Rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the CAST/Ei strain on a C57BL/6 genetic background.

Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan's blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1ß and IL-18, were examined. Topical application to the mesentery of IL-1ß but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1ß antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1ß in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1ß. These results demonstrate that vessel leakage and alterations to blood flow are part of the rapid response in mice resistant to B. anthracis infection.

The time course of metonymic language text processing by older and younger adults.

The influence of aging on the processing of figurative language was investigated by utilizing Frisson and Pickering's (Journal of Experimental Psychology: Learning, Memory, and Cognition, 25, 1366-1383, 1999) paradigm, monitoring eye fixation times to target words in sentences. First fixation times and total fixation times were analyzed for familiar and unfamiliar metonymies and literal control sentences. Frisson and Pickering found that processing figurative and literal expressions yielded similar patterns of eye fixations. In the current study, these methods and results were replicated and extended to include older adults' processing of metonymies. This investigation replicated their findings for young adults and found that older adults produced the same processing patterns as the younger adults.