Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth

A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene expression levels, uterine weights, and histologic parameters were analyzed 1, 2, 4, 8, 24, 48, and 72 hr after exposure to the reference physiologic estrogen 17β-estradiol (E(2)). A multistep analysis method, involving unsupervised hierarchical clustering followed by supervised gene ontology–driven clustering, was used to define the transcriptional program associated with E(2)-induced uterine growth and to identify groups of genes that may drive specific histologic changes in the uterus. This revealed that uterine growth and maturation are preceded and accompanied by a complex, multistage molecular program. The program begins with the induction of genes involved in transcriptional regulation and signal transduction and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation, and epithelial cell differentiation. Furthermore, we have identified genes with common molecular functions that may drive fluid uptake, coordinated cell division, and remodeling of luminal epithelial cells. These data define the mechanism by which an estrogen induces organ growth and tissue maturation, and demonstrate that comparison of temporal changes in gene expression and conventional toxicology end points can facilitate the phenotypic anchoring of toxicogenomic data

'The cutting edge of cocking about': Top Gear, automobility and law

This paper argues that the British Broadcasting Corporation’s (BBC) television series Top Gear (2002-) presents a significant opportunity to think about automobility, masculinity and law. As a show about cars and car culture it can be seen, and dismissed, as a gratuitous celebration of 'combustion masculinity.' However, its irony, humour and nostalgia combine to highlight that this way of being male lies in the past. Focusing on Top Gear series 13 (June-August 2009) it is argued that the essence of combustion masculinity lies not only in risk and competition but law. However, the show goes further. In its excessive performance of combustion masculinity it engages in gentle critique. In the post-industrial era where the motor vehicle’s cultural status is declining Top Gear is itself a vehicle allowing combustion masculinity to be overtaken by less risky, less violent and more lawful ways of being male