Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity.

Prions can exist as different strains that consist of conformational variants of the misfolded, pathogenic prion protein isoform PrPSc. Defined by stably transmissible biological and biochemical properties, strains have been identified in a spectrum of prion diseases, including chronic wasting disease (CWD) of wild and farmed cervids. CWD is highly contagious and spreads via direct and indirect transmission involving extraneural sites of infection, peripheral replication and neuroinvasion of prions. Here, we investigated the impact of infection route on CWD prion conformational selection and propagation. We used gene-targeted mouse models expressing deer PrP for intracerebral or intraperitoneal inoculation with fractionated or unfractionated brain homogenates from white-tailed deer, harboring CWD strains Wisc-1 or 116AG. Upon intracerebral inoculation, Wisc-1 and 116AG-inoculated mice differed in conformational stability of PrPSc. In brains of mice infected intraperitoneally with either inoculum, PrPSc propagated with identical conformational stability and fewer PrPSc deposits in most brain regions than intracerebrally inoculated animals. For either inoculum, PrPSc conformational stability in brain and spinal cord was similar upon intracerebral infection but significantly higher in spinal cords of intraperitoneally infected animals. Inoculation with fractionated brain homogenates resulted in lower variance of survival times upon intraperitoneal compared to intracerebral infection. In summary, we demonstrate that extraneural infection mitigates the impact of PrPSc quaternary structure on infection and reduces conformational variability of PrPSc propagated in the brain. These findings provide new insights into the evolution of stable CWD strains in natural, extraneural transmissions.

Migration analysis of Cr, Ni, Al, Fe, Mn, Cu, Zn, and Mo in internet-bought food serving stainless-steel utensils by ICP-MS and XRF.

A total of 120 internet bought stainless-steel utensil samples intended for food serving were analysed for their release of Cr, Ni, Al, Fe, Mn, Cu, Zn, and Mo. Samples were extracted using simulants under continuous and discontinuous test conditions, extracts were analysed by ICP-MS, and metallic compositions of utensils were indicated by XRF analysis. r2 values for all analytes were determined between 0.9982 and 0.9997. RSD and WRm values ranged between 4.5-8.5% and 80-107% for all analytes, respectively, and LOD was in the range of 0.11-25.8 µg/l. Migration results show that 35% of total sample types show non-compliance with the SMLs established by the Nordic guidelines. XRF data show good correlation between the metals' migration levels and their respective compositions in the utensil, and toxicological exposure estimates no significant adverse health effects from food served with articles exceeding the SMLs for Fe, Al, and Ni.