Highlights d Serine deprivation diminishes LPS-induced IL-1b mRNA expression d LPS stimulates serine generation of glycine for glutathione synthesis d Glutathione is necessary to maintain LPS induction of IL-1b production d Inhibition of de novo serine synthesis promotes survival of mice exposed to LPS

The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the NLRP3 inflammasome through several mechanisms including generation of mitochondrial reactive oxygen species (ROS). Here, we report that mitochondrial electron transport chain (ETC) complex I, II, III and V inhibitors all prevent NLRP3 inflammasome activation. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI1) or Ciona intestinalis alternative oxidase, which can complement the functional loss of mitochondrial complex I or III, respectively, without generation of ROS, rescued NLRP3 inflammasome activation in the absence of endogenous mitochondrial complex I or complex III function. Metabolomics revealed phosphocreatine (PCr), which can sustain ATP levels, as a common metabolite that is diminished by mitochondrial ETC inhibitors. PCr depletion decreased ATP levels and NLRP3 inflammasome activation. Thus, the mitochondrial ETC sustains NLRP3 inflammasome activation through PCr-dependent generation of ATP, but via a ROS-independent mechanism.

No abstract

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

The migratory response of Echinostoma caproni to host feeding was examined in female ICR mice. Thirty-six mice were each infected with 20 metacercariae of E. caproni . Twenty-eight days post-infection, food, but not water, was withheld for 24 hr. Mice were haphazardly divided into 4 groups of 9, and each group received one of the following treatments: (1) 0.25 g glucose, (2) access to standard lab chow, (3) 0.5 ml saline, and (4) continued fasting. Three mice from each treatment group were killed 1, 2, and 4 hr post-treatment. The intestine of each mouse was removed, flash-frozen, and stored in a conventional freezer for later examination. Intestines were partially thawed, measured, and opened longitudinally, and the position of each worm, or worm cluster was measured. The intestine was divided into equal 5% segments based on the initial measurement and locations of worms, and worm clusters were recorded from the appropriate section of the intestine for analysis. There was no significant effect of treatment in the position of worms at 1 hr. There was a posterior shift in worm position in all treatment groups at 2 hr, except in the saline-treated mice; however, only worms in the glucose-fed mice were significantly posterior to the unfed controls. From 2 to 4 hr, there was a significant anterior movement of worms in both the glucose and chow-fed mice. The data strongly suggest that E. caproni responds to the initiation of gastric activity of the host by migrating anteriorly in the ileum. The specific stimulus for this migration is unknown.

No abstract