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See detailMultistability of genetic regulatory networks
Pan, Wei UL; Zhang, Z.; Liu, H.

in International Journal of Systems Science (2010), 41(1), 107-118

Multistability is found to be an important recurring theme in synthesis biology. In this article, the multistability analysis problem is investigated by applying control theory and mathematical tools ... [more ▼]

Multistability is found to be an important recurring theme in synthesis biology. In this article, the multistability analysis problem is investigated by applying control theory and mathematical tools. Both the modelling and analysis issues are discussed. Specifically, the genetic regulatory networks (GRNs) with multistability are modelled as switched systems with interval time-varying delays and parameter uncertainties, where the piecewise-affine models are used to approximate the inherent non-linearities existing in the GRNs. Then, by using a novel Lyapunov functional approach and linear matrix inequality (LMI) techniques, a few delay-dependent criteria for the multistability of such genetic regulatory networks are established in the form of LMIs, which can be readily verified by using standard numerical software. A three-component network and a genetic toggle switch with bistability are employed to illustrate the applicability and usefulness of the developed theoretical results. [less ▲]

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See detailExpression and functional analyses of novel mutations of ATP-binding cassette transporter-1 in Japanese patients with high-density lipoprotein deficiency
Nishida, Y.; Hirano, K.; Tsukamoto, K. et al

in Biochemical and Biophysical Research Communications (2002), 290(2), 713-721

ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three ... [more ▼]

ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three different ABCA1 mutations associated with FHD (G1158A/A255T, C5946T/R1851X, and A5226G/N1611D) with respect to their expression in the passaged fibroblasts from the patients and in the cells transfected with themutated cDNAs. Fibroblasts from the all patients showed markedly decreased cholesterol efflux to apolipoprotein (apo)-Al. In the fibroblasts homozygous for G1158A/A255T, the immunoreactive mass of ABCA1 could not be detected, even when stimulated by 9-cisretinoic acid and 22-R- hydroxycholesterol. In the fibroblasts homozygous for C5946T/R1851X, ABCA1 mRNA was comparable. Because the mutant ABCA1 protein (R1851X) was predicted to lack the epitope for the antibody used, we transfected FLAG-tagged truncated mutant (R1851X/ABCA1-FLAG) cDNA into Cos-7 cells, showing that the mutant protein expression was markedly reduced. The expression of N1611D ABCA1 protein was comparable in both fibroblasts and overexpressing cells, although cholesterol efflux from the cells was markedly reduced. These data indicated that, in the three patients investigated, the abnormalities and dysfunction of ABCA1 occurred at the different levels, providing important information about the expression, regulation, and function of ABCA1. [less ▲]

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