Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals

Technological Innovation: A Structurational Process View

Introduction The central aim of our research is to describe and explain how the introduction of a computer-based technology, which supports co-operative work in engineering departments, induces change processes. The employment of computer-based technologies in product development organisations to support co-operative work practices has become a major practical and theoretical issue over the last years. Although there seem to be many technological possibilities to realise this kind of support, in practice, outcomes of technological change processes are usually different from those anticipated by management. We aim at explaining this phenomenon by investigating the relationship and interaction among the two major components - computer-based technology and organisation -- focussing on the interrelationship, rather than on the components themselves. We use Anthony Giddens' structuration theory as an overarching framework for our investigation. The fundamental notion of Giddens' s