221 research outputs found
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 , the mean number of records is
asymptotically of order for distributions with a power law tail (the
\textit{Fr\'echet class} of extremal value statistics), of order
for distributions of exponential type (\textit{Gumbel class}), and of order
for distributions of bounded support (\textit{Weibull class}),
where the exponent 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
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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
CHASE-PL Climate Projection dataset over Poland – bias adjustment of EURO-CORDEX simulations
The CHASE-PL (Climate change impact assessment for selected sectors in
Poland) Climate Projections – Gridded Daily Precipitation and Temperature
dataset 5 km (CPLCP-GDPT5) consists of projected daily minimum and
maximum air temperatures and precipitation totals of nine EURO-CORDEX
regional climate model outputs bias corrected and downscaled to
a 5 km × 5 km grid. Simulations of one historical period
(1971–2000) and two future horizons (2021–2050 and 2071–2100) assuming two
representative concentration pathways (RCP4.5 and RCP8.5) were produced. We
used the quantile mapping method and corrected any systematic seasonal bias
in these simulations before assessing the changes in annual and seasonal
means of precipitation and temperature over Poland. Projected changes
estimated from the multi-model ensemble mean showed that annual means of
temperature are expected to increase steadily by 1 °C until
2021–2050 and by 2 °C until 2071–2100 assuming the RCP4.5
emission scenario. Assuming the RCP8.5 emission
scenario, this can reach up to almost 4 °C by 2071–2100.
Similarly to temperature, projected changes in regional annual means of
precipitation are expected to increase by 6 to 10 % and by 8 to
16 % for the two future horizons and RCPs, respectively. Similarly,
individual model simulations also exhibited warmer and wetter conditions on
an annual scale, showing an intensification of the magnitude of the change at
the end of the 21st century. The same applied for projected changes in
seasonal means of temperature showing a higher winter warming rate by up to
0.5 °C compared to the other seasons. However, projected
changes in seasonal means of precipitation by the individual models largely
differ and are sometimes inconsistent, exhibiting spatial variations which
depend on the selected season, location, future horizon, and RCP. The overall
range of the 90 % confidence interval predicted by the ensemble of
multi-model simulations was found to likely vary between −7 %
(projected for summer assuming the RCP4.5 emission scenario) and
+40 % (projected for winter assuming the RCP8.5 emission scenario) by
the end of the 21st century. Finally, this high-resolution bias-corrected
product can serve as a basis for climate change impact and adaptation studies
for many sectors over Poland. The CPLCP-GDPT5 dataset is publicly available
at http://dx.doi.org/10.4121/uuid:e940ec1a-71a0-449e-bbe3-29217f2ba31d
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
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