Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys:The Same Complex Proteinopathy Appearing after Very Different Incubation Times

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a “species barrier,” often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys (Saimiri sp., here designated SQ) with serial dilutions of a bovine brain suspension containing the BSE agent and monitored them for as long as ten years. Previously, we showed that SQ infected with the original “classical” BSE agent (SQ-BSE) developed a neurological disease resembling that seen in humans with variant CJD (vCJD). Here, we report the final characterization of the SQ-BSE model. We observed an unexpectedly marked difference in incubation times between two animals inoculated with the same dilution and volume of the same C-BSE bovine brain extract on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis typical of TSEs, a complex proteinopathy with severe accumulations of protease-resistant prion protein (PrP(TSE)), hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein, but without any amyloid plaques or β-amyloid protein (Aβ) typical of Alzheimer’s disease. These results suggest that PrP(TSE) enhanced the accumulation of several key proteins characteristically seen in human neurodegenerative diseases. The marked variation in incubation periods in the same experimental TSE should be taken into account when modeling the epidemiology of human TSEs

Examining Seasonal Anthrax Risk in Wildlife: Comparing Home Ranges and Site Fidelity in Sero-Positive and Sero-Negative Ungulates

Anthrax is frequently reported from wildlife and livestock in the US.  While useful in reducing risk in livestock, vaccination, the primary method of prevention, is untenable for free-ranging wildlife. Because of this, accurate surveillance and carcass clean-up are the most efficacious control measures for wildlife.  However, surveillance is expensive and requires significant personnel across large landscapes. Likewise, the transmission pathways are poorly understood in most species. Wildlife telemetry improves our understanding of movement patterns during risk periods. At the same time, serological surveys provide data on host exposure. Such data allow us to test hypotheses about host/pathogen interactions on the landscape. Starting in 2010, we initiated GPS telemetry and sero-prevalence studies for managed bison, Bison bison bison, and free-range elk (Cervus elaphus) in Montana. Here we will evaluate summertime home ranges in bulls from both species in western Montana. We compared home ranges and site fidelity metrics in sero-positive and sero-negative animals. Serological tests indicated that ~30% of bull elk and ~27% of unvaccinated bison were sero-positive for anthrax exposure, suggesting that low-level exposure is frequent on this landscape. Seasonal ranges can be useful for defining areas where animals may have increased likelihood of anthrax, comparing ranges to niche-based estimates of B. anthracis. Fidelity metrics suggest both species spent considerable time in niche-based high risk areas. Inter-annual data from elk suggest long-term range fidelity and overlap with high risk areas. These data can be used to prioritize surveillance efforts in those areas to maximize disease control, while managing search costs

Quantum codewords contradict local realism

Quantum codewords are highly entangled combinations of two-state systems. The standard assumptions of local realism lead to logical contradictions similar to those found by Bell, Kochen and Specker, Greenberger, Horne and Zeilinger, and Mermin. The new contradictions have some noteworthy features that did not appear in the older ones.Comment: 9 pages LaTeX, 1 figur

Characterizing K2 planet discoveries : a super-Earth transiting the bright K dwarf HIP 116454

We report the first planet discovery from the two-wheeled Kepler (K2) mission: HIP 116454 b. The host star HIP 116454 is a bright (V = 10.1, K = 8.0) K1 dwarf with high proper motion and a parallax-based distance of 55.2 ± 5.4 pc. Based on high-resolution optical spectroscopy, we find that the host star is metal-poor with [Fe/H] =–0.16 ± 0.08 and has a radius R = 0.716 ± 0.024 R ☉ and mass M = 0.775 ± 0.027 M ☉. The star was observed by the Kepler spacecraft during its Two-Wheeled Concept Engineering Test in 2014 February. During the 9 days of observations, K2 observed a single transit event. Using a new K2 photometric analysis technique, we are able to correct small telescope drifts and recover the observed transit at high confidence, corresponding to a planetary radius of pR = 2.53 ± 0.18 R ⊕. Radial velocity observations with the HARPS-N spectrograph reveal a 11.82 ± 1.33 M ⊕ planet in a 9.1 day orbit, consistent with the transit depth, duration, and ephemeris. Follow-up photometric measurements from the MOST satellite confirm the transit observed in the K2 photometry and provide a refined ephemeris, making HIP 116454 b amenable for future follow-up observations of this latest addition to the growing population of transiting super-Earths around nearby, bright stars.Publisher PDFPeer reviewe

Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation?

BACKGROUND: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication. OBJECTIVE: To explore the role of reverse causation in risk factors of asthma symptoms. METHODS: We compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels. RESULTS: There were 131 924 children aged 6-7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97-2.16), early life antibiotic use (1.65; 1.58-1.73) and open fire cooking (1.44; 1.26-1.65). In school level analyses, these risk factors again showed increased risks. There were 238 586 adolescents aged 13-14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75-1.86), cooking on an open fire (1.32; 1.22-1.43) and maternal tobacco use (1.23; 1.18-1.27). In school level analyses, these risk factors again showed increased risks. CONCLUSIONS & CLINICAL RELEVANCE: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation

Tight regulation of unstructured proteins: from transcript synthesis to protein degradation

Altered abundance of several intrinsically unstructured proteins ( IUPs) has been associated with perturbed cellular signaling that may lead to pathological conditions such as cancer. Therefore, it is important to understand how cells precisely regulate the availability of IUPs. We observed that regulation of transcript clearance, proteolytic degradation, and translational rate contribute to controlling the abundance of IUPs, some of which are present in low amounts and for short periods of time. Abundant phosphorylation and low stochasticity in transcription and translation indicate that the availability of IUPs can be finely tuned. Fidelity in signaling may require that most IUPs be available in appropriate amounts and not present longer than needed.Royal Society; MRC Special Training Fellowship; Medical Research Council [MC_U105161047, MC_U105185859, G0600158]info:eu-repo/semantics/publishedVersio

Are environmental factors for atopic eczema in ISAAC Phase Three due to reverse causation?

Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors. ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. 546,348 children from 53 countries were included. At age 6-7 the strongest individual-level associations were with current paracetamol use (odds ratio=1.45, 95% confidence interval 1.37-1.54), which persisted at school-level (1.55, 1.10-2.21), antibiotics (1.41, 1.34-1.48) and early life paracetamol use (1.28, 1.21-1.36) with the former persisting at school-level while the latter was no longer observed (1.35, 1.00-1.82 and 0.94, 0.69-1.28 respectively). At age 13-14 the strongest associations at individual-level were with current paracetamol use (1.57, 1.51-1.63) and open-fire cooking (1.46, 1.33-1.62); both were stronger at school-level (2.57, 1.84-3.59 and 2.38, 1.52-3.73 respectively). Association with exposure to heavy traffic (1.31, 1.27-1.36) also persisted at school-level (1.40, 1.07-1.82). Most individual- and school level effects were consistent tending to exclude reverse causation

The role of assistance dogs in society

Assistance dogs are specially trained to undertake a variety of tasks to help individuals with disabilities. This review gives an overview of the different types of assistance dogs in the UK, including guide dogs, hearing dogs, mobility assistance dogs, service dogs and dual purpose dogs. The literature describes many benefits of assistance dogs, including their impact on physical wellbeing and safety of their ‘owners,’ as well as on psychological wellbeing and social inclusion. The role of assistance dogs in society is widely recognized by the public, but is not currently acknowledged in government social policy. The current evidence on the benefits of assistance dogs is limited by the type and scale of current research. This article highlights the need for independent funding for high quality research to enable social care and policy makers to make evidence-based decisions on the value of assistance dogs to people with disabilities

KELT-11b: A Highly Inflated Sub-Saturn Exoplanet Transiting the V=8 Subgiant HD 93396

We report the discovery of a transiting exoplanet, KELT-11b, orbiting the bright ($V=8.0$) subgiant HD 93396. A global analysis of the system shows that the host star is an evolved subgiant star with $T_{\rm eff} = 5370\pm51$ K, $M_{*} = 1.438_{-0.052}^{+0.061} M_{\odot}$, $R_{*} = 2.72_{-0.17}^{+0.21} R_{\odot}$, log $g_*= 3.727_{-0.046}^{+0.040}$, and [Fe/H]$= 0.180\pm0.075$. The planet is a low-mass gas giant in a $P = 4.736529\pm0.00006$ day orbit, with $M_{P} = 0.195\pm0.018 M_J$, $R_{P}= 1.37_{-0.12}^{+0.15} R_J$, $\rho_{P} = 0.093_{-0.024}^{+0.028}$ g cm$^{-3}$, surface gravity log ${g_{P}} = 2.407_{-0.086}^{+0.080}$, and equilibrium temperature $T_{eq} = 1712_{-46}^{+51}$ K. KELT-11 is the brightest known transiting exoplanet host in the southern hemisphere by more than a magnitude, and is the 6th brightest transit host to date. The planet is one of the most inflated planets known, with an exceptionally large atmospheric scale height (2763 km), and an associated size of the expected atmospheric transmission signal of 5.6%. These attributes make the KELT-11 system a valuable target for follow-up and atmospheric characterization, and it promises to become one of the benchmark systems for the study of inflated exoplanets.Comment: 15 pages, Submitted to AAS Journal