Summary We show mice with a targeted deficiency in the gene encoding the lipogenic transcription factor SREBP-1a are resistant to endotoxic shock and systemic inflammatory response syndrome induced by cecal ligation and puncture (CLP). When macrophages from the mutant mice were challenged with bacterial lipopolysaccharide they failed to activate lipogenesis as well as two hallmark inflammasome functions, activation of Caspase-1 and secretion of IL-1β. We show that SREBP-1a not only activates genes required for lipogenesis in macrophages but also the gene encoding Nlrp1a, which is a core inflammasome component. Thus, SREBP-1a links lipid metabolism to the innate immune response, which supports our hypothesis that SREBPs evolved to regulate cellular reactions to external challenges that range from nutrient limitation and hypoxia to toxins and pathogens.

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Blends of poly(l-lactic acid) (PLA) and poly-(butylene succinate) (PBS) were prepared with various compositions by a melt-mixing method and the phase behavior, miscibility, and morphology were investigated using differential scanning calorimetry, wide-angle X-ray diffraction, small-angle X-ray scattering techniques, and polarized optical microscopy. The blend system exhibited a single glass transition over the entire composition range and its temperature decreased with an increasing weight fraction of the PBS component, but this depression was not significantly large. The DSC thermograms showed two distinct melting peaks over the entire composition range, indicating that these materials was classified as semicrystalline/semicrystalline blends. A depression of the equilibrium melting point of the PLA component was observed and the interaction parameter between PLA and PBS showed a negative value of Ϫ0.15, which was derived using the Flory-Huggins equation. Small-angle X-ray scattering revealed that, in the blend system, the PBS component was expelled out of the interlamellar regions of PLA, which led to a significant decrease of a long-period, amorphous layer thickness of PLA. For more than a 40% PBS content, significant crystallization-induced phase separation was observed by polarized optical microscopy.

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