title: The Effect of a Myostatin Antagonist on the Healing of Burn Wounds in Skin.

authors: Fieten, Daniel John

subjects: skin

abstract: The body's remarkable ability to repair itself from damage is both very useful and extremely complex. The wound healing system is characterised by four overlapping phases: hemostasis, inflammation, proliferation, and remodelling. It is designed to heal rapidly and efficiently any breach in the protective barrier we call skin, in order to restore normal body function in the quickest possible time. However, pathological conditions such as keloids or hypertrophic scar may arise if events in the wound healing cascade are not coordinated properly, which can lead to loss of skin function and disfigurement. The purpose of this study was to determine whether myostatin plays a role in the healing of burn wounds in skin. Myostatin is best known for its powerful negative regulation of muscle development. Absence of myostatin results in a heavy muscling phenotype, whereas over-expression is associated with muscle wasting conditions. Recently, myostatin has been shown to be involved in muscle wound healing, where knockout of the myostatin gene resulted in improved healing, with decreased fibrotic scar tissue formation. It is noteworthy that the cell surface receptor to which myostatin binds is also present in skin. In consideration of this information the prospect of myostatin involvement in skin biology represents a gap in scientific knowledge. Therefore, the present investigation was designed to ascertain whether the effects of myostatin in muscle regeneration can also be seen in skin wound healing. To this end, a mouse burn wound model was designed to determine the efficacy of antagonising myostatin to bring about improved healing and decreased fibrosis of skin burns. Wounds of mice treated with the myostatin antagonist showed no significant difference compared to saline-treated controls in collagen content at any time point. Gene expression studies on TGF-β1, TGF-β3, decorin and fibromodulin revealed that differences between antagonist-treated and saline-treated groups were possibly masked by the effect of the burn injury but were present in uninjured skin. Similarly, uninjured skin of antagonist-treated animals exhibited a significantly higher fluid content than uninjured skin of saline-treated animals, whereas the effect was not significant in burned skin between treatments. Histological analysis revealed that antagonist-treated wounds showed evidence of decreased wound contraction which may indicate improved scar resolution and decreased risk of fibrosis. Interestingly, the gene expression results in many ways parallel those seen in foetal skin, which after injury, heals without scar. These results warrant further study into the subject area, especially to observe whether further improvements can be made by adjusting the treatment regimen.

text: The Effect of a Myostatin Antagonist on the Healing of Burn Wounds in Skin. The body's remarkable ability to repair itself from damage is both very useful and extremely complex. The wound healing system is characterised by four overlapping phases: hemostasis, inflammation, proliferation, and remodelling. It is designed to heal rapidly and efficiently any breach in the protective barrier we call skin, in order to restore normal body function in the quickest possible time. However, pathological conditions such as keloids or hypertrophic scar may arise if events in the wound healing cascade are not coordinated properly, which can lead to loss of skin function and disfigurement. The purpose of this study was to determine whether myostatin plays a role in the healing of burn wounds in skin. Myostatin is best known for its powerful negative regulation of muscle development. Absence of myostatin results in a heavy muscling phenotype, whereas over-expression is associated with muscle wasting conditions. Recently, myostatin has been shown to be involved in muscle wound healing, where knockout of the myostatin gene resulted in improved healing, with decreased fibrotic scar tissue formation. It is noteworthy that the cell surface receptor to which myostatin binds is also present in skin. In consideration of this information the prospect of myostatin involvement in skin biology represents a gap in scientific knowledge. Therefore, the present investigation was designed to ascertain whether the effects of myostatin in muscle regeneration can also be seen in skin wound healing. To this end, a mouse burn wound model was designed to determine the efficacy of antagonising myostatin to bring about improved healing and decreased fibrosis of skin burns. Wounds of mice treated with the myostatin antagonist showed no significant difference compared to saline-treated controls in collagen content at any time point. Gene expression studies on TGF-β1, TGF-β3, decorin and fibromodulin revealed that differences between antagonist-treated and saline-treated groups were possibly masked by the effect of the burn injury but were present in uninjured skin. Similarly, uninjured skin of antagonist-treated animals exhibited a significantly higher fluid content than uninjured skin of saline-treated animals, whereas the effect was not significant in burned skin between treatments. Histological analysis revealed that antagonist-treated wounds showed evidence of decreased wound contraction which may indicate improved scar resolution and decreased risk of fibrosis. Interestingly, the gene expression results in many ways parallel those seen in foetal skin, which after injury, heals without scar. These results warrant further study into the subject area, especially to observe whether further improvements can be made by adjusting the treatment regimen.

year: 2009

title: Distribution of small mammals in five New Zealand forest habitats

authors: Watkins, Alison Fern

subjects: small mammals

abstract: This project aimed to reanalyse two large historical data sets from two different locations in New Zealand (Fiordland in the South Island and Pureora Forest Park in the North Island). The data describe populations of mice (Mus musculus), rats (Rattus rattus and R. norvegicus), and stoats (Mustela erminea) collected using standard monitoring techniques from five distinct types of forest habitat. The new analysis methods selected were an index of patchiness and Site Occupancy analysis.

The objectives of the analysis were (1) to evaluate whether the patchiness index and Site Occupancy analysis methods might contribute to improved protocols for monitoring small mammal populations in the future, and (2) to use formal tests of five hypotheses to evaluate two of the assumptions made by the conventional density index often used in small mammal studies.

I describe the results of the analyses for each species, including any problems encountered (such as the inability of the Site Occupancy method to analyse very sparse data sets). I also describe the results pooled from each of the two study locations and potential consequences for small mammal monitoring and control.

This analysis has suggested that in most cases the density index is not a rigorous measure of small mammal populations. However, both the index of patchiness and Site Occupancy analysis provided useful, new information about these populations of rodents and stoats, despite the fact that these historical data sets were not designed for use with modern methods of analysis.

Please note: some figures and tables were printed separately and added to the thesis as unnumbered pages.  These can be found in the file 03Plates_and_Tables.pdf.

text: Distribution of small mammals in five New Zealand forest habitats This project aimed to reanalyse two large historical data sets from two different locations in New Zealand (Fiordland in the South Island and Pureora Forest Park in the North Island). The data describe populations of mice (Mus musculus), rats (Rattus rattus and R. norvegicus), and stoats (Mustela erminea) collected using standard monitoring techniques from five distinct types of forest habitat. The new analysis methods selected were an index of patchiness and Site Occupancy analysis.

The objectives of the analysis were (1) to evaluate whether the patchiness index and Site Occupancy analysis methods might contribute to improved protocols for monitoring small mammal populations in the future, and (2) to use formal tests of five hypotheses to evaluate two of the assumptions made by the conventional density index often used in small mammal studies.

I describe the results of the analyses for each species, including any problems encountered (such as the inability of the Site Occupancy method to analyse very sparse data sets). I also describe the results pooled from each of the two study locations and potential consequences for small mammal monitoring and control.

This analysis has suggested that in most cases the density index is not a rigorous measure of small mammal populations. However, both the index of patchiness and Site Occupancy analysis provided useful, new information about these populations of rodents and stoats, despite the fact that these historical data sets were not designed for use with modern methods of analysis.

Please note: some figures and tables were printed separately and added to the thesis as unnumbered pages.  These can be found in the file 03Plates_and_Tables.pdf.

year: 2007

title: Kaupapa Maori research: An indigenous approach to creating knowledge

authors: Bishop, Russell

subjects: Maori

abstract: This paper seeks to identify how issues of epistemological racism are addressed in practice
within an indigenous Kaupapa (philosophy) Maori approach to research, and how such
considerations may impact on the Western trained and positioned researcher. One fundamental
understanding to a Kaupapa Maori approach to research is that it is the discursive practice
that is Kaupapa Maori that positions researchers in such a way as to operationalise selfdetermination
(agentic positioning and behaviour) for research participants. This is because the
cultural aspirations, understandings and practices of Maori people implement and organise the
research process. Further, the research issues of power; initiation, benefits, representation,
legitimation, and accountability are addressed and understood in practice by practitioners of
Kaupapa Maori research through the development of a participatory mode of consciousness.

text: Kaupapa Maori research: An indigenous approach to creating knowledge This paper seeks to identify how issues of epistemological racism are addressed in practice
within an indigenous Kaupapa (philosophy) Maori approach to research, and how such
considerations may impact on the Western trained and positioned researcher. One fundamental
understanding to a Kaupapa Maori approach to research is that it is the discursive practice
that is Kaupapa Maori that positions researchers in such a way as to operationalise selfdetermination
(agentic positioning and behaviour) for research participants. This is because the
cultural aspirations, understandings and practices of Maori people implement and organise the
research process. Further, the research issues of power; initiation, benefits, representation,
legitimation, and accountability are addressed and understood in practice by practitioners of
Kaupapa Maori research through the development of a participatory mode of consciousness.

year: 1999