Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1β produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into five groups: ) control,) sham, ) BOO + vehicle,) BOO + the NLRP3 inhibitor glyburide, or ) BOO + the IL-1β receptor antagonist anakinra. Fibrosis was assessed by Masson's trichrome stain, collagen secretion via Sirius Red, and protein localization by immunofluorescence. BOO increased collagen production in the bladder, which was blocked by glyburide and anakinra, clearly implicating the NLRP3/IL-1β pathway in fibrosis. The collagen was primarily found in the lamina propria and the smooth muscle, while IL-1 receptor 1 and prolyl 4-hydroylase (an enzyme involved in the intracellular modification of collagen) both localized to the urothelium and the smooth muscle. Lysyl oxidase, the enzyme involved in the final extracellular assembly of mature collagen fibrils, was found to some extent in the lamina propria where its expression was greatly enhanced during BOO. In vitro studies demonstrated isolated urothelial cells from BOO rats secreted substantially more collagen than controls, and collagen expression in control cultures could be directly stimulated by IL-1β. In summary, NLRP3-derived-IL-1β triggers fibrosis during BOO, most likely through an autocrine loop in which IL-1β acts on urothelia to drive collagen production.

Irritative voiding symptoms (e.g. increased frequency and urgency) occur in many common pathologic conditions such as urinary tract infections and bladder outlet obstruction, and these conditions are well-established to have underlying inflammation that directly triggers these symptoms. However, it remains unclear as to how such diverse stimuli individually generate a common inflammatory process. Jürg Tschopp provided substantial insight into this conundrum when, working with extracts from THP-1 cells, he reported the existence of the inflammasome. He described it as a structure that senses multiple diverse signals from intracellular/extracellular sources and pathogens and triggers inflammation by the maturation and release of the pro-inflammatory cytokines interleukin-1β and interleukin-18. Recently, many of these sensors were found in the bladder and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, has been shown to be a central mediator of inflammation in several urological diseases. In this review, we introduce the nucleotide-binding domain, leucine-rich-containing family, pyrin domaincontaining-3 inflammasome, highlight its emerging role in several common urologic conditions, and speculate on the potential involvement of other inflammasomes in bladder pathology.

Few studies of diving predators have explicitly addressed the 3-dimensional nature of interactions between predators and prey at the spatial and temporal scales relevant to an individual predator's search behavior Here, we present a new method for examining such interactions using the results from an acoustic survey of krill availability to foraging penguins Analyses of fine-scale krill distributions within a 1852 X 1852 X 50 m volume of ocean revealed substantial prey patchiness in all dimensions. Our survey detected the presence of at least 6 krill aggregations in the survey area. The surface distribution of penguins was associated with the edges of these aggregations and was nonrandomly associated with kl-ill dellsitirs above 0.1 krill m-' in the 30 to 40 m depth layer. The latter association was masked when krill abundance was integrated over the entire water column. Given that lilean daytlme dlve depths for chinstrap penguins fall betwccn 30 and 40 m, our data suggest penguins may fail to detect or choose to pass by shallow, denser prey aggregations and successfully forage on deeper, more homogeneously distributed krill offering higher encounter probabilities per unit volume searched. Thrse findings reveal biologically important features of prey patchiness that cannot be addressed within the limitations of a primarily 2-dimensional analysls of predator-prey distributions. We emphasize that if we hope to gain a predictive understanding of the foraging behavior of dlving predators, then we must consider fine-scale, 3-dimensional patterns of prey patchiness when assessing the availability of prey to diving predators.

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