A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Comparison of molecular markers to detect fresh sewage in environmental waters

Human-specific Bacteroides HF183 (HS-HF183), human-specific Enterococci faecium esp (HS-esp), human-specific adenoviruses (HS-AVs) and human-specific polyomaviruses (HS-PVs) assays were evaluated in freshwater, seawater and distilled water to detect fresh sewage. The sewage spiked water samples were also tested for the concentrations of traditional fecal indicators (i.e., Escherichia coli, enterococci and Clostridium perfringens) and enteric viruses such as enteroviruses (EVs), sapoviruses (SVs), and torquetenoviruses (TVs). The overall host-specificity of the HS-HF183 marker to differentiate between humans and other animals was 98%. However, the HS-esp, HS-AVs and HS-PVs showed 100% hostspecificity. All the human-specific markers showed >97% sensitivity to detect human fecal pollution. E. coli, enterococci and, C. perfringens were detected up to dilutions of sewage 10_5, 10_4 and 10_3 respectively.HS-esp, HS-AVs, HS-PVs, SVs and TVs were detected up to dilution of sewage 10_4 whilst EVs were detected up to dilution 10_5. The ability of the HS-HF183 marker to detect freshsewagewas3–4 orders ofmagnitude higher than that of the HS-esp and viral markers. The ability to detect fresh sewage in freshwater, seawater and distilled water matrices was similar for human-specific bacterial and viral marker. Based on our data, it appears that human-specific molecular markers are sensitive measures of fresh sewage pollution, and the HS-HF183 marker appears to be the most sensitive among these markers in terms of detecting fresh sewage. However, the presence of the HS-HF183 marker in environmental waters may not necessarily indicate the presence of enteric viruses due to their high abundance in sewage compared to enteric viruses. More research is required on the persistency of these markers in environmental water samples in relation to traditional fecal indicators and enteric pathogens.

Interactions of phenyldithioesters with gold nanoparticles (AuNPs): Implications for AuNP functionalization and molecular barcoding of AuNP assemblies

The interactions of phenyldithioesters with gold nanoparticles (AuNPs) have been studied by monitoring changes in the surface plasmon resonance (SPR), depolarised light scattering, and surface enhanced Raman spectroscopy (SERS). Changes in the SPR indicated that an AuNP-phenyldithioester charge transfer complex forms in equilibrium with free AuNPs and phenyldithioester. Analysis of the Langmuir binding isotherms indicated that the equilibrium adsorption constant, Kads, was 2.3 ± 0.1 × 106 M−1, which corresponded to a free energy of adsorption of 36 ± 1 kJ mol−1. These values are comparable to those reported for interactions of aryl thiols with gold and are of a similar order of magnitude to moderate hydrogen bonding interactions. This has significant implications in the application of phenyldithioesters for the functionalization of AuNPs. The SERS results indicated that the phenyldithioesters interact with AuNPs through the C═S bond, and the molecules do not disassociate upon adsorption to the AuNPs. The SERS spectra are dominated by the portions of the molecule that dominate the charge transfer complex with the AuNPs. The significance of this in relation to the use of phenyldithioesters for molecular barcoding of nanoparticle assemblies is discussed.

The Media City: Media, Architecture and Urban Space

The article reviews the book "The Media City: Media, Architecture and Urban Space," by Scott McQuire.

Complex modelling of open system design for sustainable architecture

This paper argues a model of complex system design for sustainable architecture within a framework of entropy evolution. The spectrum of sustainable architecture consists of the efficient use of energy and material resource in life-cycle of buildings, the active involvement of the occupants in micro-climate control within buildings, and the natural environmental context. The interactions of the parameters compose a complex system of sustainable architectural design, of which the conventional linear and fragmented design technologies are insufficient to indicate holistic and ongoing environmental performance. The complexity theory of dissipative structure states a microscopic formulation of open system evolution, which provides a system design framework for the evolution of building environmental performance towards an optimization of sustainability in architecture.

Bushfire responsive architecture : strategies for reconciling bushfire and biodiversity with daily life

My perspective on the problems associated with building in bushfire prone landscapes comes from 12 years of study of the biophysical and cultural landscapes in the Great Southern Region of WA which resulted in the design and construction of the ‘Hhouse’ at Bremer Bay. The house was developed using a ‘ground up’ approach whereby I conducted a topographical survey and worked with a local botanist and a bushfire risk consultant to ascertain the level of threat that fire presented to this particular site. My intention from the outset however, was not to design a bushfire resistant house per se, but to develop a design which would place the owners in close proximity to the highly biodiverse heath vegetation of the site. I was also seeking a means—through architectural design—of linking the patterns of usage of the house with other site specific conditions related to the prevailing winds, solar orientation and seasonal change.

The modern movement architecture of four South African cities

South Africa's modern architecture is not confined to the cities, but the ideas of the movement were mostly disseminated by architects and academics in Johannesburg, Pretoria, Durban and Cape Town, its four major urban centres. The lay out of significant areas of each city was also influenced by international modernist plans. In outlining the achievements and innovative designs of architects in these cities between the 1930s and 1970s, this article draws a picture of the importance of modernism in South African urban space, and of its diversity. It also draws attention to the political nature of the South African landscape and space, where modernist design was used for racial purposes, and to past and present conservation ideologies. The second part of the article concerns the conservation of modern buildings in these centres; it quotes bibliographies and lists the registers, those existing or under construction. It concludes with an overview of the conservation legislation in place and the challenges of conservation in a context of changing cultural values.

Rhetoric of landscape architecture and interior design discourses : preparation for cross-disciplinary practice

The rhetoric of the pedagogic discourses of landscape architectural students and interior design students is described as part of a doctoral study undertaken to document practices and orientations prior to cross-disciplinary collaboration. We draw on the theoretical framework of Basil Bernstein, an educational sociologist, and the rhetorical method of Kenneth Burke, a literary dramatist, to study the grammars of ‘landscape’ representation employed within these disciplinary examples. We investigate how prepared final year students are for working in a cross-disciplinary manner. The discursive interactions of their work, as illustrated by four examples of drawn images and written text, are described. Our findings suggest that we need to concern ourselves aspects of our pedagogic discourse that brings uniqueness and value to our disciplines ,as well as that shared discourses between disciplines.

Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds : accelerated versus simulated physiological conditions

The increasing use of biodegradable devices in tissue engineering and regenerative medicine means it is essential to study and understand their degradation behaviour. Accelerated degradation systems aim to achieve similar degradation profiles within a shorter period of time, compared with standard conditions. However, these conditions only partially mimic the actual situation, and subsequent analyses and derived mechanisms must be treated with caution and should always be supported by actual long-term degradation data obtained under physiological conditions. Our studies revealed that polycaprolactone (PCL) and PCL-composite scaffolds degrade very differently under these different degradation conditions, whilst still undergoing hydrolysis. Molecular weight and mass loss results differ due to the different degradation pathways followed (surface degradation pathway for accelerated conditions and bulk degradation pathway for simulated physiological conditions). Crystallinity studies revealed similar patterns of recrystallization dynamics, and mechanical data indicated that the scaffolds retained their functional stability, in both instances, over the course of degradation. Ultimately, polymer degradation was shown to be chiefly governed by molecular weight, crystallinity susceptibility to hydrolysis and device architecture considerations whilst maintaining its thermodynamic equilibrium.

Victoria regia's bequest to modern architecture

This paper will explore the relationship between the giant South American waterlily, the Victoria regia (today named Victoria amazonica), and the 1914 Glashaus exposition building by the German architect, Bruno Taut. Starting with a general botanical introduction of Victoria regia, the paper exposes the first European cultivation of the lily by Joseph Paxton at Chatsworth,England, in 1849. Following this initial cultivation, Paxton subsequently develops a specialist greenhouse for the plant, that later becomes the prototype for all Victoria regia greenhouses. However, from about 1860 as Victoria regia cultivation spreads to continental Europe, a greenhouse that differs from Paxton’s prototype subsequently evolves. An investigation of these later continental European greenhouses, coupled with an exposure of Taut’s own writings concerning Victoria regia, reveals startling similarities to the Glashaus, which ultimately reveals the Glashaus as directly inspired by Victoria regia.

Cluster-based Intrusion Detection (CBID) architecture for mobile ad hoc networks

The ad hoc networks are vulnerable to attacks due to distributed nature and lack of infrastructure. Intrusion detection systems (IDS) provide audit and monitoring capabilities that offer the local security to a node and help to perceive the specific trust level of other nodes. The clustering protocols can be taken as an additional advantage in these processing constrained networks to collaboratively detect intrusions with less power usage and minimal overhead. Existing clustering protocols are not suitable for intrusion detection purposes, because they are linked with the routes. The route establishment and route renewal affects the clusters and as a consequence, the processing and traffic overhead increases due to instability of clusters. The ad hoc networks are battery and power constraint, and therefore a trusted monitoring node should be available to detect and respond against intrusions in time. This can be achieved only if the clusters are stable for a long period of time. If the clusters are regularly changed due to routes, the intrusion detection will not prove to be effective. Therefore, a generalized clustering algorithm has been proposed that can run on top of any routing protocol and can monitor the intrusions constantly irrespective of the routes. The proposed simplified clustering scheme has been used to detect intrusions, resulting in high detection rates and low processing and memory overhead irrespective of the routes, connections, traffic types and mobility of nodes in the network. Clustering is also useful to detect intrusions collaboratively since an individual node can neither detect the malicious node alone nor it can take action against that node on its own.

DDX : A distributed software architecture for robotic systems

The Dynamic Data eXchange (DDX) is our third generation platform for building distributed robot controllers. DDX allows a coalition of programs to share data at run-time through an efficient shared memory mechanism managed by a store. Further, stores on multiple machines can be linked by means of a global catalog and data is moved between the stores on an as needed basis by multi-casting. Heterogeneous computer systems are handled. We describe the architecture of DDX and the standard clients we have developed that let us rapidly build complex control systems with minimal coding.

A secure architecture for Australia’s index based e-health environment

This paper proposes a security architecture for the basic cross indexing systems emerging as foundational structures in current health information systems. In these systems unique identifiers are issued to healthcare providers and consumers. In most cases, such numbering schemes are national in scope and must therefore necessarily be used via an indexing system to identify records contained in pre-existing local, regional or national health information systems. Most large scale electronic health record systems envisage that such correlation between national healthcare identifiers and pre-existing identifiers will be performed by some centrally administered cross referencing, or index system. This paper is concerned with the security architecture for such indexing servers and the manner in which they interface with pre-existing health systems (including both workstations and servers). The paper proposes two required structures to achieve the goal of a national scale, and secure exchange of electronic health information, including: (a) the employment of high trust computer systems to perform an indexing function, and (b) the development and deployment of an appropriate high trust interface module, a Healthcare Interface Processor (HIP), to be integrated into the connected workstations or servers of healthcare service providers. This proposed architecture is specifically oriented toward requirements identified in the Connectivity Architecture for Australia’s e-health scheme as outlined by NEHTA and the national e-health strategy released by the Australian Health Ministers.

Effect of poly(acrylic acid) molecular mass and end-group functionality on calcium oxalate crystal morphology and growth

A number of series of poly(acrylic acids) (PAA) of differing end-groups and molecular mass were used to study the inhibition of calcium oxalate crystallization. The effects of the end-group on crystal speciation and morphology were significant and dramatic, with hexyl-isobutyrate end groups giving preferential formation of calcium oxalate dihydrate (COD) rather than the more stable calcium oxalate monohydrate (COM), while both more hydrophobic end-groups and less-hydrophobic end groups led predominantly to formation of the least thermodynamically stable form of calcium oxalate, calcium oxalate trihydrate. Conversely, molecular mass had little impact on calcium oxalate speciation or crystal morphology. It is probable that the observed effects are related to the rate of desorption of the PAA moiety from the crystal (lite) surfaces and that the results point to a major role for end-group as well as molecular mass in controlling desorption rate.