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The title of the conference that inspired this collection of essays can be interpreted as implying that the International Polar Years (IPY) were the catalyst for the globalization of science. To read the title in this way can be misleading, especially if this implies the conference was an argument that the IPYs were representing a new path for science. It is the contention of this essay that there was little that was radical about the IPYs. For the most part, they were logical outgrowths of what historians have identified as two well-established traditions in Euro-American science.

We examined long-term variations in kelp growth in coincidence with recent (2004– 2006) measurements of underwater photosynthetically active radiation (PAR), light attenuation coeffi cients, chlorophyll concentrations, and total suspended solids (TSS) to determine the impact of sediment resuspension on the productivity of an isolated kelp bed community on the Alaskan Beaufort Sea coast. Attenuation coeffi cients exhibited distinct geographical patterns and interannual variations between 2004 and 2006 that were correlated with temporal and geographical patterns in TSS (range 3.5– 23.8 mg L 1). The low chlorophyll levels ( 3.0 g L 1) in all three years were unlikely to have contributed signifi cantly to periods of low summer water transparency. Blade elongation rates in the arctic kelp, Laminaria solidungula, are excellent integrators of water transparency since their annual growth is completely dependent on PAR received during the summer open-water period. We noted that blade growth at all sites steadily increased between 2004 and 2006, refl ective of increased underwater PAR in each successive year. Mean blade growth at all sites was clearly lowest in 2003 ( 8 cm) compared to 2006 (18– 47 cm). We attribute the low growth in 2003 to reported intense storm activity that likely produced extremely turbid water conditions that resulted in low levels of ambient light. Examination of a 30-year record of annual growth at two sites revealed other periods of low annual growth that were likely related to summers characterized by exceptional strong storm activity. Although kelp growth is expected to be higher at shallower sites, the reverse occurs, since sediment re-suspension is greatest at shallower water depths. The exceptionally low growth of kelp in 2003 indicates that these plants are living near their physiological light limits, but represent excellent indicators of interannual changes in water transparency that result from variations in local climatology.

It has long been appreciated that a drop in eosinophils is associated with acute bacterial infection while, in contrast, blood levels of monocytes and neutrophils rise. The initial eosinopenic response is believed to be secondary to margination of circulating eosinophils to blood vessel walls, but the mechanism for prolonged eosinophil depletion with bacterial infection remains undefined. In a culture system developed to differentiate mature eosinophils from low density bone marrow progenitors, IL-5 stimulation of progenitors resulted in induced expression of six TLRs with highest expression of TLR2 and TLR4 noted throughout eosinophil development. Surface expression of TLR4 was confirmed on CD34+ progenitors by FACS. Stimulation of progenitors with LPS markedly inhibited IL-5-mediated eosinophil production. Further, LPS administration in vivo specifically reduced numbers of eosinophil progenitors in the bone marrow. Treatment of developing eosinophils with LPS induced the generation of pro-inflammatory mediators, including IL-6, IL-10, IFN-γ and TNF-α, but mechanistic studies demonstrated that suppression of eosinophil production by LPS was independent of these mediators. Taken together, these findings suggest a direct effect of LPS on eosinophil progenitors as an explanation for eosinopenia following bacterial infections and a potentially novel therapeutic strategy for depleting eosinophil progenitors and inhibiting peripheral eosinophilia in eosinophil-associated diseases.

Clinical studies have shown acidification of airways in asthma. Importantly, studies have suggested that acidification contributes to the pathophysiological process. However, the mechanism of acidification is unclear. We developed a novel method for measuring the acidity of mouse airways and demonstrated that mouse airways are acidified during models of allergic airway inflammation. Our studies determined that airway acidification does not develop in IL-13-deficient mice and that IL-13 delivery alone is sufficient to induce airway acidification. There are multiple ways IL-13 could lead to acidification, including direct effects on epithelial cells or through recruitment of inflammatory cells. We demonstrated a partial role for eosinophils in airway acidification as CCR3 and IL-5-deficient mice had decreased extent of airway acidification in allergen-challenged mice. Furthermore, using dimethyl amiloride, a specific inhibitor of the Na+/H+ exchanger, we demonstrated significant inhibition of airway acidification in allergic airway inflammation, suggesting a role for ion (proton) channels. In summary, our studies demonstrate that mouse airways are acidified during allergic airway inflammation. We also showed that the mechanism of airway acidification in asthma involves IL-13-mediated pathways including eosinophils and proton channels. These results have considerable implications for the development of therapies that target airway acidification.

RATIONALE: Eosinophilic esophagitis (EE) is an emerging disease and we previously demonstrated that adaptive T cell immunity is critical in the disease pathogenesis. However, the specific subsets of T cells that promote esophageal eosinophilia are not yet understood. Therefore, we focused our studies to examine the role of CD45RB T subsets, as the pathogenic and regulatory activity of T cells depends on the expression levels of CD45RB. METHODS: A flow cytometric analysis was performed to examine the frequency of CD45RBhigh and CD45RBlow T cell subsets in the mouse esophagus. A real time PCR analysis was performed to examine the pathogenic and anti-inflammatory characteristics of both subsets of T cells. In addition, we adoptively transferred these purified cell subsets in mice with experimental EE and examined their role in the disease pathogenesis. RESULTS: An increase of CD4+CD45RBhigh and a decrease of CD4+CD45RBlow cells were observed in mouse esophagus following the induction of experimental EE. A relatively high transcript level of IL-5 and IL-13 in CD4+CD45RBhigh and IL-10 and TGF-β1 in CD4+CD45RBlow spleen purified cells was observed. Further, our initial experimentation revealed that mice adoptively transferred with 4X105 CD4+CD45RBlow T cells/week were protected from the induction of esophageal eosinophilia compared to control mice that did not received adoptively transferred cells. Mice receiving CD4+CD45RBhigh T cell had no significant change in the number of eosinophils in the esophagus compared to control mice following allergen challenge. CONCLUSIONS: CD4+CD45RBlow T cells have a critical role in down-regulating allergen-induced eosinophil recruitment to the mouse esophagus.