Metabolite identification is the greatest challenge when analysing metabolomics data, as only a small proportion of metabolite reference standards exist. Clustering MS/MS spectra is a common method to identify similar compounds, however interrogation of underlying signature fragmentation patterns within clusters can be problematic. Previously published high-resolution LC-MS/MS data from the bioluminescent beetle (Photinus pyralis) provided an opportunity to mine new specialized metabolites in the lucibufagin class, compounds important for defense against predation. We aimed to 1) provide a workflow for hierarchically clustering MS/MS spectra for metabolomics data enabling users to cluster, visualise and easily interrogate the identification of underlying cluster ion profiles, and 2) use the workflow to identify key fragmentation patterns for lucibufagins in the hemolymph of P. pyralis. Features were aligned to their respective MS/MS spectra, then product ions were dynamically binned and resulting spectra were hierarchically clustered and grouped based on a cutoff distance threshold. Using the simplified visualization and the interrogation of cluster ion tables the number of lucibufagins was expanded from 17 to a total of 29.Previous studies of the association between parity and long-term cognitive changes have primarily focused on women and have shown conflicting results. We investigated this association by analyzing data collected on 303,196 subjects from the UK Biobank. We found that in both females and males, having offspring was associated with a faster response time and fewer mistakes made in the visual memory task. Subjects with two or three children had the largest differences relative to those who were childless, with greater effects observed in men. We further analyzed the association between parity and relative brain age (n = 13,584), a brain image-based biomarker indicating how old one's brain structure appears relative to peers. We found that in both sexes, subjects with two or three offspring had significantly reduced brain age compared to those without offspring, corroborating our cognitive function results. Our findings suggest that lifestyle factors accompanying having offspring, rather than the physical process of pregnancy experienced only by females, contribute to these associations and underscore the importance of studying such factors, particularly in the context of sex.Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Although green tea catechins (GTCs) are known to improve exercise endurance by enhancing lipid metabolism in skeletal muscle, little is known about the relationship between ammonia metabolism and the endurance-improving effect of GTCs. Here, we examined how ammonia affects endurance capacity and how GTCs affect ammonia metabolism in vivo in mice and how GTCs affect mouse skeletal muscle and liver in vitro. In mice, blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation-related gene expression in skeletal muscle. Repeated ingestion of GTCs combined with regular exercise training improved endurance capacity and the expression of urea cycle-related genes in liver. In C2C12 myotubes, hyperammonaemia suppressed mitochondrial respiration; however, pre-incubation with GTCs rescued this suppression.  https://www.selleckchem.com/products/sf2312.html  Together, our results demonstrate that hyperammonaemia decreases both mitochondrial respiration in myotubes and whole-body aerobic metabolism. Thus, GTC-mediated increases in ammonia metabolism in liver and resistance to ammonia-induced suppression of mitochondrial respiration in skeletal muscle may underlie the endurance-improving effect of GTCs.Inflammation of the gastrointestinal tract contributes to the development of inflammatory bowel disease (IBD). Human IBD is modeled by administering dextran sulfate sodium (DSS) to mice. In humans and mice, inflammatory M1 macrophages contribute to the progression of IBD whereas immunosuppressive M2 macrophages protect against colitis. The TLR2/1 agonist PAM3CSK4 (PAM3) induces human and murine monocytes to differentiate into immunosuppressive M2 macrophages, suggesting that PAM3 might be of benefit in the prevention/treatment of colitis. PAM3 was therefore administered to mice treated with DSS. As hypothesized, the number of M2 macrophages rose and disease severity decreased. The critical role of M2 macrophages in this process was established by transferring purified M2 macrophages from PAM3 treated control donors into DSS recipients and reducing colitis. These findings suggest that PAM3 may represent a novel approach to the treatment of human IBD.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Introduced mammals have devastated island nesting seabird populations worldwide. Declines in breeding seabirds on St Kilda, UK, have been linked to climate change and predation from great skuas Stercorarius skuas, but the introduced St Kilda field mouse Apodemus sylvaticus hirtensis may also play a role by feeding on adults, chicks or eggs. Here, we use stable isotopes in St Kilda mouse blood and potential dietary items to investigate their foraging ecology, specifically focussing on the importance of seabirds and marine foods in their diet. Mice were seasonally sampled at three sites on Hirta, St Kilda over three consecutive years (2010-2012). The δ13C and δ15N ratios were used in analyses, including isotope niche and dietary source mixing models, to examine foraging behaviour among locations and between seabird breeding seasons. Mice sampled in Carn Mor - where the majority of the island's seabirds nest - had consistently higher δ13C than other locations throughout the year, with δ15N also being significantly higher for all but one comparison. The isotopic niche width (SEAs) of Carn Mor mice in each season were distinct from the other locations, and became smaller during the seabird breeding season. Dietary mixing models revealed that seabirds made up a large proportion of the diet for mice from Carn Mor, particularly during the seabird breeding season. In conclusion, our work reveals that seabird-derived foods are likely to form a significant part of the diet of St Kilda mice populations located in and around breeding colonies. It is unclear however, whether this is from scavenging or predation of seabirds, or through their discarded food items. Given that mice have had significant effects on seabird populations elsewhere, it is important to carry out further work to determine whether mice are a significant cause of seabird mortality in this island ecosystem.