Everything is connected: network thinking in entomology

Editorial

Identification of Binding Regions of Bilirubin in the Ligand-Binding Pocket of the Peroxisome Proliferator-Activated Receptor-A (PPARalpha)

Recent work has shown that bilirubin has a hormonal function by binding to the peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that drives the transcription of genes to control adiposity. Our previous in silico work predicted three potential amino acids that bilirubin may interact with by hydrogen bonding in the PPARα ligand-binding domain (LBD), which could be responsible for the ligand-induced function. To further reveal the amino acids that bilirubin interacts with in the PPARα LBD, we harnessed bilirubin’s known fluorescent properties when bound to proteins such as albumin. Our work here revealed that bilirubin interacts with threonine 283 (T283) and alanine 333 (A333) for ligand binding. Mutational analysis of T283 and A333 showed significantly reduced bilirubin binding, reductions of 11.4% and 17.0%, respectively. Fenofibrate competitive binding studies for the PPARα LBD showed that bilirubin and fenofibrate possibly interact with different amino acid residues. Furthermore, bilirubin showed no interaction with PPARγ. This is the first study to reveal the amino acids responsible for bilirubin binding in the ligand-binding pocket of PPARα. Our work offers new insight into the mechanistic actions of a well-known molecule, bilirubin, and new fronts into its mechanisms

The evolution of RNAi as a defence against viruses and transposable elements

RNA interference (RNAi) is an important defence against viruses and transposable elements (TEs). RNAi not only protects against viruses by degrading viral RNA, but hosts and viruses can also use RNAi to manipulate each other's gene expression, and hosts can encode microRNAs that target viral sequences. In response, viruses have evolved a myriad of adaptations to suppress and evade RNAi. RNAi can also protect cells against TEs, both by degrading TE transcripts and by preventing TE expression through heterochromatin formation. The aim of our review is to summarize and evaluate the current data on the evolution of these RNAi defence mechanisms. To this end, we also extend a previous analysis of the evolution of genes of the RNAi pathways. Strikingly, we find that antiviral RNAi genes, anti-TE RNAi genes and viral suppressors of RNAi all evolve rapidly, suggestive of an evolutionary arms race between hosts and parasites. Over longer time scales, key RNAi genes are repeatedly duplicated or lost across the metazoan phylogeny, with important implications for RNAi as an immune defence

Inducing cold-sensitivity in the frigophilic fly Drosophila montana by RNAi

The work was supported by CNPq (Fellowship to FMV) and a NERC Studentship to DJP.Cold acclimation is a critical physiological adaptation for coping with seasonal cold. By increasing their cold tolerance individuals can remain active for longer at the onset of winter and can recover more quickly from a cold shock. In insects, despite many physiological studies, little is known about the genetic basis of cold acclimation. Recently, transcriptomic analyses in Drosophila virilis and D.montana revealed candidate genes for cold acclimation by identifying genes upregulated during exposure to cold. Here, we test the role of myo-inositol-1-phosphate synthase (Inos), in cold tolerance in D. montana using an RNAi approach. D. montana has a circumpolar distribution and overwinters as an adult in northern latitudes with extreme cold. We assessed cold tolerance of dsRNA knock-down flies using two metrics: chill-coma recovery time (CCRT) and mortality rate after cold acclimation. Injection of dsRNAInos did not alter CCRT,either overall or in interaction with the cold treatment, however it did induced cold specific mortality, with high levels of mortality observed in injected flies acclimated at 5°C but not at 19°C. Overall, injection with dsRNAInos induced a temperature sensitive mortality rate of over 60% in this normally cold-tolerant species. qPCRanalysis confirmed that dsRNA injection successfully reduced gene expression of Inos. Thus, our results demonstrate the involvement of Inos in increasing cold tolerance in D. montana. The potential mechanisms involved by which Inos increases cold tolerance are also discussed.Publisher PDFPeer reviewe

Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle

This work was funded by UK NERC grants to M.G.R. and A.J.M. an NERC studentship to D.J.P. the University of Georgia and a US NSF grant to A.J.M. and M.G.R.Parenting in the burying beetle Nicrophorus vespilloides is complex and, unusually, the sex and number of parents that can be present is flexible. Such flexibility is expected to involve specialized behaviour by the two sexes under biparental conditions. Here, we show that offspring fare equally well regardless of the sex or number of parents present. Comparing transcriptomes, we find a largely overlapping set of differentially expressed genes in both uniparental and biparental females and in uniparental males including vitellogenin, associated with reproduction, and takeout, influencing sex-specific mating and feeding behaviour. Gene expression in biparental males is similar to that in non-caring states. Thus, being ‘biparental’ in N. vespilloides describes the family social organization rather than the number of directly parenting individuals. There was no specialization; instead, in biparental families, direct male parental care appears to be limited with female behaviour unchanged. This should lead to strong sexual conflict.Publisher PDFPeer reviewe

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD

The evolution of RNAi as a defence against viruses and transposable elements

RNA interference (RNAi) is an important defence against viruses and transposable elements (TEs). RNAi not only protects against viruses by degrading viral RNA, but hosts and viruses can also use RNAi to manipulate each other's gene expression, and hosts can encode microRNAs that target viral sequences. In response, viruses have evolved a myriad of adaptations to suppress and evade RNAi. RNAi can also protect cells against TEs, both by degrading TE transcripts and by preventing TE expression through heterochromatin formation. The aim of our review is to summarize and evaluate the current data on the evolution of these RNAi defence mechanisms. To this end, we also extend a previous analysis of the evolution of genes of the RNAi pathways. Strikingly, we find that antiviral RNAi genes, anti-TE RNAi genes and viral suppressors of RNAi all evolve rapidly, suggestive of an evolutionary arms race between hosts and parasites. Over longer time scales, key RNAi genes are repeatedly duplicated or lost across the metazoan phylogeny, with important implications for RNAi as an immune defence

Rats Genetically Selected for High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin by Upregulation of Hepatic Biliverdin Reductase-A (BVRA) and Suppression of UGT1A1

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome proliferator-activated receptor-α (PPARα), a ligand-induced transcription factor, and the higher bilirubin HCR rats had significantly increased PPARα-target genes Fgf21, Abcd3, and Gys2. These are known to promote liver function and glycogen storage, which we found by Periodic acid–Schiff (PAS) staining that hepatic glycogen content was higher in the HCR versus the LCR. Our results demonstrate that exercise stimulates pathways that raise plasma bilirubin through alterations in hepatic enzymes involved in bilirubin synthesis and metabolism, improving liver function, and glycogen content. These mechanisms may explain the beneficial effects of exercise on plasma bilirubin levels and health in humans

Complete Genome Sequence of Serotype III Streptococcus agalactiae Sequence Type 17 Strain 874391.

Here we report the complete genome sequence of Streptococcus agalactiae strain 874391. This serotype III isolate is a member of the hypervirulent sequence type 17 (ST-17) lineage that causes a disproportionate number of cases of invasive disease in humans and mammals. A brief historical context of the strain is discussed

A seasonal cycle in the export of bottom water from the Weddell Sea

Dense water formed over the Antarctic continental shelf rapidly descends into the deep ocean where it spreads throughout the global ocean as Antarctic Bottom Water1, 2. The coldest and most voluminous component of this water mass is Weddell Sea bottom water1, 3, 4, 5, 6, 7. Here we present observations over eight years of the temperature and salinity stratification in the lowermost ocean southeast of the South Orkney Islands, marking the export of Weddell Sea bottom water. We observe a pronounced seasonal cycle in bottom temperatures, with a cold pulse in May/June and a warm one in October/November, but the timing of these phases varies each year. We detect the coldest bottom water in 1999 and 2002, whereas there was no cold phase in 2000. On the basis of current velocities and water mass characteristics, we infer that the pulses originate from the southwest Weddell Sea. We propose that the seasonal fluctuations of Weddell Sea bottom-water properties are governed by the seasonal cycle of the winds over the western margin of the Weddell Sea. Interannual fluctuations are linked to the variability of the wind-driven Weddell Sea gyre and hence to large-scale climate phenomena such as the Southern Annular Mode and El Niño/Southern Oscillation