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.

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.

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Liver-X-receptors (LXRs) are cholesterol sensing nuclear receptors that are not only key regulators of lipid metabolism and transport, but they also suppress inflammatory signaling in macrophages through a unique mechanism of transrepression. In this brief review, we focus on the regulatory actions of LXR primarily in macrophages responding to a proatherogenic environment. LXR potentially interferes with atherosclerosis by two different agonist dependent signaling pathways. The first is through promoting reverse cholesterol transport (RCT) by directly activating genes of cellular cholesterol export. The second is through a general inhibitory action on pro-inflammatory genes where sumo-modified and agonist bound LXR recruits negative co-regulatory proteins to NF-κB at immune response gene promoters through protein-protein interactions. The anti-inflammatory actions of LXR may be a direct response to the pro-inflammatory actions recently proposed for cholesterol on inflammasome activity in the vessel wall.

Chemical oxidative polymerization of aniline was studied in a conventional aqueous solution and in micellar solutions of sodium dodecyl sulfate (SDS, anionic surfactant) and nonylphenol ethoxylate(9) (NP-9, nonionic surfactant) to investigate the effect of molecular structure of surfactants on the polymerization kinetics and particle size. The polymerization kinetics in NP-9 micellar solution were very slow, and this result was explained based on the structural characteristics of surfactant. SDS micellar solutions resulted in a highly transparent solution without any precipitates, whereas some precipitates were visually observed in the NP-9 micellar solution after the reaction finished. The electrical conductivities of polyaniline pellets formed with particles prepared in SDS and NP-9 micellar solutions and aqueous solution showed about 20, 4, and 4 S/cm, respectively. The highest electrical conductivity of particles from SDS micellar solution might be due to the smallest size of particles and the highest doping level of polyaniline.

A solution for overcoming the low reactivity of terephthalic acid and isosorbide (ISB) is proposed that uses 1,4cyclohexane dimethanol and ethylene glycol. Using the different reactivities, volatilities, and degree of steric hindrances among the three diols, a highly heat-resistive biobased terpolyester (PEICT; glass transition temperature = 93−143 °C) was synthesized with a high degree of polymerization (weight-average molecular weight 65 400; number-average molecular weight 25 400). After esterification, most of the oligomer end groups were found to consist of ISB, which decreases the overall reactivity of transesterification due to its characteristics. However, this end group changed gradually into ethylene units, which accelerated the transesterification and chain growth in the polycondensation process via chain scission at the carbonyl carbon adjacent to the ethylene unit. To substantiate this mechanism, the Fukui function was used to calculate the reactivity difference between monomers. The sequence distribution was analyzed using 13 C-nuclear magnetic resonance to elucidate the function of each diol unit in transesterification. Finally, a polycondensation process for the PEICT terpolyester is proposed.