Gap junctions and connexin hemichannels underpin hemostasis and thrombosis

BACKGROUND: Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have now examined the role of connexins in platelets, blood cells that circulate in isolation, but upon tissue injury adhere to each other and the vessel wall to prevent blood loss and facilitate wound repair. METHODS AND RESULTS: We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses prior to platelet-platelet contact, and reduced laser induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion and clot retraction indicating an important role for Cx37 hemichannels and gap junctions in platelet thrombus function. CONCLUSIONS: Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of haemostasis and thrombosis and represent potential therapeutic targets.

Effects of seed addition on beetle assemblages during the re-creation of species-rich lowland hay meadows

Species-rich lowland hay meadows are of conservation importance for both plants and invertebrates; however, they have declined in area across Europe as a result of conversion to other land uses and management intensification. The re-creation of these grasslands on ex-arable land provides a valuable approach to increasing the extent and conservation value of this threatened habitat. Over a 3-year period a replicated block design was used to test whether introducing seeds promoted the re-creation of both plant and phytophagous beetle assemblages typical of a target hay meadow. Seeds were harvested from local hay meadows, and applied to experimental plots in the form of either green hay or brush harvesting seeds. Green hay spreading achieved the greatest success in re-creating plant and phytophagous beetle assemblages. While re-creation success increased over time for both taxa, for the phytophagous beetles the greatest increase in re-creation success relative to the establishment year also occurred where green hay was applied. We also considered the phytophagous beetles in terms of functional traits that describe host plant specificity, larval feeding location and dispersal. Phytophagous beetle functional trait composition was most similar to the target hay meadow assemblage where some form of seed addition was used, i.e. hay spreading or brush harvested seeds. This study identified the importance of introducing target plant species as a mechanism to promote the re-creation of phytophagous beetle communities. Seed addition methods (e.g. green hay spreading) are crucial to successful hay meadow re-creation.

The acrylamide problem: a plant and agronomic science issue.

Acrylamide, a chemical that is probably carcinogenic in humans and has neurological and reproductive effects, forms from free asparagine and reducing sugars during high-temperature cooking and processing of common foods. Potato and cereal products are major contributors to dietary exposure to acrylamide and while the food industry reacted rapidly to the discovery of acrylamide in some of the most popular foods, the issue remains a difficult one for many sectors. Efforts to reduce acrylamide formation would be greatly facilitated by the development of crop varieties with lower concentrations of free asparagine and/or reducing sugars, and of best agronomic practice to ensure that concentrations are kept as low as possible. This review describes how acrylamide is formed, the factors affecting free asparagine and sugar concentrations in crop plants, and the sometimes complex relationship between precursor concentration and acrylamide-forming potential. It covers some of the strategies being used to reduce free asparagine and sugar concentrations through genetic modification and other genetic techniques, such as the identification of quantitative trait loci. The link between acrylamide formation, flavour, and colour is discussed, as well as the difficulty of balancing the unknown risk of exposure to acrylamide in the levels that are present in foods with the well-established health benefits of some of the foods concerned. Key words: Amino acids, asparagine, cereals, crop quality, food safety, Maillard reaction, potato, rye, sugars, wheat.

Bayesian estimation of the spatial Durbin error model with an application to voter turnout in the 2004 presidential election

The potential for spatial dependence in models of voter turnout, although plausible from a theoretical perspective, has not been adequately addressed in the literature. Using recent advances in Bayesian computation, we formulate and estimate the previously unutilized spatial Durbin error model and apply this model to the question of whether spillovers and unobserved spatial dependence in voter turnout matters from an empirical perspective. Formal Bayesian model comparison techniques are employed to compare the normal linear model, the spatially lagged X model (SLX), the spatial Durbin model, and the spatial Durbin error model. The results overwhelmingly support the spatial Durbin error model as the appropriate empirical model.

Organic certification, export market access and the impacts of policy: Bayesian estimation of avocado smallholder “times-to-organic certification” in Michoacán Mexico

This study analyzes organic adoption decisions using a rich set of time-to-organic durations collected from avocado small-holders in Michoacán Mexico. We derive robust, intrasample predictions about the profiles of entry and exit within the conventional-versus-organic complex and we explore the sensitivity of these predictions to choice of functional form. The dynamic nature of the sample allows us to make retrospective predictions and we establish, precisely, the profile of organic entry had the respondents been availed optimal amounts of adoption-restraining resources. A fundamental problem in the dynamic adoption literature, hitherto unrecognized, is discussed and consequent extensions are suggested.

Does training improve understanding of core concepts in cognitive behaviour therapy by people with intellectual disabilities? A randomized experiment

Background. People with intellectual disabilities (ID) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments. Cognitive behaviour therapy (CBT) is effective for a wide range of disorders in the general population. However, there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT. Aims. To test if people with ID can learn skills required for CBT, specifically the ability to distinguish between thoughts, feelings, and behaviours and to link thoughts and feelings (cognitive mediation). Method. A randomized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills. Thirty-four adults with ID were randomly allocated to the experimental condition ðN ¼ 18Þ or to the control condition ðN ¼ 16Þ. CBT skills were assessed blind at baseline and after the intervention. Results. The training led to significant improvements in participants’ ability to link thoughts and feelings, and this skill was generalized to new material. There was no effect of training on participants’ ability to distinguish amongst thoughts, feelings, and behaviours. People with ID can, therefore, learn some skills required for CBT. This implies that preparatory training for CBT might be useful for people with ID. The results might be applicable to other groups who find aspects of CBT difficult.

A kinetic model for the formation of acrylamide during the finish-frying of commercial French fries

Acrylamide is formed from reducing sugars and asparagine during the preparation of French fries. The commercial preparation of French fries is a multi-stage process involving the preparation of frozen, par-fried potato strips for distribution to catering outlets where they are finish fried. The initial blanching, treatment in glucose solution and par-frying steps are crucial since they determine the levels of precursors present at the beginning of the finish frying process. In order to minimize the quantities of acrylamide in cooked fries, it is important to understand the impact of each stage on the formation of acrylamide. Acrylamide, amino acids, sugars, moisture, fat and color were monitored at time intervals during the frying of potato strips which had been dipped in varying concentrations of glucose and fructose during a typical pretreatment. A mathematical model of the finish-frying was developed based on the fundamental chemical reaction pathways, incorporating moisture and temperature gradients in the fries. This showed the contribution of both glucose and fructose to the generation of acrylamide, and accurately predicted the acrylamide content of the final fries.

Kinetic model for the formation of acrylamide during the finish-frying of commercial French fries

Acrylamide is formed from reducing sugars and asparagine during the preparation of French fries. The commercial preparation of French fries is a multistage process involving the preparation of frozen, par-fried potato strips for distribution to catering outlets, where they are finish-fried. The initial blanching, treatment in glucose solution, and par-frying steps are crucial because they determine the levels of precursors present at the beginning of the finish-frying process. To minimize the quantities of acrylamide in cooked fries, it is important to understand the impact of each stage on the formation of acrylamide. Acrylamide, amino acids, sugars, moisture, fat, and color were monitored at time intervals during the frying of potato strips that had been dipped in various concentrations of glucose and fructose during a typical pretreatment. A mathematical model based on the fundamental chemical reaction pathways of the finish-frying was developed, incorporating moisture and temperature gradients in the fries. This showed the contribution of both glucose and fructose to the generation of acrylamide and accurately predicted the acrylamide content of the final fries.

Acrylamide is formed in the Maillard reaction

Reports of the presence of acrylamide in a range of fried and oven-cooked foods have caused worldwide concern because this compound has been classified as probably carcinogenic in humans. Here we show how acrylamide can be generated from food components during heat treatment as a result of the Maillard reaction between amino acids and reducing sugars. We find that asparagine, a major amino acid in potatoes and cereals, is a crucial participant in the production of acrylamide by this pathway.

Gut microbial activity, implications for health and disease: the potential role of metabolite analysis

Microbial metabolism of proteins and amino acids by human gut bacteria generates a variety of compounds including phenol, indole, and sulfur compounds and branched chain fatty acids, many of which have been shown to elicit a toxic effect on the lumen. Bacterial fermentation of amino acids and proteins occurs mainly in the distal colon, a site that is often fraught with symptoms from disorders including ulcerative colitis (UC) and colorectal cancer (CRC). In contrast to carbohydrate metabolism by the gut microbiota, proteolysis is less extensively researched. Many metabolites are low molecular weight, volatile compounds. This review will summarize the use of analytical methods to detect and identify compounds in order to elucidate the relationship between specific dietary proteinaceous substrates, their corresponding metabolites, and implications for gastrointestinal health.

Flavour profile of three novel acidic varieties of muskmelon (Cucumis melo L.)

Novel acidic varieties of muskmelon (Cucumis melo L.) are emerging onto the UK market. These melons contain almost twice the amount of citric acid compared to standard melons and are described as ‘zesty and fresh’. This study compared the flavour components of three acidic varieties with a standard Galia-type melon. The volatile and semivolatile compounds were extracted using dynamic headspace extraction (DHE) or solid-phase microextraction (SPME) and solid phase extraction (SPE) respectively, followed by gas chromatography – mass spectrometry (GC-MS) and gas chromatography – olfactometry (GC-O). More than 50 volatile and 50 semivolatile compounds were identified in the headspace and the SPE extracts respectively. GC-O revealed 15 odour-active components in the headspace, with esters being consistently higher in acidic variety. This study showed quantitative and qualitative differences between all four varieties and key differences between acidic varieties and standard melons.

Representing the acquisition and use of energy by individuals in agent-based models of animal populations

Summary 1. Agent-based models (ABMs) are widely used to predict how populations respond to changing environments. As the availability of food varies in space and time, individuals should have their own energy budgets, but there is no consensus as to how these should be modelled. Here, we use knowledge of physiological ecology to identify major issues confronting the modeller and to make recommendations about how energy budgets for use in ABMs should be constructed. 2. Our proposal is that modelled animals forage as necessary to supply their energy needs for maintenance, growth and reproduction. If there is sufficient energy intake, an animal allocates the energy obtained in the order: maintenance, growth, reproduction, energy storage, until its energy stores reach an optimal level. If there is a shortfall, the priorities for maintenance and growth/reproduction remain the same until reserves fall to a critical threshold below which all are allocated to maintenance. Rates of ingestion and allocation depend on body mass and temperature. We make suggestions for how each of these processes should be modelled mathematically. 3. Mortality rates vary with body mass and temperature according to known relationships, and these can be used to obtain estimates of background mortality rate. 4. If parameter values cannot be obtained directly, then values may provisionally be obtained by parameter borrowing, pattern-oriented modelling, artificial evolution or from allometric equations. 5. The development of ABMs incorporating individual energy budgets is essential for realistic modelling of populations affected by food availability. Such ABMs are already being used to guide conservation planning of nature reserves and shell fisheries, to assess environmental impacts of building proposals including wind farms and highways and to assess the effects on nontarget organisms of chemicals for the control of agricultural pests. Keywords: bioenergetics; energy budget; individual-based models; population dynamics.

Concentrations of free amino acids and sugars in nine potato varieties: effects of storage and relationship with acrylamide formation

Acrylamide forms during cooking and processing predominately from the reaction of free asparagine and reducing sugars in the Maillard reaction. The identification of low free asparagine and reducing sugar varieties of crops is therefore an important target. In this study, nine varieties of potato (French fry varieties Maris Piper (from two suppliers), Pentland Dell, King Edward, Daisy, and Markies; and chipping varieties Lady Claire, Lady Rosetta, Saturna, and Hermes) grown in the United Kingdom in 2009 were analyzed at monthly intervals through storage from November 2009 to July 2010. Acrylamide formation was measured in heated flour and chips fried in oil. Analysis of variance revealed significant interactions between varieties nested within type (French fry and chipping) and storage time for most free amino acids, glucose, fructose, and acrylamide formation. Acrylamide formed in chips correlated significantly with acrylamide formed in flour and with chip color. There were significant correlations between glucose or total reducing sugar concentration and acrylamide formation in both variety types, but with fructose the correlation was much stronger for chipping than for French fry varieties. Conversely, there were significant correlations with acrylamide formation for both total free amino acid and free asparagine concentration in the French fry but not chipping varieties. The study showed the potential of variety selection for preventing unacceptable levels of acrylamide formation in potato products and the variety-dependent effect of long-term storage on acrylamide risk. It also highlighted the complex relationship between precursor concentration and acrylamide risk in potatoes.

The researcher-farmer interface in the rice-wheat system: moving from agricultural productivity to livelihoods

This chapter explores some of the implications of adopting a research approach that focuses on people and their livelihoods in the rice-wheat system of the Indo-Gangetic Plains. We draw on information from a study undertaken by the authors in Bangladesh and then consider the transferability of our findings to other situations. We conclude that if our research is to bridge the researcher-farmer interface, ongoing technical research must be supported by research that explores how institutional, policy, and communication strategies determine livelihood outcomes. The challenge that now faces researchers is to move beyond their involvement in participatory research to understand how to facilitate a process in which they provide information and products for others to test. Building capacity at various levels for openness in sharing information and products–seeing research as a public good for all–seems to be a prerequisite for more effective dissemination of the available information and technologies.