Mobilisation of enterocyte fat stores by oral glucose in humans

Background and aims: When a high fat oral load is followed several hours later by further ingestion of nutrients, there is an early postprandial peak in plasma triacylglycerol (TG). The aim of this study was to investigate the location and release of lipid from within the gastrointestinal tract. Methods: Ten healthy patients undergoing oesopho-gastro-duodenoscopy (OGD) were recruited. At t=0, all patients consumed a 50 g fat emulsion and at t=5 hours they consumed either water or a 38 g glucose solution. OGD was performed at t=6 hours and jejunal biopsy samples were evaluated for fat storage. A subgroup of five subjects then underwent a parallel metabolic study in which postprandial lipid and hormone measurements were taken during an identical two meal protocol. Results: Following oral fat at t=0, samples from patients that had subsequently ingested glucose exhibited significantly less staining for lipid within the mucosa and submucosa of the jejunum than was evident in patients that had consumed only water (p=0.028). There was also less lipid storage within the cytoplasm of enterocytes (p=0.005) following oral glucose. During the metabolic study, oral glucose consumed five hours after oral fat resulted in a postprandial peak in plasma TG, chylomicron-TG, and apolipoprotein B48 concentration compared with oral water. Conclusion: After a fat load, fat is retained within the jejunal tissue and released into plasma following glucose ingestion, resulting in a peak in chylomicron-TG which has been implicated in the pathogenesis of atherosclerosis.

Steering across scales: applying Strategic-Relational Approach to a study of land mobilisation for road widening in Kochi

This paper argues for the relevance of paying attention to structuring participation processes across scales as one of the ways in which participation of multi-organisational partnerships that involve conflicting interests might be managed. Issue wise the paper deals with problems in connection with land mobilisation for road widening in complex and concentrated high value urban settings. It discusses a case study of plan implementation involving individual landowners, the land development market, the local government, other governmental and non-governmental organisations and the state government, which together achieved objectives that seemed impossible at first sight. In theoretical terms, the paper engages with Jessop's (2001) Strategic-Relational Approach (SRA), arguing for its potential for informing action in a way that is capable of achieving steering outputs. The claim for SRA is demonstrated by re-examining the case study. The factors that come through as SRA is applied are drawn out and it is suggested that the theory though non-deterministic, helps guide action by highlighting certain dynamics of systems that can be used for institutional intervention. These dynamics point to the importance of paying attention to scale and the way in which participation and negotiation processes are structured so as to favour certain outcomes rather than others

Comparison of EDTA and EDDS as potential soil amendments for enhanced phytoextraction of heavy metals

Phytoextraction has been proposed as an alternative remediation technology for soils polluted with heavy metals or radionuclides, but is generally conceived as too slow working. Enhancing the accumulation of trace pollutants in harvestable plant tissues is a prerequisite for the technology to be practically applicable. The chelating aminopolycarboxylic acid, ethylene diamine tetraacetate (EDTA), has been found to enhance shoot accumulation of heavy metals. However, the use of EDTA in phytoextraction may not be suitable due to its high environmental persistence, which may lead to groundwater contamination. This paper aims to assess whether ethylene diamine disuccinate (EDDS), a biodegradable chelator, can be used for enhanced phytoextraction purposes. A laboratory experiment was conducted to examine mobilisation of Cd, Cu, Cr, Ni, Pb and Zn into the soil solution upon application of EDTA or EDDS. The longevity of the induced mobilisation was monitored for a period of 40 days after application. Estimated effect half lives ranged between 3.8 and 7.5 days for EDDS, depending on the applied dose. The minimum observed effect half life of EDTA was 36 days, while for the highest applied dose no decrease was observed throughout the 40 day period of the mobilisation experiment. Performance of EDTA and EDDS for phytoextraction was evaluated by application to Helianthus annuus. Two other potential chelators, known for their biodegradability in comparison to EDTA, were tested in the plant experiment: nitrilo acetic acid (NTA) and citric acid. Uptake of heavy metals was higher in EDDS-treated pots than in EDTA-treated pots. The effects were still considered insufficiently high to consider efficient remediation. This may be partly due to the choice of timing for application of the soil amendment. Fixing the time of application at an earlier point before harvest may yield better results. NTA and citric acid induced no significant effects on heavy metal uptake. (C) 2004 Elsevier Ltd. All rights reserved.

Mitigation of diffuse phosphorus pollution during rewetting of fen peat soils: A trans-European case study

Intensive cultivation of fen peat soils (Eutric Histosols) for agricultural purposes, started in Europe about 250 years ago, resulting in decreased soil fertility, increased oxidation of peat and corresponding CO2-emissions to the atmosphere, nutrient transfer to aquatic ecosystems and losses in the total area of the former native wetlands. To prevent these negative environmental effects set-aside programs and rewetting measures were promoted in recent years. Literature results and practical experiences showed that large scale rewetting of intensively used agricultural Histosols may result in the mobilisation of phosphorus (P), its transport to adjacent surface waters and an accelerated eutrophication risk. The paper summarises results from an international European Community sponsored research project and demonstrates how results obtained at different scales and from different scientific disciplines were compiled to derive a strategy to carry out rewetting measures. A decision support system (DSS) for a hydrologically sensitive area in the Droemling catchment in north-eastern Germany was developed and is presented as a tool to regulate rewetting in order to control P release. It is demonstrated that additional laboratory experiments to identify essential processes of P release during rewetting and the site-specific management of the water table, the involvement of specific knowledge and experience of the stakeholders are necessary to develop an applicable DSS. The presented DSS is practically used to prevent freshwater resources from diffuse P pollution.

Mapping quantitative trait loci for flag leave senescence as a yield determinant in winter wheat under optimal and drought stressed environments

The timing of flag leaf senescence (FLS) is an important determinant of yield under stress and optimal environments. A doubled haploid population derived from crossing the photo period-sensitive variety Beaver,with the photo period-insensitive variety Soissons, varied significantly for this trait, measured as the percent green flag leaf area remaining at 14 days and 35 days after anthesis. This trait also showed a significantly positive correlation with yield under variable environmental regimes. QTL analysis based on a genetic map derived from 48 doubled haploid lines using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers, revealed the genetic control of this trait. The coincidence of QTL for senescence on chromosomes 2B and 2D under drought-stressed and optimal environments, respectively, indicate a complex genetic mechanism of this trait involving the re-mobilisation of resources from the source to the sink during senescence.

The role of polyphenolic compounds in the diet as inhibitors of platelet function

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary components that are able to inhibit platelet function and therefore decrease the risk of cardiovascular disease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including a group of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5 d. Platelet aggregation and plasma flavonols were measured at baseline and after 5 d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P = 0.001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compounds on platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.

Analysis of second messenger pathways stimulated by different chemokines acting at the chemokine receptor

The chemokine receptor, CCR5, responds to several chemokines leading to changes in activity in several signalling pathways. Here, we investigated the ability of different chemokines to provide differential activation of pathways. The effects of five CC chemokines acting at CCR5 were investigated for their ability to inhibit forskolin- stimulated 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation and to stimulate Ca2+ mobilisation. in Chinese hamster ovary (CHO) cells expressing CCR5. Macrophage inflammatory protein 1 alpha (D26A) (MIP-1 alpha (D26A), CCL3 (D26A)), regulated on activation, normal T-cell expressed and secreted (RANTES, CCLS), MIP-1 beta (CCL4) and monocyte chemoattractant protein 2 (MCP-2, CCL8) were able to inhibit forskolin -stimulated CAMP accumulation, whilst MCP-4 (CCL13) could not elicit a response. CCL3 (D26A), CCL4, CCLS, CCL8 and CCL13 were able to stimulate Ca2+ mobilisation. through CCRS, although CCL3 (D26A) and CCL5 exhibited biphasic concentration-response curves. The Ca2+ responses induced by CCL4, CCL5, CCL8 and CCL13 were abolished by pertussis toxin, whereas the response to CCL3 (D26A) was only partially inhibited by pertussis toxin, indicating G(i/o)-independent signalling induced by this chemokine. Although the rank order of potency of chemokines was similar between the two assays, certain chemokines displayed different pharmacological profiles in cAMP inhibition and Ca2+ mobilisation assays. For instance, whilst CCL13 could not inhibit forskolin-stimulated cAMP accumulation, this chemokine was able to induce Ca2+ mobilisation via CCR5. It is concluded that different chemokines acting at CCR5 can induce different pharmacological responses, which may account for the broad spectrum of chemokines that can act at CCRS. (C) 2007 Elsevier Inc. All rights reserved.

Impact of the earthworm Lumbricus terrestris (L.) on As, Cu, Pb and Zn mobility and speciation in contaminated soils

To assess the risks that contaminated soils pose to the environment properly a greater understanding of how soil biota influence the mobility of metal(loid)s in soils is required. Lumbricus terrestris L. were incubated in three soils contaminated with As, Cu, Pb and Zn. The concentration and speciation of metal(loid)s in pore waters and the mobility and partitioning in casts were compared with earthworm-free soil. Generally the concentrations of water extractable metal(loid)s in earthworm casts were greater than in earthworm-free soil. The impact of the earthworms on concentration and speciation in pore waters was soil and metal specific and could be explained either by earthworm induced changes in soil pH or soluble organic carbon. The mobilisation of metal(loid)s in the environment by earthworm activity may allow for leaching or uptake into biota.

Impact of gut passage and mucus secretion by the earthworm Lumbricus terrestris on mobility and speciation of arsenic in contaminated soil

Earthworms inhabiting arsenic contaminated soils may accelerate the leaching of As into surface and ground waters. We carried out three experiments to determine the impact of passage of As contaminated soil (1150 mgAs kg−1) through the gut of the earthworm Lumbricus terrestris on the mobility and speciation of As and the effects of earthworm mucus on As mobility. The concentration of water soluble As in soil increased (from 1.6 to 18 mg kg−1) after passage through the earthworm gut. Casts that were aged for 56 days still contained more than nine times greater water soluble As than bulk earthworm inhabited soil. Changes were due to increases in As(V) mobility, with no change in As(III). Dilute mucus extracts reduced As mobility through the formation of As-amino acid-iron oxide ternary complexes. More concentrated mucus extracts increased As mobility. These changes, together with those due to the passage through the gut, were due to increases in pH, phosphate and soluble organic carbon. The mobilisation of As from contaminated soils in the environment by cast production and mucus secretion may allow for accelerated leaching or uptake into biota which is underestimated when bulk soil samples are analysed and the influence of soil biota ignored.

The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function

Background: Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function. Objectives: Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this report we aim to report the role of one of these enzymes - ERp57 in the regulation of platelet function. Methods/Results: Using enzyme activity function blocking antibodies, we demonstrate a role for ERp57 in platelet aggregation, dense granule secretion, fibrinogen binding, calcium mobilisation and thrombus formation under arterial conditions. In addition to the effects of ERp57 on isolated platelets, we observe the presence of ERp57 in the developing thrombus in vivo. Furthermore the inhibition of ERp57 function was found to reduce laser-injury induced arterial thrombus formation in a murine model of thrombosis. Conclusions: These data suggest that ERp57 is important for normal platelet function and opens up the possibility that the regulation of platelet function by a range of cell surface thiol isomerases may represent a broad paradigm for the regulation of haemostasis and thrombosis.

Rhinocetin, a venom-derived integrin-specific antagonist inhibits collagen-induced platelet and endothelial cell functions

Snaclecs are small non-enzymatic proteins present in viper venoms reported to modulate haemostasis of victims through effects on platelets, vascular endothelial and smooth muscle cells. In this study, we have isolated and functionally characterised a snaclec which we named rhinocetin from the venom of West African gaboon viper, Bitis gabonica rhinoceros. Rhinocetin was shown to comprise α and β chains with the molecular masses of 13.5 and 13kDa respectively. Sequence and immunoblot analysis of rhinocetin confirmed this to be a novel snaclec. Rhinocetin inhibited collagen-stimulated activation of human platelets in dose dependent manner, but displayed no inhibitory effects on glycoprotein VI (collagen receptor) selective agonist, CRP-XL-, ADP- or thrombin-induced platelet activation. Rhinocetin antagonised the binding of monoclonal antibodies against the α2 subunit of integrin α2β1 to platelets and coimmunoprecipitation analysis confirmed integrin α2β1 as a target for this venom protein. Rhinocetin inhibited a range of collagen induced platelet functions such as fibrinogen binding, calcium mobilisation, granule secretion, aggregation and thrombus formation. It also inhibited integrin α2β1 dependent functions of human endothelial cells. Together, our data suggest rhinocetin to be a modulator of integrin α2β1 function and thus may provide valuable insights into the role of this integrin in physiological and pathophysiological scenarios including haemostasis, thrombosis and envenomation.

Safeguarding inheritance and enhancing the resilience of orphaned young people living in child- and youth-headed households in Tanzania and Uganda

This paper explores the resilience of orphaned young people in safeguarding the physical assets (land and property) that they inherited from their parents and in sustaining their households without a co-resident adult relative. Drawing on the concept of resilience and the sustainable livelihoods framework, this paper analyses the findings of an exploratory study conducted with 15 orphaned young people heading households,18 of their siblings and 39 NGO workers and community members in Tanzania and Uganda. The research suggests that inherited land and property represent key determining factors in the formation and viability of child- and youth-headed households in both rural and urban areas. Despite experiences of stigma and marginalisation in the community, social networks were crucial in enabling young people to protect themselves and their property, in providing access to material and emotional resources and in enhancing their skills and capabilities to develop sustainable livelihoods. Support for child- and youth-headed households needs to recognise young people's agency and adopt a holistic approach to their lives that analyses the physical assets, material resources, human and social capital available to the household, as well as individual young people's wellbeing, outlook and aspirations. Alongside cash transfers and material support, youth-led collective mobilisation that is sustained over time may also help to build resilience and foster more supportive social environments that challenge property grabbing and the stigmatisation of child- and youth-headed households.

Behaviour change in the UK climate debate : an assessment of responsibility, agency and political dimensions

This paper explores the politics around the role of agency in the UK climate change debate. Government interventions on the demand side of consumption have increasingly involved attempts to obtain greater traction with the values, attitudes and beliefs of citizens in relation to climate change and also in terms of influencing consumer behaviour at an individual level. With figures showing that approximately 40% of the UK’s carbon emissions are attributable to household and transport behaviour, policy initiatives have progressively focused on the facilitation of “sustainable behaviours”. Evidence suggests however, that mobilisation of pro-environmental attitudes in addressing the perceived “value-action gap” has so far had limited success. Research in this field suggests that there is a more significant and nuanced “gap” between context and behaviour; a relationship that perhaps provides a more adroit reflection of reasons why people do not necessarily react in the way that policy-makers anticipate. Tracing the development of the UK Government’s behaviour change agenda over the last decade, we posit that a core reason for the limitations of this programme relates to an excessively narrow focus on the individual. This has served to obscure some of the wider political and economic aspects of the debate in favour of a more simplified discussion. The second part of the paper reports findings from a series of focus groups exploring some of the wider political views that people hold around household energy habits, purchase and use of domestic appliances, and transport behaviour-and discusses these insights in relation to the literature on the agenda’s apparent limitations. The paper concludes by considering whether the aims of the Big Society approach (recently established by the UK’s Coalition Government) hold the potential to engage more directly with some of these issues or whether they merely constitute a “repackaging” of the individualism agenda.

The national dialogue on behaviour change in UK climate policy: some observations on responsibility, agency and political dimensions

This chapter explores the politics around the role of agency in the UK climate change debate. Government interventions on the demand side of consumption have increasingly involved attempts to obtain greater traction with the values, attitudes and beliefs of citizens in relation to climate change and also in terms of influencing consumer behaviour at an individual level. With figures showing that approximately 40% of the UK’s carbon emissions are attributable to household and transport behaviour, policy initiatives have progressively focused on the facilitation of “sustainable behaviours”. Evidence suggests however, that mobilisation of pro-environmental attitudes in addressing the perceived “value-action gap” has so far had limited success. Research in this field suggests that there is a more significant and nuanced “gap” between context and behaviour; a relationship that perhaps provides a more adroit reflection of reasons why people do not necessarily react in the way that policy-makers anticipate. Tracing the development of the UK Government’s behaviour change agenda over the last decade, we posit that a core reason for the limitations of this programme relates to an excessively narrow focus on the individual. This has served to obscure some of the wider political and economic aspects of the debate in favour of a more simplified discussion. The second part of the chapter reports findings from a series of focus groups exploring some of the wider political views that people hold around household energy habits, purchase and use of domestic appliances, and transport behaviour-and discusses these insights in relation to the literature on the agenda’s apparent limitations. The chapter concludes by considering whether the aims of the Big Society approach (recently established by the UK’s Coalition Government) hold the potential to engage more directly with some of these issues or whether they merely constitute a “repackaging” of the individualism agenda.