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<p>Neurodegeneration is a critical problem in aging populations and is characterized by severe central nervous system (CNS) inflammation. Macrophages closely regulate inflammation in the CNS and periphery by taking on different activation states. The source of inflammation in many neurodegenerative diseases has been preliminarily linked to a decrease in the CNS M2 macrophage population and a subsequent increase in M1-mediated neuroinflammation. The Recepteur D’Origine Nantais (Ron) is a receptor tyrosine kinase expressed on tissue-resident macrophages including microglia. Activation of Ron by its ligand, macrophage-stimulating protein, attenuates obesity-mediated inflammation in the periphery. An in vivo deletion of the ligand binding domain of Ron (Ron^−/−) promotes inflammatory (M1) and limits a reparative (M2) macrophage activation. However, whether or not this response influences CNS inflammation has not been determined. In this study, we demonstrate that in homeostasis Ron^−/− mice developed an inflammatory CNS niche with increased tissue expression of M1-associated markers when compared to age-matched wild-type (WT) mice. Baseline metabolic analysis of CNS tissue indicates exacerbated levels of metabolic stress in Ron^−/− CNS. In a disease model of multiple sclerosis, experimental autoimmune encephalomyelitis, Ron^−/− mice exhibit higher disease severity when compared to WT mice associated with increased CNS tissue inflammation. In a model of diet-induced obesity (DIO), Ron^−/− mice exhibit exacerbated CNS inflammation with decreased expression of the M2 marker Arginase-1 (Arg-1) and a robust increase in M1 markers compared to WT mice following 27 weeks of DIO. Collectively, these results illustrate that activation of Ron in the CNS could be a potential therapeutic approach to treating various grades of CNS inflammation underlying neurodegeneration.</p

MOESM1 of Reversing methanogenesis to capture methane for liquid biofuel precursors

Additional file 1. This file consists of four supplemental tables and six supplemental figures. Table S1 lists the components in the HS medium used to grow ANME-1 Mcr-producing M. acetivorans on methane and 0.1 mM or 10 mM FeCl3. Table S2 shows the fold changes of differentially expressed genes in M. acetivorans/pES1-MATmcr3 grown on methane and 0.1 mM FeCl3, in comparison to the same strain grown on methanol. Table S3 lists the strains and plasmids, and Table S4 lists the oligonucleotides, used in this study. Figure S1 shows the three promoters used to express ANME-1 mcrBGA genes. Figure S2 shows the detected McrA-FLAG in M. acetivorans/pES1-MATmcr3-flag grown on methane after five days. Figure S3 shows the detection of ANME-1 mcrA after 30 days of growth on methane. Figure S4 shows the GC/MS spectra of culture supernatants used to identify acetate from H13CO. Figure S5 shows the flux through the various reactions in the methanogenesis pathway of M. acetivorans estimated by 13C-metabolic flux analysis using 13C-labeled bicarbonate as the input tracer. Figure S6 shows a simplified methanogenesis pathway from CO2 and CH3OH of M. acetivorans