Stepwise isolation of low-valent, low-coordinate Sn and Pb mono- and dications in the coordination sphere of platinum.

Synthetic access to low-coordinate Pb mono- and dications is in general impeded due to their poor solubility and highly electrophilic nature. However, the electrophilicity of these cations can be tamed by attaching them to electron-rich transition metals. Following this principle we have isolated low-valent Pb mono- ([(CyP)Pt-PbCl][AlCl], ) and dications ([(CyP)Pt(Pb)][AlCl], ) in the coordination sphere of platinum.

Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation.

The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome drives many inflammatory processes and mediates IL-1 family cytokine release. Inflammasome activators typically damage cells and may release lysosomal and mitochondrial products into the cytosol. Macrophages triggered by the NLRP3 inflammasome activator nigericin show reduced mitochondrial function and decreased cellular ATP.

The second transmembrane domain of P2X7 contributes to dilated pore formation.

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor.

Visualization of bacterial toxin induced responses using live cell fluorescence microscopy.

Bacterial toxins bind to cholesterol in membranes, forming pores that allow for leakage of cellular contents and influx of materials from the external environment. The cell can either recover from this insult, which requires active membrane repair processes, or else die depending on the amount of toxin exposure and cell type(1). In addition, these toxins induce strong inflammatory responses in infected hosts through activation of immune cells, including macrophages, which produce an array of pro-inflammatory cytokines(2).

Macrophage responses to bacterial toxins: a balance between activation and suppression.

Toxins secreted by bacteria can impact the host in a number of different ways. In some infections, toxins play a crucial and central role in pathogenesis (i.e.