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Gururao Hariprasad Divya Kota Sundararajan Baskar Singh Alagiri Srinivasan Souparno Adhikary 《Indian journal of clinical biochemistry : IJCB》2014,29(4):430-441
Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A2, an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a β-wing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidine-aspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA2 described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis.
Electronic supplementary material
The online version of this article (doi:10.1007/s12291-013-0377-1) contains supplementary material, which is available to authorized users. 相似文献2.
Colin Conrad Qi Deng Isabelle Caron Oksana Shkurska Paulette Skerrett Binod Sundararajan 《British journal of educational technology : journal of the Council for Educational Technology》2022,53(3):534-557
Practitioner notes
What is already known about this topic- University transitions to online learning during the Covid-19 pandemic were undertaken by faculty and students who had little online learning experience.
- The transition to online learning was often described as having a negative influence on students' learning experience and mental health.
- Varieties of cognitive load are known predictors of effective online learning experiences and satisfaction.
- Information overload and perceptions of technical abilities are demonstrated to predict students' difficulty and satisfaction with online learning.
- Students express negative attitudes towards factors that influence information overload, technical factors, and asynchronous course formats.
- Communication quantity was not found to be a significant factor in predicting either perceived difficulty or negative attitudes.
- We identify ways that educators in higher education can improve their online offerings and implementations during future disruptions.
- We offer insights into student experience concerning online learning environments during an abrupt transition.
- We identify design factors that contribute to effective online delivery, educators in higher education can improve students' learning experiences during difficult periods and abrupt transitions to online learning.
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In this article we introduce the notion of I-acceleration convergence of sequences. We prove the decomposition theorem for I-acceleration convergence of sequences as well as for subsequence transformations. We study different properties of I-acceleration convergence of sequences. 相似文献
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