PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer

Up to 15% of free-ranging mule deer in northeastern Colorado and southeastern Wyoming, USA, are afflicted with a prion disease, or transmissible spongiform encephalopathy (TSE), known as chronic wasting disease (CWD). CWD is similar to a subset of TSEs including scrapie and variant Creutzfeldt¿Jakob disease in which the abnormal prion protein isoform, PrPCWD, accumulates in lymphoid tissue. Experimental scrapie studies have indicated that this early lymphoid phase is an important constituent of prion replication interposed between mucosal entry and central nervous system accumulation. To identify the lymphoid target cells associated with PrPCWD, we used triple-label immunofluorescence and high-resolution confocal microscopy on tonsils from naturally infected deer in advanced disease. We detected PrPCWD primarily extracellularly in association with follicular dendritic and B cell membranes as determined by frequent co-localization with antibodies against membrane bound immunoglobulin and CD21. There was minimal co-localization with cytoplasmic labels for follicular dendritic cells (FDC). This finding could indicate FDC capture of PrPCWD, potentially in association with immunoglobulin or complement, or PrPC conversion on FDC. In addition, scattered tingible body macrophages in the germinal centre contained coarse intracytoplasmic aggregates of PrPCWD, reflecting either phagocytosis of PrPCWD on FDC processes, apoptotic FDC or B cells, or actual PrPCWD replication within tingible body macrophages. To compare lymphoid cell targets in early and advanced disease, we also examined: (i) PrPCWD distribution in lymphoid cells of fawns within 3 months of oral CWD exposure and (ii) tonsil biopsies from preclinical deer with naturally acquired CWD. These studies revealed that the early lymphoid cellular distribution of PrPCWD was similar to that in advanced disease, i.e. in a pattern suggesting FDC association. We conclude that in deer, PrPCWD accumulates primarily extracellularly and associated with FDCs and possibly B cells ¿ a finding which raises questions as to the cells responsible for pathological prion productio

Assessing telluric correction methods for Na detections with high-resolution exoplanet transmission spectroscopy.

Using high-resolution ground-based transmission spectroscopy to probe exoplanetary atmospheres is difficult due to the inherent telluric contamination from absorption in Earth's atmosphere. A variety of methods have previously been used to remove telluric features in the optical regime and calculate the planetary transmission spectrum. In this paper we present and compare two such methods, specifically focusing on Na detections using high-resolution optical transmission spectra: (a) calculating the telluric absorption empirically based on the airmass, and (b) using a model of the Earth's transmission spectrum. We test these methods on the transmission spectrum of the hot Jupiter HD 189733 b using archival data obtained with the HARPS spectrograph during three transits. Using models for Centre-to-Limb Variation and the Rossiter-McLaughlin effect, spurious signals which are imprinted within the transmission spectrum are reduced. We find that correcting tellurics with an atmospheric model of the Earth is more robust and produces consistent results when applied to data from different nights with changing atmospheric conditions. We confirm the detection of sodium in the atmosphere of HD 189733 b, with doublet line contrasts of -0.64 $\pm$ 0.07 % (D2) and -0.53 $\pm$ 0.07 % (D1). The average line contrast corresponds to an effective photosphere in the Na line located around 1.13 $R_p$. We also confirm an overall blueshift of the line centroids corresponding to net atmospheric eastward winds with a speed of 1.8 $\pm$ 1.2 km/s. Our study highlights the importance of accurate telluric removal for consistent and reliable characterisation of exoplanetary atmospheres using high-resolution transmission spectroscopy

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results

Stress reducing effects of real and artificial nature in a hospital waiting room

Objectives: This field study investigated the potential stress-reducing effects of exposure to real or artificial nature on patients in a hospital waiting room. Additionally, it was investigated whether perceived attractiveness of the room could explain these effects. Design: In this between-patients experimental design, patients were exposed to one of the following: real plants, posters of plants, or no nature (control). These conditions were alternately applied to two waiting rooms. Location: The location of this study was two waiting rooms at the Radiology Department of a Dutch hospital. Subjects: The subjects comprised 457 patients (60% female and 40% male) who were mostly scheduled for echocardiogram, dual-energy x-ray absorptiometry, magnetic resonance imaging, computed tomography scans, or nuclear research. Results: Patients exposed to real plants, as well as patients exposed to posters of plants, report lower levels of experienced stress compared to the control condition. Further analyses show that these small but significant effects of exposure to nature are partially mediated by the perceived attractiveness of the waiting room. Conclusions: Natural elements in hospital environments have the potential to reduce patients' feelings of stress. By increasing the attractiveness of the waiting room by adding either real plants or posters of plants, hospitals can create a pleasant atmosphere that positively influences patients' well-being

Skin measurement devices to assess skin quality: A systematic review on reliability and validity

Background: Many treatments aim to slow down or reverse the visible signs of skin aging and thereby improve skin quality. Measurement devices are frequently employed to measure the effects of these treatments to improve skin quality, for example, skin elasticity, color, and texture. However, it remains unknown which of these devices is most reliable and valid. Materials and methods: MEDLINE, Embase, Cochrane Central, Web of Science, and Google Scholar databases were searched. Instruments were scored on reporting construct validity by means of convergent validity, interobserver, intraobserver, and interinstrument reliability. Results: For the evaluation of skin color, 11 studies were included describing 16 measurement devices, analyzing 3172 subjects. The most reliable device for skin color assessment is the Minolta Chromameter CR-300 due to good interobserver, intraobserver, and interinstrument reliability. For skin elasticity, seven studies assessed nine types of devices analyzing 290 subjects in total. No intra and interobserver reliability was reported. Skin texture was assessed in two studies evaluating 72 subjects using three different types of measurement devices. The PRIMOS device reported excellent intra and interobserver reliability. None of the included reviewed devices could be determined to be valid based on construct validity. Conclusion: The most reliable devices to evaluate skin color and texture in ordinary skin were, respectively, the Minolta Chromameter and PRIMOS. No reliable device is available to measure skin elasticity in ordinary skin and none of the included devices could be determined to be designated as valid

N- and KRAS mutations in primary testicular germ cell tumors: Incidence and possible biological implications

Recently, conflicting results have been reported on the incidence of RAS mutations in primary testicular germ cell tumors of adults (TGCTs). In four studies a low incidence of mutations (less than 15%) in a variety of TGCTs or derived cell lines was found, whereas in two other studies a high incidence of N- or KRAS mutations (over 40%) was shown. A total of 62 testicular seminomas (SE) and 34 nonseminomatous TGCTs (NS) were studied thus far. The largest series consisted of 42 TGCTs, studied on paraffin embedded tissue. We present the results of analysis for the presence of N- and KRAS mutations, in codons 12, 13, and 61, in snap frozen samples of 100 primary TGCTs, comprising 40 SE and 60 NS. Using the polymerase chain reaction (PCR) and allele specific oligonucleotide hybridization (ASO), mutations were found in five SE (three in NRAS and two in KRAS, all codon 12), and in one NS (KRAS, codon 12). To exclude underestimation of the incidence of RAS mutations in TGCTs due to the presence of an excess of wild type alleles in the analyzed sample, a PCR technique preferentially ampli

Dopant-induced crossover from 1D to 3D charge transport in conjugated polymers

The interplay between inter- and intra-chain charge transport in bulk polythiophene in the hopping regime has been clarified by studying the conductivity as a function of frequency (up to 3 THz), temperature and doping level. We present a model which quantitatively explains the observed crossover from quasi-one-dimensional transport to three-dimensional hopping conduction with increasing doping level. At high frequencies the conductivity is dominated by charge transport on one-dimensional conducting chains.Comment: 4 pages, 2 figure

Multiproxy analysis of permafrost preserved faeces provides an unprecedented insight into the diets and habitats of extinct and extant megafauna

The study of faecal samples to reconstruct the diets and habitats of extinct megafauna has traditionally relied on pollen and macrofossil analysis. DNA metabarcoding has emerged as a valuable tool to complement and refine these proxies. While published studies have compared the results of these three proxies for sediments, this comparison is currently lacking for permafrost preserved mammal faeces. Moreover, most metabarcoding studies have focused on a single plant-specific DNA marker region. In this study, we target both the commonly used chloroplast trnL P6 loop as well as nuclear ribosomal ITS (nrITS). The latter can increase taxonomic resolution of plant identifications but requires DNA to be relatively well preserved because of the target length (∼300–500 bp). We compare DNA results to pollen and macrofossil analyses from permafrost and ice-preserved faeces of Pleistocene and Holocene megafauna. Samples include woolly mammoth, horse, steppe bison as well as Holocene and extant caribou. Most plant identifications were found using DNA, likely because the studied faeces contained many vegetative remains that could not be identified using macrofossils or pollen. Several taxa were, however, identified to lower taxonomic levels uniquely with macrofossil and pollen analysis. The nrITS marker provides species level taxonomic resolution for commonly encountered plant families that are hard to distinguish using the other proxies (e.g. Asteraceae, Cyperaceae and Poaceae). Integrating the results from all proxies, we are able to accurately reconstruct known diets and habitats of the extant caribou. Applying this approach to the extinct mammals, we find that the Holocene horse and steppe bison were not strict grazers but mixed feeders living in a marshy wetland environment. The mammoths showed highly varying diets from different non-analogous habitats. This confirms the presence of a mosaic of habitats in the Pleistocene ‘mammoth steppe’ that mammoths could fully exploit due to their flexibility in food choice