title: Developmental gene expression profile of Vmo1 in the mouse auditory system

authors: Forrester-Gauntlett, Blaise Kelly Erin

abstract: Hearing loss (HL) is a sensory disorder that affects an estimated 250 million people worldwide and can greatly affect quality of life. In New Zealand, more than 10% of the population is affected by HL with the Māori population being overrepresented among all age groups. Therefore, understanding the mechanism of HL is extremely important for the development of new pharmaceuticals for the prevention or treatment of HL disorders.
The main aim of the research undertaken in this thesis was to characterise the function of the Mus musculus (mouse) vitelline membrane outer layer one (Vmo1) gene. This gene is considered an excellent candidate for being involved in human HL and/or balance disorders. Our hypothesis is based on its restricted gene localisation within the mouse inner ear and the postulated function of Reissner’s membrane.
Two methods were used to address this aim. Firstly, comparative genomics was used to determine the level of nucleotide and amino acid conservation of VMO1 across mammalian species, and to search for DNA motifs that may imply a biological function. Secondly, molecular biology and histochemical techniques were used to DNA sequence the Vmo1 gene, detect the expression of 22 kDa VMO1 protein within mouse tissues, and to localise the expression of VMO1 protein within the mouse inner ear.
Comparative genomics results showed VMO1 to be highly conserved across 36 species. An in-depth analysis of the differences and similiarites between the mouse, human and chicken indicated a high level of gene conservation with an even greater degree of identity and similarity seen at a proteomic level. In addition, a high level of conservation across amino acids involved in the formation and stabilisation of the three dimensional structure. Thus, results suggest an important function for the VMO1 protein.
Two commerical VMO1 antibodies were purchased to determine the localisation of the mouse VMO1 protein. They were validated for specificity using western blot analysis of protein lysates dissected from postnatal day 28 mice (P28). VMO1 was identified within the inner ear protein lysate and tear gland protein lysate of an expected molecular weight size of 20-37kDa with additional binding observed in the ear sample at 250kDa.
Immunohistochemistry detected high concentrations of VMO1 protein within the tectorial membrane (TM) and inner pillar cells (IPC) in inner ear sections from the mouse at P5. In agreement with the comparative genomics analysis, VMO1 is a secreted protein.
The movement of the hair cells (HC) relative to the TM is is essential for the transduction of sound into electrical signals. The IPC act as supporting cells for the hair cells, and help to couple movement of the basilar membrane to the HC. In conclusion, the importance of the TM and IPC in hearing function, and the localisation of the VMO1 protein within these structures implies an important role for VMO1 in hearing function. We recommend further studies to examine the specificity of the VMO1 antibody, and the development of a Vmo1 knockout mouse to support the functional analysis of Vmo1 in the auditory system.

text: Developmental gene expression profile of Vmo1 in the mouse auditory system Hearing loss (HL) is a sensory disorder that affects an estimated 250 million people worldwide and can greatly affect quality of life. In New Zealand, more than 10% of the population is affected by HL with the Māori population being overrepresented among all age groups. Therefore, understanding the mechanism of HL is extremely important for the development of new pharmaceuticals for the prevention or treatment of HL disorders.
The main aim of the research undertaken in this thesis was to characterise the function of the Mus musculus (mouse) vitelline membrane outer layer one (Vmo1) gene. This gene is considered an excellent candidate for being involved in human HL and/or balance disorders. Our hypothesis is based on its restricted gene localisation within the mouse inner ear and the postulated function of Reissner’s membrane.
Two methods were used to address this aim. Firstly, comparative genomics was used to determine the level of nucleotide and amino acid conservation of VMO1 across mammalian species, and to search for DNA motifs that may imply a biological function. Secondly, molecular biology and histochemical techniques were used to DNA sequence the Vmo1 gene, detect the expression of 22 kDa VMO1 protein within mouse tissues, and to localise the expression of VMO1 protein within the mouse inner ear.
Comparative genomics results showed VMO1 to be highly conserved across 36 species. An in-depth analysis of the differences and similiarites between the mouse, human and chicken indicated a high level of gene conservation with an even greater degree of identity and similarity seen at a proteomic level. In addition, a high level of conservation across amino acids involved in the formation and stabilisation of the three dimensional structure. Thus, results suggest an important function for the VMO1 protein.
Two commerical VMO1 antibodies were purchased to determine the localisation of the mouse VMO1 protein. They were validated for specificity using western blot analysis of protein lysates dissected from postnatal day 28 mice (P28). VMO1 was identified within the inner ear protein lysate and tear gland protein lysate of an expected molecular weight size of 20-37kDa with additional binding observed in the ear sample at 250kDa.
Immunohistochemistry detected high concentrations of VMO1 protein within the tectorial membrane (TM) and inner pillar cells (IPC) in inner ear sections from the mouse at P5. In agreement with the comparative genomics analysis, VMO1 is a secreted protein.
The movement of the hair cells (HC) relative to the TM is is essential for the transduction of sound into electrical signals. The IPC act as supporting cells for the hair cells, and help to couple movement of the basilar membrane to the HC. In conclusion, the importance of the TM and IPC in hearing function, and the localisation of the VMO1 protein within these structures implies an important role for VMO1 in hearing function. We recommend further studies to examine the specificity of the VMO1 antibody, and the development of a Vmo1 knockout mouse to support the functional analysis of Vmo1 in the auditory system.

year: 2013

title: Unifying state and process determinism

authors: Reeves, Steve

subjects: computer science

abstract: If a coin is given to a deterministic robot that interacts with a deterministic vending machine then is the drink that the robot is delivered determined? Using process definitions of determinism from CSP, CCS or ACP the answer is "no", whereas state-based definitions of determinism can reasonably be construed as giving the answer "yes". In order to unify what we see as discrepancies in state- and action-based notions of determinism we will consider process algebras over two sets of actions: the active or casual actions of the robot and the passive or reactive actions of the vending machine. In addition we will add priority to the actions and when two τ actions are possible then the τ action with the highest priority will be executed.

text: Unifying state and process determinism If a coin is given to a deterministic robot that interacts with a deterministic vending machine then is the drink that the robot is delivered determined? Using process definitions of determinism from CSP, CCS or ACP the answer is "no", whereas state-based definitions of determinism can reasonably be construed as giving the answer "yes". In order to unify what we see as discrepancies in state- and action-based notions of determinism we will consider process algebras over two sets of actions: the active or casual actions of the robot and the passive or reactive actions of the vending machine. In addition we will add priority to the actions and when two τ actions are possible then the τ action with the highest priority will be executed.

year: 2004-02

title: Heritage-making in Aotearoa planning: Unsettling norms in contested urban space

authors: Hill, Carolyn Joy

subjects: Authorised heritage discourse

abstract: Heritage is currently a high-profile and often contentious topic in urban environments. As cities face growing challenges of climate change, intensification needs and cultural contestation, state-mandated heritage continues to have a significant influence on how cities are perceived, whose pasts are remembered, and what future change can be. However, this is being increasingly tested as urban pressures bring questions of who has a right to the city to the fore. 
Situated within the field of critical heritage studies, this thesis critically examines how heritage is officially “made” in the cities of Aotearoa New Zealand, and how emerging views and values may reshape these established norms for more spatially and culturally just futures. Focused on urban locations within the so-called “CANZUS” states (Canada, Australia, New Zealand and the United States of America (USA)), the thesis centres on statutory heritage – the objects and places that are identified and managed within state-mandated planning systems that create dominant assumptions about what is worthy of protection. As such, its contribution is at the intersection of heritage and planning as it critically queries heritage’s future legacy claims and considers what other legacies may be imagined. 
The thesis includes four key enquiries. First, it explores the history of state-led heritage-making in Aotearoa, focusing on the city of Tāmaki Makaurau / Auckland. It examines the tension between contemporary urban intensification priorities and heritage / special character regulation, critiquing the narrative of heritage as a “public good” given its entanglement with spatial and cultural inequity. Second, it studies three cases of urban heritage protest across Australia, Aotearoa and the USA. These cases expose the continued inadequacy of statutory heritage-making for Indigenous and emerging aspirations, as normative approaches are embedded not only by the heritage sector itself but by the planning and legislation systems that structure its mandate. 
Third, the thesis explores the current thinking of those shaping and working within heritage’s statutory framing across Aotearoa. It finds that heritage policy leaders are cognisant of, and concerned to change, heritage’s entrenched Eurocentricity, expert dominance and material orientation, but that shifting established practice remains a multi-dimensional challenge. Finally, it investigates the perspectives of young emerging planners in the city of Kirikiriroa / Hamilton, which again foregrounds the obstacles to displacing systemic norms but also highlights planning policy’s significant potential to shape different heritage futures. 
This thesis has important implications both for Aotearoa’s urban environments and for CANZUS cities more broadly. Grounded in contemporary real-world examples, it not only exposes heritage’s imbrication with issues of urban inequity but its deeper role in maintaining settler state security, making “home” on Indigenous land. It finds that unpicking this legacy will involve more than adding the heritages of “others” into the existing canon. Rather, deeper reconsideration of heritage’s societal purpose as part of Indigenous, multi-storied and dynamic cities is required. Finally, it highlights the central role for planning in transforming the heritage field, both through statutory policy reform and through integration with broader urban objectives. However, planners will need to be better equipped for critical engagement with heritage if they are to creatively support more inclusive, democratic and malleable alternatives.

text: Heritage-making in Aotearoa planning: Unsettling norms in contested urban space Heritage is currently a high-profile and often contentious topic in urban environments. As cities face growing challenges of climate change, intensification needs and cultural contestation, state-mandated heritage continues to have a significant influence on how cities are perceived, whose pasts are remembered, and what future change can be. However, this is being increasingly tested as urban pressures bring questions of who has a right to the city to the fore. 
Situated within the field of critical heritage studies, this thesis critically examines how heritage is officially “made” in the cities of Aotearoa New Zealand, and how emerging views and values may reshape these established norms for more spatially and culturally just futures. Focused on urban locations within the so-called “CANZUS” states (Canada, Australia, New Zealand and the United States of America (USA)), the thesis centres on statutory heritage – the objects and places that are identified and managed within state-mandated planning systems that create dominant assumptions about what is worthy of protection. As such, its contribution is at the intersection of heritage and planning as it critically queries heritage’s future legacy claims and considers what other legacies may be imagined. 
The thesis includes four key enquiries. First, it explores the history of state-led heritage-making in Aotearoa, focusing on the city of Tāmaki Makaurau / Auckland. It examines the tension between contemporary urban intensification priorities and heritage / special character regulation, critiquing the narrative of heritage as a “public good” given its entanglement with spatial and cultural inequity. Second, it studies three cases of urban heritage protest across Australia, Aotearoa and the USA. These cases expose the continued inadequacy of statutory heritage-making for Indigenous and emerging aspirations, as normative approaches are embedded not only by the heritage sector itself but by the planning and legislation systems that structure its mandate. 
Third, the thesis explores the current thinking of those shaping and working within heritage’s statutory framing across Aotearoa. It finds that heritage policy leaders are cognisant of, and concerned to change, heritage’s entrenched Eurocentricity, expert dominance and material orientation, but that shifting established practice remains a multi-dimensional challenge. Finally, it investigates the perspectives of young emerging planners in the city of Kirikiriroa / Hamilton, which again foregrounds the obstacles to displacing systemic norms but also highlights planning policy’s significant potential to shape different heritage futures. 
This thesis has important implications both for Aotearoa’s urban environments and for CANZUS cities more broadly. Grounded in contemporary real-world examples, it not only exposes heritage’s imbrication with issues of urban inequity but its deeper role in maintaining settler state security, making “home” on Indigenous land. It finds that unpicking this legacy will involve more than adding the heritages of “others” into the existing canon. Rather, deeper reconsideration of heritage’s societal purpose as part of Indigenous, multi-storied and dynamic cities is required. Finally, it highlights the central role for planning in transforming the heritage field, both through statutory policy reform and through integration with broader urban objectives. However, planners will need to be better equipped for critical engagement with heritage if they are to creatively support more inclusive, democratic and malleable alternatives.

year: 2024-12-16