Trabecular Architecture During Growth - Does It Determine Metaphyseal Peak Bone Strength In Adulthood?
Funder
National Health and Medical Research Council
Funding Amount
$165,339.00
Summary
Skeletal fragility is common is elderly people but has its origin in childhood. Strong bone established during growth will provide more protection against occurrence of fragility fracture in old age. Identifying individuals during childhood who are at high risk of skeletal fragility, and early intervention is a strategic approach managing the burden of skeletal fragility on the ageing population.
Maintenance Of Bone Strength In Aged Rats: The Vitamin D Requirement
Funder
National Health and Medical Research Council
Funding Amount
$543,301.00
Summary
Hip fracture remains the most devastating of the osteoporotic fractures particularly in women in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone s ....Hip fracture remains the most devastating of the osteoporotic fractures particularly in women in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone strength. This project will determine the level of vitamin D required to maintain optimal bone strength in aged rats using a simple blood test which could then be used to screen the elderly and identify those at risk of hip fracture from low vitamin D levels. The project will also investigate the effects of vitamin D on the bone cells that maintain optimal skeletal architecture. This information is essential for comparison with the current knowledge of other biochemical bone markets in blood and vitamin D status in the elderly, in order to develop nutritional recommendations to reduce the incidence of hip fracture.Read moreRead less
Hip fracture remains the most devastating of the osteoporotic fractures particularly in women, in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone ....Hip fracture remains the most devastating of the osteoporotic fractures particularly in women, in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone strength. This project will determine the level of vitamin Drequired to maintain optimal bone strength in adult and senescent rats using a simple blood test which could then be used to screen the elderly and identify those at risk a hip fracture from low vitamin D levels. The project will also investigate the effects of vitamin D on bone cells which is necessary to maintain optimal skeletal architecture. This information is essential for comparison with the current knowledge of other biochemical bone markers in blood and vitamin D status in the elderly, in order to develop nutritional recommendations to reduce the incidence of hip fracture.Read moreRead less
Mechanisms By Which Chromatin Modulates Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is both capable of blocking and activating gene expression. Therefore one important ....Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is both capable of blocking and activating gene expression. Therefore one important function of chromatin is to tightly regulate gene expression which is essential to allow an organism to develop properly. When gene expression is not accurately controlled by chromatin developmental defects or cancer can result from the production of incorrect proteins. To control correct gene expression, highly specific mechanisms must operate in the cell to remove, or modify, nucleosomes at certain genes at a precise time during development. One mechanism that we believe to be important is changing the make-up of a nucleosome. This can be achieved in the cell by the replacement of histones with different specialized forms of these histones (variants). We believe that these histone variants can specifically generate chromosomal domains which could in some cases expose or in other cases hide certain genes and thereby turn them on or off. Employing a new approach, we will study one of these histone variants to discover the role it plays in determining the type of chromosomal domain made and the role of this domain has in turning genes on or off at precise times in early development during the formation of different specialized cell types. This new information may define targets for the prevention of incorrect gene expression during cancer progression or abnormal development.Read moreRead less
Every cell in our body has an intrinsic orientation that is controlled by a universal set of genes known as polarity genes. Loss of this orientation is a common and early feature of cancer. We have identified the gene Scribble as a gene that controls cell orientation and is essential to prevent the development of prostate cancer. We propose experiments to discover how Scribble controls prostate cancer and whether it can be used to better predict outcome for prostate cancer patients.
Neurobiological Effects Of Sleep Apnea And Sleepiness
Funder
National Health and Medical Research Council
Funding Amount
$320,437.00
Summary
Sleep apnea affects over one million Australians. It not only affects the quality of a persons sleep and the oxygen supply to their brain, but can cause sleepiness during the day which can in turn affect the ability of the person to conduct their normal activities. Over 30,000 sleep studies are conducted annually in Australia and current therapies result in significant improvements in the quality of life of the patient. However, the data analysis during these studies does not give a clear indica ....Sleep apnea affects over one million Australians. It not only affects the quality of a persons sleep and the oxygen supply to their brain, but can cause sleepiness during the day which can in turn affect the ability of the person to conduct their normal activities. Over 30,000 sleep studies are conducted annually in Australia and current therapies result in significant improvements in the quality of life of the patient. However, the data analysis during these studies does not give a clear indication of the degree to which individual patients may have problems with performing their normal tasks during the day. Tasks like driving vehicles are of particular interest due to the potential for accidents through fatigue or a lack of concentration. This research is designed to investigate the impact of sleep apnea on brain function and daytime performance using certain new techniques - more sophisticated analysis of the brain's activity, detection of brain chemicals and metabolism using a specific form of brain scan called MR spectroscopy, a special monotonous computer based driving simulator, an other tests of performance. We will assess a large group of patients with sleep apnea to determine how the impact of sleep apnea on performance may be differ throughout the population and how this may be affected by the current standard treatment for sleep apnea. We will examine the impact on brain function and performance of removing the current standard therapy in a group of patients previously diagnosed with sleep apnea (as this is a common occurrence in the community). We will also repeat some specific measurements on a control group without any symptoms of sleep apnea for the purpose of comparison. We plan to show a relationship between the effects of sleep apnea and the ability of a person to carry out activities such as driving and thinking. We will then be able to better assess the risk a patient may face and the most appropriate way to treat them.Read moreRead less
Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a grade ....Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.Read moreRead less
Impact Of Sleep Disordered Breathing On Cardiovascular, Behavioural And Neurocognitive Function In Preschool Children
Funder
National Health and Medical Research Council
Funding Amount
$425,703.00
Summary
Studies in school age children have shown that disruption to normal sleep patterns resulting from sleep disordered breathing (SDB) has severe consequences for both the cardiovascular system and neurocognition. To date there have been limited investigations of the effects of SDB in pre-school children despite the knowledge that disruptions to breathing during sleep are maximal at this age and the central nervous system which is immature and developing at this time, is most vulnerable to injury.
Cardiovascular, Neurophysiological And Neurocognitive Assessments To Define Sleep Disordered Breathing In Children
Funder
National Health and Medical Research Council
Funding Amount
$324,008.00
Summary
Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a ....Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a significant impact on daytime functioning and school performance. It is also known that cardiovascular disease is a long-term consequence of untreated sleep disordered breathing in adults, however the long-term effects on the cardiovascular system in children are unknown. This study will examine both the neurocognitive and cardiovascular effects of a range of severities of sleep disordered breathing in children and will identify new more sensitive markers of sleep disruption in order to predict neurocognitive dysfunction. In order to address this most important issue, this project will combine the expertise of scientists and clinicians in the fields of paediatric sleep, cardiovascular control and neuropsychological assessment from Monash and Melbourne Universities, and the Monash Medical Centre and Royal Children's Hospital.Read moreRead less
This study investigates how much an individual's genes and environment account for the wide variation in brain structure and function. Using MRI we will examine in what way a twin's brain is the same or different from that of their co-twin, and carry out analysis of their DNA to identify some of the many genes influencing the structure and function of the brain. The study will provide fundamental information on genetic mechanisms influencing variation in brain structure and function.