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Ināianei, i Mua, ā Muri Ake – Now, then, next: A whakapapa analysis of engagement approaches to tangata, whenua and wai: A community case study in Te Tai Tokerau (Northland)
No full textThrough case study research located in Tautoro, Northland, Aotearoa New Zealand, this thesis investigates the challenges hapū (kin-community groups) and their marae (ancestral centers of tribal identity, meeting houses) face in their traditional role as kaitiaki (guardians) of land and water.
Harnessing connection and whakapapa (genealogy) to gather ancestral narratives while living and working within the community at the center of the case study, coupled with examinations of legal documents, historical land transfers and western scientific studies, the past and present relationship between hapū, Pākehā (New Zealand Europeans) and the local environment is explored.
Ināianei, i Mua, ā Muri Ake – Now, Then, Next: A Whakapapa Analysis of Engagement Approaches to Tangata, Whenua and Wai: A Case Study in Te Tai Tokerau (Northland) finds that for the hapū of Tautoro, water and land are viewed in a contrasting way to Eurocentric capitalist models. It establishes clearly that ancestral rights exist, and that consultation with hapū over proposed sale and development of land and related water take has historically been performed poorly, resulting in harm to local environments and thus harm to the people of the land.
We see through the case study how a kanohi-ki-te-kanohi (face-to-face), marae-based negotiation with hapū, acknowledging water as a taonga (treasure) with its own inherent mauri (life force) and the kaitiaki role of local hapū, can result in improved outcomes for all parties, and for the local environment.
The purpose of this thesis is to gather narratives for future descendants of the hapū of Tautoro, inform policy at local and central government level in relation to collaboration with hapū, and provide a template for capitalist enterprises whose activities on the land threaten the kaitiakitanga (guardianship) of local hapū. In a climate-change environment, this is important not only to Aotearoa New Zealand’s hapū groups, but also to indigenous communities elsewhere in the world facing similar crises
The impact of anti-CRISPRs on horizontal gene transfer (HGT) and their regulation in mobile genetic elements
No full textCRISPR-Cas systems are common in bacterial genomes, providing adaptive immunity against bacterial viruses (bacteriophages). CRISPR-Cas systems are diverse, with two classes, six types and thirty-three subtypes. Bacteriophages circumvent this host defence by using anti-CRISPRs. Anti-CRISPR proteins may have a massive impact on microbial evolution and bacteriophage biology.
This thesis explores the potential of anti-CRISPRs for the horizontal transmission of acquired traits (e.g. antibiotic resistance) across microbiomes. We hypothesized that selection for antibiotic resistance might have resulted in an accumulation of anti-CRISPR genes in genomes that harbour CRISPR-Cas systems and horizontally-acquired antibiotic resistance genes. Our genome-wide correlation analysis of over 100,000 bacterial genomes, with a focus on pathogens, found a significant positive association between the presence of anti-CRISPRs and acquired antibiotic resistance in Pseudomonas aeruginosa.
Furthermore, genome mining identified novel type I anti-CRISPRs from human and plant pathogens. We, along with our collaborators uncovered 11 type I-F and/or I-E anti-CRISPR genes encoded on chromosomal and extrachromosomal mobile genetic elements (MGEs) within Enterobacteriaceae and Pseudomonas. These were cloned and tested experimentally in Pectobacterium and Serratia systems, validating the anti-CRISPR activity of some. The new acr genes cluster with genes encoding inhibitors of other distinct bacterial defence systems.
In most cases, anti-CRISPR genes are located before of DNA binding helix-turn-helix (HTH) transcription factors, named anti-CRISPR associated proteins (Aca). Recent studies had shown three of these Acas act as repressors of anti-CRISPR expression. Here, we computationally analysed bacterial, phage, and plasmid genomes to determine the possible mode of actions of Aca families. The investigation of the promoter regions of acr genes suggests a widespread DNA repression mechanism of regulation by the Aca proteins in the control of anti-CRISPR expression.
Overall, the study has broadened our knowledge of anti-CRISPR mediated HGT and its regulation in MGEs
Historical Trauma, Indigenous People, and Libraries
No full textHistorical trauma theory (HTT) built on understanding of Holocaust survivors and subsequent
generations (Pihama et. al., 2014) and articulated how colonization and genocide against
Indigenous peoples also resulted in historical trauma and intergenerational grief (Brave Heart &
DeBruyn, 1998; Methot, 2019). In this research report, I examine how modern libraries reinforce
historical trauma for Indigenous library users and workers through library origins, professional
credentialing, staffing demographics, and policies. While historical trauma theory is rooted in
social work (Brave Heart & DeBruyn, 1998), it is applicable to librarianship as a profession of
public service that impacts Indigenous access to knowledge and self-discovery.
I conducted my research using kaupapa Māori and autoethnography frameworks, to interview
five Indigenous librarians from Aotearoa, Canada, and the United States. Over Zoom,
participants detailed their unique experiences as Indigenous people using libraries, studying
library science, and working in libraries.
Participants spoke candidly about the racism and microaggressions they routinely encounter; and
the isolating nature of often being the only Indigenous worker in their team or place of
employment. In particular, participants recounted how historical trauma resurfaced when facing
inadequate resources to support Indigenous knowledge, or when organizations reinforced
policies that conflicted with Indigenous practices and worldviews.
However, participants also described hope and progress towards equity, aligning with
contemporary shifts toward valuing Indigenous peoples in libraries. I make and acknowledge
several recommendations in this report ranging from practical changes to library policies and
practices, to frameworks to address historical trauma within library spaces. These practices can
be applied beyond libraries into higher education, government work, and other sectors
NZDep2018 analysis of census 2018 variables - DHB09: Taranaki
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - DHB13: Hutt Valley
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - TA026: Kawerau District
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
N-Alkylation of imidazoles
No full textThe regioselectivity of N-alkylation in unsymmetrical imidazoles was studied.
The ambident nature of imidazole was scrutinised in an examination of substrate (ie. substituent(s)), alkylating agent, and medium effects on the ratios of isomeric N-alkylated products obtained under standardised alkylation conditions. To this end various 4-mono- and 4-nitro-5-substituted-imidazoles were synthesised and subsequently treated with alkylating reagents in both "neutral" (ethanolic) and basic (aqueous sodium hydroxide) reaction media to produce isomeric products in proportions rigorously determined by 1H nmr analysis.
A number of factors were shown to affect the product ratios. It is generally accepted that the free base is methylated by an SE2' process while the imidazole anion obeys SE2cB kinetics. The ratios of 1-alkyl-4- : 1-alkyl-5-substituted products determined from reaction in basic medium depend largely on polar and steric factors. Electron-withdrawing groups in the 4(5)-position render the more remote nitrogen the least deactivated to electrophilic attack. Correlation of the results obtained is much better with ơ1 or ơm than with ơp substituent constants, indicating that the major effect of the substituent is inductive. Steric effects play a very significant role in the overall regiochemistry of alkylation. An increased preference for the less-hindered nitrogen is demonstrated as both the size of the substituent and the size of the incoming electrophile increases. In "neutral" conditions matters are more complex. Certainly steric effects can be seen, but the expected electronic effects are overcome by a dominant tautomeric effect when the substituent is an electron-withdrawing group. KT values were determined for a number of substrates and these demonstrate that the 4-substituted tautomer is dominant when the substituent is electron-withdrawing, and even though this is the less-reactive tautomer in an SE2' reaction, it still controls the product ratio,
leading to high proportions of 1-alkyl-5-substituted imidazole in the product
mixture.
Diazomethane methylation was also briefly examined. Substitution is predominantly at the nitrogen proximate to an electron-withdrawing group, and reaction yields are seen to be dependent on substrate acidity
The Application of Circulating Tumour DNA to the Management of Gastrointestinal Cancers.
No full textCirculating tumour DNA (ctDNA) are small fragments of DNA released by tumours
into the circulation. These fragments contain pathogenic mutations which can be
detected and quantified by various next generation sequencing approaches to monitor
tumour burden. Many ctDNA analyses rely on sequencing of tumour tissue using large
sequencing panels, querying hundreds of genes to find candidate ctDNA biomarkers for
follow-up. Whilst this approach has been successfully implemented to track changes in
tumour burden over time, it requires the sequencing of tumour tissue – which is
difficult to obtain and may not accurately represent the entire genomic landscape of
tumours. Hence, this study designed a targeted DNA sequencing panel to detect
pathogenic mutations directly from the plasma of gastric and colorectal cancer patients.
In addition, the criteria of selecting ctDNA biomarkers was investigated in colorectal
cancers by comparing the ability of mutations in tumour suppressor genes and
oncogenes to track changes in tumour burden throughout chemotherapy treatment.
The gastrointestinal cancer sequencing panel (GI cancer panel) designed in this study
successfully identified pathogenic mutations in the plasma of gastric and colorectal
cancer patients. By restricting the panel to only 21 genes, and designing specialised
oligonucleotide sequencing primers, a high analytical sensitivity was reached.
Mutations were successfully identified down to a frequency of 0.5%. This study also
identified technical challenges associated with ctDNA sequencing approaches –such as
distinguishing pathogenic mutations from sequencing errors and benign variants found
in the plasma. Finally, this study highlighted several factors that should be considered
when selecting ctDNA biomarkers – including the necessity to monitor multiple
mutations to better represent the total tumour burden. Overall, this study has generated
evidence supporting the implementation of ctDNA technologies into the healthcare
system to better manage gastrointestinal cancers
The Role of Large Extracellular Vesicles in Human Papillomavirus-Associated Immune Modulation of Langerhans Cells
No full textHuman papillomavirus type 16 (HPV16) is an oncogenic virus that infects basal keratinocytes of stratified squamous epithelium. Langerhans cells (LCs) reside within the stratified squamous epithelium and initiate immune responses against invading pathogens. The suppression of LC function is one of the many mechanisms of HPV immune evasion, which can contribute to viral persistence and cancer development. Extracellular vesicles (EVs) are small, cell-derived particles that are key players to carcinogenesis, immunity and viral spread. Previous work in the Hibma laboratory has attributed impairment of LC activation and suppression of the cytotoxic T cell response to interactions with large EVs (lEVs) shed by keratinocytes expressing HPV16 E7.
The present study aimed to understand the effects of both HPV16 E6 and E7 (E6/E7) genes on the production of lEVs by keratinocytes and investigate the regulatory roles of lEVs produced by keratinocytes expressing HPV16 E6/E7 on the activation of and cross-presentation by LCs.
Mouse (C57Bl/6) immortalised keratinocyte (PDV) cell lines expressing HPV16 E6/E7 or empty vector control were established following lentivirus transduction. Cell lines were validated, and lEVs from the cell culture supernatants of PDV cells expressing HPV16 E6/E7 (E6/E7 lEVs) or empty vector control (Ctrl lEVs) were purified by differential centrifugation. The purification step was followed by a number of methods to characterise the protein profile, morphology, size and numbers of lEVs. In addition, co-culture experiments were conducted to investigate the effects of E6/E7 lEVs on the activation of LC-like cells (LCLCs) differentiated from the bone marrow progenitors of C57Bl/6 mice.
We found that the overall amounts of lEVs determined by counts and total protein were increased from PDV cells expressing HPV16 E6/E7 compared with empty vector control. Following co-culture with E6/E7 lEVs, LCLCs expressing intracellular IL-12 were markedly downregulated when compared with Ctrl lEVs. In contrast, expression of cell surface co- stimulatory molecules, CD40, CD80 and CD86, on LCLCs was not affected. Furthermore, the effect of E6/E7 lEVs on cross-presentation by LCLCs was examined by measuring the proliferation of CD8+ T cells in response to LCLC-presented ovalbumin. Co-incubations with E6/E7 lEVs resulted to a significantly reduced proliferation of CD8+ T cells when compared with Ctrl lEVs. This effect was ablated when LCLCs derived from Transporter associated with Antigen Processing (TAP1) knockout mice were used, suggesting the involvement of TAP-dependent cross-presentation pathways.
In conclusion, lEVs produced by keratinocytes expressing HPV16 E6/E7 impair LCLC activation and function. A better understanding of E6/E7 lEVs may translate to the production of drugs to inhibit their release and synergise with therapeutic vaccines in development to improve their efficacy in treating HPV-associated malignancies
New Zealand Deprivation Index 2018 - TA50: South Wairarapa District
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/