Inflammasomes are protein complexes assembled upon recognition of infection or cell damage signals, and serve as platforms for clustering and activation of procaspase-1. Oligomerisation of initiating proteins such as AIM2 (absent in melanoma-2) and NLRP3 (NOD-like receptor family, pyrin domain-containing-3) recruits procaspase-1 via the inflammasome adapter molecule ASC (apoptosis-associated speck-like protein containing a CARD). Active caspase-1 is responsible for rapid lytic cell death termed pyroptosis. Here we show that AIM2 and NLRP3 inflammasomes activate caspase-8 and -1, leading to both apoptotic and pyroptotic cell death. The AIM2 inflammasome is activated by cytosolic DNA. The balance between pyroptosis and apoptosis depended upon the amount of DNA, with apoptosis seen at lower transfected DNA concentrations. Pyroptosis had a higher threshold for activation, and dominated at high DNA concentrations because it happens more rapidly. Gene knockdown showed caspase-8 to be the apical caspase in the AIM2-and NLRP3-dependent apoptotic pathways, with little or no requirement for caspase-9. Procaspase-8 localised to ASC inflammasome 'specks' in cells, and bound directly to the pyrin domain of ASC. Thus caspase-8 is an integral part of the inflammasome, and this extends the relevance of the inflammasome to cell types that do not express caspase-1.

We constructed an energetic model to determine the optimal focal point current velocity (i.e. microhabitat) for rainbow trout (Oncorhynchus mykiss) and rosyside dace (Clinostomus funduloides) in Coweeta Creek, a fifth—order stream in North Carolina, USA. Energetic costs were evaluated by quantifying the metabolic expenditure associated with swimming at a given velocity. We estimated bebefits by measuring potential energetic gains of feeding at a given velocity. This included estimates of the ability of the fish to capture prey at different current velocities as well as etimates of the frequency and the energy content of drifting prey at various velocities. We derived separate models for small (53—70 mm SL [standard length]) and medium (71—125 mm SL) trout, and medium (47—52 mm SL) and large (53—70 mm SL) dace for all seasons, deriving net energy gain as a function of current velocity. We predicted fishes would occupy velocities at which net energy gain was maximized. Predicted velocities were compared with those utilized by fishes inhabiting Coweeta Creek. Optimal velocities predicted by energetic models ranged from 7.7 to 22.1 cm/s, and closely matched actual velocity use (average deviation = 2.6 cm/s). Prey capture success appeared to be the most important component in the models. Consequently, we constructed models based solely upon aspects of capture success; the average deviation from veolocity use with these models was only 1.8 cm/s. Thus, the ability of dace and trout to capture prey at varying velocities appears to be the dominant factor affecting microhabitat selection in these species.

Background: Pyrin domains (PYDs) mediate the assembly of inflammasome complexes, but PYD interaction modes are not well characterized. Results: Interaction sites were identified on the PYD of the inflammasome adaptor protein, ASC. Conclusion: ASC PYD has multiple binding sites allowing self-association and interaction with binding partners. Significance: Understanding molecular details of inflammasome assembly may lead to development of anti-inflammatory agents.

The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated "death receptor." The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a "hydrophobic patch" in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.