49 research outputs found
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-1Ξ², 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-ΞΊB 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