Reproducible model development in the Cardiac Electrophysiology Web Lab

The modelling of the electrophysiology of cardiac cells is one of the most mature areas of systems biology. This extended concentration of research effort brings with it new challenges, foremost among which is that of choosing which of these models is most suitable for addressing a particular scientific question. In a previous paper, we presented our initial work in developing an online resource for the characterisation and comparison of electrophysiological cell models in a wide range of experimental scenarios. In that work, we described how we had developed a novel protocol language that allowed us to separate the details of the mathematical model (the majority of cardiac cell models take the form of ordinary differential equations) from the experimental protocol being simulated. We developed a fully-open online repository (which we termed the Cardiac Electrophysiology Web Lab) which allows users to store and compare the results of applying the same experimental protocol to competing models. In the current paper we describe the most recent and planned extensions of this work, focused on supporting the process of model building from experimental data. We outline the necessary work to develop a machine-readable language to describe the process of inferring parameters from wet lab datasets, and illustrate our approach through a detailed example of fitting a model of the hERG channel using experimental data. We conclude by discussing the future challenges in making further progress in this domain towards our goal of facilitating a fully reproducible approach to the development of cardiac cell models

Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

BACKGROUND: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. METHODS: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). RESULTS: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. CONCLUSIONS: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating

Young stars and non-stellar emission in the aligned radio galaxy 3C 256

We present ground-based images of the z=1.824 radio galaxy 3C 256 in the standard BVRIJHK filters and an interference filter centered at 8800A, a Hubble Space Telescope image in a filter dominated by Ly-alpha emission (F336W), and spectra covering rest-frame wavelengths from Ly-alpha to [O III] 5007. Together with published polarimetry observations, we use these to decompose the overall spectral energy distribution into nebular continuum emission, scattered quasar light, and stellar emission. The nebular continuum and scattered light together comprise half (one third) of the V-band (K-band) light within a 4-arcsec aperture, and are responsible for the strong alignment between the optical/near-infrared light and the radio emission. The stellar emission is dominated by a population estimated to be 100-200 Myr old (assuming a Salpeter IMF), and formed in a short burst with a peak star formation rate of 1-4x10^3 Msun/yr. The total stellar mass is estimated to be no more than 2x10^{11} Msun, which is far less than other luminous radio galaxies at similar redshifts, and suggests that 3C 256 will undergo further star formation or mergers.Comment: 35 pages including 10 figures; to appear in Nov 10 Ap

Examining volumetric gradients based on the frustum surface ratio in the brain in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is accompanied by neurodevelopmental differences in regional cortical volume (CV), and a potential layer-specific pathology. Conventional measures of CV, however, do not indicate how volume is distributed across cortical layers. In a sample of 92 typically developing (TD) controls and 92 adult individuals with ASD (aged 18-52 years), we examined volumetric gradients by quantifying the degree to which CV is weighted from the pial to the white surface of the brain. Overall, the spatial distribution of Frustum Surface Ratio (FSR) followed the gyral and sulcal pattern of the cortex and approximated a bimodal Gaussian distribution caused by a linear mixture of vertices on gyri and sulci. Measures of FSR were highly correlated with vertex-wise estimates of mean curvature, sulcal depth, and pial surface area, although none of these features explained more than 76% variability in FSR on their own. Moreover, in ASD, we observed a pattern of predominant increases in the degree of FSR relative to TD controls, with an atypical neurodevelopmental trajectory. Our findings suggest a more outward-weighted gradient of CV in ASD, which may indicate a larger contribution of supragranular layers to regional differences in CV

Re‐parameterization of a mathematical model of African horse sickness virus using data from a systematic literature search

African horse sickness (AHS) is a vector-borne disease transmitted by Culicoides spp., endemic to sub-Saharan Africa. There have been many examples of historic and recent outbreaks in the Middle East, Asia and Europe. However, not much is known about infection dynamics and outbreak potential in these naive populations. In order to better inform a previously published ordinary differential equation model, we performed a systematic literature search to identify studies documenting experimental infection of naive (control) equids in vaccination trials. Data on the time until the onset of viraemia, clinical signs and death after experimental infection of a naive equid and duration of viraemia were extracted. The time to viraemia was 4.6 days and the time to clinical signs was 4.9 days, longer than the previously estimated latent period of 3.7 days. The infectious periods of animals that died/were euthanized or survived were found to be 3.9 and 8.7 days, whereas previous estimations were 4.4 and 6 days, respectively. The case fatality was also found to be higher than previous estimations. The updated parameter values (along with other more recently published estimates from literature) resulted in an increase in the number of host deaths, decrease in the duration of the outbreak and greater prevalence in vectors

The Phylum Cnidaria: A Review of Phylogenetic Patterns and Diversity 300 Years After Linnaeus

Systema Naturae includes representatives of every major lineage of the animal phylum Cnidaria. However, Linnaeus did not classify the members of the phylum as is now done, and the diversity of the group is not well represented. We contrast the Linnaean perspective on cnidarian diversity with the modern, phylogenetic perspective. For each order, we detail diversity at the family level, providing phylogenetic context where possible