Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

Carolinensis minutus (Dujardin, 1845) Travassos 1937 (Nematoda, Heligmonellidae) in Microtus agrestis in the United Kingdom

The heligmonellid nematode Carolinensis minutus (Dujardin, 1845) Travassos, 1937 is recorded for the first time in Microtus agrestis (Linnaeus, 1761) in the United Kingdom. Small heligmosomoid specimens were recovered from a M. agrestis vole inhabiting mole (Talpa europaea Linnaeus, 1758) tunnels in mid Wales. The identity of these specimens was confirmed as C. minutus by >99% nucleotide identity with internally transcribed spacer (ITS) 1 and ITS 2 sequences in French C. minutus

Not going with the flow : locomotor activity does not constrain immunity in a wild fish

Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model (Gasterosteus aculeatus) we combined a 25-month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (counter-current swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment we set flow velocity and duration (10 cm s-1 for 48 h) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune-associated genes and infectious disease resistance through a standard challenge with an ecologically-relevant monogenean infection (Gyrodactylus gasterostei). In the wild, there was a strong association of water flow with the expression of immune-associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well-powered and based on a scenario near the limits of swimming performance in stickleback, detected no counter-current swimming effect on immune-associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do

Mediastinal Lymphangioma and Chylothorax: Thoracic Involvement of Gorham's Disease

We report a case of mediastinal lymphangioma associated with Gorham's disease in a 38-year-old man who had suffered recurrent clavicular fractures during a seven-year period. Mediastinal widening associated with osteolysis of the clavicles and the sternal manubrium was revealed by chest radiography, while computed tomography demonstrated a cystic anterior mediastinal mass infiltrating mediastinal fat and associated with osseous destruction of the clavicles and manubrium. Chylothorax recurred during the course of the disease

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals, can also employ a tolerance strategy to maintain good health in the face of on-going infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and non-immune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other non-genetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease

The Cosmic Lens All-Sky Survey: statistical strong lensing, cosmological parameters, and global properties of galaxy populations

Extensive analyses of statistical strong gravitational lensing are performed based on the final Cosmic Lens All Sky Survey (CLASS) well-defined statistical sample of flat spectrum radio sources and current estimates of galaxy luminosity functions per morphological type. The analyses are done under the assumption that galactic lenses are well-approximated by singular isothermal ellipsoids and early-type galaxies evolved passively since redshift $z \sim 1$. Depending on how the late-type galaxy population is treated (i.e., whether its characteristic velocity dispersion is constrained or not), we find for a flat universe with a cosmological constant that the present matter fraction of the present critical density $\Omega_{\rm m} = 0.31^{+0.27}_{-0.14}$ (68%) for the unconstrained case or $0.40^{+0.28}_{-0.16}$ (68%) for the constrained case, with an additional systematic uncertainty of $\approx 0.11$ arising from the present uncertainty in the distribution of CLASS sources in redshift and flux density. For a flat universe with a constant equation of state for dark energy w = $p_x$(pressure)/$\rho_x$(energy density), we find that $w < -0.55^{+0.18}_{-0.11}$ (68%) for the unconstrained case or $w < -0.41^{+0.28}_{-0.16}$ (68%) for the constrained case. For the equal frequencies of oblates and prolates, we find that $\sigma_{*}^{(e)} = 198^{+22}_{-18}$ km s$^{-1}$ (68%) for a `steep' $\alpha^{(e)}=-1$ or $\sigma_{*}^{(e)} = 181^{+18}_{-15}$ km s$^{-1}$ (68%) for a `shallow' $\alpha^{(e)}=-0.54$. Finally, from the relative frequencies of doubly-imaged sources and quadruply-imaged sources, we find that a mean projected mass ellipticity of early-type galaxies $\bar{\epsilon}_{\rm mass} = 0.42$ with a 68% lower limit of 0.28. (Abridged)Comment: 31 pages, 12figures, 6 tables, to appear in MNRAS (referee comments incorporated, a section on future prospects added

Scaling in Complex Systems: Analytical Theory of Charged Pores

In this paper we find an analytical solution of the equilibrium ion distribution for a toroidal model of a ionic channel, using the Perfect Screening Theorem (PST). The ions are charged hard spheres, and are treated using a variational Mean Spherical Approximation (VMSA) . Understanding ion channels is still a very open problem, because of the many exquisite tuning details of real life channels. It is clear that the electric field plays a major role in the channel behaviour, and for that reason there has been a lot of work on simple models that are able to provide workable theories. Recently a number of interesting papers have appeared that discuss models in which the effect of the geometry, excluded volume and non-linear behaviour is considered. We present here a 3D model of ionic channels which consists of a charged, deformable torus with a circular or elliptical cross section, which can be flat or vertical (close to a cylinder). Extensive comparisons to MC simulations were performed. The new solution opens new possibilities, such as studying flexible pores, and water phase transformations inside the pores using an approach similar to that used on flat crystal surfaces

Drugs-related death soon after hospital discharge among drug treatment clients in Scotland:record linkage, validation and investigation of risk factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting

Incidental findings found in "healthy" volunteers during imaging performed for research: current legal and ethical implications

Incidental findings found in “healthy” volunteers during research imaging are common and have important implications for study design and performance, particularly in the areas of informed consent, subjects' rights, clinical image analysis and disclosure. In this study, we aimed to determine current practice and regulations concerning information that should be given to research subjects when obtaining consent, reporting of research images, who should be informed about any incidental findings and the method of disclosure. We reviewed all UK, European and international humanitarian, legal and ethical agencies' guidance. We found that the guidance on what constitutes incidental pathology, how to recognise it and what to do about it is inconsistent between agencies, difficult to find and less complete in the UK than elsewhere. Where given, guidance states that volunteers should be informed during the consent process about how research images will be managed, whether a mechanism exists for identifying incidental findings, arrangements for their disclosure, the potential benefit or harm and therapeutic options. The effects of incidentally discovered pathology on the individual can be complex and far-reaching. Radiologist involvement in analysis of research images varies widely; many incidental findings might therefore go unrecognised. In conclusion, guidance on the management of research imaging is inconsistent, limited and does not address the interests of volunteers. Improved standards to guide management of research images and incidental findings are urgently required