Vitamin D and subsequent all-age and premature mortality: a systematic review

<br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt

Feature enhancement of reverberant speech by distribution matching and non-negative matrix factorization

This paper describes a novel two-stage dereverberation feature enhancement method for noise-robust automatic speech recognition. In the first stage, an estimate of the dereverberated speech is generated by matching the distribution of the observed reverberant speech to that of clean speech, in a decorrelated transformation domain that has a long temporal context in order to address the effects of reverberation. The second stage uses this dereverberated signal as an initial estimate within a non-negative matrix factorization framework, which jointly estimates a sparse representation of the clean speech signal and an estimate of the convolutional distortion. The proposed feature enhancement method, when used in conjunction with automatic speech recognizer back-end processing, is shown to improve the recognition performance compared to three other state-of-the-art techniques

Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype

Background: Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. Methodology and Principal Findings: When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid β-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. Conclusions: These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders

Determinants of Aortic Stiffness: 16-Year Follow-Up of the Whitehall II Study

Aortic stiffness is a strong predictor of cardiovascular disease endpoints. Cross-sectional studies have shown associations of various cardiovascular risk factors with aortic pulse wave velocity, a measure of aortic stiffness, but the long-term impact of these factors on aortic stiffness is unknown.In 3,769 men and women from the Whitehall II cohort, a wide range of traditional and novel cardiovascular risk factors were determined at baseline (1991-1993) and aortic pulse wave velocity was measured at follow-up (2007-2009). The prospective associations between each baseline risk factor and aortic pulse wave velocity at follow-up were assessed through sex stratified linear regression analysis adjusted for relevant confounders. Missing data on baseline determinants were imputed using the Multivariate Imputation by Chained Equations.Among men, the strongest predictors were waist circumference, waist-hip ratio, heart rate and interleukin 1 receptor antagonist, and among women, adiponectin, triglycerides, pulse pressure and waist-hip ratio. The impact of 10 centimeter increase in waist circumference on aortic pulse wave velocity was twice as large for men compared with women (men: 0.40 m/s (95%-CI: 0.24;0.56); women: 0.17 m/s (95%-CI: -0.01;0.35)), whereas the opposite was true for the impact of a two-fold increase in adiponectin (men: -0.30 m/s (95%-CI: -0.51;-0.10); women: 0.61 m/s (95%-CI: -0.86;-0.35)).In this large prospective study, central obesity was a strong predictor of aortic stiffness. Additionally, heart rate in men and adiponectin in women predicted aortic pulse wave velocity suggesting that strategies to prevent aortic stiffening should be focused differently by sex

General destabilizing effects of eutrophication on grassland productivity at multiple spatial scales

Eutrophication is a widespread environmental change that usually reduces the stabilizing effect of plant diversity on productivity in local communities. Whether this effect is scale dependent remains to be elucidated. Here, we determine the relationship between plant diversity and temporal stability of productivity for 243 plant communities from 42 grasslands across the globe and quantify the effect of chronic fertilization on these relationships. Unfertilized local communities with more plant species exhibit greater asynchronous dynamics among species in response to natural environmental fluctuations, resulting in greater local stability (alpha stability). Moreover, neighborhood communities that have greater spatial variation in plant species composition within sites (higher beta diversity) have greater spatial asynchrony of productivity among communities, resulting in greater stability at the larger scale (gamma stability). Importantly, fertilization consistently weakens the contribution of plant diversity to both of these stabilizing mechanisms, thus diminishing the positive effect of biodiversity on stability at differing spatial scales. Our findings suggest that preserving grassland functional stability requires conservation of plant diversity within and among ecological communities

A comparative study between mixed-type tumours from human salivary and canine mammary glands

<p>Abstract</p> <p>Background</p> <p>In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours.</p> <p>Methods</p> <p>Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin.</p> <p>Results</p> <p>After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions.</p> <p>Conclusion</p> <p>There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.</p

Effects of metal-on-metal wear on the host immune system and infection in hip arthroplasty

Methods We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk. Results Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism. Interpretation Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future

Green Sturgeon Physical Habitat Use in the Coastal Pacific Ocean

The green sturgeon (Acipenser medirostris) is a highly migratory, oceanic, anadromous species with a complex life history that makes it vulnerable to species-wide threats in both freshwater and at sea. Green sturgeon population declines have preceded legal protection and curtailment of activities in marine environments deemed to increase its extinction risk. Yet, its marine habitat is poorly understood. We built a statistical model to characterize green sturgeon marine habitat using data from a coastal tracking array located along the Siletz Reef near Newport, Oregon, USA that recorded the passage of 37 acoustically tagged green sturgeon. We classified seafloor physical habitat features with high-resolution bathymetric and backscatter data. We then described the distribution of habitat components and their relationship to green sturgeon presence using ordination and subsequently used generalized linear model selection to identify important habitat components. Finally, we summarized depth and temperature recordings from seven green sturgeon present off the Oregon coast that were fitted with pop-off archival geolocation tags. Our analyses indicated that green sturgeon, on average, spent a longer duration in areas with high seafloor complexity, especially where a greater proportion of the substrate consists of boulders. Green sturgeon in marine habitats are primarily found at depths of 20–60 meters and from 9.5–16.0°C. Many sturgeon in this study were likely migrating in a northward direction, moving deeper, and may have been using complex seafloor habitat because it coincides with the distribution of benthic prey taxa or provides refuge from predators. Identifying important green sturgeon marine habitat is an essential step towards accurately defining the conditions that are necessary for its survival and will eventually yield range-wide, spatially explicit predictions of green sturgeon distribution

Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation