Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

<p>Abstract</p> <p>Background</p> <p>Classical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrP^Sc) in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrP^Schas been detected in peripheral blood mononuclear cells (PBMCs), plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay.</p> <p>Results</p> <p>Serial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrP^Scimmunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15), CD72⁺B lymphocytes (3/3), CD21⁺B lymphocytes (3/3) or platelet-rich plasma (2/3) fractions. As expected, whole blood (11/13) and buffy coat (5/5) recipients showed positive PrP^Sclabeling in lymphoid follicles. However, at 549 days post-transfusion, PrP^Scwas not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction.</p> <p>Conclusions</p> <p>Prion infectivity was detected in circulating PBMCs, CD72⁺pan B lymphocytes, the CD21⁺subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrP^Scdetection levels in blood samples.</p

Measurement of the Zero Crossing in a Feshbach Resonance of Fermionic 6-Li

We measure a zero crossing in the scattering length of a mixture of the two lowest hyperfine states of 6-Li. To locate the zero crossing, we monitor the decrease in temperature and atom number arising from evaporation in a CO2 laser trap as a function of magnetic field B. The temperature decrease and atom loss are minimized for B=528(4) G, consistent with no evaporation. We also present preliminary calculations using potentials that have been constrained by the measured zero crossing and locate a broad Feshbach resonance at approximately 860 G, in agreement with previous theoretical predictions. In addition, our theoretical model predicts a second and much narrower Feshbach resonance near 550 G.Comment: Five pages, four figure

All-Optical Production of a Degenerate Fermi Gas

We achieve degeneracy in a mixture of the two lowest hyperfine states of $^6$Li by direct evaporation in a CO$_2$ laser trap, yielding the first all-optically produced degenerate Fermi gas. More than $10^5$ atoms are confined at temperatures below $4 \mu$K at full trap depth, where the Fermi temperature for each state is $8 \mu$K. This degenerate two-component mixture is ideal for exploring mechanisms of superconductivity ranging from Cooper pairing to Bose condensation of strongly bound pairs.Comment: 4 pgs RevTeX with 2 eps figs, to be published in Phys. Rev. Let

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020