• Title/Summary/Keyword: Molecular Dynamic

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Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle

  • Heo, Jun-Won;No, Mi-Hyun;Park, Dong-Ho;Kang, Ju-Hee;Seo, Dae Yun;Han, Jin;Neufer, P. Darrell;Kwak, Hyo-Bum
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.567-577
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    • 2017
  • Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in $O_2$ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.

Quantitative Analysis of Lysophosphatidic Acid in Human Plasma by Tandem Mass Spectrometry

  • Kim, Ho-Hyun;Yoon, Hye-Ran;Pyo, Dong-Jin
    • Bulletin of the Korean Chemical Society
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    • v.23 no.8
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    • pp.1139-1143
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    • 2002
  • Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

Combination of Epstein-Barr Virus-Based Plasmid and Nonviral Polymeric Vectors for Enhanced and Prolonged Gene Expression

  • Choi, Hye;Park, Key Sun;Bae, Seon Joo;Song, Su Jeong;Kim, Kyoon Eon;Park, Jong-Sang;Choi, Joon Sig
    • Bulletin of the Korean Chemical Society
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    • v.33 no.11
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    • pp.3676-3680
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    • 2012
  • An Epstein-Barr virus (EBV)-based plasmid contains the EBV nuclear antigen 1 (EBNA1) gene and EBV replication origin (oriP) sequence. Since EBNA1 (the only EBV-encoded protein) is combined with oriP, it is replicated simultaneously with chromosomal DNA in human, primate, and canine cells and is faithfully segregated at a stable copy number upon cell division. Consequently, it can be used to stably express gene inserts over a prolonged time in target cells. We have previously shown that the polyamidoamine (PAMAM) dendrimer can be surface-modified with L-arginine. Arginine is present at a high frequency in the transactivator of transcription (Tat) sequences of human immunodeficiency virus (HIV). It presents high membrane permeability and permits effective transfer of DNA inside the cells. In this study, we constructed two kinds of recombinant DNA by inserting the luciferase gene and enhanced green fluorescence protein (eGFP) gene as reporter genes into the pCEP4 plasmid vector. We measured dynamic light scattering (DLS) and zeta potential after preparing PAMAM-based cationic polymer/EBV-based plasmid complexes. We performed transfection of HEK 293 cell lines with the polyplexes, and monitored luciferase activity and green fluorescence protein (GFP) expression. Our results show that PAMAM-based cationic polymer/EBV plasmid complexes provide enhanced and sustained gene expression.

Low mass star formation using the SPH simulation

  • Yun, Hye-Ryeon;Son, Jeong-Ju;Huvver, David Anthony
    • 한국지구과학회:학술대회논문집
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    • 2010.04a
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    • pp.118-119
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    • 2010
  • star formation is one of the hottest areas in astromy and increasing evidence is showing that star formation is actually a highly dynamic precess driven and strongly influenced by turbulent dynamics of molecular clouds. despite significant progress ir observation in process of star formation, earliest stage of star formation remains imcomplete. so, computer simulations are essential tool since the complex dynamics of star formation. We have performed simulation about the process of low mass star formation using the SPH simulation. we use the dragon-code, the most advanced star formation N-body Smoothed Particle Hydrodynamics (SPH) codes. We present how change the internal properties and how should evolve, while changing the values for Mass turbulence, central density and so on. ( mass range of values is 0.1 < M < $5\;M{\odot}$) based on this results, we discussed their circumstellar, characteristics they were borned and how they will evove while the Birth of low mass stars from interstellar cloud.

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Shape Optimization of an Active Micro-Mixer for Improving Mixing Efficiency (혼합 효율 향상을 위한 마이크로 동적 믹서의 형상최적화)

  • Park, Jae-Yong;Kim, Sang-Rak;Lee, Won-Gu;Yoo, Jin-Sik;Kim, Young-Dae;Maeng, Joo-Seung;Han, Seog-Young
    • Transactions of the Korean Society of Machine Tool Engineers
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    • v.16 no.6
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    • pp.146-152
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    • 2007
  • An active micro-mixer, which was composed of an oscillating micro-stirrer in the microchannel to provide rapid, effective mixing at high flow, rates was analyzed. The effects of molecular diffusion and disturbance by the stirrer were considered with regard to two types of mixer models: the simple straight microchannel and microchannel with an oscillating stirrer. Two types of mixer models were studied by analyzing mixing behaviors such as their interaction after the stirrer. The mixing was calculated by Lattice Boltzmann methods using the D2Q9 model. In this study, the time-averaged mixing index formula was used to estimate the mixing performance of time-dependent flow. The mixing indices of the two models compared. From the results, it was found that the mixer with an oscillating stirrer was much more enhanced and stabilized. Therefore, an optimum design for a dynamic micro-mixer with an oscillating stirrer was performed using Taguchi method in order to obtain a robust solution. The design parameters were established as the frequency, the length and the angle of the stirrer and the optimal values were determined to be 2, 0.8D and ${\pm}75^{\circ}$, respectively. It was found that the mixing index of the optimal design increased 80.72% compared with that of the original design.

Calcium Signaling in Salivary Secretion

  • Kim, Jin Man;Lee, Sang-Woo;Park, Kyungpyo
    • Journal of Korean Dental Science
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    • v.10 no.2
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    • pp.45-52
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    • 2017
  • Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular $Ca^{2+}$ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular $Ca^{2+}$ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, $Ca^{2+}$ activates $K^+$ and $Cl^-$ channels to transport water and electrolyte constituting whole saliva. We also focus on the $Ca^{2+}$ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic $Ca^{2+}$ patterns. In particular, inositol triphosphate signal is a main trigger for inducing $Ca^{2+}$ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and $Ca^{2+}$ pumps generate a self-limiting pattern of $Ca^{2+}$ efflux, resulting in $Ca^{2+}$ oscillations. The regenerative $Ca^{2+}$ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of $Ca^{2+}$ signals in regulating salivary secretion.

Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Suggests an Alternative Assembly Mode

  • Kim, Jin-Sik;Jeong, Hyeongseop;Song, Saemee;Kim, Hye-Yeon;Lee, Kangseok;Hyun, Jaekyung;Ha, Nam-Chul
    • Molecules and Cells
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    • v.38 no.2
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    • pp.180-186
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    • 2015
  • Escherichia coli AcrAB-TolC is a multidrug efflux pump that expels a wide range of toxic substrates. The dynamic nature of the binding or low affinity between the components has impeded elucidation of how the three components assemble in the functional state. Here, we created fusion proteins composed of AcrB, a transmembrane linker, and two copies of AcrA. The fusion protein exhibited acridine pumping activity, suggesting that the protein reflects the functional structure in vivo. To discern the assembling mode with TolC, the AcrBA fusion protein was incubated with TolC or a chimeric protein containing the TolC aperture tip region. Three-dimensional structures of the complex proteins were determined through transmission electron microscopy. The overall structure exemplifies the adaptor bridging model, wherein the funnel-like AcrA hexamer forms an intermeshing cogwheel interaction with the ${\alpha}$-barrel tip region of TolC, and a direct interaction between AcrB and TolC is not allowed. These observations provide a structural blueprint for understanding multidrug resistance in pathogenic Gram-negative bacteria.

Transforming Growth Factor β1/Smad4 Signaling Affects Osteoclast Differentiation via Regulation of miR-155 Expression

  • Zhao, Hongying;Zhang, Jun;Shao, Haiyu;Liu, Jianwen;Jin, Mengran;Chen, Jinping;Huang, Yazeng
    • Molecules and Cells
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    • v.40 no.3
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    • pp.211-221
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    • 2017
  • Transforming growth factor ${\beta}1$ $(TGF{\beta}1)/Smad4$ signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through $TGF{\beta}1/Smad4$ signaling. Here, we present that $TGF{\beta}1$ elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by $TGF{\beta}1$. The results of luciferase reporter experiments and ChIP assays demonstrated that $TGF{\beta}1$ promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the $TGF{\beta}1/Smad4$ pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the $TGF{\beta}1$-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that $TGF{\beta}1/Smad4$ signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.

Production properties of pyrolytic matter of PP and PS plastics in n low temperature pyrolysis condition (저온 열분해조건에서 PP 및 PS계 플라스틱의 열분해물 생성특성 연구)

  • Kim, Sang-Hoon;Jang, Hyun-Tae;Cha, Wang-Seog
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.8 no.4
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    • pp.867-873
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    • 2007
  • Thermal degradation characteristics of polypropylene and polystyrene have been studied in the thermogravimetric(TG) reactor and batch-type microreactor. The dynamic thermogravimetric curve of TG provided a valuable information about pyrolysis temperature. It was found that PS was thermally degraded at lower temperature of $30{\sim}50^{\circ}C$ than PP. It was found that the yield and molecular weight of liquid product in the microreactor were decreased with the increase of reaction temperature and time in the case of PP. The production of styrene monomer was significantly increased by the promotion of depolymerization with the increase of temperature and time. The chain-end scission rate parameters were determined to be 50.0 kcal/mole of PP, 45.2 kcal/mole of PS by the Arrhenius plot.

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A Study on the Curing Behaviors of Glass/Epoxy Prepreg by Dielectrometer and the Thermal Properties of Cured Glass/Epoxy Composites (Dielectrometer를 이용한 Glass/Epoxy 프리프레그의 경화거동 및 경화물의 열적 특성연구)

  • 제갈영순;이원철;전영재;윤남균
    • Polymer(Korea)
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    • v.24 no.3
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    • pp.350-357
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    • 2000
  • Curing behaviors of glass/epoxy prepreg for printed circuit boards (PCB) were studied by using dielectrometer and differential scanning calorimeter. This prepreg was showed the lowest ionic viscosity at about 115$^{\circ}C$, and then the ionic viscosity was gradully increased up to 15$0^{\circ}C$. This indicated that the curing reaction of this prepreg started at 115$^{\circ}C$ and the molecular weight was increased by the accelerated thermal cross-linking reaction. The loss factor and tan $\delta$ values were also measured and discussed. The dielectric behaviors of this prepreg system were also measured according to the cure cycle for PCB. This material was found to be thermally stable up to about 30$0^{\circ}C$ and then was showed an abrupt decomposition beyond this temperature.

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