FK506 and Cyclosporin A Enhance IL-6 Production in Monocytes: A single-Cell Assay

The effect of FK506 and cyclosporin A (CsA) on the production of interleukin 6 (IL-6) in adherent monocytes was studied at a single-cell level by the avidinbiotin- peroxidase complex methods. The percentage of IL-6-producing monocytes increased when stimulated with lipopolysaccharide (LPS) at concentrations between 10 ng/ml and 10 μg/ml, in a dose dependent manner. Both FK506 and CsA enhanced the percentage of IL-6- producing monocytes stimulated with 100 pg/ml-1 μg/ml of LPS up to values near those obtained with 10 μg/ml of LPS. The enhancement by FK506 and CsA was not seen when monocytes were stimulated with a high concentration of LPS (10 μg/ml). When monocytes were stimulated with a low concentration of LPS (10 ng/ml), FK506 and CsA enhanced IL-6 production in a dose dependent manner, at a drug concentration of 0.12 nM–1.2 μM (0.1–1 000 ng/ml) for FK506 and 0.83 nM–8.3 μM (1–10 000 ng/ml) for CsA. The optimal effect of FK506 was achieved at a concentration 7-fold lower than that of CsA. In contrast, production of turnout necrosis factor-α (TNFα and interleukin 1β (IL-1β) was slightly suppressed by FK506 and CsA at the concentrations tested. Moreover, pretreatment of monocytes with FK506 and CsA had a significant enhancing effect on LPS-induced IL-6 production, while treatment with FK506 or CsA after LPS stimulation had no effects on IL-6 production, suggesting that the enhancing effect of each drug is exerted before LPS stimulation or at an early stage of the post-receptor pathway after LPS stimulation. These experiments demonstrate that FK506 and CsA can selectively enhance IL-6 production in monocytes under certain conditions in vitro and, possibly, also in vivo

Linear-stability analysis of plane beds under flows with suspended loads

Plane beds develop under flows in fluvial and marine environments; they are recorded as parallel lamination in sandstone beds, such as those found in turbidites. However, whereas turbidites typically exhibit parallel lamination, they rarely feature dune-scale cross-lamination. Although the reason for the scarcity of dune-scale cross-lamination in turbidites is still debated, the formation of dunes may be dampened by suspended loads. Here, we perform, for the first time, linear-stability analysis to show that flows with suspended loads facilitate the formation of plane beds. For a fine-grained bed, a suspended load can promote the formation of plane beds and dampen the formation of dunes. These results of theoretical analysis were verified with observational data of plane beds under open-channel flows. Our theoretical analysis found that suspended loads promote the formation of plane beds, which suggests that the development of dunes under turbidity currents is suppressed by the presence of suspended loads.</p

Membrane Potential and Bicarbonate Secretion in Isolated Interlobular Ducts from Guinea-pig Pancreas

The interlobular duct cells of the guinea-pig pancreas secrete HCO3− across their luminal membrane into a HCO3−-rich (125 mM) luminal fluid against a sixfold concentration gradient. Since HCO3− transport cannot be achieved by luminal Cl−/HCO3− exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. To determine whether the electrochemical potential gradient across the luminal membrane would favor HCO3− efflux, we have measured the intracellular potential (Vm) in microperfused, interlobular duct segments under various physiological conditions. When the lumen was perfused with a 124 mM Cl−-25 mM HCO3− solution, a condition similar to the basal state, the resting potential was approximately −60 mV. Stimulation with dbcAMP or secretin caused a transient hyperpolarization (∼5 mV) due to activation of electrogenic Na+-HCO3− cotransport at the basolateral membrane. This was followed by depolarization to a steady-state value of approximately −50 mV as a result of anion efflux across the luminal membrane. Raising the luminal HCO3− concentration to 125 mM caused a hyperpolarization (∼10 mV) in both stimulated and unstimulated ducts. These results can be explained by a model in which the depolarizing effect of Cl− efflux across the luminal membrane is minimized by the depletion of intracellular Cl− and offset by the hyperpolarizing effects of Na+-HCO3− cotransport at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO3− that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO3− to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO3−

Rapid coral mortality following doldrums-like conditions on Iriomote, Japan

Coral bleaching can be induced by many different stressors, however, the most common cause of mass bleaching in the field is higher than average sea surface temperatures (SST). Here, we describe an unusual bleaching event that followed very calm sea conditions combined with higher than average SST. Patterns of mortality differed from typical bleaching in four ways: 1) mortality was very rapid; 2) a different suite of species were most affected; 3) tissue mortality in Acropora spp. was often restricted to the center of the colony; 4) the event occurred early in summer. The two weeks prior to the event included 8 days where the average wind speed was less than 3 ms-1. In addition, SSTs in the weeks preceding and during the event were 1.0-1.5°C higher than the mean for the last 30 years. We hypothesize that this unusual bleaching event was caused by anoxia resulting from a lack of water movement induced by low wind speeds combined with high SST