In smell's shadow: Materials and politics at the edge of perception.

This article examines the politics of smell at the edge of perception. In January 2014, the municipal water supply of Charleston, West Virginia was contaminated by an under-characterized chemical, crude MCHM. Even when instrumental measurements no longer detected the chemical, people continued to smell its licorice-like odor. In a space where nothing was certain, smell became the only indicator of potential harm. Officials responded by commissioning state-funded sensory testing of crude MCHM to determine its sensory threshold. Via the critical passage point of sensory science, some instances of embodied attunement were allowed to enter into the evidentiary regimes of perception, while other, similarly trained moments of attunement were excluded from the process. This, I show, produced knowledge about the spilled chemical that maintained the systems that contributed to the spill in the first place. Drawing on new materialist thought, I riff on biology and 'transduce' the ephemeral phenomena of smelling crude MCHM into a new medium: Rather than thinking of smell as a volatile molecular material (an odorant), I show that consideration of smell as a manipulable object that one can imagine as having tangible substance and shape offers a way to experiment with disciplinary forms. I suggest an alternate future, where sensory science acts to record sensory labor that produces facts about collective experience that cannot (easily) travel through current systems, a process that is one possible way of beginning to unravel entrenched systems of toxic harm.

Sensory politics: The tug-of-war between potability and palatability in municipal water production.

Sensory information signaled the acceptability of water for consumption for lay and professional people into the early twentieth century. Yet as the twentieth century progressed, professional efforts to standardize water-testing methods have increasingly excluded aesthetic information, preferring to rely on the objectivity of analytic information. Despite some highly publicized exceptions, consumer complaints remain peripheral to the making and regulating of drinking water. This exclusion is often attributed to the unreliability of the human senses in detecting danger. However, technical discussions among water professionals during the twentieth century suggest that this exclusion is actually due to sensory politics, the institutional and regulatory practices of inclusion or exclusion of sensory knowledge from systems of action. Water workers developed and turned to standardized analytical methods for detecting chemical and microbiological contaminants, and more recently sensory contaminants, a process that attempted to mitigate the unevenness of human sensing. In so doing, they created regimes of perception that categorized consumer sensory knowledge as aesthetic. By siloing consumers' sensory knowledge about water quality into the realm of the aesthetic instead of accommodating it in the analytic, the regimes of perception implemented during the twentieth century to preserve health have marginalized subjective experiences. Discounting the human experience with municipal water as irrelevant to its quality, control and regulation is out of touch with its intended use as an ingestible, and calls for new practices that engage consumers as valuable participants.

ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5.

Extracellular signal-regulated kinase 8 (ERK8) is the most recently identified member of the ERK subfamily of MAPKs. Although other members of the ERK subfamily are established regulators of signaling pathways involved in cell growth and/or differentiation, less is known about ERK8. To understand the cellular function of ERK8, a yeast two-hybrid screen of a human lung library was performed to identify binding partners. One binding partner identified was Hic-5 (also known as ARA55), a multiple LIM domain containing protein implicated in focal adhesion signaling and the regulation of specific nuclear receptors, including the androgen receptor and the glucocorticoid receptor (GR). Co-immunoprecipitation experiments in mammalian cells confirmed the interaction between Hic-5 and both ERK8 and its rodent ortholog ERK7. The C-terminal region of ERK8 was not required for the interaction. Although the LIM3 and LIM4 domains of Hic-5 were sufficient and required for this interaction, the specific zinc finger motifs in these domains were not. Transcriptional activation reporter assays revealed that ERK8 can negatively regulate transcriptional co-activation of androgen receptor and GRalpha by Hic-5 in a kinase-independent manner. Knockdown of endogenous ERK8 in human airway epithelial cells enhanced dexamethasone-stimulated transcriptional activity of endogenous GR. Transcriptional regulation of GRalpha and interaction with its ligand binding domain by ERK8 were dependent on the presence of Hic-5. These results provide the first physiological function for human ERK8 as a negative regulator of human GRalpha, acting through Hic-5, and suggest a broader role for ERK8 in the regulation of nuclear receptors beyond estrogen receptor alpha.

Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines.

3-Hydroxyethyl- and 3-hydroxypropyl-7-substituted-tetrahydroisoquinolines (9, 10, 16, and 17) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although alpha(2)-adrenoceptor affinity decreased for these compounds, selectivity was not gained over the parent 3-hydroxymethyl compounds (1, 2) due to a loss in PNMT inhibitory potency.