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    ABSTRACT: The nematode Caenorhabditis elegans (C. elegans), a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We devel-oped a virtual C. elegans based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural cir-cuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic move-ment. Computer simulation confirmed that the virtual C. elegans realizes motor control similar qualitatively to that of the actual organism. Specified classes of neu-rons are killed in the neural circuit model correspond-ing to actual unc mutants, demonstrating that result-ing movement of the virtual C. elegans resembles that of actual mutants.
    Full-text · Article · Jul 2015
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    ABSTRACT: Visualization of metabolic dynamism is important for various types of metabolic studies including studies on optimization of bio-production processes and studies of metabolism-related diseases. Many methodologies have been developed for metabolic studies. Among these, metabolic turnover analysis (MTA) is often used to analyze metabolic dynamics. MTA involves observation of changes in the isotopomer ratio of metabolites over time following introduction of isotope-labeled substrates. MTA has several advantages compared with 13C-metabolic flux analysis, including the diversity of applicable samples, the variety of isotope tracers, and the wide range of target pathways. However, MTA produces highly complex data from which mining useful information becomes difficult. For easy understanding of MTA data, a new approach was developed using principal component analysis (PCA). The resulting PCA score plot visualizes the “metabolic distance”, which is defined as distance between metabolites on the real metabolic map. And the score plot gives us some hints of interesting metabolism for further study. We used this method to analyze the central metabolism of Saccharomyces cerevisiae under moderated aerobic conditions, and time course data for 77 isotopomers of 14 metabolites were obtained. The PCA score plot for this dataset represented a metabolic map and indicated interesting phenomena such as activity of fumarate reductase under aerated condition. These findings show the importance of a multivariate analysis to MTA. In addition, because the approach is not biased, this method has potential application for analysis of less-studied pathways and organisms.
    No preview · Article · Sep 2014 · Journal of Bioscience and Bioengineering
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    ABSTRACT: Understanding mechanisms that govern cell fate determination of human induced pluripotent stem cells (hiPSCs) could assist in maintenance of the undifferentiated state during cell expansion. We used polyamidoamine dendrimer surfaces with first-generation (G1), third-generation (G3) and fifth-generation (G5) of dendron structure in cultures of hiPSCs with SNL feeder cells. Cells on the G1 surface formed tightly packed colony with close cell–cell contacts during division and migration; those on the G3 surface exhibited loose or dispersed colony pattern by enhanced migration. On the G5 surface, formation of aggregated colony with ring-like structures occurred spontaneously. We found that the substrate-adsorbed fibronectin and feeder cell-secreted fibronectin appeared elevated levels with the varied generation numbers of dendrimer surfaces. This subsequently resulted in cell migration and in activation of paxillin of hiPSCs. Location-dependent expression of Rac1 induced rearrangement of E-cadherin-mediated cell–cell interactions on dendrimer surfaces, and was associated with alterations in the cell and colony morphology, and migratory behavior. Furthermore, caspase-3 occurred in apoptotic cells on dendrimer surfaces, concomitant with the loss of E-cadherin-mediated cell–cell interactions. Cells on the G1 surface were maintained in an undifferentiated state, while those on the G5 surface exhibited the early commitment to differentiation toward endodermal fates. We conclude that morphological changes associated with altered migration on the dendrimer surfaces were responsible for the coordinated regulation of balance between cell–cell and cell–substrate interactions, thereby switching their transition from self-renewal state to early endoderm differentiation in hiPSCs.
    No preview · Article · Jul 2014 · Biomaterials
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