6,527 research outputs found
Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery
No full textHereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across genotypes despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms. This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes
Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis
No full textExtent: 12 p.The deubiquitylating enzyme Usp9x is highly expressed in the developing mouse brain, and increased Usp9x expression enhances the self-renewal of neural progenitors in vitro. USP9X is a candidate gene for human neurodevelopmental disorders, including lissencephaly, epilepsy and X-linked intellectual disability. To determine if Usp9x is critical to mammalian brain development we conditionally deleted the gene from neural progenitors, and their subsequent progeny. Mating Usp9xloxP/loxP mice with mice expressing Cre recombinase from the Nestin promoter deleted Usp9x throughout the entire brain, and resulted in early postnatal lethality. Although the overall brain architecture was intact, loss of Usp9x disrupted the cellular organization of the ventricular and sub-ventricular zones, and cortical plate. Usp9x absence also led to dramatic reductions in axonal length, in vivo and in vitro, which could in part be explained by a failure in Tgf-β signaling. Deletion of Usp9x from the dorsal telencephalon only, by mating with Emx1-cre mice, was compatible with survival to adulthood but resulted in reduction or loss of the corpus callosum, a dramatic decrease in hippocampal size, and disorganization of the hippocampal CA3 region. This latter phenotypic aspect resembled that observed in Doublecortin knock-out mice, which is an Usp9x interacting protein. This study establishes that Usp9x is critical for several aspects of CNS development, and suggests that its regulation of Tgf-β signaling extends to neurons.Shane Stegeman, Lachlan A. Jolly, Susitha Premarathne, Jozef Gecz, Linda J. Richards, Alan Mackay-Sim and Stephen A. Woo
‘Health sniffers’: Ability, use and perceived importance of smell in a group of health professionals
No full textThe ability to smell is an important component in the arsenal of healthcare professionals diagnostic tool kit. Patient assessment and subsequent health investigation and treatment often depends on effective use of sensory systems in those most immediately responsible for their care; most commonly nurses. Moreover, our previous research suggest that olfaction is one sensory system which, in otherwise healthy people, appears not to decline with age [1]. Odours from breath, tissue and other clinical samples often contribute to clinical diagnosis and the instigation of treatment regimens. Despite this, we have yet to find a published study that examines smelling ability in any singificant professional group or in students who are training in a specific profession, irrespective of how significant smelling is to that profession. Thus we explored the sense of smell in experienced nurses and student nurses. We compared their ability to that of the normative Australian population [2]. This study applied the sniffin' sticks test of olfactory ability [3], coupled with simple questionnaire data, to a group of nursing students (n=45) and experienced nurses (n=30). These data were compared to demographically similar Australian data in non-health professionals using the current Australian olfactory data base held at GU. Nurses reported much greater attention to and importance of their sense of smell than either of the other groups. However, there were no significant differences (p>0.05) between the actual or the perceived ability to smell by nursing students, nurses and the normative Australian population for odour identification, odour discrimination or threshold for odour detection. This study is a significant beginning to our understanding of the use and importance of olfaction in the work-place. It enables us to begin to build an understanding of how attention to olfactory cues (often indicating disease) may develop during clinical experience and thus to understand how we can best prepare students in healthcare and medical associated professions for their future 'information-rich' clinical olfactory environment. [1] Mackay-Sim et al., Chemical Senses 2006, 23, 763-71. [2] Mackay-Sim et al., Journal of Clinical Neuroscience 2004, 11, 874-879. [3] Hummel et al., Eur Arch Otorhinolaryngol, 2007, 264, 237-43.Griffith Health, School of Nursing and MidwiferyNo Full Tex
The future of pornography - panel debate. Speakers | Finn Mackay, Rowan Pelling, Peter Tatchell
No full textMany believe that porn's dark fantasies risk corrupting relationships and society. Has this arisen because pornography is largely created by men? Could feminist pornography featuring authentic sex, diverse bodies and female perspectives offer a truly liberating alternative? Or is porn fundamentally incompatible with intimacy and a problem for all of us until its abolished? Feminist thinker Finn Mackay, author of Belle de Jour: Diary of a London Call Girl Brooke Magnanti, human rights campaigner Peter Tatchell and Erotic Review editor Rowan Pelling imagine the future of pornography.In association with the New College of the Humanities
Contribution to laser scanning confocal microscope
No full textA/Pr Alan Mackay-Sim$AUD 10,000.00NHMRC Infrastructure GrantsEquipment Gran
Duurzame energie: Een nuchter verhaal
No full textEen samenvatting van het boek 'Sustainable Energy - without the hot air' van David J.C. MacKay. Professor MacKay is hoogleraar aan de Universiteit van Cambridge en Chief Scientific Advisor to the Department of Energy and Climate Change van de Britse regering. In het boek vergelijkt hij het gebruik van energie met de hoeveelheid energie die opgewekt kan worden met duurzame energie.Delft Research Initiative
STRUCTURED ILLUMINATION MICROSCOPY USING DIGITAL MICROMIRROR DEVICE
No full textStructured illumination microscopy (SIM) increases resolution of optical microscopes substantially. However, simulation of this process using mathematical models is still a novel notion. Purpose: To design a program to simulate the process of SIM and study its application on biological samples. Method: Pre-defined images of microscopic samples were blurred and then reconstructed using a simulation designed in MATLAB. Experimental application of SIM and simulated reconstruction of images obtained using a microscope was then performed. Results: Considerably high resolution images were obtained from the simulation, which was also supported by the pixel intensity plots, signal to noise ratio and peak signal to noise ratio analyses. Resolution of images of samples obtained from experimentally performing SIM on a microscope were also similar to their simulated reconstruction. Conclusion: SIM is a desirable option for optimally imaging biological microscopic samples, physically as well as through simulation process
A study of the biochemical factors which control and di rect the development of nerv cells
No full textA/Pr Alan Mackay-Sim$AUD 158,833.21NHMRC Project GrantsStandard Project Gran
A study of the mechanism of odour detection
No full textA/Pr Alan Mackay-Sim$AUD 149,049.81NHMRC Project GrantsStandard Project Gran
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