Calcium binding activity of the epidermal growth factor-like domains of the apicomplexan microneme protein EtMIC4

Microneme proteins are secreted from apicomplexan parasites during invasion of host cells and they play crucial roles in parasite-host cell adhesion. EtMIC4 is a 240 kDa transmembrane protein from Eimeria tenella that contains 31 tandemly arranged epidermal growth factor (EGF), like repeats within its extracellular domain. The majority of these repeats have calcium binding (cb) consensus sequences. Little is known about cbEGFs in apicomplexan parasites but their presence in microneme proteins suggests that they may contribute to parasite-host interactions. To investigate the potential role of cbEGFs we have expressed and correctly refolded a cbEGF triplet from EtMIC4 (cbEGF7-9) and demonstrated that this triplet binds calcium. Circular dichroism spectroscopic analysis of cbEGF7-9 demonstrates that the molecule undergoes a gradual change in conformation with increasing levels of calcium. In the presence of calcium, the triplet becomes resistant to proteolytic degradation by a variety of proteases, a characteristic feature of cbEGF repeats from higher eukaryotic proteins, such as fibrillin, suggesting that calcium binding induces the formation of a rigid conformation. Moreover, mass spectrometric mapping of the cleavage sites that are protected by calcium shows that these sites are located both close to and distant from the calcium binding sites, indicating that protection is not due to steric hindrance by calcium ions, but rather due to the overall conformation adopted by the triplet in the presence of calcium. Thus, the tandemly-arranged cbEGF repeats within EtMIC4 provide a mechanism whereby, in the calcium-rich extracellular environment, the molecule could adopt a protease-resistant, rigid structure that could favour its interaction with host cell ligands

Zero-temperature random-field Ising model on a bilayered Bethe lattice

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Economics of tillage management systems in northeastern Alberta

Non-Peer ReviewedThe economic returns and riskiness of continuous barley production using four tillage management systems were compared at five sites in three soil zones in northeastern Alberta. The study used five years of data from a tillage experiment in northeastern Alberta. The four tillage systems included conventional one (C1), which leaves 5% standing stubble, conventional two (C2), which leaves 50% standing stubble, minimum-tillage (Min), and zero-tillage (ZT). Economic calculations were based on 1992 input costs and product prices. The systems were evaluated at barley prices of $46,$69, and $92 t-1, calculated with and without all risk crop insurance. Over the five sites the expected net returns were generally higher for ZT at all barley prices. Income variability was usually lower for ZT and C2 depending on the site. The study concluded that use of reduced tillage management systems by producers in northeastern Alberta could increase farm-level returns and reduce the risk of financial loss, while potentially decreasing the amount of soil erosion

The Anisotropic Bak-Sneppen model

The Bak-Sneppen model is shown to fall into a different universality class with the introduction of a preferred direction, mirroring the situation in spin systems. This is first demonstrated by numerical simulations and subsequently confirmed by analysis of the multitrait version of the model, which admits exact solutions in the extremes of zero and maximal anisotropy. For intermediate anisotropies, we show that the spatiotemporal evolution of the avalanche has a power law `tail' which passes through the system for any non-zero anisotropy but remains fixed for the isotropic case, thus explaining the crossover in behaviour. Finally, we identify the maximally anisotropic model which is more tractable and yet more generally applicable than the isotropic system

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

Epidemics in Networks of Spatially Correlated Three-dimensional Root Branching Structures

Using digitized images of the three-dimensional, branching structures for root systems of bean seedlings, together with analytical and numerical methods that map a common 'SIR' epidemiological model onto the bond percolation problem, we show how the spatially-correlated branching structures of plant roots affect transmission efficiencies, and hence the invasion criterion, for a soil-borne pathogen as it spreads through ensembles of morphologically complex hosts. We conclude that the inherent heterogeneities in transmissibilities arising from correlations in the degrees of overlap between neighbouring plants, render a population of root systems less susceptible to epidemic invasion than a corresponding homogeneous system. Several components of morphological complexity are analysed that contribute to disorder and heterogeneities in transmissibility of infection. Anisotropy in root shape is shown to increase resilience to epidemic invasion, while increasing the degree of branching enhances the spread of epidemics in the population of roots. Some extension of the methods for other epidemiological systems are discussed.Comment: 21 pages, 8 figure

Framing interculturality: a corpus-based analysis of on-line promotional discourse of higher education intercultural communication courses

This paper examines how intercultural communication (ICC) and the notion of culture are framed in on-line promotional discourse of higher education intercultural communication courses. It analyses a specialised corpus comprised of 14,842 words from 43 course websites of master’s programmes in intercultural communication in the UK and the US—internationally, the two largest providers of such programmes. Through combining corpus tools with a ‘situated meaning’ approach, the analysis reveals that while a small number of courses acknowledge cultural ‘complexity’, culture is still very often reduced to an essentialised and static notion, despite growing criticism against such an approach in ICC literature. Intercultural communication is valorised as a combination of desirable skills and knowledge conducive to effective communication of different cultural groups and for those working in international arenas. Significant differences between the UK and US courses are identified with regard to the extent of associations with diversity-related social categories. The lack of interpretive, critical and constructivist positions on culture in promotional discourse is discussed in the context of neoliberal discourse and the current thinking towards professional competences dominant in Britain, North America, and other parts of the world

Development and techno-economic analyses of a novel hydrogen production process via chemical looping

In this work, a novel hydrogen production process (Integrated Chemical Looping Water Splitting “ICLWS”) has been developed. The modelled process has been optimised via heat integration between the main process units. The effects of the key process variables (i.e. the oxygen carrier-to-fuel ratio, steam flow rate and discharged gas temperature) on the behaviour of the reducer and oxidiser reactors were investigated. The thermal and exergy efficiencies of the process were studied and compared against a conventional steam-methane reforming (SMR) process. Finally, the economic feasibility of the process was evaluated based on the corresponding CAPEX, OPEX and first-year plant cost per kg of the hydrogen produced. The thermal efficiency of the ICLWS process was improved by 31.1% compared to the baseline (Chemical Looping Water Splitting without heat integration) process. The hydrogen efficiency and the effective efficiencies were also higher by 11.7% and 11.9%, respectively compared to the SMR process. The sensitivity analysis showed that the oxygen carrier–to-methane and -steam ratios enhanced the discharged gas and solid conversions from both the reducer and oxidiser. Unlike for the oxidiser, the temperature of the discharged gas and solids from the reducer had an impact on the gas and solid conversion. The economic evaluation of the process indicated hydrogen production costs of $1.41 and$1.62 per kilogram of hydrogen produced for Fe-based oxygen carriers supported by ZrO2 and MgAl2O4, respectively - 14% and 1.2% lower for the SMR process H2 production costs respectively

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries