127 resultados para (NA ,K )-ATPASE ACTIVITY
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Concrete structures in marine environments are subjected to cyclic wetting and drying, corrosion of reinforcement due to chloride ingress and biological deterioration. In order to assess the quality of concrete and predict the corrosion activity of reinforcing steel in concrete in this environment, it is essential to monitor the concrete continuously right from the construction phase to the end of service life of the structure. In this paper a novel combination of sensor techniques which are integrated in a sensor probe is used to monitor the quality of cover concrete and corrosion of the reinforcement. The integrated sensor probe was embedded in different concrete samples exposed to an aggressive marine environment at the Hangzhou Bay Bridge in China. The sensor probes were connected to a monitoring station, which enabled the access and control of the data remotely from Belfast, UK. The initial data obtained from the monitoring station reflected the early age properties of the concretes and distinct variations in these properties were observed with different concrete types.
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Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency, such that acetate (C2) has been described as FFA2 selective while propionate (C3) is non-selective. Although C2 was confirmed to be selective for human FFA2 over FFA3, this ligand was not selective between the mouse orthologs. Moreover, although C3 was indeed not selective between the human orthologs it displayed clear selectivity for mouse FFA3 over mouse FFA2. This altered selectivity to C2 and C3 resulted from broad differences in SCFAs potency at the mouse orthologs. In studies to define the molecular basis for these observations marked variation in ligand-independent, constitutive activity was identified. The orthologs with higher potency for the SCFAs, human FFA2 and mouse FFA3, displayed high constitutive activity while the orthologs with lower potency for the agonist ligands, mouse FFA2 and human FFA3, did not. Sequence alignments of the 2nd extracellular loop identified single negatively charged residues in FFA2 and FFA3 not conserved between species and predicted to form ionic lock interactions with arginine residues within the FFA2 or FFA3 agonist binding pocket to regulate constitutive activity and SCFA potency. Reciprocal mutation of these residues between species orthologs resulted in the induction (or repression) of constitutive activity, and in most cases also yielded corresponding changes in SCFA potency.
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This paper describes a simple application for mobile devices which automatically recognizes different physical activity. This application could be used to log exercise sessions for the purpose of aiding weight management or improving sporting performance. © 2012 IEEE.
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Seabirds are central place foragers during the breeding season and, as marine food resources are often patchily distributed, flexibility in foraging behaviour may be important in maintaining prey delivery rates to chicks. We developed a methodological approach using a combination of GPS data loggers and temperature-depth recorders that allowed us to describe the behaviour of surface-feeding seabirds. Specifically, we tested whether differences in foraging behaviour of black-legged kittiwakes Rissa tridactyla could be linked with reproductive success by comparing 2 consecutive years at 2 sites. At Rathlin Island (Northern Ireland) during 2010, foraging differed markedly from that during 2009 and from that at Lambay Island (Republic of Ireland) during both years. Birds exhibited foraging trips of greater duration, travelled a greater total distance, spent more time in transit and spent longer recuperating on the surface of the water. This notable shift was associated with a decline in breeding success, with greater loss of eggs to predation and lower prey delivery rates, resulting in the starvation of 15 % of chicks. We suggest that food resources were reduced or geographically less accessible during 2010, with suitable foraging areas located further from the colony. Birds did not invest greater amounts of time attempting to catch prey. Thus, our results indicate that kittiwakes at Rathlin modulated their foraging behaviour not by increasing foraging effort through feeding more intensively within prey patches but by extending their range to increase the probability of encountering more profitable prey patches. © Inter-Research 2012.
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meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 µg of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT.
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During alcoholic fermentation, the products build up and can, ultimately, kill the organism due to their effects on the cell's macromolecular systems. The effects of alcohols on the steady-state kinetic parameters of the model enzyme ß-galactosidase were studied. At modest concentrations (0 to 2 M), there was little effect of methanol, ethanol, propanol and butanol on the kinetic constants. However, above these concentrations, each alcohol caused the maximal rate, V (max), to fall and the Michaelis constant, K (m), to rise. Except in the case of methanol, the chaotropicity of the solute, rather than its precise chemical structure, determined and can, therefore, be used to predict inhibitory activity. Compounds which act as compatible solutes (e.g. glycerol and other polyols) generally reduced enzyme activity in the absence of alcohols at the concentration tested (191 mM). In the case of the ethanol- or propanol-inhibited ß-galactosidase, the addition of compatible solutes was unable to restore the enzyme's kinetic parameters to their uninhibited levels; addition of chaotropic solutes such as urea tended to enhance the effects of these alcohols. It is possible that the compatible solutes caused excessive rigidification of the enzyme's structure, whereas the alcohols disrupt the tertiary and quaternary structure of the protein. From the point of view of protecting enzyme activity, it may be unwise to add compatible solutes in the early stages of industrial fermentations; however, there may be benefits as the alcohol concentration increases.
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Facial activity is strikingly visible in infants reacting to noxious events. Two measures that reduce this activity to composite events, the Neonatal Facial Coding System (NFCS) and the Facial Action Coding System (FACS), were used to examine facial expressions of 56 neonates responding to routine heel lancing for blood sampling purposes. The NFCS focuses upon a limited subset of all possible facial actions that had been identified previously as responsive to painful events, whereas the FACS is a comprehensive system that is inclusive of all facial actions. Descriptions of the facial expressions obtained from the two measurement systems were very similar, supporting the convergent validity of the shorter, more readily applied system. As well, the cluster of facial activity associated with pain in this sample, using either measure, was similar to the cluster of facial activity associated with pain in adults and other newborns, both full-term and preterm, providing construct validity for the position that the face encodes painful distress in infants and adults.
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BACKGROUND: For many, physical activity has been engineered out of daily life, leading to high levels of sedentariness and obesity. Multi-faceted physical activity interventions, combining individual, community and environmental approaches, have the greatest potential to improve public health, but few have been evaluated. METHODS: Approximately 100 000 people may benefit from improved opportunities for physical activity through an urban regeneration project in Northern Ireland, the Connswater Community Greenway. Using the macro-simulation PREVENT model, we estimated its potential health impacts and cost-effectiveness. To do so, we modelled its potential impact on the burden from cardiovascular disease, namely, ischaemic heart disease, type 2 diabetes mellitus and stroke, and colon and breast cancer, by the year 2050, if feasible increases in physical activity were to be achieved. RESULTS: If 10% of those classified as 'inactive' (perform less than 150 minutes of moderate activity/week) became 'active', 886 incident cases (1.2%) and 75 deaths (0.9%) could be prevented with an incremental cost-effectiveness ratio of £4469/disability-adjusted life year. For effectiveness estimates as low as 2%, the intervention would remain cost-effective (£18 411/disability-adjusted life year). Small gains in average life expectancy and disability-adjusted life expectancy could be achieved, and the Greenway population would benefit from 46 less years lived with disability. CONCLUSION: The Greenway intervention could be cost-effective at improving physical activity levels. Although the direct health gains are predicted to be small for any individual, summed over an entire population, they are substantial. In addition, the Greenway is likely to have much wider benefits beyond health.
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Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain-containing family of demethylases comprises 27 members which can demethylate mono-, di- and tri-methylated lysine residues of histone (or non-histone) targets. To evaluate their role in regulation of hematopoietic stem cell (HSC) behaviour we performed a RNAi-based screen and found that demethylases JARID1B (H3K4) and JHDM1F (H3K9) play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSC with preserved long term in vivo lympho-myeloid differentiation potential. Jarid1b knockdown was associated with an increase in expression levels of 5’ Hoxa cluster genes and CxCl5 , and reduced levels of Pu.1, Egr1 and Cav1. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative, and Jhdmlf as a positive regulator of HSC activity.
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Objectives To examine whether exposure to workplace stressors predicts changes in physical activity and the risk of insufficient physical activity.
Methods Prospective data from the Finnish Public Sector Study. Repeated exposure to low job control, high job demands, low effort, low rewards and compositions of these (job strain and effort-reward imbalance) were assessed at Time 1 (2000-2002) and Time 2 (2004). Insufficient physical activity (<14 metabolic equivalent task hours per week) was measured at Time 1 and Time 3 (2008). The effect of change in workplace stressors on change in physical activity was examined using fixed-effects (within-subject) logistic regression models (N=6665). In addition, logistic regression analysis was applied to examine the associations between repeated exposure to workplace stressors and insufficient physical activity (N=13 976). In these analyses, coworker assessed workplace stressor scores were used in addition to individual level scores.
Results The proportion of participants with insufficient physical activity was 24% at baseline and 26% at follow-up. 19% of the participants who were sufficiently active at baseline became insufficiently active at follow-up. In the fixed-effect analysis, an increase in workplace stress was weakly related to an increase in physical inactivity within an individual. In between-subjects analysis, employees with repeated exposure to low job control and low rewards were more likely to be insufficiently active at follow-up than those with no reports of these stressors; fully adjusted ORs ranged from 1.11 (95% CI 1.00 to 1.24) to 1.21 (95% CI 1.05 to 1.39).
Conclusions Workplace stress is associated with a slightly increased risk of physical inactivity.
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Epithelia play important immunological roles at a variety of mucosal sites. We examined NFkappaB activity in control and TNF-alpha treated bovine mammary epithelial monolayers (BME-UV cells). A region of the bovine IL-8 (bIL-8) promoter was sequenced and a putative kappaB consensus sequence was identified bioinformatically. We used this sequence to analyse nuclear extracts for IL-8 specific NFkappaB activity. As a surrogate marker of NFkappaB activation, we investigated IL-8 release in two models. Firstly in BME-UV monolayers, IL-8 release in the presence of pro- and anti-inflammatory agents was determined by enzyme-linked immunosorbent assay (ELISA). Secondly, we measured IL-8 secretion from a novel model of intact mucosal sheets of bovine teat sinus. IL-8 release into bathing solutions was assessed following treatment with pro- and anti-inflammatory agents. TNF-alpha enhanced NFkappaB activity in bovine mammary epithelial monolayers. p65 NFkappaB homodimer was identified in both control and TNF-alpha treated cells. Novel sequencing of the bovine IL-8 promoter identified a putative kappaB consensus sequence, which specifically bound TNF-alpha inducible p50/p65 heterodimer. TNF-alpha induced primarily serosal IL-8 release in the cell culture model. Pre-treatment with anti-TNF or dexamethasone inhibited TNF-alpha induced IL-8 release. High dose interleukin-1beta (IL-1beta) induced IL-8 release, however significantly less potently than TNF-alpha. Bovine mammary mucosal tissue released high basal levels of IL-8 which were unaffected by TNF-alpha or IL-1beta but inhibited by both dexamethasone and anti-TNF. These data support a role for TNF-alpha in activation of NFkappaB and release of IL-8 from bovine mammary epithelial cells.
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Background: Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer’s perspective.
Methods: Employees used a ‘loyalty card’ to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates.
Results: The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds.
Conclusions: The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer’s perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable “business model” which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges.