Obesity and diabetes gene discovery approaches

New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and  biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the  pathogenesis of these diseases is critical to this process, however  identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and / or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.

Bryan the builder-residential work only

The High Court, in the 1995 landmark case of Bryan v Maloney, held a builder of a residential house liable to a subsequent owner for economic loss suffered by way of the reduction in value of the house caused by its defective foundations. Since that decision, several cases in state courts have indicated that any extension of the principle in Bryan to commercial properties is a matter for the High Court. This year, Woolcock Street Investments Pty Ltd v CDG Pty Ltd provided the vehicle for the High Court to revisit the Bryan principle in a commercial context. Faced with the question 'can a subsequent owner of a commercial property who discovers faulty foundations sue the builder for the costs of fixing the problem before it causes any physical damage to person or property?', the resounding response from the High Court has been 'no'. Gleeson CJ, Gummow, Hayne and Heydon JJ in a joint judgment and McHugh J and Callinan J in separate judgements rejected any 'extension' of the Bryan principle to commercial premises. Much to the relief of the construction industry, the Court made it clear that it will be difficult for a subsequent owner to make out a case in negligence against the original builder unless it can show special vulnerability to the risk of injury. Kirby J, in a dissenting judgment, suggested that the extension of liability to commercial builders fits quite comfortably with general principles and lamented the 'incremental' approach to liability presently favoured by the Court. Consequent upon the retirement of Gaudron J, Kirby J appears to be a lonely light on the hill, shining a solitary beacon on matters of principle.

The revisitation of Bryan has long been anticipated. However, Woolcock does not provide the solid bricks and mortar craved by the construction industry. Close examination of the reasoning of the Court suggests that it may itself rest on faulty foundations. In his dissenting judgment, Kirby J questions some of the assumptions made by the majority and highlights the deficiencies of the 'stated case' procedure for a re-examination of this particular area of law, thus suggesting that Woolcock may not be completely sound.

Association of genetic vatiation within UBL5 with phenotypes of metabolic syndrome

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

A discussion on passive location discovery in emitter networks using angle-only measurements

In this paper we discuss the ghost node problem found when triangulation of 2 or more nodes is required. We present and discuss a simple algorithm, termed ABLE (Angle Based Location Estimation), that will position randomly placed emitters in a wireless sensor network using a mobile antenna array. The individual nodes in the network are relieved of the localization task by the mobile antenna system and require no modifications to account for location determination. Furthermore, no beacon nodes (i.e. nodes that know their own position) are required. We provide analysis that indicates a reasonably small number of measurements are required to guarantee the successful
localization of the emitting nodes and demonstrate our results through simulation.

Teacher is here to ask for your help : a story of schools, employers and networks

This paper explores the development of the Jobs4Kids (J4K) campaign, a joint initiative of the SGR LLEN Employer Reference Group and the Beacon Foundation. Involving a three-year business plan, the J4K campaign aims to broker young people into employment in local jobs in the region. The campaign is the result of the intersection between an evolving project within the LLEN and the growth of an established program of the Beacon Foundation. The paper will use a Deleuzian lens to explore the ground shifts that have occurred in the process of forming this connection; I am concerned with the intersecting movements of different orders that have created a necessary transitory coordination. Within such a 'rhizome' there are only lines: dimensional lines of segmentarity and stratification and lines of flight as 'the maximum dimension after which the multiplicity undergoes metamorphosis, changes in nature' (Deleuze & Guattari 1987 p.21). My perspective of this metamorphosis is specifically focused on SGR LLEN; I close with a consideration of the possibilities of this change in nature for the continuing work of the LLEN.

A prospective study on building quality : enforcement of control in the Australian housing industry

The Australian housing industry is beset with quality issues with repeated building defects causing problems with customer satisfaction and housing performance. These defects are caused by a combination of initial poor workmanship and poor quality materials and subsequently by poorly executed or inadequate maintenance. These poor work practices increase the cost and maintenance of housing. The waste and rectification work generated by such practices means that the housing industry generally is not engaged with sustainability. Building Control is part of achieving quality of building output. Whilst the Australian Building Code has regulations for initial-build material quality and workmanship, there is no continuing control and effective enforcement over a house over its life span. Sustainability is not dealt with as a topic at all in the Building Code with only energy efficiency concerns regulated. Inadequate knowledge transfer, to the mainly small builders who produce the majority of Australia’s housing, is seen to be a key issue. Mechanisms to make the transfer of knowledge to those who need to use it need to be improved. Building regulations, for example, could be more visual and accessible in their content and small builders should be encouraged to update their knowledge and skills. This comparative research will guide industry service providers in improving their performance and suggest how overall housing quality can be improved (thereby reducing wasteful practices), by considering more appropriate mechanisms for knowledge transfer among industry service providers in the Australian housing industry.

Therapeutic molecules

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

Therapeutic molecules

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

Reclaiming the shrew

Adaptation of Taming the Shrew in partnership with Valleyskids and Artworks

Composição dos tubérculos, extração e caracterização de amidos de diferentes cultivares de batata

Pós-graduação em Agronomia (Energia na Agricultura) - FCA

Social cohesion: inclusion and a sense of belonging in Latin America and the Caribbean. Summary

Includes bibliography