Dendrimers are perfectly branched macromolecules possessing large internal cavities and a known number and location of terminal groups. This unique architecture leads to many interesting properties and countless potential applications have been discussed. Their synthesis involves numerous repetitive steps, often requiring protection and deprotection chemistry and complex purification procedures. This limits their availability and leads to extremely high costs, a factor that has limited their use. Polyamidoamine (PAMAM) dendrimers, the first well-established series of dendrimers, were reported in the mid nineteen eighties. For many applications the synthetic difficulties associated with dendrimers are so great that many potential applications are prohibited. Hyperbranched polymers are produced by a simpler synthetic route, the step growth polymerisation of AB(_x) monomers in a one-pot procedure. They lack the architectural perfection of dendrimers but retain the large number of terminal groups and high degree of branching. Crucially, these polymers can be produced for a fraction of the cost of dendrimers. The synthesis of hyperbranched analogues to both the full and half generation PAMAM dendrimers from AB(_2) monomers is reported here. Attempts to extend this method to control the molecular weight, degree of branching and the terminal group functionality are discussed, as is the synthesis of a related series of polyamides. The characterisation of these materials and their physical properties are also described.

archives@tulane.edu / As the average life expectancy continues to increase globally, the scientific community must meet the parallel challenge of extending the healthy life expectancy of the ever-growing aged population. Aging-related decline in motor control is a crucial aspect of this challenge because it diminishes independence and hinders daily living abilities, leading to greater disability burden on the remaining population. While peripheral nervous and motor systems are certainly involved in this impairment, attention to those structures has come at the expense of more complete understanding of motor control by the aged central nervous system. This dissertation expands our knowledge of this area with a specific focus on the cortex. First, this has been achieved by identifying differences in steady-state structural plasticity in the primary motor cortex (M1) of young and aged mice using chronic in vivo imaging of dendritic spines, the sites of excitatory input to pyramidal neurons that process the bulk of outgoing information from this brain area. These results indicate that at baseline conditions the dendritic spines of the aged M1 are subject to increased turnover, including formation and stabilization, while enduring decreased rates of long-term survival. Secondly, ensuing work combined in vivo imaging with motor skill training and revealed that, while unsuccessful at causing learning-induced structural plasticity of dendritic spines, motor training results in a muted learning-induced structural plasticity response by the en passant boutons (EPBs) of L2/3 parvalbumin-expressing interneurons in the aged M1. These experiments also uncovered a baseline decrease in EPB density and increase in EPB size on the aged axon. Lastly, mesoscale, awake imaging equipment was designed and built to enable future study of brain-wide engagement of various cortical areas during motor learning and performance. The product of this dissertation is a greater understanding of the impact of normal aging on the M1 at the cellular and synaptic level outside of and during motor skill practice, and it also provides an avenue for further study of larger scale changes in cortical connectivity with aging. / 1 / Andrew Davidson

A new route to the AB(_2) monomer dimethyl 5-(2-hydroxyethoxy) isophthalate and its subsequent polymerisation is reported. Hyperbranched polyesters were prepared by melt condensation polymerisation of the AB(_2) monomer and also by copolymerisation with suitable core molecules. Unusual molecular weight growth characteristics were demonstrated. The number average molecular weight (Mn) reached a plateau value after relatively short polymerisation time, whereas the weight average molecular weight (M(_n)) continued to increase. This limit to the attainable number average molecular weight is thought to be a consequence of intramolecular cyclisation reactions, evidence of which was provided by MALDI-TOF MS. The weight average molecular weight continues to increase after complete cyclisation and it is postulated that this is due to a redistribution of polymer chains by ester interchange reactions. The plausibility of the occurrence of ester exchange processes was demonstrated by the successful incorporation of a dimethyl isophthalate core molecule into a fully cyclised hyperbranched polyester. The amount of branching in the hyperbranched polyesters was in agreement with the theoretical value for a statistical distribution at high conversion, as determined by quantitative (^13)C NMR spectroscopy. The solution properties of the hyperbranched polyesters were studied and revealed these materials to be soluble in common organic solvents. Solutions of the hyperbranched polyesters had characteristically low intrinsic viscosities ([n]) and Mark-Houwink plots showed a linear relationship between log M(_w) and log[n]. The thermal properties of the hyperbranched polyesters were examined by differential scanning calorimetry, which showed the polymers to be amorphous materials exhibiting a glass transition temperature (T(_g)) but no melting point. The T(_g) varied with molecular weight, was proportional to 1/M(_w) and reached a limiting value of 86ºC at high conversion.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

No description available.

No description available.

No description available.

No description available.

A range of dendritic molecules that are designed to bind to a cotton surface has been synthesised. The architecture of the molecules allows the location of various functional, property modifying units at the focus and the attachment of recognition groups at the periphery of a dendritic molecule with wedge topology. The synthesis and characterisation of dendrimer wedges up to the second-generation using a divergent approach has been performed. These wedges are readily built up using a simple and efficient stepwise pathway from the central core, and surface recognising species are subsequently attached to the molecule utilising procedures developed in conjunction with Unilever Research Laboratories. Work has been carried out to assess their adsorption onto a cotton surface and the postulated adsorption mechanism is discussed.

Ca2+ influx through ionotropic glutamate receptors regulates a variety of developmental processes including neurite outgrowth and naturally occurring cell death. In the CNS, NMDA receptors were originally thought to be the sole source of Ca2+ influx through glutamate receptors; however, AMPA receptors also allow a significant influx of Ca2+ ions. The Ca2+ permeability of AMPA receptors is regulated by the insertion of one or more edited GluR2 subunits into the receptors. Although Ca2+-permeable AMPA receptors are a familiar feature in developing neurons, the developmental function of these receptors during the formation of the nervous system has yet to be established. This study was designed to investigate the expression and functional role of Ca2+-permeable AMPA receptors in developing chicken spinal motoneurons. Our results demonstrate that chicken lumbar motoneurons express functional AMPA receptors as early as embryonic day (E) 5. Electrophysiological recordings of kainate-evoked currents indicate a significant reduction in the Ca2+ permeability of AMPA receptors between E6 and E11. During this developmental period, the Ca2+ permeability of AMPA receptors decreases three-fold. Reduction in the Ca2+ permeability of AMPA receptors is accompanied by increased expression of GluR2 mRNA in the spinal motoneuron pool. Changes in GluR2 mRNA expression occur in parallel to changes in GluR2 protein expression in the chicken ventral spinal cord. Changes in the Ca2+-permeability of AMPA receptors are not mediated by age-dependent changes in the editing pattern of GluR2 subunits. At early stages of development, functional AMPA receptors were composed of a combination of GluR3 and GluR4 subunits. mRNA analysis indicates that GluR4 is the most abundant subunit in the chicken ventral spinal cord between E6 and E11. Immunohistochemistry analysis of spinal cord sections also demonstrated that both GluR3 and GluR4 proteins are expressed at E6 and E11. Expression of Ca2+-permeable AMPA receptors regulates the maturation of dendritic outgrowth in developing spinal motoneurons. Measurements of dendritic length and branching pattern demonstrate significant changes in the dendritic morphology of spinal motoneurons between E6 and E11. Blockade of AMPA receptor activation with CNQX between E5 and E8 causes a significant increase in dendritic outgrowth in lumbar motoneurons, when compared with vehicle-treated embryos. Treatment of chicken embryos with CNQX between E8 and E11, when AMPA receptors become Ca2+-impermeable, has no affect on dendritic morphology. However, blockade of NMDA receptor activation with MK-801 causes a significant reduction in dendritic outgrowth of lumbar motoneurons by E11. These findings indicate that AMPA receptor activation between E5 and E8 limits dendritic outgrowth in developing motoneurons, whereas NMDA receptor activation is involved in dendritic remodeling after the establishment of synaptic contacts with sensory afferents.