• Title/Summary/Keyword: molecular processes

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Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation

  • Janghyun Kim;Bora Lee;Young Kim;Byeong C. Kim;Joon-Tae Kim;Hyong-Ho Cho
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.2.1-2.14
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    • 2023
  • Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

Molecular cloning, Expression and purification of Anthrax toxin from Bacillus anthracis

  • Yoon, Moon-Young
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.323-325
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    • 2002
  • Bacillus Anthracis is the causative agent of anthrax. The major virulence factors are a poly-D glutamic acid capsule and three-protein component exotoxin, which is collectively known as anthrax toxin, protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). These three proteins individually have no known toxic activities, but in combination with PA form two toxins (lethal toxin and edema toxin), causing different pathogenic responses in animals and cultured cells. However, it remains to be elucidated for pathogenic mechanism of anthrax toxin. In this study, we constructed toxin component in bacterial overexpression system and purified the native toxin from Bacillus anthracis delta sterne F32 using FPLC system. Recombinant toxin showed high homogeneity and rapid purification processes. Also, this recombinant toxin was comparable to B. anthracis native toxin in terms of cytotoxic effects on cultured cell lines.

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Nanotechnology Applications in Functional Foods; Opportunities and Challenges

  • Singh, Harjinder
    • Preventive Nutrition and Food Science
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    • v.21 no.1
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    • pp.1-8
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    • 2016
  • Increasing knowledge on the link between diet and human health has generated a lot of interest in the development of functional foods. However, several challenges, including discovering of beneficial compounds, establishing optimal intake levels, and developing adequate food delivering matrix and product formulations, need to be addressed. A number of new processes and materials derived from nanotechnology have the potential to provide new solutions in many of these fronts. Nanotechnology is concerned with the manipulation of materials at the atomic and molecular scales to create structures that are less than 100 nm in size in one dimension. By carefully choosing the molecular components, it seems possible to design particles with different surface properties. Several food-based nanodelivery vehicles, such as protein-polysaccharide coacervates, multiple emulsions, liposomes and cochleates have been developed on a laboratory scale, but there have been very limited applications in real food systems. There are also public concerns about potential negative effects of nanotechnology-based delivery systems on human health. This paper provides an overview of the new opportunities and challenges for nanotechnology-based systems in future functional food development.

Thermal Conductivity Analysis of Amorphous Silicon Formed by Natural Cooling: A Molecular-dynamics Study

  • Lee, Byoung Min
    • Journal of the Korean Ceramic Society
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    • v.53 no.3
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    • pp.295-300
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    • 2016
  • To investigate the thermal conductivity and the structural properties of naturally cooled excimer-laser annealed Si, molecular-dynamics (MD) simulations have been performed. The thermal conductivity of crystalline Si (c-Si) was measured by direct method at 1000 K. Steady-state heat flow was measured using a stationary temperature profile; significant deviations from Fourier's law were not observed. Reliable processes for measuring the thermal conductivity of c-Si were presented. A natural cooling process to admit heat flow from molten Si (l-Si) to c-Si was performed using an MD cell with a size of $48.9{\times}48.9{\times}97.8{\AA}^3$. During the cooling process, the temperature of the bottom $10{\AA}$ of the MD cell was controlled at 300 K. The results suggest that the natural cooling system described the static structural property of amorphous Si (a-Si) well.

Promising Pharmacological Directions in the World of Lysophosphatidic Acid Signaling

  • Stoddard, Nicole C.;Chun, Jerold
    • Biomolecules & Therapeutics
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    • v.23 no.1
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    • pp.1-11
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    • 2015
  • Lysophosphatidic acid (LPA) is a signaling lipid that binds to six known lysophosphatidic acid receptors (LPARs), named $LPA_1-LPA_6$. These receptors initiate signaling cascades relevant to development, maintenance, and healing processes throughout the body. The diversity and specificity of LPA signaling, especially in relation to cancer and autoimmune disorders, makes LPA receptor modulation an attractive target for drug development. Several LPAR-specific analogues and small molecules have been synthesized and are efficacious in attenuating pathology in disease models. To date, at least three compounds have passed phase I and phase II clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. This review focuses on the promising therapeutic directions emerging in LPA signaling toward ameliorating several diseases, including cancer, fibrosis, arthritis, hydrocephalus, and traumatic injury.

Influence of indenter shape on nanoindentation: an atomistic study

  • Lai, Chia-Wei;Chen, Chuin-Shan
    • Interaction and multiscale mechanics
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    • v.6 no.3
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    • pp.301-316
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    • 2013
  • The influence of indenter geometry on nanoindentation was studied using a static molecular dynamics simulation. Dislocation nucleation, dislocation locks, and dislocation movements during nanoindentation into Al (001) were studied. Spherical, rectangular, and Berkovich indenters were modeled to study the material behaviors and dislocation activities induced by their different shapes. We found that the elastic responses for the three cases agreed well with those predicted from elastic contact theory. Complicated stress fields were generated by the rectangular and Berkovich indenters, leading to a few uncommon nucleation and dislocation processes. The calculated mean critical resolved shear stresses for the Berkovich and rectangular indenters were lower than the theoretical strength. In the Berkovich indenter case, an amorphous region was observed directly below the indenter tip. In the rectangular indenter case, we observed that some dislocation loops nucleated on the plane. Furthermore, a prismatic loop originating from inside the material glided upward to create a mesa on the indenting surface. We observed an unusual softening phenomenon in the rectangular indenter case and proposed that heterogeneously nucleating dislocations are responsible for this.

Canonical Sampling Method for Initial Conditions for Reactive Flux Calculations Using Nose-Hoover Chains

  • Lee, Song-Hi;Pak, Young-Shang
    • Bulletin of the Korean Chemical Society
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    • v.25 no.4
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    • pp.533-538
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    • 2004
  • Canonical sampling method has been presented to generate the initial conditions for reactive flux studies of organic reactions in water. Velocity Verlet version of Nose-Hoover chain dynamics algorithm has been employed to sample the initial conditions according to canonical distribution. The unstable normal mode of a transition state has been introduced to define a dividing plane separating reactant and product regions in reaction processes. This method has been implemented and tested for the case iels-Alder reaction of methyl vinyl ketone (MVK) and cyclopentadiene (CPD) in water, providing a reliable tool for further reactive flux molecular dynamics studies in condensed media.

Structure and Function of the Developmental Signaling Molecule Hedgehog

  • Leahy, Daniel J.
    • BMB Reports
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    • v.32 no.2
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    • pp.103-111
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    • 1999
  • Hh proteins represent a new signaling paradigm in metazoan development. In species ranging from fruit flies to humans, Hh proteins mediate multiple processes vital to appropriate pattern formation in the developing embryo. Hh proteins undergo an autoprocessing event in which the full-length protein is cleaved into N-terminal and C-terminal domains (Hh-N and Hh-C, respectively), and a cholesterol moiety becomes covalently attached to Hh-N. All known signaling activities of Hh proteins are mediated by Hh-N while both the cleavage and cholesterol transfer reactions are mediated by Hh-C. The cholesterol attached to Hh-N is required to retrict the range of Hh signaling and may be involved in ensuring appropriate reception of the Hh signal in target tissues. Disruptions of Hh signaling pathways lead to severe developmental defects in newborns and cancers in adults. While studies of Hh proteins have yielded a wealth of new insight into the molecular mechanisms of metazoan development, many outstanding questions concerning Hh signaling mechanisms ensure that unraveling the secrets of this molecule will keep scientists well entertained for the foreseeable future.

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The Hsp90 chaperone machinery: from structure to drug development

  • Hahn, Ji-Sook
    • BMB Reports
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    • v.42 no.10
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    • pp.623-630
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    • 2009
  • Hsp90, an evolutionarily conserved molecular chaperone, is involved in the folding, stabilization, activation, and assembly of a wide range of 'client' proteins, thus playing a central role in many biological processes. Especially, several oncoproteins act as Hsp90 client proteins and tumor cells require higher Hsp90 activity than normal cells to maintain their malignancy. For this reason, Hsp90 has emerged as a promising target for anti-cancer drug development. It is still largely unknown how Hsp90 can recognize structurally unrelated client proteins. However, recent progress in structural studies on Hsp90 and its interaction with various co-chaperones has broadened our knowledge of how the Hsp90 ATPase activity, which is essential for its chaperone function, is regulated and coupled with the conformational changes of Hsp90 dimer. This review focuses on the roles of various Hsp90 co-chaperones in the regulation of the Hsp90 ATPase cycle, as well as in the selection of client proteins. In addition, the current development of Hsp90 inhibitors based on the structural information will be discussed.

Quantitative Structure-Activity Relationships for Radical Scavenging Activities of Flavonoid Compounds by GA-MLR Technique

  • Om, Ae-Son;Ryu, Jae-Chun;Kim, Jae-Hyoun
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.170-176
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    • 2008
  • The quantitative structure-activity relationship (QSAR) of a set of 35 flavonoid compounds presenting antioxidant activity was established by means of Genetic Algorithm-Multiple Linear Regression (GA-MLR) technique. Four-parametric models for two sets of data, the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity $(R^2=0.788,\;Q^2_{cv}=0.699\;and\;Q^2_{ext}=0.577)$ and scavenging activity of reactive oxgen species (ROS) induced by $H_2O_2 (R^=0.829,\;Q^2_{cv}=0.754\;and\;Q^2_{ext}=0.573)$ were obtained with low external predictive ability on a mass basis, respectively. Each model gave some different mechanistic aspects of the flavonoid compounds tested in terms of the radical scavenging activity. Topological charge, H-bonding complex and deprotonation processes were likely to be involved in the radical scavenging activity.