The mechanisms of calcium homeostasis and signalling in the lens

Excessive Ca2+ can be detrimental to cells and raised levels of Ca2+ in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca2+ homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca2+ plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca2+ ([Ca2+]i) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca2+ levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca2+]i. The Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+-ATPase (PMCA) actively remove Ca2+ from the cells, whereas the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ in the endoplasmic reticulum (ER) Ca2+ store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca2+]i can be increased in a number of ways. Ca2+ influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca2+ channels (VOCCs), receptor-operated Ca2+ channels (ROCCs) and channels mediating store-operated Ca2+ entry (SOCE). Ca2+ signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP3-gated channels (IP3Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca2+]i and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca2+ homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca2+ overload as occurs in the process of cataract formation

A boundary element regularised Stokeslet method applied to cilia and flagella-driven flow

A boundary element implementation of the regularised Stokeslet method of Cortez is applied to cilia and flagella-driven flows in biology. Previously-published approaches implicitly combine the force discretisation and the numerical quadrature used to evaluate boundary integrals. By contrast, a boundary element method can be implemented by discretising the force using basis functions, and calculating integrals using accurate numerical or analytic integration. This substantially weakens the coupling of the mesh size for the force and the regularisation parameter, and greatly reduces the number of degrees of freedom required. When modelling a cilium or flagellum as a one-dimensional filament, the regularisation parameter can be considered a proxy for the body radius, as opposed to being a parameter used to minimise numerical errors. Modelling a patch of cilia, it is found that: (1) For a fixed number of cilia, reducing cilia spacing reduces transport. (2) For fixed patch dimension, increasing cilia number increases the transport, up to a plateau at $9\times 9$ cilia. Modelling a choanoflagellate cell it is found that the presence of a lorica structure significantly affects transport and flow outside the lorica, but does not significantly alter the force experienced by the flagellum.Comment: 20 pages, 7 figures, postprin

The Birmingham-CfA cluster scaling project - II. Mass composition and distribution

We investigate the spatial distribution of the baryonic and non-baryonic mass components in a sample of 66 virialized systems. We have used X-ray measurements to determine the deprojected temperature and density structure of the intergalactic medium and have employed these to map the underlying gravitational potential. In addition, we have measured the deprojected spatial distribution of galaxy luminosity for a subset of this sample, spanning over 2 decades in mass. With this combined X-ray/optical study we examine the scaling properties of the baryons and address the issue of mass-to-light (M/L) ratio in groups and clusters of galaxies. We measure a median mass-to-light ratio of 224 h70 M/L (solar) in the rest frame B_j band, in good agreement with other measurements based on X-ray determined masses. There is no trend in M/L with X-ray temperature and no significant trend for mass to increase faster than luminosity: M \propto \L_{B,j}^{1.08 +/- 0.12}. This implied lack of significant variation in star formation efficiency suggests that gas cooling cannot be greatly enhanced in groups, unless it drops out to form baryonic dark matter. Correspondingly, our results indicate that non-gravitational heating must have played a significant role in establishing the observed departure from self-similarity in low mass systems. The median baryon fraction for our sample is 0.162 h70^{-3/2}, which allows us to place an upper limit on the cosmological matter density, Omega_m <= 0.27 h70^{-1}, in good agreement with the latest results from WMAP. We find evidence of a systematic trend towards higher central density concentration in the coolest haloes, indicative of an early formation epoch and consistent with hierarchical formation models.Comment: 14 pages, 11 figures; published in MNRAS. Corrected mistake in photometric conversion (equation 2): Bj luminosities increased for A2218, N2563 & N5846. Conclusions unchange

Equivariant configuration spaces

The compression theorem is used to prove results for equivariant configuration spaces that are analogous to the well-known non-equivariant results of May, Milgram and Segal

Public Awareness of Genetic Influence on Chronic Disease Risk: Are Genetic and Lifestyle Causal Beliefs Compatible?

Background/Aims: There is concern that raising awareness about the role of genetics in chronic disease etiology could undermine public belief that lifestyles are important, leading to adverse effects on public health. We tested the hypothesis that people who believe genetics influence chronic disease risk are less likely to believe lifestyles play a role. Methods: Open-ended questions about cancer and heart disease risk factors were included in a population-based survey of 1,747 British adults. Responses were coded for causal beliefs about genetics and lifestyle (smoking, diet, alcohol, exercise). Results: One third of the respondents identified genetic factors as influencing cancer (35%) and heart disease (36%) risk. Identifying genetic risk was associated with female gender, older age and education for both diseases, as well as with family history for heart disease. Individuals identifying genetic influences on cancer risk were more likely to identify diet (p < 0.001) and exercise (p < 0.05), and mentioned more lifestyle factors overall (p < 0.05), independent of demographics and family history. Patterns were similar for heart disease. Conclusion: People who recognize that genetics influence chronic disease risk appear more, not less, likely to recognize the role of lifestyles, contradicting suggestions that the public takes an 'either/or' view of the etiology of these potentially preventable diseases. Copyright (C) 2010 S. Karger AG, Base

The Birmingham-CfA cluster scaling project - III: entropy and similarity in galaxy systems

We examine profiles and scaling properties of the entropy of the intergalactic gas in a sample of 66 virialized systems, ranging in mass from single elliptical galaxies to rich clusters, for which we have resolved X-ray temperature profiles. Some of the properties we derive appear to be inconsistent with any of the models put forward to explain the breaking of self-similarity in the baryon content of clusters. In particular, the entropy profiles, scaled to the virial radius, are broadly similar in form across the sample, apart from a normalization factor which differs from the simple self-similar scaling with temperature. Low mass systems do not show the large isentropic cores predicted by preheating models, and the high entropy excesses reported at large radii in groups by Finoguenov et al (2002) are confirmed, and found to extend even to moderately rich clusters. We discuss the implications of these results for the evolutionary history of the hot gas in clusters, and suggest that preheating may affect the entropy of intracluster gas primarily by reducing the density of material accreting into groups and clusters along cosmic filaments.Comment: 13 pages, 8 figures - accepted for publication in MNRA

The effect of flight line spacing on radioactivity inventory and spatial feature characteristics of airborne gamma-ray spectrometry data

Airborne Gamma Spectrometry (AGS) is well suited to the mapping of radioactivity in the environment. Flight parameters (e.g. speed and line spacing) directly affect the rate of area coverage, cost, and data quality of any survey. The influences of line spacing have been investigated for data from inter‐tidal, coastal and upland environments with a range of &lt;sup&gt;137&lt;/sup&gt;Cs activity concentrations and depositional histories. Estimates of the integrated &lt;sup&gt;137&lt;/sup&gt;Cs activity (‘inventory’) within specified areas and the shapes of depositional features were calculated for subsets of the data at different line spacings. Features with dimensions greater than the line spacing show variations in inventory and area of less than 3%, and features with dimensions less than the line spacing show larger variations and a decreased probability of detection. The choice of line spacing for a task is dependent on the dimensions of the features of interest and required edge definition. Options for line spacing for different tasks are suggested. It is noted that for regional mapping, even 5–10 km line spacing can produce useful data