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One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.
RESUMO
BACKGROUND: Allergen-induced T-helper type 2 (Th2) responses can be inhibited with Th1 directing vaccines. However, studies comparing the efficacy of the different adjuvants have not been performed in detail. OBJECTIVE: For this reason we compare the effects of live Bacillus-Calmette-Guerin(BCG), heat-killed (hk)-BCG, CpG-ODN (oligodeoxynucleotide) or PPD on the development of allergen-induced Th2 responses in mice. METHODS: Ovalbumin (OVA)-specific allergic responses were induced in C57BL/6 mice by two intraperitoneally (i.p.) applications of OVA/alum followed by the intranasal challenge with OVA. The different Th1-inducing adjuvants were applied to the mice together with OVA/alum i.p. during the OVA-sensitization period and, subsequently, different parameters of allergic immune responses were evaluated. RESULTS: All the adjuvants were effective in inhibiting the development of allergen-induced airway eosinophilia, mucous production and, with the exception of PPD, also airway hyper-reactivity, when they were applied together with OVA/alum. However, allergen-specific IgG1 and IgE serum levels were only reduced in live BCG- and PPD-treated mice. Suppression of airway eosinophilia was not observed in IFN-gamma- or IL-12-deficient mice (hk-BCG, CpG-ODN and PPD). Interestingly, live BCG was still able to suppress allergen-induced Th2 responses in the absence of either IFN-gamma or IL-12. When mice vaccinated with the different adjuvants together with OVA/alum were subjected to a second period of OVA/alum immunization, only live and hk-BCG were able to efficiently suppress the development of airway inflammation. This effect could be adoptively transferred by splenic CD4(+) T cells. CONCLUSIONS: Taken together our data suggest that live BCG>hk-BCG>CpG-ODN >PPD are effective in suppressing allergen-induced Th2 responses. The degree of suppression and the component of the Th2 response affected (airway inflammation vs. the production of allergen-specific IgE and IgG1) were dependent upon the adjuvant used and how it was applied. Our results contribute to the design of novel vaccines protecting humans from developing allergic disorders.