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[1] Proxy data constraining land and ocean surface paleotemperatures indicate that the Middle Miocene Climate Optimum (MMCO), a global warming event at $15 Ma, had a global annual mean surface temperature of 18.4°C, about 3°C higher than present and equivalent to the warming predicted for the next century. We apply the latest National Center for Atmospheric Research (NCAR) Community Atmosphere Model CAM3.1 and Land Model CLM3.0 coupled to a slab ocean to examine sensitivity of MMCO climate to varying ocean heat fluxes derived from paleo sea surface temperatures (SSTs) and atmospheric carbon dioxide concentrations, using detailed reconstructions of Middle Miocene boundary conditions including paleogeography, elevation, vegetation and surface temperatures. Our model suggests that to maintain MMCO warmth consistent with proxy data, the required atmospheric CO 2 concentration is about 460 -580 ppmv, narrowed from the most recent estimate of 300-600 ppmv. Citation: You, Y., M. Huber, R. D. Müller, C.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria have been responsible for substantial morbidity and mortality in hospitals because they usually have multidrug resistance. Some natural products are candidates as new antibiotic substances. In the present study, we investigated the antimicrobial activity of berberine, the main antibacterial substance of Coptidis rhizoma (Coptis chinensis Franch) and Phellodendri cortex (Phellodendron amurense Ruprecht), against clinical isolates of MRSA, and the effects of berberine on the adhesion to MRSA and intracellular invasion into human gingival fibroblasts (HGFs). Berberine showed antimicrobial activity against all tested strains of MRSA. Minimum inhibition concentrations (MICs) of berberine against MRSA ranged from 32 to 128 microg/mL. Ninety percent inhibition of MRSA was obtained with 64 microg/mL or less of berberine. In the checkerboard dilution test, berberine markedly lowered the MICs of ampicillin and oxacillin against MRSA. An additive effect was found between berberine and ampicillin, and a synergistic effect was found between berberine and oxacillin against MRSA. In the presence of 1-50 microg/mL berberine, MRSA adhesion and intracellular invasion were notably decreased compared with the vehicle-treated control group. These results suggest that berberine may have antimicrobial activity and the potential to restore the effectiveness of beta-lactam antibiotics against MRSA, and inhibit the MRSA adhesion and intracellular invasion in HGFs.

[1] Utilizing general circulation models (GCMs) for paleoclimate study requires the construction of appropriate model boundary conditions. We present a middle Miocene paleotopographic and paleobathymetric reconstruction geographically constrained at 15 Ma for use in GCMs. Paleotopography and paleogeography are reconstructed using a published global plate rotation model and published geological data. Paleobathymetry is reconstructed through application of an age-depth relationship to a middle Miocene global digital isochron map, followed by the overlay of reconstructed sediment thickness and large igneous provinces. Adjustments are subsequently made to ensure our reconstruction may be utilized in GCMs.