Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice

Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail -/- mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.Siân P. Cartland, Hanis H. Harith, Scott W. Genner, Lei Dang, Victoria C. Cogger, Melissa Vellozzi, Belinda A. Di Bartolo, Shane R. Thomas, Leon A. Adams, Mary M. Kavurm

Non‐specific amplification compromises environmental DNA metabarcoding with COI

1. Metabarcoding extra-organismal DNA from environmental samples is now a key technique in aquatic biomonitoring and ecosystem health assessment. However, choice of genetic marker and primer set is a critical consideration when designing experiments, especially so when developing community standards and legislative frameworks. Mitochondrial cytochrome c oxidase subunit I (COI), the standard DNA barcode marker for animals, with its extensive reference library, taxonomic discriminatory power, and predictable sequence variation, is the natural choice for many metabarcoding applications such as the bulk sequencing of invertebrates. However, the overall utility of COI for environmental sequencing of targeted taxonomic groups has yet to be fully scrutinised. 2. Here, by using a case study of marine and freshwater fishes from the British Isles, we quantify the in silico performance of twelve mitochondrial primer pairs from COI, cytochrome b, 12S and 16S, in terms of reference library coverage, taxonomic discriminatory power, and primer universality. We subsequently test in vitro three COI primer pairs and one 12S pair for their specificity, reproducibility, and congruence with independent datasets derived from traditional survey methods at five estuarine and coastal sites in the English Channel and North Sea coast. 3. Our results show that for aqueous extra-organismal DNA at low template concentrations, both metazoan and fish-targeted COI primers perform poorly in comparison to 12S, exhibiting low levels of reproducibility due to non-specific amplification of prokaryotic and non-target eukaryotic DNAs. 4. An ideal metabarcode would have an extensive reference library for which custom primer sets can be designed for either broad assessments of biodiversity or taxon specific surveys, but unfortunately, low primer specificity hinders the use of COI, while the paucity of reference sequences is problematic for 12S. The latter, however, can be mitigated by expanding the concept of DNA barcodes to include whole mitochondrial genomes generated by genome-skimming existing tissue collections

Whole-genome sequences of Malawi cichlids reveal multiple radiations interconnected by gene flow.

The hundreds of cichlid fish species in Lake Malawi constitute the most extensive recent vertebrate adaptive radiation. Here we characterize its genomic diversity by sequencing 134 individuals covering 73 species across all major lineages. The average sequence divergence between species pairs is only 0.1-0.25%. These divergence values overlap diversity within species, with 82% of heterozygosity shared between species. Phylogenetic analyses suggest that diversification initially proceeded by serial branching from a generalist Astatotilapia-like ancestor. However, no single species tree adequately represents all species relationships, with evidence for substantial gene flow at multiple times. Common signatures of selection on visual and oxygen transport genes shared by distantly related deep-water species point to both adaptive introgression and independent selection. These findings enhance our understanding of genomic processes underlying rapid species diversification, and provide a platform for future genetic analysis of the Malawi radiation

Effects of acute and chronic temperature changes on the functional responses of the dogfish Scyliorhinus canicula (Linnaeus, 1758) towards amphipod prey Echinogammarus marinus (Leach, 1815)

Predation is a strong driver of population dynamics and community structure and it is essential to reliably quantify and predict predation impacts on prey populations in a changing thermal landscape. Here, we used comparative functional response analyses to assess how predator-prey interactions between dogfish and invertebrate prey change under different warming scenarios. The Functional Response Type, attack rate, handling time and maximum feeding rate estimates were calculated for Scyliorhinus canicula preying upon Echinogammarus marinus under temperatures of 11.3 °C and 16.3 °C, which represent both the potential daily variation and predicted higher summer temperatures within Strangford Lough, N. Ireland. A two x two design of “Predator Acclimated”, “Prey Acclimated”, “Both Acclimated”, and “Both Unacclimated” was implemented to test functional responses to temperature rise. Attack rate was higher at 11.3 °C than at 16.3 °C, but handling time was lower and maximum feeding rates were higher at 16.3 °C. Non-acclimated predators had similar maximum feeding rate towards non-acclimated and acclimated prey, whereas acclimated predators had significantly higher maximum feeding rates towards acclimated prey as compared to non-acclimated prey. Results suggests that the predator attack rate is decreased by increasing temperature but when both predator and prey are acclimated the shorter handling times considerably increase predator impact. The functional response of the fish changed from Type II to Type III with an increase in temperature, except when only the prey were acclimated. This change from population destabilizing Type II to more stabilizing Type III could confer protection to prey at low densities but increase the maximum feeding rate by Scyliorhinus canicula in the future. However, predator movement between different thermal regimes may maintain a Type II response, albeit with a lower maximum feeding rate. This has implications for the way the increasing population Scyliorhinus canicula in the Irish Sea may exploit valuable fisheries stocks in the future