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

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Nanobiomaterial advances in cardiovascular tissue engineering

Myocardial infarction (MI) is projected to increase globally in the coming decades. The long-term outlook for patients with ischemic heart injury undergoing current treatment modalities is bleak, due to the lack of regenerative capacity of native heart tissue. Tissue engineering and regenerative medicine have developed numerous strategies to repair or replace injured myocardium. One of the most promising strategies to date is the attempt to engineer tissues and cells at the nanoscale by utilizing nanobiomaterials to mimic the native nanoscale structure of the heart. Nanobiomaterials have proliferated enormously in the past few decades and have great potential for creating biomimetic systems that can replace or repair injured myocardium. Tissue engineering scaffolds with precisely controlled nanotopography, electrically conductive nanomaterials with the potential for mimicking conductive pathways in the heart, and numerous nanocarriers for targeted cardiac drug delivery have now been achieved. In this chapter we review the rationale for engineering biological tissues at the nanoscale as well as recent applications in nanofabrication and nanomedicine for cardiac regeneration