An in vitro method for determining the bioaccessibility of pharmaceuticals in wildlife

Wildlife can be exposed to human pharmaceuticals via prey that have accumulated the compounds from wastewater, surface water, sediment and soil. One factor affecting internal absorption of pharmaceuticals is bioaccessibility, the proportion of the compound that enters solution in the gastrointestinal tract. Currently, the bioaccessibility of most pharmaceuticals in prey remains unknown for most wildlife species. Here, we evaluate the potential of a two-compartment in vitro gastrointestinal tract model to compare the bioaccessibility of the antidepressant fluoxetine from invertebrate prey for birds and mammals. Samples of gizzard (or stomach) and intestinal phase digestive juices were obtained from the in vitro models along with the residual solid material. HPLC analysis revealed that the bioaccessibility of fluoxetine in the avian in vitro models (75.9% and 78.6%) was statistically significantly lower than in the mammalian models (88.2-89.6%) as a percentage of what was recovered; however there were no statistically or biologically significant inter-species difference in terms of the amount recovered per gram of 'food' inserted at the start of the simulation. Nevertheless, this in vitro model provides a useful method of comparing the bioaccessibility of pharmaceuticals in different prey for species with different gastrointestinal conditions. There may be merit for ecological risk assessments in further developing this in vitro approach to improve estimates of internal exposure for organics. This article is protected by copyright. All rights reserved

Fur : A non-invasive approach to monitor metal exposure in bats

This paper presents a novel assessment of the use of fur as a non-invasive proxy to biomonitor metal contamination in insectivorous bats. Concentrations of metals (cadmium, copper, lead and zinc) were measured using ICP-MS in tissues (kidneys, liver, stomach and stomach content, bones and fur) obtained from 193 Pipistrellus pipistrellus/pygmaeus bats. The bats were collected across a gradient of metal pollution in England and Wales. The utility of small samples of fur as an indicator of metal exposure from the environment was demonstrated with strong relationships obtained between the concentrations of non-essential metals in fur with concentrations in stomach content, kidneys, liver and bones. Stronger relationships were observed for non-essential metals than for essential metals. Fur analyses might therefore be a useful non-invasive proxy for understanding recent, as well as long term and chronic, metal exposure of live animals. The use of fur may provide valuable information on the level of endogenous metal exposure and contamination of bat populations and communities

Higgs and Dark Matter Hints of an Oasis in the Desert

Recent LHC results suggest a standard model (SM)-like Higgs boson in the vicinity of 125 GeV with no clear indications yet of physics beyond the SM. At the same time, the SM is incomplete, since additional dynamics are required to accommodate cosmological dark matter (DM). In this paper we show that interactions between weak scale DM and the Higgs which are strong enough to yield a thermal relic abundance consistent with observation can easily destabilize the electroweak vacuum or drive the theory into a non-perturbative regime at a low scale. As a consequence, new physics--beyond the DM itself--must enter at a cutoff well below the Planck scale and in some cases as low as O(10 - 1000 TeV), a range relevant to indirect probes of flavor and CP violation. In addition, this cutoff is correlated with the DM mass and scattering cross-section in a parameter space which will be probed experimentally in the near term. Specifically, we consider the SM plus additional spin 0 or 1/2 states with singlet, triplet, or doublet electroweak quantum numbers and quartic or Yukawa couplings to the Higgs boson. We derive explicit expressions for the full two-loop RGEs and one-loop threshold corrections for these theories.Comment: 29 pages, 13 figure

Impact of diagnosis and treatment of clinically localized prostate cancer on health-related quality of life for older Americans: A population-based study

Few studies have measured the longitudinal change in health-related quality of life (HRQOL) of prostate cancer patients starting prior to cancer diagnosis, or provide simultaneous comparisons with a matched non-cancer cohort. Our study addresses these gaps by providing unique estimates of the effects of a cancer diagnosis on HRQOL accounting for the confounding effects of ageing and comorbidity

A Prescription for Building the Milky Way's Halo from Disrupted Satellites

We develop a semi-analytic method for determining the phase-space population of tidal debris along the orbit of a disrupting satellite galaxy and illustrate its use with a number of applications. We use this method to analyze Zhao's proposal that the microlensing events towards the Large Magellanic Cloud (LMC) might be explained by an appropriately placed tidal streamer, and find that his scenarios lead either to unacceptably high overdensities (10 -- 100%) in faint star counts (apparent magnitudes 17.5 -- 20.5) away from the Galactic plane or short timescales for the debris to disperse (10^8 years). We predict that the tidal streamers from the LMC and the Sagittarius dwarf galaxy currently extend over more than $2\pi$ in azimuth along their orbits. Assuming that each satellite has lost half of its primordial mass, we find that the streamers will have overdensities in faint star counts of 10 -- 100% and < 1% respectively, and conclude that this mass loss rate is unlikely for the LMC, but possible for Sagittarius. If the Galaxy has accreted one hundred $10^5-10^6 M_{\odot}$ objects (comparable to its current population of globular clusters) at distances of 20 -- 100 kpc during its lifetime then 10% of the sky will now be covered by tidal streamers.Comment: 35 pages, LaTeX, 12 postscript figures included. Submitted to Ap

Considering sex as a biological variable in preclinical research

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154390/1/fsb2fj201600781r.pd

Direct and indirect effects of chemical contaminants on the behaviour, ecology and evolution of wildlife

Chemical contaminants (e.g. metals, pesticides, pharmaceuticals) are changing ecosystems via effects on wildlife. Indeed, recent work explicitly performed under environmentally realistic conditions reveals that chemical contaminants can have both direct and indirect effects at multiple levels of organization by influencing animal behaviour. Altered behaviour reflects multiple physiological changes and links individual- to population-level processes, thereby representing a sensitive tool for holistically assessing impacts of environmentally relevant contaminant concentrations. Here, we show that even if direct effects of contaminants on behavioural responses are reasonably well documented, there are significant knowledge gaps in understanding both the plasticity (i.e. individual variation) and evolution of contaminant-induced behavioural changes. We explore implications of multi-level processes by developing a conceptual framework that integrates direct and indirect effects on behaviour under environmentally realistic contexts. Our framework illustrates how sublethal behavioural effects of contaminants can be both negative and positive, varying dynamically within the same individuals and populations. This is because linkages within communities will act indirectly to alter and even magnify contaminant-induced effects. Given the increasing pressure on wildlife and ecosystems from chemical pollution, we argue there is a need to incorporate existing knowledge in ecology and evolution to improve ecological hazard and risk assessments

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell