The effects of the cellular and infectious prion protein on the neuronal adaptor protein X11α.

BACKGROUND: The neuronal adaptor protein X11α is a multidomain protein with a phosphotyrosine binding (PTB) domain, two PDZ (PSD_95, Drosophila disks-large, ZO-1) domains, a Munc Interacting (MI) domain and a CASK interacting region. Amongst its functions is a role in the regulation of the abnormal processing of the amyloid precursor protein (APP). It also regulates the activity of Cu/Zn Superoxide dismutase (SOD1) through binding with its chaperone the copper chaperone for SOD1. How X11α production is controlled has remained unclear. METHODS: Using the neuroblastoma cell line, N2a, and knockdown studies, the effect of the cellular and infectious prion protein, PrP(C) and PrP(Sc), on X11α is examined. RESULTS: We show that X11α expression is directly proportional to the expression of PrP(C), whereas its levels are reduced by PrP(Sc). We also show PrP(Sc) to affect X11α at a functional level. One of the effects of prion infection is lowered cellular SOD1 levels, here by knockdown of X11α we identify that the effect of PrP(Sc) on SOD1 can be reversed indicating that X11α is involved in prion disease pathogenesis. CONCLUSIONS: A role for the cellular and infectious prion protein, PrP(C) and PrP(Sc), respectively, in regulating X11α is identified in this work. GENERAL SIGNIFICANCE: Due to the multiple interacting partners of X11α, dysfunction or alteration in X11α will have a significant cellular effect. This work highlights the role of PrP(C) and PrP(Sc) in the regulation of X11α, and provides a new target pathway to control X11α and its related functions.

Understanding why landholders choose to participate or withdraw from conservation programs: a case study from a Queensland conservation auction.

Ensuring adequate participation by private landholders in a conservation scheme is a challenge for program managers around the world. This paper uses a case study of the Vegetation Incentives Program from Queensland, Australia, to contribute additional information to the literature on influences on participation in conservation, and to offer insight into ways to improve program design to optimise participation. The research is particularly of interest to programs that include a tender mechanism or conservation covenant in their designs. Participation in the Vegetation Incentives Program was limited outside two small geographic areas, with the result that the budget was not expended. A survey of participants revealed that a narrow subset of the rural population was attracted to participate, namely highly educated, experienced landholders with positive environmental attitudes and a low opportunity cost of participation. The research also investigated why some landholders chose to withdraw from the program before full participation. Both qualitative and quantitative methods were used in the analysis. There were a variety of reasons for making the decision to leave, including disliking the requirement for permanent protection, the tender mechanism employed, and not understanding the process well enough. This information can help improve conservation outcomes by understanding where to target limited efforts in a catchment, and clarifying the likely limitations of some aspects of scheme design.

Motivations for kerbside dumping: Evidence from Brisbane, Australia.

Illegal dumping of waste on kerbsides outside residences is a problem in many urban areas around the world. Despite this, there has been little research undertaken on the reasons behind the practice or the barriers to alternative, legal disposal mechanisms. This study interviewed householders in Brisbane, Australia in an attempt to fill this gap. The interviews revealed that kerbside dumping is a complex behaviour with a variety of motivations. Unlike many other illegal activities, participants and observers of kerbside dumping did not necessarily realise that what they were doing was illegal. They also identified many positive benefits such as sharing items with other people. In addition, some residents felt they had no choice even though they were aware that it was illegal. For them, barriers such as lack of transport to the waste disposal facility and lack of storage until the official kerbside collection meant that the practice continued.

The structure function relationship for the Prion protein.

Central to Prion diseases is the normal endogenous Prion protein, PrPC. In spite of years of research the exact function of this protein remains enigmatic. Numerous binding partners have been identified for PrPC and due to the presence of a repeated sequence of PHGGGWGQ in the proteins amino-terminus it can bind metal ions. The protein is a complex molecule and each portion of PrPC possesses different roles for function and/ or trafficking. As understanding the role of PrPC is central to these disorders the structure/function relationship will be reviewed here.