Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing

PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay between osteocytogenesis and biomineralisation. Further studies are required to dissect the molecular processes underlying the regulatory influences exerted by PHOSPHO1 on the skeleton with ageing

Inverse Association between trans Isomeric and Long-Chain Polyunsaturated Fatty Acids in Pregnant Women and Their Newborns: Data from Three European Countries

Background: trans unsaturated fatty acids are thought to interfere with essential fatty acid metabolism. To extend our knowledge of this phenomenon, we investigated the relationship between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their infants at birth. Methods: Fatty acid composition of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and 30th week of gestation, at delivery and in their newborns. Results: At the 20th week of gestation, the sum of trans fatty acids in PE was significantly (p < 0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values in PE were significantly (p < 0.01) higher in Hungarian {[}5.65 (2.09)] than in Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p < 0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women, and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001), but not in Hungarian (r = -0.02) women. Significant inverse correlations were seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n = 241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in cord lipids (n = 218, r = -0.28, p < 0.001). Conclusion: Because humans cannot synthesize trans isomeric fatty acids, the data obtained in the present study support the concept that high maternal trans isomeric fatty acid intake may interfere with the availability of LCPUFA both for the mother and the fetus. Copyright (C) 2011 S. Karger AG, Base

Statistical mechanics of voting

Decision procedures aggregating the preferences of multiple agents can produce cycles and hence outcomes which have been described heuristically as `chaotic'. We make this description precise by constructing an explicit dynamical system from the agents' preferences and a voting rule. The dynamics form a one dimensional statistical mechanics model; this suggests the use of the topological entropy to quantify the complexity of the system. We formulate natural political/social questions about the expected complexity of a voting rule and degree of cohesion/diversity among agents in terms of random matrix models---ensembles of statistical mechanics models---and compute quantitative answers in some representative cases.Comment: 9 pages, plain TeX, 2 PostScript figures included with epsf.tex (ignore the under/overfull \vbox error messages

Endogenous mediators of growth

In the present review it is not possible to discuss the effects of the numerous endogenous mediators of growth. What we have attempted to do is to indicate the areas of controversy and the need for further research. In our view, four main questions arise. First, what are the relative contributions of the direct and indirect effects of GH? Indeed, if GH can produce all its effects by local production of IGF, is the original somatomedin hypothesis still tenable? Second, how is the biological activity of the IGF modified by the presence of binding proteins? Because of the role of binding proteins in modulating IGF bioactivity, care must be taken when interpreting results from immunoassays for IGF because this will only represent the concentration of IGF not the level of biological activity, a situation which is analogous to that which pertains with certain polypeptide hormones (for review, see Robertson et al. 1987). Third, how are the activities of the osteoblast and osteoclast coupled so that in the mature adult, bone formation and bone resorption are roughly equivalent? Understanding of this process will undoubtedly involve the elucidation of the roles and interactions between a number of locally acting growth factors and systemic hormones and will lead to the understanding of certain metabolic bone diseases such as osteoporosis. Last, how is the response to local stimuli such as mechanical stress transduced? This is again probably dependent on the activity of local growth factors but may also involve changes in the interactions between bone cells and their underlying matrix components (Skerry et al. 1988)

Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia

Tibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadherin and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects than previously thought

Introducing Volcanica: The first diamond open-access journal for volcanology

Welcome to Volcanica's first issue! Our community of editors and Volcanica supporters are excited to present you with our inaugural issue of peer-reviewed volcano research. This editorial accompanies the first issue of Volcanica so that we can provide you with some background to the Volcanica initiative, explain some of the evidence-based motivation for starting a new journal, and explore ways in which we can improve universal access to published research. We discuss our model of "diamond open access", which is entirely free for authors to publish and free for everyone to read. We will explain how this model is possible and state explicitly the challenges related to how this project can be sustainable and scalable. Finally, we will signpost the information you may need to publish with Volcanica as we continue to grow

Derivation of lowland riparian wetland deposit architecture using geophysical image analysis and interface detection

For groundwater-surface water interactions to be understood in complex wetland settings, the architecture of the underlying deposits requires investigation at a spatial resolution sufficient to characterize significant hydraulic pathways. Discrete intrusive sampling using conventional approaches provides insufficient sample density and can be difficult to deploy on soft ground. Here a noninvasive geophysical imaging approach combining three-dimensional electrical resistivity tomography (ERT) and the novel application of gradient and isosurface-based edge detectors is considered as a means of illuminating wetland deposit architecture. The performance of three edge detectors were compared and evaluated against ground truth data, using a lowland riparian wetland demonstration site. Isosurface-based methods correlated well with intrusive data and were useful for defining the geometries of key geological interfaces (i.e., peat/gravels and gravels/Chalk). The use of gradient detectors approach was unsuccessful, indicating that the assumption that the steepest resistivity gradient coincides with the associated geological interface can be incorrect. These findings are relevant to the application of this approach in settings with a broadly layered geology with strata of contrasting resistivities. In addition, ERT revealed substantial structures in the gravels related to the depositional environment (i.e., braided fluvial system) and a complex distribution of low-permeability putty Chalk at the bedrock surface—with implications for preferential flow and variable exchange between river and groundwater systems. These results demonstrate that a combined approach using ERT and edge detectors can provide valuable information to support targeted monitoring and inform hydrological modeling of wetlands

The Banks set and the Uncovered Set in budget allocation problems

We examine how a society chooses to divide a given budget among various regions, projects or individuals. In particular, we characterize the Banks set and the Uncovered Set in such problems. We show that the two sets can be proper subsets of the set of all alternatives, and at times are very pointed in their predictions. This contrasts with well-known "chaos theorems," which suggest that majority voting does not lead to any meaningful predictions when the policy space is multidimensional