of continental drift is in conflict with the theory of Earth shrinkage, which is an existing static model. In other words, it deviates from the existing mechanistic world view by presenting a dynamic model in which the Earth is created and changes, as opposed to a static model in which the Earth is already completed, fixed, and unchanged. As a result, old geology was weakened and new geophysics was born. The theory of continental drift and continued exploration by subsequent generations of scholars brought about a revolution in earth science. This can be said to be a good subject of investigation as educational material for various methodologies for students in earth science education, and as educational material for changing students' worldview.