Diverse fibrillar peptides directly bind the Alzheimer’s amyloid precursor protein and amyloid precursor-like protein 2 resulting in cellular accumulation

The Alzheimer’s disease Aβ peptide can increase the levels of cell-associated amyloid precursor protein (APP) in vitro. To determine the specificity of this response for Aβ and whether it is related to cytotoxicity, we tested a diverse range of fibrillar peptides including amyloid-β (Aβ), the fibrillar prion peptides PrP106–126 and PrP178–193 and human islet-cell amylin. All these peptides increased the levels of APP and amyloid precursor-like protein 2 (APLP2) in primary cultures of astrocytes and neurons. Specificity was shown by a lack of change to amyloid precursor-like protein 1, τ-1 and cellular prion protein (PrPc) levels. APP and APLP2 levels were elevated only in cultures exposed to fibrillar peptides as assessed by electron microscopy and not in cultures treated with non-fibrillogenic peptide variants or aggregated lipoprotein. We found that PrP106–126 and the non-toxic but fibril-forming PrP178–193 increased APP levels in cultures derived from both wild-type and PrPc-deficient mice indicating that fibrillar peptides up-regulate APP through a non-cytotoxic mechanism and irrespective of parental protein expression. Fibrillar PrP106–126 and Aβ peptides bound recombinant APP and APLP2 suggesting the accumulation of these proteins was mediated by direct binding to the fibrillated peptide. This was supported by decreased APP accumulation following extensive washing of the cultures to remove fibrillar aggregates. Pre-incubation of fibrillar peptide with recombinant APP18–146, the putative fibril binding site, also abrogated the accumulation of APP. These findings show that diverse fibrillogenic peptides can induce accumulation of APP and APLP2 and this mechanism could contribute to pathogenesis in neurodegenerative disorders.

Below the styx : a novel

Martin Frobisher has been beating close family members about the head with an epergne. Frobisher, successful publisher and community leader, is in the City Remand Centre, awaiting trial for murder. What shadow has fallen across the comfortable lives of Frobisher, his ambitious wife Coralie and her flaky sister Madeleine? What has led a cultivated and reflective man, known to shoo spiders and earwigs out of the harm's way, to such reckless acts of violence?
With the prospect of imprisonment for the Term of his Natural Life, can Frobisher and his research assistant Petra find guidance in the life and fortunes of a brilliant young Englishman, marooned in Australia, 'the land of vulgarity and mob rule' more than a century earlier, and obsessed with the darker moments in the nation's history? Why does Frobisher appear to care more, in the end, about the life of Marcus Clarke than he does about his own?

Grafts in myringoplasty : utilizing a silk fibroin scaffold as a novel device

Chronic perforations of the eardrum or tympanic membrane represent a significant source of morbidity worldwide. Myringoplasty is the operative repair of a perforated tympanic membrane and is a procedure commonly performed by otolaryngologists. Its purpose is to close the tympanic membrane, improve hearing and limit patient susceptibility to middle ear infections. The success rates of the different surgical techniques used to perform a myringoplasty, and the optimal graft materials to achieve complete closure and restore hearing, vary significantly in the literature. A number of autologous tissues, homografts and synthetic materials are described as graft options. With the advent and development of tissue engineering in the last decade, a number of biomaterials have been studied and attempts have been made to mimic biological functions with these materials. Fibroin, a core structural protein in silk from silkworms, has been widely studied with biomedical applications in mind. Several cell types, including keratinocytes, have grown on silk biomaterials, and scaffolds manufactured from silk have successfully been used in wound healing and for tissue engineering purposes. This review focuses on the current available grafts for myringoplasty and their limitations, and examines the biomechanical properties of silk, assessing the potential benefits of a silk fibroin scaffold as a novel device for use as a graft in myringoplasty surgery.

Hydrologic model for the Woady Yaloak River catchment

A hydrologic model was developed to predict the long-term impacts of land use change on the hydrology of the Woady Yaloak River catchment. The model can be used by catchment managers to formulate management decisions about land use changes expected to occur across the catchment in the future.

Last supper

A creative reimagining of the life of Alexander Pearce (1790?-1824), the 'cannibal convict' of Van Diemen's Land, seeking a more historically accurate portrayal than the narrow stereotypes seen in literature, such as the brutish character Gabbett in Marcus Clarke's 1874 novel "For the term of his natural life." The critical exegesis surveys the literary tradition of the convict novel in Australia.

Self in architecture

Presents the hypothesis that within the making of architecture a buried, perhaps unconscious, aspect of self finds its way into the architectural project. Field study interviews were conducted with architects working in practice.

Preliminary results of the application of a silk fibroin scaffold to otology

The surgical treatment to repair chronic tympanic membrane perforations is myringoplasty. Although multiple autologous grafts, allografts, and synthetic graft materials have been used over the years, no single graft material is superior for repairing all perforation types. Recently, the remarkable properties of silk fibroin protein have been studied, with biomedical and tissue engineering applications in mind, across a number of medical and surgical disciplines. The present study examines the use of silk fibroin for its potential suitability as an alternative graft in myringoplasty surgery by investigating the growth and proliferation of human tympanic membrane keratinocytes on a silk fibroin scaffold in vitro. Light microscopy, immunofluorescent staining, and confocal imaging all reveal promising preliminary results. The biocompatibility, transparency, stability, high tensile strength, and biodegradability of fibroin make this biomaterial an attractive option to study for this utility.

Australian universities, government research and the application of climate change knowledge in Australian coastal zone management

One of the key issues in Australia for sustainable management of the coastal zone is that the science of climate change has not been widely used by decision-makers to inform coastal governance. There exist opportunities to enhance the dialogue between knowledge-makers and decision-makers, and universities have a key role to play in researching and fostering better linkages. At the heart of these linkages lies the principle of more informed engagement between historically disparate groups. In Australia, the new ‘Flagship’ research programme, funded by the Commonwealth Scientific and Industrial Research Organization (CSIRO), emphasizes their partnering with universities in a more systematic and collaborative manner than previously achieved in such research projects. In order to address sustainability in general and coastal adaptation to climate change in particular, interdisciplinary learning needs to occur between the social and natural sciences; also, transdisciplinary understanding of that interaction needs to be fully developed. New methods of communicative engagement such as computer visualizations and animations, together with deliberative techniques, can help policy-makers and planners reach a better understanding of the significance of the science of climate change impacts on the coast. Deeper engagement across historically disparate groups can lead to the development of epistemological and methodological synergies between social and natural scientists, adaptive learning, reflexive governance, and greater analytical and deliberative understanding among scientists, policymakers and the wider public. This understanding can lead in turn to enhance coastal governance for climate adaptation on the coast.

Designing adaptive artificial agents for an economic production and conflict model

Production and conflict models have been used over the past 30 years to represent the effects of unproductive resource allocation in economics. Their major applications are in modelling the assignment of property rights, rentseeking and defense economics. This paper describes the process of designing an agent used in a production and conflict model. Using the capabilities of an agent-based approach to economic modelling, we have enriched a simple decision-maker of the kind used in classic general equilibrium economic models, to build an adaptive and interactive agent which uses its own attributes, its neighbors’ parameters and information from its environment to make resource allocation decisions. Our model presents emergent and adaptive behaviors than cannot be captured using classic production and conflict agents. Some possible extensions for future applications are also recommended.

An analysis of trading in target stocks before successful takeover announcements

In this paper we examine both informed and contraire trading preceding successful takeover announcements on US target firms from 2001 to 2006. We find that both informed trading and contraire trading exist within the period preceding successful takeover announcements on the stock market, as evident through abnormal returns and trading volumes and on the option market by analyzing only abnormal trading volume. In regard to contraire trading, we investigate possible explanations for its existence. This study finds, through analysis of an unbiased sample of rumored target firms, that deliberate contraire trading appears to be profitable which is likely an explanation for such trading.

Structure and properties of biomedical films prepared from aqueous and acidic silk fibroin solutions

Silk fibroin films are promising materials for a range of biomedical applications. To understand the effects of casting solvents on film properties, we used water (W), formic acid (FA), and trifluoroacetic acid (TFA) as solvents. We characterized molecular weight, secondary structure, mechanical properties, and degradation behavior of cast films. Significant degradation of fibroin was observed for TFA-based film compared to W and TA-based films when analyzed by SDS-PAGE. Fibroin degradation resulted in a significant reduction in tensile strength and modulus of TFA-based films. Compared to water, TFA-based films demonstrated lower water solubility (19.6% vs. 62.5% in 12 h) despite having only a marginal increase in their ß-sheet content (26.9% vs. 23.7%). On the other hand, FA-based films with 34.3% ß-sheet were virtually water insoluble. Following solubility treatment, ß-sheet content in FA-based films increased to 50.9%. On exposure to protease XIV, water-annealed FA-based films lost 74% mass in 22 days compared to only 30% mass loss by ethanol annealed FA films. This study demonstrated that a small variation in the ß-sheet percentage and random coil conformations resulted in a significant change in the rates of enzymatic degradation without alteration to their tensile properties. The film surface roughness changed with the extent of enzymatic hydrolysis.

Warrock collection: original line drawings by fourth year Deakin University architecture students of the Warrock Homestead, a local heritage listed property in Victoria

This collection includes the original line drawings by fourth year Deakin University architecture students of a well known local heritage listed property, the Warrock homestead. The Warrock homestead consisted of detailed original timber structures of the 19th century. The drawings are the result of a conservation project funded by the Commonwealth Government of Australia National Estate Grants program. In 1999 a further deposit of original reports relating to individual buildings on the property was received. The collection consists of monographs, photographs and photograph negatives, architectural drawings, VHS tapes and ephemera.

Lost in Hanoi : disorientation, travel, and urban space

Using a 2010 trip to Hanoi, Vietnam, this article looks at the ways that disorientation is used as a  trope within the urban environment and to create the traveling subject. Suggesting that travel is a form of deliberate disorientation/ orientation, the article focuses on ideas of disorientation within the urban environment and the ways they have been portrayed in Western cultural forms (the flâneur; the dérive) while suggesting these forms are not sufficient to understand the dynamics of travel. Moreover, the article focuses on two forms of travel as disorientation derived from John Zilcosky—the trope of being “lost and found” and that of  “the return.” Finally, the article suggests that Marcus Auge’s idea of non-place is not only a sufficient way of conceptualizing contemporary notions of travel, but is also an indicator of something beyond its scope—that of globalization.

Web tools for the prioritization of candidate disease genes

Despite increasing sequencing capacity, genetic disease investigation still frequently results in the identification of loci containing multiple candidate disease genes that need to be tested for involvement in the disease. This process can be expedited by prioritizing the candidates prior to testing. Over the last decade, a large number of computational methods and tools have been developed to assist the clinical geneticist in prioritizing candidate disease genes. In this chapter, we give an overview of computational tools that can be used for this purpose, all of which are freely available over the web.