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Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and(More)
Glial proliferation and activation are associated with disease progression in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia. In this study, we describe a unique platform to address the question of cell autonomy in transactive response DNA-binding protein (TDP-43) proteinopathies. We generated functional astroglia from human induced(More)
The glial environment is an important determinant of neuronal health in experimental models of neurodegeneration. Specifically, astrocytes have been shown, dependent on context, to be both injurious and protective. Human pluripotent stem cells offer a powerful new system to improve our understanding of the mechanisms underlying astrocyte-mediated(More)
Recovery of function following traumatic brain injury (TBI) is partly through neuronal plasticity. However plasticity is limited in the adult CNS compared with young animals. In order to test whether treatments that enhance CNS plasticity might improve functional recovery after TBI, a new rat head injury model was developed, in which a computer-controlled(More)
Rats with a crush in the dorsal funiculi of the C4 segment of the spinal cord were treated with chondroitinase ABC delivered to the lateral ventricle, receiving 6 intraventricular injections on alternate days. In order to investigate the time window of efficacy of chondroitinase, treatment was begun at the time of injury or after a 2, 4 or 7 days delay.(More)
We have developed a compartmentalised culture model for the purification of axonal mRNA from embryonic, neonatal and adult rat dorsal root ganglia. This mRNA was used un-amplified for RT-qPCR. We assayed for the presence of axonal mRNAs encoding molecules known to be involved in axon growth and guidance. mRNAs for beta-actin, beta-tubulin, and several(More)
Hypothermia is potently neuroprotective, but the molecular basis of this effect remains obscure. Changes in neuronal tau protein are of interest, since tau becomes hyperphosphorylated in injury-resistant, hypothermic brains. Noting inter-species differences in tau isoforms, we have used functional cortical neurons differentiated from human pluripotent stem(More)
Rodent-based studies have shown that the membrane properties of oligodendrocytes play prominent roles in their physiology and shift markedly during their maturation from the oligodendrocyte precursor cell (OPC) stage. However, the conservation of these properties and maturation processes in human oligodendrocytes remains unknown, despite their dysfunction(More)
OBJECTIVE To examine the environmental life cycle from poppy farming through to production of 100 mg in 100 mL of intravenous morphine (standard infusion bag). DESIGN 'Cradle-to-grave' process-based life cycle assessment (observational). SETTINGS Australian opium poppy farms, and facilities for pelletising, manufacturing morphine, and sterilising and(More)
This talk aims to discuss risk factors for perioperative mortality with particular emphasis on preoperative patient factors and postoperative complications. In 2010 we published a study of perioperative mortality and complications in Anaesthesia. 1 We called this study the REASON study; a slightly dodgy acronym: Research into Elderly Patient Anaesthesia and(More)