Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature

The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrPd). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research

Records in a changing world

In the context of this paper, a record is an entry in a sequence of random variables (RV's) that is larger or smaller than all previous entries. After a brief review of the classic theory of records, which is largely restricted to sequences of independent and identically distributed (i.i.d.) RV's, new results for sequences of independent RV's with distributions that broaden or sharpen with time are presented. In particular, we show that when the width of the distribution grows as a power law in time $n$, the mean number of records is asymptotically of order $\ln n$ for distributions with a power law tail (the \textit{Fr\'echet class} of extremal value statistics), of order $(\ln n)^2$ for distributions of exponential type (\textit{Gumbel class}), and of order $n^{1/(\nu+1)}$ for distributions of bounded support (\textit{Weibull class}), where the exponent $\nu$ describes the behaviour of the distribution at the upper (or lower) boundary. Simulations are presented which indicate that, in contrast to the i.i.d. case, the sequence of record breaking events is correlated in such a way that the variance of the number of records is asymptotically smaller than the mean.Comment: 12 pages, 2 figure

The emergence of classical BSE from atypical/Nor98 scrapie

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE

Focus on high energy particles and atmospheric processes

The letters published in the ‘Focus issue on high energy particles and atmospheric processes’ serve to broaden the discussion about the influence of high energy particles on the atmosphere beyond their possible effects on clouds and climate. These letters link climate and meteorological processes with atmospheric electricity, atmospheric chemistry, high energy physics and aerosol science from the smallest molecular cluster ions through to liquid droplets. Progress in such a disparate and complex topic is very likely to benefit from continued interdisciplinary interactions between traditionally distinct science areas

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed

Air temperature variations and gradients along the coast and fjords of western Spitsbergen

Daily temperature measurements from six meteorological stations along the coast and fjords of western Spitsbergen have been digitized and quality controlled in a Norwegian, Russian and Polish collaboration. Complete daily data series have been reconstructed back to 1948 for all of the stations. One of the station’s monthly temperature series has previously been extended back to 1898 and is included in this study. The long-term series show large temperature variability on western Spitsbergen with colder periods in the 1910s and 1960s and warmer periods in the 1930s, 1950s and in the 21st century. The most recent years are the warmest ones in the instrumental records. There is a positive and statistically significant trend in the annual times series for all of the stations; however, the strongest warming is seen in winter and spring. For the period 1979-2015, the linear trends range from 1.0 to 1.38°C/decade for the annual series and from 2.0 to 2.38°C/decade in winter. Threshold statistics demonstrate a decrease in the number of cold days per year and an increase in the number of warm days. A decreasing inter-annual variability is observed. In winter, spring and autumn, the stations in the northernmost areas of west Spitsbergen and in the innermost parts of Isfjorden are the coldest ones. In summer, however, the southernmost station is the coldest one