Interference coloration as an anti-predator defence

Interference coloration, in which the perceived colour varies predictably with the angle of illumination or observation, is extremely widespread across animal groups. However, despite considerable advances in our understanding of the mechanistic basis of interference coloration in animals, we still have a poor understanding of its function. Here, I show, using avian predators hunting dynamic virtual prey, that the presence of interference coloration can significantly reduce a predator's attack success. Predators required more pecks to successfully catch interference-coloured prey compared with otherwise identical prey items that lacked interference coloration, and attacks against prey with interference colours were less accurate, suggesting that changes in colour or brightness caused by prey movement hindered a predator's ability to pinpoint their exact location. The pronounced antipredator benefits of interference coloration may explain why it has evolved independently so many times. © 2015 The Author(s) Published by the Royal Society. All rights reserved

Evaluation of two interaction techniques for visualization of dynamic graphs

Several techniques for visualization of dynamic graphs are based on different spatial arrangements of a temporal sequence of node-link diagrams. Many studies in the literature have investigated the importance of maintaining the user's mental map across this temporal sequence, but usually each layout is considered as a static graph drawing and the effect of user interaction is disregarded. We conducted a task-based controlled experiment to assess the effectiveness of two basic interaction techniques: the adjustment of the layout stability and the highlighting of adjacent nodes and edges. We found that generally both interaction techniques increase accuracy, sometimes at the cost of longer completion times, and that the highlighting outclasses the stability adjustment for many tasks except the most complex ones.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known

Micro-pharmacokinetics: quantifying local drug concentration at live cell membranes

Fundamental equations for determining pharmacological parameters, such as the binding afnity of a ligand for its target receptor, assume a homogeneous distribution of ligand, with concentrations in the immediate vicinity of the receptor being the same as those in the bulk aqueous phase. It is, however, known that drugs are able to interact directly with the plasma membrane, potentially increasing local ligand concentrations around the receptor. We have previously reported an infuence of ligand-phospholipid interactions on ligand binding kinetics at the β2-adrenoceptor, which resulted in distinct “micro-pharmacokinetic” ligand profles. Here, we directly quantifed the local concentration of BODIPY630/650-PEG8-S-propranolol (BY-propranolol), a fuorescent derivative of the classical β-blocker propranolol, at various distances above membranes of single living cells using fuorescence correlation spectroscopy. We show for the frst time a signifcantly increased ligand concentration immediatel adjacent to the cell membrane compared to the bulk aqueous phase. We further show a clear role of both the cell membrane and the β2-adrenoceptor in determining high local BY-propranolol concentrations at the cell surface. These data suggest that the true binding afnity of BY-propranolol for the β2-adrenoceptor is likely far lower than previously reported and highlights the critical importance of understanding the “micro-pharmacokinetic” profles of ligands for membrane-associated proteins

Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Pathogenesis of aerosolized Eastern Equine Encephalitis virus infection in guinea pigs

Mice and guinea pigs were experimentally exposed to aerosols containing regionally-distinct strains (NJ1959 or ArgM) of eastern equine encephalitis virus (EEEV) at two exclusive particle size distributions. Mice were more susceptible to either strain of aerosolized EEEV than were guinea pigs; however, clinical signs indicating encephalitis were more readily observed in the guinea pigs. Lower lethality was observed in both species when EEEV was presented at the larger aerosol distribution (> 6 μm), although the differences in the median lethal dose (LD50) were not significant. Virus isolation and immunohistochemistry indicated that virus invaded the brains of guinea pigs within one day postexposure, regardless of viral strain or particle size distribution. Immunohistochemistry further demonstrated that neuroinvasion occurred through the olfactory system, followed by transneuronal spread to all regions of the brain. Olfactory bipolar neurons and neurons throughout the brain were the key viral targets. The main microscopic lesions in infected guinea pigs were neuronal necrosis, inflammation of the meninges and neuropil of the brain, and vasculitis in the brain. These results indicate that guinea pigs experimentally infected by aerosolized EEEV recapitulate several key features of fatal human infection and thus should serve as a suitable animal model for aerosol exposure to EEEV

Fatty Acid and Peptide Profiles in Plasma Membrane and Membrane Rafts of PUFA Supplemented RAW264.7 Macrophages

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers

Initial validation of the mindful eating scale

Published Mindfulness, 2013, 5(6), pp. 719-729. The final publication is available at Springer via http://dx.doi.org/10.1007/s12671-013-0227-5Self-report scales for mindfulness are now widely used in applied settings, and have made a contribution to research, for instance in demonstrating mediation effects. To date there are no convincing data as to whether mindfulness skills generalise fully across life domains, and so some researchers have developed mindfulness scales for particular domains of behaviour. We present the development of a self-report scale to measure mindfulness with respect to eating behaviours