Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3

Eph receptor tyrosine kinases (Ephs) function as molecular relays that interact with cell surface-bound ephrin ligands to direct the position of migrating cells. Structural studies revealed that, through two distinct contact surfaces on opposite sites of each protein, Eph and ephrin binding domains assemble into symmetric, circular heterotetramers. However, Eph signal initiation requires the assembly of higher order oligomers, suggesting additional points of contact. By screening a random library of EphA3 binding-compromised ephrin-A5 mutants, we have now determined ephrin-A5 residues that are essential for the assembly of high affinity EphA3 signaling complexes. In addition to the two interfaces predicted from the crystal structure of the homologous EphB2 center dot ephrin-B2 complex, we identified a cluster of 10 residues on the ephrin-A5 E alpha-helix, the E-F loop, the underlying H beta-strand, as well as the nearby B - C loop, which define a distinct third surface required for oligomerization and activation of EphA3 signaling. Together with a corresponding third surface region identified recently outside of the minimal ephrin binding domain of EphA3, our findings provide experimental evidence for the essential contribution of three distinct protein-interaction interfaces to assemble functional EphA3 signaling complexes.

Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.

Solid-state synthesis of embedded single-crystal metal oxide and phosphate nanoparticles and in situ crystallization

A new solid state organometallic route to embedded nanoparticle-containing inorganic materials is shown, through pyrolysis of metal-containing derivatives of cyclotriphosphazenes. Pyrolysis in air and at 800 °C of new molecular precursors gives individual single-crystal nanoparticles of SiP2O7, TiO2, P4O7, WP2O7 and SiO2, depending on the precursor used. High resolution transmission electron microscopy investigations reveal, in most cases, perfect single crystals of metal oxides and the first nanostructures of negative thermal expansion metal phosphates with diameters in the range 2–6 nm for all products. While all nanoparticles are new by this method, WP2O7 and SiP2O7 nanoparticles are reported for the first time. In situ recrystallization formation of nanocrystals of SiP2O7 was also observed due to electron beam induced reactions during measurements of the nanoparticulate pyrolytic products SiO2 and P4O7. The possible mechanism for the formation of the nanoparticles at much lower temperatures than their bulk counterparts in both cases is discussed. Degrees of stabilization from the formation of P4O7 affects the nanocrystalline products: nanoparticles are observed for WP2O7, with coalescing crystallization occurring for the amorphous host in which SiP2O7 crystals form as a solid within a solid. The approach allows the simple formation of multimetallic, monometallic, metal-oxide and metal phosphate nanocrystals embedded in an amorphous dielectric. The method and can be extended to nearly any metal capable of successful coordination as an organometallic to allow embedded nanoparticle layers and features to be deposited or written on surfaces for application as high mobility pyrophosphate lithium–ion cathode materials, catalysis and nanocrystal embedded dielectric layers.

Some surface profiles of a strip after plane-strain indentation by rigid bodies with serrated surfaces

This paper is concerned with the surface profiles of a strip after rigid bodies with serrated (saw-teeth) surfaces indent the strip and are subsequently removed. Plane-strain conditions are assumed. This has application in roughness transfer of final metal forming process. The effects of the semi-angle of the teeth, the depth of indentation and the friction on the contact surface on the profile are considered.

Understanding the physical processes of pollutant build-up and wash-off on roof surfaces

Pollutants originating with roof runoff can have a significant impact to urban stormwater quality. This signifies the importance of understanding pollutant processes on roof surfaces. Additionally, knowledge of pollutant processes on roof surfaces is important as roofs are used as the primary catchment surface for domestic rainwater harvesting. In recent years, rainwater harvesting has become one of the primary sustainable water management techniques to counteract the growing demand for potable water. Similar to all impervious services, pollutants associated with roof runoff undergo two primary processes: build-up and wash-off. The knowledge relating to these processes is limited. This paper presents outcomes of an in-depth research study into pollutant build-up and wash-off for roof surfaces. The knowledge will be important in order to develop appropriate strategies to safeguard rainwater users from possible health risks.

How the whiteness embedded in health services impacts on the health and well-being of Aboriginal peoples

Aboriginal women are treated differently by non-indigenous health care providers based on perceptions of Aboriginality and skin colour and white race privilege within health care environments. The experiences shared below are from some of the Aboriginal woman respondents in a research project undertaken within Rockhampton, a regional area in Central Queensland (Fredericks, 2003). The experiences give an insight into how the Aboriginal women interviewed felt and their observations of how other Aboriginal women were treated within health care settings based on skin colour and perceptions of Aboriginality. A number of the women demonstrated a personal in-depth analysis of the issues surrounding place, skin colour and Aboriginality. For example, one of the women, who I named Kay, identified one particular health service organisation and stated that, ‘it is a totally white designed space. There is nothing that identifies me to that place. I just won’t go there as a client because I don’t feel they cater for me as a black woman’. Kay’s words give us an understanding of the reality experienced by Aboriginal women as they move in and out of places within health environments and broader society. Some of these experiences are examples of direct racism, whilst other examples are subtle and demonstrate how whiteness manifests and plays out within places. I offer acknowledgement and honour to the Aboriginal women who shared their stories and gave me a glimpse of their realities in the research project from which the findings presented in this chapter are taken. It is to this research project that is the subject of this chapter.