Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

OBJECTIVES: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1ß (IL-1ß) have been implicated in pancreatic ß cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic ß cell death could allow for selective T2D treatment without compromising all IL-1ß-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic ß cell death, thereby preventing the onset of T2D. METHODS: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic ß cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. RESULTS: MCC950 was a potent inhibitor of NLRP3-induced IL-1ß in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1ß. CONCLUSIONS: NLRP3 driven-pancreatic IL-1ß inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

The importance of carcass volatiles as attractants for the hide beetle Dermestes maculatus (De Geer).

A decaying cadaver emits volatile organic compounds that are used by necrophilous and necrophagous insects in order to find their brood substrate. Although volatile organic compounds (VOCs) that are released by carcasses have been identified, little is known about the specific compounds that are used by these insects while searching for a brood substrate. Therefore, we have investigated the chemical ecology involved in the attraction of the necrophagous hide beetle Dermestes maculatus, which feeds as an adult and larva upon decomposing carcasses. Our aims have been to identify the responsible compounds in the odours of the carcass that are important for the attraction of the beetles. Furthermore, we have studied sex- and age-related differences in beetle attraction and tested whether the hide beetle can distinguish between various stages of decomposition by means of the emitted odours. Headspace collection of volatiles released from piglet carcasses (bloated stage, post-bloating stage, advanced decay and dry remains), coupled gas chromatography-mass spectrometry (GC-MS), gas chromatography with electroantennographic detection (GC-EAD) and bioassays were conducted to identify the volatiles responsible for the attraction of the beetles. Freshly emerged male beetles were attracted by the odour of piglets in the post-bloating stage (9 days after death; T(mean) = 27 °C) and the EAD-active compound benzyl butyrate. Statistical analysis revealed a higher relative proportion of benzyl butyrate in the odour bouquet of the post-bloating stage in comparison with the other stages. We therefore conclude that this compound plays an important role in the attraction of hide beetles to carcass odour. This underlines the potential use of D. maculatus for the estimation of the post mortem interval. The decomposition stage at which the female beetles are attracted to the odour of a cadaver remains unknown, as does the nature of this attraction. Pheromones (sexual or aggregation pheromones) might play an essential role correlated with their attraction to carrion and consequently with their attraction to the substrate for mating and ovipositioning.

How promptly do blowflies colonise fresh carcasses? A study comparing indoor with outdoor locations.

We investigated the time taken by blowflies to find and oviposit on fresh carcasses placed outdoors and indoors. Paired dead piglets, one in the open and the other in a nearby room (on the first floor of an occupied, detached, suburban house near Cologne, Germany, with a window opened 9 cm) were exposed simultaneously on nine occasions. The species visiting both locations and the number of egg batches deposited by blowflies between both locations were monitored 2, 8, 24 and 48 h after exposure. In all cases the indoor piglet carcass was exclusively infested by Calliphora vicina; only in one case, on a very hot day after a 48-h exposure did Lucilia sericata infest an indoor carcass. The outdoor piglets were infested by a variety of common corpse-visiting species: L. sericata, L. caesar, L. illustris, C. vicina and C. vomitoria. A significant difference in the number of egg batches was detected between indoors and outdoors. Furthermore, in only two of nine runs did oviposition occur within the first 24h of exposure indoors. Ambient temperature, daylength and rainfall had no significant effect on the number of egg batches. Moreover, we observed fewer larvae on indoor piglets, too few to form maggot masses. This might result in slower larval development than in the case of outdoor piglets. We conclude that post-mortem interval (PMI) estimation for corpses found indoors must be handled carefully as oviposition might have taken place with a delay up to 24h.