SHAFTS: A Hybrid Approach for 3D Molecular Similarity Calculation. 2. Prospective Case Study in the Discovery of Diverse p90 Ribosomal S6 Protein Kinase 2 Inhibitors To Suppress Cell Migration

2011 ◽  
Vol 54 (10) ◽  
pp. 3564-3574 ◽  
Author(s):  
Weiqiang Lu ◽  
Xiaofeng Liu ◽  
Xianwen Cao ◽  
Mengzhu Xue ◽  
Kangdong Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Molecular Similarity ◽  
Hybrid Approach ◽  
Similarity Calculation

scholarly journals Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70S6K signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sutthaorn Pothongsrisit ◽  
Kuntarat Arunrungvichian ◽  
Yoshihiro Hayakawa ◽  
Boonchoo Sritularak ◽  
Supachoke Mangmool ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cancer Metastasis ◽  
Small Cell ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Cell Metastasis

AbstractCancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

scholarly journals Path Planning for Autonomous Ships: A Hybrid Approach Based on Improved APF and Modified VO Methods

2021 ◽  
Vol 9 (7) ◽  
pp. 761
Author(s):  
Liang Zhang ◽  
Junmin Mou ◽  
Pengfei Chen ◽  
Mengxia Li
Keyword(s):  
Path Planning ◽  
Local Minimum ◽  
Hybrid Approach ◽  
Artificial Potential Field ◽  
Whole Process ◽  
International Regulations ◽  
Local Path ◽  
Velocity Obstacle ◽  
Global And Local

In this research, a hybrid approach for path planning of autonomous ships that generates both global and local paths, respectively, is proposed. The global path is obtained via an improved artificial potential field (APF) method, which makes up for the shortcoming that the typical APF method easily falls into a local minimum. A modified velocity obstacle (VO) method that incorporates the closest point of approach (CPA) model and the International Regulations for Preventing Collisions at Sea (COLREGS), based on the typical VO method, can be used to get the local path. The contribution of this research is two-fold: (1) improvement of the typical APF and VO methods, making up for previous shortcomings, and integrated COLREGS rules and good seamanship, making the paths obtained more in line with navigation practice; (2) the research included global and local path planning, considering both the safety and maneuverability of the ship in the process of avoiding collision, and studied the whole process of avoiding collision in a relatively entirely way. A case study was then conducted to test the proposed approach in different situations. The results indicate that the proposed approach can find both global and local paths to avoid the target ship.

Investigation of the molecular similarity in closely related protein systems: The PrP case study

2015 ◽  
Vol 83 (10) ◽  
pp. 1751-1765 ◽  
Author(s):  
Loriano Storchi ◽  
Roberto Paciotti ◽  
Nazzareno Re ◽  
Alessandro Marrone
Keyword(s):  
Molecular Similarity ◽  
Related Protein

scholarly journals Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-β Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity

2009 ◽  
Vol 20 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Wei Zuo ◽  
Ye-Guang Chen
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Coated Pits ◽  
Mapk Activation ◽  
Mitogen Activated Protein

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

scholarly journals From Co-Actionality to Extended Intersubjectivity: Drawing on Language Change and Ontogenetic Development

2018 ◽  
Vol 41 (2) ◽  
pp. 185-214 ◽  
Author(s):  
Vittorio TANTUCCI
Keyword(s):  
Applied Research ◽  
Ad Hoc ◽  
Language Change ◽  
Developmental Psychology ◽  
Profile Analysis ◽  
First Language ◽  
Hybrid Approach ◽  
Specific Context ◽  
Behavioural Profile

Abstract This article combines research results centred on theory of mind (ToM) from cognitive and developmental psychology (Goldman 2006; Apperly 2010; Wilkinson and Ball 2012) with the notion of intersubjectivity in usage-based linguistics (i.a. Verhagen 2005; Nuyts 2012; Traugott 2012). It identifies some of the controversies in the literature from both domains and suggests the desiderata for a hybrid approach to intersubjectivity, which is distinctively designed to tackle applied research in social and cognitive sciences. This model is based on a mismatch between interaction as mere ‘co-action’ vs. interaction as spontaneously communicated awareness of an(other) mind(s). It provides a case study centred on the first language acquisition of pre-nominal usage of this/that and such. From, respectively, a distinctive collexeme (Gries and Stefanowitsch 2004) and behavioural profile analysis (Gries 2010) will emerge that beyond expressions of joint attention, children’s ToM ability progressively underpins ‘ad-hoc’ generalized instantiations based on extended intersubjectivity, viz. the socio-cognitive skill to problematize what a general persona would act, feel, or think in a specific context.

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