Dynapenic obesity and the risk of incident Type 2 diabetes: the English Longitudinal Study of Ageing

Aim Obesity is a well‐established risk factor for developing Type 2 diabetes. Evidence suggests that sarcopenia, the age‐related decline in muscle mass and strength, may exacerbate diabetes risk in obese individuals. The aim of this study was to determine the combined effect of obesity and low muscle strength, dynapenia, on the risk of incident Type 2 diabetes in older adults. Methods Participants were 5953 (1670 obese) men and women from the English Longitudinal Study of Ageing without known Type 2 diabetes at baseline and for whom handgrip strength, biochemical and other clinical data were collected. A diagnosis of Type 2 diabetes was recorded from self‐reported physician diagnosis over 6 years. Results For each unit increase in grip strength, there was a reduction in diabetes risk (age‐, sex‐ and BMI adjusted HR; 0.98; 95% CI 0.96–0.99). The risk of Type 2 diabetes was elevated in all obese participants, but was greatest in those with low handgrip strength (HR = 4.93, 95% CI 2.85, 8.53) compared with non‐obese individuals with high handgrip strength. Eleven per cent of the sample met the threshold for weakness (handgrip strength: men < 26 kg; women < 16 kg) that was associated with elevated Type 2 diabetes risk in obese (HR = 3.57, 95% CI 2.04, 6.24) but not in non‐obese (HR = 0.86, 95% CI, 0.44, 1.68) compared with normal/non‐obese participants. Conclusion Dynapenic obesity, determined by high BMI and low handgrip strength, is associated with increased risk of incident Type 2 diabetes in older people

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

Decreased functional connectivity within a language subnetwork in benign epilepsy with centrotemporal spikes.

OBJECTIVE: Benign epilepsy with centrotemporal spikes (BECTS, also known as Rolandic epilepsy) is a common epilepsy syndrome that is associated with literacy and language impairments. The neural mechanisms of the syndrome are not known. The primary objective of this study was to test the hypothesis that functional connectivity within the language network is decreased in children with BECTS. We also tested the hypothesis that siblings of children with BECTS have similar abnormalities. METHODS: Echo planar magnetic resonance (MR) imaging data were acquired from 25 children with BECTS, 12 siblings, and 20 healthy controls, at rest. After preprocessing with particular attention to intrascan motion, the mean signal was extracted from each of 90 regions of interest. Sparse, undirected graphs were constructed from adjacency matrices consisting of Spearman's rank correlation coefficients. Global and nodal graph metrics and subnetwork and pairwise connectivity were compared between groups. RESULTS: There were no significant differences in graph metrics between groups. Children with BECTS had decreased functional connectivity relative to controls within a four-node subnetwork, which consisted of the left inferior frontal gyrus, the left superior frontal gyrus, the left supramarginal gyrus, and the right inferior parietal lobe (p = 0.04). A similar but nonsignificant decrease was also observed for the siblings. The BECTS groups had significant increases in connectivity within a five-node, five-edge frontal subnetwork. SIGNIFICANCE: The results provide further evidence of decreased functional connectivity between key mediators of speech processing, language, and reading in children with BECTS. We hypothesize that these decreases reflect delayed lateralization of the language network and contribute to specific cognitive impairments

Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

DNA Methylome Alterations are Associated with Airway Macrophage Differentiation and Phenotype During Lung Fibrosis

RATIONALE: Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, knowledge of epigenetics of AMs in IPF are limited. METHODS: We undertook DNA methylation profiling using Illumina EPIC (850k) arrays in sorted AMs from Healthy (n=14) and IPF (n=30) donors. Cell-type deconvolution was performed using reference myeloid-cell DNA methylomes. MEASUREMENTS AND MAIN RESULTS: Our analysis revealed epigenetic heterogeneity was a key characteristic of IPF-AMs. DNAm 'clock' analysis indicated epigenetic alterations in IPF-AMs was not associated with accelerated ageing. In differential DNAm analysis, we identified numerous differentially methylated positions (DMPs, n=11) and regions (DMRs, n=49) between healthy and IPF AMs respectively. DMPs and DMRs encompassed genes involved in lipid (LPCAT1) and glucose (PFKFB3) metabolism and importantly, DNAm status was associated with disease severity in IPF. CONCLUSIONS: Collectively, our data identify that changes in the epigenome are associated with development and function of AMs in the IPF lung

Natural images from the birthplace of the human eye

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about 5000 six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.Comment: Submitted to PLoS ON

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Newsprint coverage of smoking in cars carrying children : a case study of public and scientific opinion driving the policy debate

Acknowledgements Date of Acceptance:17/10/2014 Acknowledgements: This project was funded by Cancer Research UK (MC_U130085862) and the Scottish School of Public Health Research. Cancer Research UK and the Scottish School of Public Health Research was not involved in the collection, analysis, and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication. Shona Hilton, Karen Wood, Josh Bain and Chris Patterson are funded by the UK Medical Research Council as part of the Understandings and Uses of Public Health Research programme (MC_UU_12017/6) at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow. We thank Alan Pollock who provided assistance with coding.Peer reviewedPublisher PD

Modern space-time and undecidability

The picture of space-time that Minkowski created in 1907 has been followed by two important developments in physics not contained in the original picture: general relativity and quantum mechanics. We will argue that the use of concepts of those theories to construct space-time implies conceptual modifications in quantum mechanics. In particular one can construct a viable picture of quantum mechanics without a reduction process that has outcomes equivalent to a picture with a reduction process. One therefore has two theories that are entirely equivalent experimentally but profoundly different in the description of reality they give. This introduces a fundamental level of undecidability in physics of a kind that has not been present before. We discuss some of the implications.Comment: 8 pages, no figures, Revtex, contribution to the volume "Minkowski spacetime: a hundred years later", edited by Vesselin Petko