Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology

Fish represent the planet's most diverse group of vertebrates and they can be exposed to a wide range of pharmaceuticals. For practical reasons, extrapolation of pharmaceutical effects from 'model' species to other fish species is adopted in risk assessment. Here, we critically assess this approach. First, we show that between 65% and 86% of human drug targets are evolutionarily conserved in 12 diverse fish species. Focusing on nuclear steroid hormone receptors, we further show that the sequence of the ligand binding domain that plays a key role in drug potency is highly conserved, but there is variation between species. This variation for the oestrogen receptor, however, does not obviously account for observed differences in receptor activation. Taking the synthetic oestrogen ethinyloestradiol as a test case, and using life-table-response experiments, we demonstrate significant reductions in population growth in fathead minnow and medaka, but not zebrafish, for environmentally relevant exposures. This finding contrasts with zebrafish being ranked as more ecologically susceptible, according to two independent life-history analyses. We conclude that while most drug targets are conserved in fish, evolutionary divergence in drug-target activation, physiology, behaviour and ecological life history make it difficult to predict population-level effects. This justifies the conventional use of at least a 10× assessment factor in pharmaceutical risk assessment, to account for differences in species susceptibility.Swedish Foundation for Strategic Environmental Research (Mistra)UK Natural Environment Research Council (NERC)AstraZeneca's Global SHE Research Programm

Photon capture cones and embedding diagrams of the Ernst spacetime

The differences between the character of the Schwarzschild and Ernst spacetimes are illustrated by comparing the photon capture cones, and the embedding diagrams of the $t=\mathrm{const}$ sections of the equatorial planes of both the ordinary and optical reference geometry of these spacetimes. The non-flat asymptotic character of the Ernst spacetime reflects itself in two manifest facts: the escape photon cones correspond to purely outward radial direction, and the embedding diagrams of both the ordinary and optical geometry shrink to zero radius asymptotically. Using the properties of the embedding diagrams, regions of these spacetimes which could have similar character are estimated, and it is argued that they can exist for the Ernst spacetimes with a sufficiently low strength of the magnetic field.Comment: 12 pages, 7 figure

Gravitational lensing in spherically symmetric static spacetimes with centrifugal force reversal

In Schwarzschild spacetime the value $r=3m$ of the radius coordinate is characterized by three different properties: (a) there is a ``light sphere'', (b) there is ``centrifugal force reversal'', (c) it is the upper limiting radius for a non-transparent Schwarschild source to act as a gravitational lens that produces infinitely many images. In this paper we prove a theorem to the effect that these three properties are intimately related in {\em any} spherically symmetric static spacetime. We illustrate the general results with some examples including black-hole spacetimes and Morris-Thorne wormholes.Comment: 18 pages, 3 eps-figure

Holography in 4D (Super) Higher Spin Theories and a Test via Cubic Scalar Couplings

The correspondences proposed previously between higher spin gauge theories and free singleton field theories were recently extended into a more complete picture by Klebanov and Polyakov in the case of the minimal bosonic theory in D=4 to include the strongly coupled fixed point of the 3d O(N) vector model. Here we propose an N=1 supersymmetric version of this picture. We also elaborate on the role of parity in constraining the bulk interactions, and in distinguishing two minimal bosonic models obtained as two different consistent truncations of the minimal N=1 model that retain the scalar or the pseudo-scalar field. We refer to these models as the Type A and Type B models, respectively, and conjecture that the latter is holographically dual to the 3d Gross-Neveu model. In the case of the Type A model, we show the vanishing of the three-scalar amplitude with regular boundary conditions. This agrees with the O(N) vector model computation of Petkou, thereby providing a non-trivial test of the Klebanov-Polyakov conjecture.Comment: 30p

Quinolone resistance mutations in the faecal microbiota of Swedish travellers to India

Background: International travel contributes to the spread of antibiotic resistant bacteria over the world. Most studies addressing travel-related changes in the faecal flora have focused on specific mobile resistance genes, or depended on culturing of individual bacterial isolates. Antibiotic resistance can, however, also spread via travellers colonized by bacteria carrying chromosomal antibiotic resistance mutations, but this has received little attention so far. Here we aimed at exploring the abundance of chromosomal quinolone resistance mutations in Escherichia communities residing in the gut of Swedish travellers, and to determine potential changes after visiting India. Sweden is a country with a comparably low degree of quinolone use and quinolone resistance, whereas the opposite is true for India. Methods: Massively parallel amplicon sequencing targeting the quinolone-resistance determining region of gyrA and parC was applied to total DNA extracted from faecal samples. Paired samples were collected from 12 Swedish medical students before and after a 4-15 week visit to India. Twelve Indian residents were included for additional comparisons. Methods known resistance mutations were common in Swedes before travel as well as in Indians, with a trend for all mutations to be more common in the Indian sub group. There was a significant increase in the abundance of the most common amino acid substitution in GyrA (S83L, from 44 to 72 %, p = 0.036) in the samples collected after return to Sweden. No other substitution, including others commonly associated with quinolone resistance (D87N in GyrA, S80I in ParC) changed significantly. The number of distinct genotypes encoded in each traveller was significantly reduced after their visit to India for both GyrA (p = 0.0020) and ParC (p = 0.0051), indicating a reduced genetic diversity, similar to that found in the Indians. Conclusions: International travel can alter the composition of the Escherichia communities in the faecal flora, favouring bacteria carrying certain resistance mutations, and, thereby, contributes to the global spread of antibiotic resistance. A high abundance of specific mutations in Swedish travellers before visiting India is consistent with the hypothesis that these mutation have no fitness cost even in the absence of an antibiotic selection pressure

Pregnancy related back pain, is it related to aerobic fitness? A longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Low back pain with onset during pregnancy is common and approximately one out of three women have disabling pain. The pathogenesis of the pain condition is uncertain and there is no information on the role of physical fitness. Whether poorer physical conditioning is a cause or effect of back pain is also disputed and information from prospective studies needed.</p> <p>Methods</p> <p>A cohort of pregnant women, recruited from maternal health care centers in central Sweden, were examined regarding estimated peak oxygen uptake by cycle ergometer test in early pregnancy, reported physical activity prior to pregnancy, basic characteristics, back pain during pregnancy and back pain postpartum.</p> <p>Results</p> <p>Back pain during the current pregnancy was reported by nearly 80% of the women. At the postpartum appointment this prevalence was 40%. No association was displayed between estimated peak oxygen uptake and incidence of back pain during and after pregnancy, adjusted for physical activity, back pain before present pregnancy, previous deliveries, age and weight. A significant inverse association was found between estimated peak oxygen uptake and back pain intensity during pregnancy and a direct association post partum, in a fully adjusted multiple linear regression analysis.</p> <p>Conclusions</p> <p>Estimated peak oxygen uptake and reported physical activity in early pregnancy displayed no influence on the onset of subsequent back pain during or after pregnancy, where the time sequence support the hypothesis that poorer physical deconditioning is not a cause but a consequence of the back pain condition. The mechanism for the attenuating effect of increased oxygen uptake on back pain intensity is uncertain.</p