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“The interferon system provides a powerful and universal intracellular defense mechanism against viruses. As one part of their survival strategies, many viruses have evolved mechanisms to counteract the host type I interferon (IFN-alpha/beta) responses. In this study, we attempt to investigate virus- and double-strand RNA (dsRNA)-triggered type I IFN Cell Cycle inhibitor signaling pathways and understand the inhibition of IFN-alpha/beta induction by viral proteins using mathematical modeling and quantitative analysis. Based on available literature and our experimental data, we develop a mathematical model of virus- and dsRNA-triggered signaling pathways leading to type

I IFN gene expression during the primary response, and use the genetic algorithm to optimize all rate constants in the model. The consistency between numerical simulation results and biological experimental data demonstrates that our model is reasonable. Further, we use the model to predict the following phenomena: (I) the dose-dependent inhibition by classical swine fever virus (CSFV) N(pro) or E(rns) protein is observed at a low dose and can reach a saturation above a certain dose, not an increase; (2) E(rns) and N(pro) have no synergic inhibitory effects on IFN-beta induction; (3) Lazertinib the different characters

in an important transcription factor, phosphorylated IRF3 (IRF3p), are exhibited because N(pro) or E(rns) counteracted dsRNA- and virus-triggered IFN-beta induction by targeting the different molecules in the signaling pathways and (4) N(pro) inhibits the IFN-beta expression not only by interacting with IFR3 but also by affecting its complex with MITA. Our approaches help to gain insight into system properties and rational therapy design, as well as to generate hypotheses for further research. (C) 2010 Elsevier Ltd. All rights reserved.”
“We used the erythropoietin enhancer

and P-type ATPase Simian virus-40 promoter to create a hypoxia-inducible gene expression system to investigate the effect of vascular endothelial growth factor (VEGF) gene therapy on neuroprotection and neurogenesis in organotypic spinal cord slice culture. The organotypic spinal cord slice culture transfected with pEpo-SV-VEGF expressed the highest amount of VEGF under hypoxic conditions and showed decreased apoptosis and increased proliferation, and evidence of neurogenesis. Our results show that the hypoxia-induced VEGF expression in an organotypic spinal cord slice culture may lead to an optimal treatment for spinal cord injury. NeuroReport 22: 55-60 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“We analyze the mechanisms by which nucleoside-analogue reverse transcriptase inhibitors, the most common class of drugs used in the treatment of HIV-1, exert their antiviral effects. We then seek to identify ways in which those known mechanisms can be employed to generate mathematical models for drug efficacy in terms of measurable physical values.