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Articles by J Lim
Total Records ( 4 ) for J Lim
  C. Y Dong , J Lim , Y Nam and K. H. Cho

Motivation: Synchronized bursting behavior is a remarkable phenomenon in neural dynamics. So, identification of the underlying functional structure is crucial to understand its regulatory mechanism at a system level. On the other hand, we noted that feedback loops (FBLs) are commonly used basic building blocks in engineering circuit design, especially for synchronization, and they have also been considered as important regulatory network motifs in systems biology. From these motivations, we have investigated the relationship between synchronized bursting behavior and feedback motifs in neural networks.

Results: Through extensive simulations of synthetic spike oscillation models, we found that a particular structure of FBLs, coupled direct and indirect positive feedback loops (PFLs), can induce robust synchronized bursting behaviors. To further investigate this, we have developed a novel FBL identification method based on sampled time-series data and applied it to synchronized spiking records measured from cultured neural networks of rat by using multi-electrode array. As a result, we have identified coupled direct and indirect PFLs.

Conclusion: We therefore conclude that coupled direct and indirect PFLs might be an important design principle that causes the synchronized bursting behavior in neuronal networks although an extrapolation of this result to in vivo brain dynamics still remains an unanswered question.

  J Lim , A Wood and B. G. Green

The objective of this study was to develop a semantically labeled hedonic scale (LHS) that would yield ratio-level data on the magnitude of liking/disliking of sensation equivalent to that produced by magnitude estimation (ME). The LHS was constructed by having 49 subjects who were trained in ME rate the semantic magnitudes of 10 common hedonic descriptors within a broad context of imagined hedonic experiences that included tastes and flavors. The resulting bipolar scale is statistically symmetrical around neutral and has a unique semantic structure. The LHS was evaluated quantitatively by comparing it with ME and the 9-point hedonic scale. The LHS yielded nearly identical ratings to those obtained using ME, which implies that its semantic labels are valid and that it produces ratio-level data equivalent to ME. Analyses of variance conducted on the hedonic ratings from the LHS and the 9-point scale gave similar results, but the LHS showed much greater resistance to ceiling effects and yielded normally distributed data, whereas the 9-point scale did not. These results indicate that the LHS has significant semantic, quantitative, and statistical advantages over the 9-point hedonic scale.

  S Sawatsubashi , T Murata , J Lim , R Fujiki , S Ito , E Suzuki , M Tanabe , Y Zhao , S Kimura , S Fujiyama , T Ueda , D Umetsu , T Ito , K. i Takeyama and S. Kato

Chromatin reorganization is essential for transcriptional control by sequence-specific transcription factors. However, the molecular link between transcriptional control and chromatin reconfiguration remains unclear. By colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced puff in the salivary gland, Drosophila DEK (dDEK) was genetically identified as a coactivator of EcR in both insect cells and intact flies. Biochemical purification and characterization of the complexes containing fly and human DEKs revealed that DEKs serve as histone chaperones via phosphorylation by forming complexes with casein kinase 2. Consistent with the preferential association of the DEK complex with histones enriched in active epigenetic marks, dDEK facilitated H3.3 assembly during puff formation. In some human myeloid leukemia patients, DEK was fused to CAN by chromosomal translocation. This mutation significantly reduced formation of the DEK complex, which is required for histone chaperone activity. Thus, the present study suggests that at least one histone chaperone can be categorized as a type of transcriptional coactivator for nuclear receptors.

  J Lim , M Zhou , T. D Veenstra and D. K. Morrison

Protein scaffolds play an important role in signal transduction, regulating the localization of signaling components and mediating key protein interactions. Here, we report that the major binding partners of the Connector Enhancer of KSR 1 (CNK1) scaffold are members of the cytohesin family of Arf guanine nucleotide exchange factors, and that the CNK1/cytohesin interaction is critical for activation of the PI3K/AKT cascade downstream from insulin and insulin-like growth factor 1 (IGF-1) receptors. We identified a domain located in the C-terminal region of CNK1 that interacts constitutively with the coiled-coil domain of the cytohesins, and found that CNK1 facilitates the membrane recruitment of cytohesin-2 following insulin stimulation. Moreover, through protein depletion and rescue experiments, we found that the CNK1/cytohesin interaction promotes signaling from plasma membrane-bound Arf GTPases to the phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) to generate a PIP2-rich microenvironment that is critical for the membrane recruitment of insulin receptor substrate 1 (IRS1) and signal transmission to the PI3K/AKT cascade. These findings identify CNK1 as a new positive regulator of insulin signaling.

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