Comparative metabolomic analysis of exudates of microcystin-producing and microcystin-free Microcystis aeruginosa strains

Cyanobacterial harmful algal blooms (cHABs) dominated by Microcystis aeruginosa threaten the ecological integrity and beneficial uses of lakes globally. In addition to producing hepatotoxic microcystins (MC), M. aeruginosa exudates (MaE) contain various compounds with demonstrated toxicity to aquatic biota. Previously, we found that the ecotoxicity of MaE differed between MC-producing and MC-free strains at exponential (E-phase) and stationary (S-phase) growth phases. However, the components in these exudates and their specific harmful effects were unclear. In this study, we performed untargeted metabolomics based on liquid chromatography-mass spectrometry to reveal the constituents in MaE of a MC-producing and a MC-free strain at both E-phase and S-phase. A total of 409 metabolites were identified and quantified based on their relative abundance. These compounds included lipids, organoheterocyclic compounds, organic acid, benzenoids and organic oxygen compounds. Multivariate analysis revealed that strains and growth phases significantly influenced the metabolite profile. The MC-producing strain had greater total metabolites abundance than the MC-free strain at S-phase, whereas the MC-free strain released higher concentrations of benzenoids, lipids, organic oxygen, organic nitrogen and organoheterocyclic compounds than the MC-producing strain at E-phase. Total metabolites had higher abundance in S-phase than in E- phase in both strains. Analysis of differential metabolites (DMs) and pathways suggest that lipids metabolism and biosynthesis of secondary metabolites were more tightly coupled to growth phases than to strains. Abundance of some toxic lipids and benzenoids DMs were significantly higher in the MC-free strain than the MC-producing one. This study builds on the understanding of MaE chemicals and their biotoxicity, and adds to evidence that non-MC-producing strains of cyanobacteria may also pose a threat to ecosystem health

Apoptosis Governs the Elimination of Schistosoma japonicum from the Non-Permissive Host Microtus fortis

The reed vole, Microtus fortis, is the only known mammalian host in which schistosomes of Schistosoma japonicum are unable to mature and cause significant pathogenesis. However, little is known about how Schistosoma japonicum maturation (and, therefore, the development of schistosomiasis) is prevented in M. fortis. In the present study, the ultrastructure of 10 days post infection schistosomula from BALB/c mice and M. fortis were first compared using scanning electron microscopy and transmission electron microscopy. Electron microscopic investigations showed growth retardation and ultrastructural differences in the tegument and sub-tegumental tissues as well as in the parenchymal cells of schistosomula from M. fortis compared with those in BALB/c mice. Then, microarray analysis revealed significant differential expression between the schistosomula from the two rodents, with 3,293 down-regulated (by ≥2-fold) and 71 up-regulated (≥2 fold) genes in schistosomula from the former. The up-regulated genes included a proliferation-related gene encoding granulin (Grn) and tropomyosin. Genes that were down-regulated in schistosomula from M. fortis included apoptosis-inhibited genes encoding a baculoviral IAP repeat-containing protein (SjIAP) and cytokine-induced apoptosis inhibitor (SjCIAP), genes encoding molecules involved in insulin metabolism, long-chain fatty acid metabolism, signal transduction, the transforming growth factor (TGF) pathway, the Wnt pathway and in development. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis, and flow cytometry revealed that the percentages of early apoptotic and late apoptotic and/or necrotic cells, as well as the level of caspase activity, in schistosomula from M. fortis were all significantly higher than in those from BALB/c mice

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets