Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

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Getting “Just Deserts” or Seeing the “Silver Lining”: The Relation between Judgments of Immanent and Ultimate Justice

People can perceive misfortunes as caused by previous bad deeds (immanent justice reasoning) or resulting in ultimate compensation (ultimate justice reasoning). Across two studies, we investigated the relation between these types of justice reasoning and identified the processes (perceptions of deservingness) that underlie them for both others (Study 1) and the self (Study 2). Study 1 demonstrated that observers engaged in more ultimate (vs. immanent) justice reasoning for a "good" victim and greater immanent (vs. ultimate) justice reasoning for a "bad" victim. In Study 2, participants' construals of their bad breaks varied as a function of their self-worth, with greater ultimate (immanent) justice reasoning for participants with higher (lower) self-esteem. Across both studies, perceived deservingness of bad breaks or perceived deservingness of ultimate compensation mediated immanent and ultimate justice reasoning respectively. © 2014 Harvey and Callan

Ocean acidification affects fish spawning but not paternity at CO2 seeps

Fish exhibit impaired sensory function and altered behaviour at levels of ocean acidification expected to occur owing to anthropogenic carbon dioxide emissions during this century. We provide the first evidence of the effects of ocean acidification on reproductive behaviour of fish in the wild. Satellite and sneaker male ocellated wrasse (Symphodus ocellatus) compete to fertilize eggs guarded by dominant nesting males. Key mating behaviours such as dominant male courtship and nest defence did not differ between sites with ambient versus elevated CO2 concentrations. Dominant males did, however, experience significantly lower rates of pair spawning at elevated CO2 levels. Despite the higher risk of sperm competition found at elevated CO2, we also found a trend of lower satellite and sneaker male paternity at elevated CO2. Given the importance of fish for food security and ecosystem stability, this study highlights the need for targeted research into the effects of rising CO2 levels on patterns of reproduction in wild fish

Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

Introduction: Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis: Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications: Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes.This study was funded by the Wellcome Trust and Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan. Supported by: Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan National Institute of Healthcare Research (Grant No: R3101002), NIHR Imperial Biomedical Research Centre (NIHR BMRC), Imperial Academic Health Science Centre (AHSC), Imperial Centre for Respiratory Infection (CRI, Grant No: 083567/Z/07/Z), Wellcome Trust (Grant No: 083429/Z/07/Z)

MOBP and HIP1 in multiple system atrophy: new α‐synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis

Aims: MSA is a fatal neurodegenerative disease. Similar to Parkinson’s disease (PD), MSA is an α‐synucleinopathy, and its pathological hallmark consists of glial cytoplasmic inclusions (GCIs) containing α‐synuclein in oligodendrocytes. We previously identified consistent changes in MOBP and HIP1 DNA methylation status in MSA. We hypothesized that if differential DNA methylation at these loci is mechanistically relevant for MSA, it should have downstream consequences on gene regulation. / Methods: We investigated the relationship between MOBP and HIP1 DNA methylation and mRNA levels in cerebellar white matter from MSA and healthy controls. Additionally, we analysed protein expression using western blotting, immunohistochemistry and proximity ligation assays. / Results: We found decreased MOBP mRNA levels significantly correlated with increased DNA methylation in MSA. For HIP1, we found a distinct relationship between DNA methylation and gene expression levels in MSA compared to healthy controls, suggesting this locus may be subjected to epigenetic remodelling in MSA. Although soluble protein levels for MOBP and HIP1 in cerebellar white matter were not significantly different between MSA cases and controls, we found striking differences between MSA and other neurodegenerative diseases, including PD and Huntington’s disease. We also found that MOBP and HIP1 are mislocalized into the GCIs in MSA, where they appear to interact with α‐synuclein. / Conclusions: This study supports a role for DNA methylation in downregulation of MOBP mRNA in MSA. Most importantly, the identification of MOBP and HIP1 as new constituents of GCIs emphasizes the relevance of these two loci to the pathogenesis of MSA

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Glutathione S-Transferase Ω 1 variation does not influence age at onset of Huntington's disease

BACKGROUND: Huntington's disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Circumstantial evidence suggests that additional features of the HD course are based on genetic traits. Therefore, it may be possible to investigate the genetic background of HD, i.e. to map the loci underlying the development and progression of the disease. Recently an association of Glutathione S-Transferase Ω 1 (GSTO1) and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD) and Parkinson's disease (PD). METHODS: We have genotyped the polymorphisms rs4925 GSTO1 and rs2297235 GSTO2 in 232 patients with HD and 228 controls. RESULTS: After genotyping GSTO1 and GSTO2 polymorphisms, firstly there was no statistically significant difference in AO for HD patients, as well as secondly for HD patients vs. controls concerning, both, genotype and allele frequencies, respectively. CONCLUSION: The GSTO1 and GSTO2 genes flanked by the investigated polymorphisms are not comprised in a primary candidate region influencing AO in HD

Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC a randomised controlled trial

BACKGROUND: Short term studies suggest that dietary nitrate supplementation may improve cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice BRJ (NR-BRJ) is a convenient dietary source of nitrate. METHODS: The ON-BC trial was a randomized, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomization to either 70 mL of NR-BRJ (400 mg NO3 -) (n=40) or an otherwise identical nitrate-depleted placebo juice Pl-BRJ (0 mg NO3 -) (n=41), once daily for 12 weeks. The primary endpoint was between group change in home SBP measurement. Secondary outcomes included change in 6-minute walking distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured. RESULTS: Compared to placebo, active treatment lowered SBP (Hodges-Lemman treatment effect MD[95% CI]; -4.5[-3.0 to -5.9] improved 6MWD (+30.0 m [15.7 to 44.2], p<0.001), RHI +0.34 (0.03 to 0.63) p=0.03, and AIx75 -7.61% [-14.3 to -0.95], p=0.026. CONCLUSIONS: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity