Exposure of mammalian cells to UV radiation was proposed to stimulate the transcription factor NF-B by a unique mechanism. Typically, rapid and strong inducers of NF-B, such as tumor necrosis factor alpha (TNF-␣) and bacterial lipopolysaccharide (LPS), lead to rapid phosphorylation and proteasomal degradation of its inhibitory protein, IB␣. In contrast, UV, a relatively slower and weaker inducer of NF-B, was suggested not to require phosphorylation of IB␣ for its targeted degradation by the proteasome. We now provide evidence to account for this peculiar degradation process of IB␣. The phospho-IB␣ generated by UV is only detectable by expressing a ⌬F-box mutant of the ubiquitin ligase -TrCP, which serves as a specific substrate trap for serine 32 and 36 phosphorylated IB␣. In agreement with this finding, we also find that the IB kinase (IKK) phospho-acceptor sites on IB␣, core components of the IKK signalsome, and IKK catalytic activity are all required for UV signaling. Furthermore, deletion and point mutation analyses reveal that both the amino-terminal IKK-binding and the carboxy-terminal putative zinc finger domains of NEMO (IKK␥) are critical for UV-induced NF-B activation. Interestingly, the zinc finger domain is also required for NF-B activation by two other slow and weak inducers, camptothecin and etoposide. In contrast, the zinc finger module is largely dispensable for NF-B activation by the rapid and strong inducers LPS and TNF-␣. Thus, we suggest that the zinc finger domain of NEMO likely represents a point of convergence for signaling pathways initiated by slow and weak NF-B-activating conditions.
This article utilizes the ongoing debates over the role of certain agricultural insecticides in causing Colony Collapse Disorder (CCD)—the phenomenon of accelerated bee die-offs in the United States and elsewhere—as an opportunity to contribute to the emerging literature on the social production of ignorance. In our effort to understand the social contexts that shape knowledge/nonknowledge production in this case, we develop the concept of epistemic form. Epistemic form is the suite of concepts, methods, measures, and interpretations that shapes the ways in which actors produce knowledge and ignorance in their professional/intellectual fields of practice. In the CCD controversy, we examine how the (historically influenced) privileging of certain epistemic forms intersects with the social dynamics of academic, regulatory, and corporate organizations to lead to the institutionalization of three interrelated and overlapping types of ignorance. We consider the effects of these types of ignorance on US regulatory policy and on the lives of different stakeholders.
In this article, we explore the politics of expertise in an ongoing controversy in the United States over the role of certain insecticides in colony collapse disorder – a phenomenon involving mass die-offs of honey bees. Numerous long-time commercial beekeepers contend that newer systemic agricultural insecticides are a crucial part of the cocktail of factors responsible for colony collapse disorder. Many scientists actively researching colony collapse disorder reject the beekeepers’ claims, citing the lack of conclusive evidence from field experiments by academic and industry toxicologists. US Environmental Protection Agency regulators, in turn, privilege the latters’ approach to the issue, and use the lack of conclusive evidence of systemic insecticides’ role in colony collapse disorder to justify permitting these chemicals to remain on the market. Drawing on semistructured interviews with key players in the controversy, as well as published documents and ethnographic data, we show how a set of research norms and practices from agricultural entomology came to dominate the investigation of the links between pesticides and honey bee health, and how the epistemological dominance of these norms and practices served to marginalize the knowledge claims and policy positions of commercial beekeepers in the colony collapse disorder controversy. We conclude with a discussion of how the colony collapse disorder case can help us think about the nature and politics of expertise.
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