A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE.

Nicotinic acetylcholine receptors (nAChRs) are best known to function as ligand-gated ion channels in the nervous system. However, recent evidence suggests that nicotine modulates inflammation by desensitizing non-neuronal nAChRs, rather than by inducing channel opening. Silent agonists are molecules that selectively induce the desensitized state of nAChRs while producing little or no channel opening. A silent agonist of α7 nAChRs has recently been shown to reduce inflammation in an animal model of inflammatory pain. The objective of this study was to determine whether a silent agonist of α7 nAChRs can also effectively modulate inflammation and disease manifestation in an animal model of multiple sclerosis. We first evaluated the effects of various nAChR ligands and of an α7 nAChR-selective silent agonist, 1-ethyl-4-(3-(bromo)phenyl)piperazine (m-bromo PEP), on the modulation of mouse bone marrow-derived monocyte/macrophage (BMDM) numbers, phenotype and cytokine production. The non-competitive antagonist mecamylamine and the silent agonist m-bromo PEP reduced pro-inflammatory BMDM numbers by affecting their viability and proliferation. Both molecules also significantly reduced cytokine production by mouse BMDMs and significantly ameliorated disease in experimental autoimmune encephalomyelitis. Finally, m-bromo PEP also reduced chronic inflammatory pain in mice. Taken together, our results further support the hypothesis that nAChRs may modulate inflammation via receptor desensitization rather than channel opening. α7 nAChR-selective silent agonists may thus be a novel source of anti-inflammatory compounds that could be used for the treatment of inflammatory disorders.

Metal Toxicity and Resistance in Plants and Microorganisms in Terrestrial Ecosystems.

Metals are major abiotic stressors of many organisms, but their toxicity in plants is not as studied as in microorganisms and animals. Likewise, research in plant responses to metal contamination is sketchy. Candidate genes associated with metal resistance in plants have been recently discovered and characterized. Some mechanisms of plant adaptation to metal stressors have been now decrypted. New knowledge on microbial reaction to metal contamination and the relationship between bacterial, archaeal, and fungal resistance to metals has broadened our understanding of metal homeostasis in living organisms. Recent reviews on metal toxicity and resistance mechanisms focused only on the role of transcriptomics, proteomics, metabolomics, and ionomics. This review is a critical analysis of key findings on physiological and genetic processes in plants and microorganisms in responses to soil metal contaminations.

Changes in enzymatic activities in metal contaminated and reclaimed lands in Northern Ontario (Canada).

Metal and sulfur dioxide (SO2) contaminations in Northern Ontario (Canada), especially in the Greater Sudbury Region (GSR) caused by mining activities have resulted in severe environmental degradations. A long term restoration program has led to significant landscape changes and healthy ecosystems. The objective of this study was to assess variation in enzymatic activities and soil respiration in metal contaminated and reclaimed ecosystems. Soil analysis revealed that respiration rates were higher in metal contaminated limed soils (65ppm) compared to adjacent unlimed areas (35ppm). The respiration rates in metal contaminated sites (55ppm) were significantly lower compared to reference (metal-uncontaminated) areas (90ppm). ß-glucosidase (BG), cellobiohydrolase (CBH), ß-N-acetylglucosaminidase (NAGase), aryl sulfatase (AS), acid phosphatase (AP), alkaline phosphatase (AlP), glycine aminopeptidase (GAP), and leucine aminopeptidase (LAP) activities were significantly higher in limed compared to unlimed sites. Metal contamination significantly reduced the activities of these enzymes with the exception of LAP. An opposite trend was observed for peroxidase (PER) activity that was lower in limed compared to corresponding unlimed areas. Likewise, PER activity values were significantly lower in metal contaminated than in uncontaminated reference sites.

Microbial Response to Soil Liming of Damaged Ecosystems Revealed by Pyrosequencing and Phospholipid Fatty Acid Analyses.

AIMS: To assess the effects of dolomitic limestone applications on soil microbial communities' dynamics and bacterial and fungal biomass, relative abundance, and diversity in metal reclaimed regions. METHODS AND RESULTS: The study was conducted in reclaimed mining sites and metal uncontaminated areas. The limestone applications were performed over 35 years ago. Total microbial biomass was determined by Phospholipid fatty acids. Bacterial and fungal relative abundance and diversity were assessed using 454 pyrosequencing. There was a significant increase of total microbial biomass in limed sites (342 ng/g) compared to unlimed areas (149 ng/g). Chao1 estimates followed the same trend. But the total number of OTUs (Operational Taxonomic Units) in limed (463 OTUs) and unlimed (473 OTUs) soil samples for bacteria were similar. For fungi, OTUs were 96 and 81 for limed and unlimed soil samples, respectively. Likewise, Simpson and Shannon diversity indices revealed no significant differences between limed and unlimed sites. Bacterial and fungal groups specific to either limed or unlimed sites were identified. Five major bacterial phyla including Actinobacteria, Acidobacteria, Chloroflexi, Firmicutes, and Proteobacteria were found. The latter was the most prevalent phylum in all the samples with a relative abundance of 50%. Bradyrhizobiaceae family with 12 genera including the nitrogen fixing Bradirhizobium genus was more abundant in limed sites compared to unlimed areas. For fungi, Ascomycota was the most predominant phylum in unlimed soils (46%) while Basidiomycota phylum represented 86% of all fungi in the limed areas. CONCLUSION: Detailed analysis of the data revealed that although soil liming increases significantly the amount of microbial biomass, the level of species diversity remain statistically unchanged even though the microbial compositions of the damaged and restored sites are different. SIGNIFICANCE AND IMPACT OF THE STUDY: Soil liming still have a significant beneficial effects on soil microbial abundance and composition > 35 years after dolomitic limestone applications.