Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

München, Techn. Universiẗat, Diss., 2007.

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

Experimental alterations of morphological traits during development can reveal life history tactics and resource allocation patterns. I examined effects of amputation of a structure directly involved with mating compared to one that is less associated with fitness. I amputated one of the paired external copulatory organs (palps) of juvenile male black widow spiders Latrodectus hesperus), and compared changes in life history traits and fitness to males with amputated legs and controls. I show that palps are more likely to be regenerated than legs, smaller juveniles are more likely to regenerate, and mating success is adversely affected in all adults that suffered early amputation. The pre-existing relationship between juvenile size and development was a critical determinant of regeneration, however no life history costs of regeneration were evident. I conclude that plasticity in life history facilitates regeneration, and that this may mask trade-offs involved in compensatory effects at the population level.

In an effort to re-establish tissue with odontogenic potential in the pulp space of immature permanent teeth, stimulated human dental pulp stem/progenitor cells (hDPSCs) have shown potential to differentiate and form mineralized matrix, marked by high expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN). Bacterial by-products have been shown to adversely affect cell differentiation. This study investigated the effect of P. gingivalis, a putative endodontic pathogen, and blockage of its host recognition on hDPSCs. Stimulated hDPSCs were exposed to varying concentrations of P. gingivalis by-product and gene expression of DSPP and OCN was measured. Cells were exposed to TLR2 blocking agents prior to exposure to the by-product. P. gingivalis affected dose-dependent suppression of the measured gene expression. Blockade of TLR2 inhibited the by-product derived suppression of gene expression. The immune-potential of by-product was confirmed to be detrimental to the differentiation of hDPSCs, and this effect could be moderated by TLR2-blockade.

Experimental alterations of morphological traits during development can reveal life history tactics and resource allocation patterns. I examined effects of amputation of a structure directly involved with mating compared to one that is less associated with fitness. I amputated one of the paired external copulatory organs (palps) of juvenile male black widow spiders Latrodectus hesperus), and compared changes in life history traits and fitness to males with amputated legs and controls. I show that palps are more likely to be regenerated than legs, smaller juveniles are more likely to regenerate, and mating success is adversely affected in all adults that suffered early amputation. The pre-existing relationship between juvenile size and development was a critical determinant of regeneration, however no life history costs of regeneration were evident. I conclude that plasticity in life history facilitates regeneration, and that this may mask trade-offs involved in compensatory effects at the population level.

In an effort to re-establish tissue with odontogenic potential in the pulp space of immature permanent teeth, stimulated human dental pulp stem/progenitor cells (hDPSCs) have shown potential to differentiate and form mineralized matrix, marked by high expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN). Bacterial by-products have been shown to adversely affect cell differentiation. This study investigated the effect of P. gingivalis, a putative endodontic pathogen, and blockage of its host recognition on hDPSCs. Stimulated hDPSCs were exposed to varying concentrations of P. gingivalis by-product and gene expression of DSPP and OCN was measured. Cells were exposed to TLR2 blocking agents prior to exposure to the by-product. P. gingivalis affected dose-dependent suppression of the measured gene expression. Blockade of TLR2 inhibited the by-product derived suppression of gene expression. The immune-potential of by-product was confirmed to be detrimental to the differentiation of hDPSCs, and this effect could be moderated by TLR2-blockade.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 87-102).

Thesis (doctoral)--Oulun Yliopisto, 2002. / Includes bibliographical references. Also available in electronic format.

Thesis (Ph. D.)--Columbia University. / Vita: 1 l. From Journal of experimental zoölogy, v. 7, no. 4, Nov., 1909. Cover title. Literature cited: p. 720-722.