432 research outputs found
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
Peer reviewedPublisher PD
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
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
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