429 results for Undergraduate

  • Does prolactin act directly on AgRP neurons in the arcuate nucleus?

    MacLeod, Morgan Anna (2016)

    Undergraduate thesis
    University of Otago

    The development of a positive energy balance occurs during pregnancy to support the growth of fetal and maternal tissues, and to increase energy stores in preparation for the metabolic demands of lactation. Leptin levels increase as pregnancy advances, along with appetite and fat deposition. This is unusual, as in the non-pregnant state, leptin decreases food intake and increases energy mobilization. Therefore, leptin is not being recognized during pregnancy. Leptin-responsive neurons, such as Agouti-related peptide (AgRP) and Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, do not respond normally to leptin during pregnancy. It is likely that changes in gestational hormonal profile have a role in mediating leptin resistance. Increased plasma prolactin is observed during pregnancy and, in addition, there are prolactin receptors in the same regions of the brain that control food intake. Prolactin is also known to have an orexigenic effect. We hypothesise that prolactin is a mediator of this increased appetite and resistance to leptin during pregnancy. The aim of this study was to examine whether prolactin directly targets leptin-responsive neurons in the arcuate nucleus. We examined the AgRP neurons, known to be involved in stimulating food intake. Transgenic mouse models and double-label immunohistochemistry were used to look at whether prolactin action is observed in neurons that express AgRP. In separate experiments, AgRP-Cre-tdTomato mice and AgRP-Cre-tauGFP mice were injected with prolactin and perfused. The brains were used to detect prolactin-induced phosphorylation of STAT5, an indicator of prolactin action. The sections were then double-labelled to identify AgRP neurons with labeling of either the tdTomato transgene or GFP respectively. AgRP neurons were readily detected in the arcuate nucleus. Many pSTAT5-stained nuclei were also detected in the arcuate nucleus of prolactin-treated animals, however, none of the AgRP neurons showed pSTAT5-positive nuclei. To confirm these results, we looked at conditional deletion of the prolactin receptor in AgRP neurons using AgRP-PRLR flox/flox mice. We looked at differences in food intake and body weight between these knockout mice and wildtype littermates, no significant differences were observed. We also used immunohistochemistry to look at GFP expression. These mice would be expected to show Cre-induced expression of GFP if the prolactin receptor was normally expressed in the AgRP neurons. vGAT-Cre-Prlr flox/flox transgenic mice were used as a positive control as previous work suggests that GABA neurons express the prolactin receptor. While GFP was readily detected in the positive controls, no staining of any neurons was visible in the non-pregnant, pregnant or lactating brains from AgRP-PRLR flox/flox mice, indicating that the prolactin receptor gene is not normally expressed in AgRP neurons. From these experiments we were able to conclude that prolactin-induced pSTAT5 does not colocalise with AgRP neurons, and that the prolactin receptor gene is not expressed in AgRP neurons. Therefore, the results obtained did not support our hypothesis that prolactin-induced increases in food intake are mediated by direct actions of prolactin by AgRP cells, and showed that prolactin does not directly act upon AgRP neurons to mediate leptin resistance during pregnancy.

    View record details
  • A novel strategy to prevent bacterial biofilm formation using methylthioadenosine-nucleosidase inhibitors

    Swadi, Tara Harith (2016)

    Undergraduate thesis
    University of Otago

    Each year there are approximately 2.9 million joint replacement surgeries performed worldwide. Great efforts have been made to reduce infection rates in these replacements in the past and yet these rates have not decreased in the past 20 years. These infections are often caused by the formation of biofilms on the surface of the implant by skin bacteria that are implanted at the time of surgery. The S-adenosylmethionine (SAM) cycle has important roles in bacterial biofilm formation. Methylthioadenosine-nucleosidase (MTAN) is an important component in this cycle. The Ferrier Institute at Victoria University have synthesized approximately thirty compounds which have been shown to inhibit the MTAN enzyme. Testing of ten organisms of each Staphylococcus aureus and Staphylococcus epidermidis all isolated from infected joint prosthesis was undertaken to determine the strongest biofilm formers. Over 90% of organisms that infect prosthetic joint replacements are found to be S. epidermidis or S. aureus, which is why these organisms were used as models. The isolates in combination with MTAN inhibitors (MTANi) were screened using a crystal violet assay to determine biofilm formation. An optical density reading was used to determine bacterial growth. Minimum inhibitory concentration (MIC) testing on four clinically relevant antibiotics was performed using a doubling dilution broth culture method. The effect of these antibiotics on the efficacy of the lead inhibitor was analysed using an optical density growth assay and static biofilm assay. Fluorescent images of the biofilms were produced using the LIVE/DEAD® BacLight™ bacterial viability method of staining. In testing of the strongest biofilm forming isolates, a lead compound (MTANi18) has been identified that inhibited biofilm formation in both S. aureus and S. epidermidis. Some effects on growth were noted at high concentrations of the MTAN inhibitor. It has been observed that MTANi18 affects the action of four clinically relevant antibiotics, in an agonistic manner. Further testing is required to determine the extent of this phenomenon. These findings have important implications in the potential therapeutic uses of the MTAN inhibitors.

    View record details
  • Umbilical Cord Serum Chemokines and the Development of Atopic Dermatitis

    Townsley, Hermaleigh (2016)

    Undergraduate thesis
    University of Otago

    Background: Atopic dermatitis (AD) is a chronic skin condition characterised by the development of pruritic and inflamed lesions. One key component of AD pathogenesis is a cutaneous hyper-reactivity to allergens influenced by a Th2-polarised immune response. Macrophage-derived chemokine (MDC) and Thymus and activation-regulated chemokine (TARC) are two chemokines involved in this pathological immune response. Research has shown a strong association between MDC and TARC levels in blood and AD severity. Recently, some cohort studies have suggested that levels of MDC and TARC in umbilical cord blood (UCB) may be predictive of whether infants will develop AD during childhood. This cohort study aimed to further investigate the potential predictive value of UCB MDC and TARC for AD development in childhood. Methods: This project involved a retrospective analysis of data obtained from the NZA2CS population birth cohort study. Information about AD-related outcomes was gathered using questionnaires at various time points, along with physical examination of flexural dermatitis and measurement of total and specific IgE levels at age six. UCB MDC levels were measured using enzyme-linked immunosorbent assay (ELISA) techniques for a total of 647 participants. Haemolysis of UCB samples was found to affect TARC measurement; therefore fewer (n = 270) samples were analysed for TARC. Haemolysis of UCB samples did not affect measurement of MDC concentration. Logistic regression was used to calculate odds ratios to determine the association between UCB chemokine levels and development of AD- related outcomes in childhood. Results: UCB MDC and TARC levels were not predictive of development of AD at age six. Neither were they consistently significantly associated with the development of AD-related outcomes such as an itchy rash or atopy. Some statistically significant associations were found, although their value is difficult to interpret as these were isolated findings. UCB MDC levels were significantly associated with the development of an itchy rash at four years of age (p = 0.027) and with the level of specific IgE to cat allergen at age six (p = 0.05). When the data was segregated by sex, UCB MDC levels in males were consistently significantly associated with development of an itchy rash during childhood (p < 0.05). Conclusion: UCB MDC and TARC concentrations are unlikely to be clinically useful biomarkers for the development of AD in childhood. This was the largest cohort study so far to investigate cord MDC and TARC levels as predictors of future AD onset, and the findings are concordant one other large cohort study. Therefore, these results do not warrant further research into UCB MDC and TARC as predictive biomarkers of AD development.

    View record details
  • Cancer Stem Cells in Squamous Cell Carcinoma of the Oral Tongue

    Baillie, Ranui Francesca (2015)

    Undergraduate thesis
    University of Otago

    Background: Given the discovery of cancer stem cells (CSCs) within haematological and solid tumours and the expression of primitive markers by infantile haemangioma, it was hypothesised that a CSC population would also be present in oral tongue squamous cell carcinoma (OTSCC). A deeper understanding of the cells that drive tumourigenesis is required for the development of mechanism-based therapies for OTSCC. Aims: This study aimed to identify and characterise the CSC population within OTSCC based on their protein and gene expression profiles. Methods: Immunohistochemical staining, Western Blotting, mass spectrometry and Nanostring analysis were employed to investigate the expression of a panel of proteins and genes in formalin-fixed paraffin-embedded tissues, and snap frozen tissues of OTSCC from 21 patients. Markers used include epithelial cancer markers (p63 and EMA), CSC markers (CD44, CD133 and SOX2) and embryonic stem cell (ESC) markers (Oct-4, Nanog and pSTAT3). Results: Widespread and overlapping expression of p63, EMA, CD44, SOX2, pSTAT3, Nanog and Oct-4 was identified within the OTSCC. Co-expression of CD44, SOX2, Oct-4, Nanog and pSTAT3, was found within the OTSCC cells, while cells scattered within the peri-tumoural stroma expressed CD44, CD133, pSTAT3, Nanog and Oct-4. A CD44+/SOX2+/Nanog+/Oct-4+/pSTAT3+ but CD133-/EMA-/p63- CSC population was identified in OTSCC. Expression of CSC and ESC markers by differentiated phenotype structures, and the presence of polyploid giant cancer cells that are CD44+/Nanog+ were novel findings. Conclusions: The unique widespread distribution of the CSC population with co-expression of epithelial cancer cell, CSC and ESC markers within OTSCC suggests that these cells are comprised of several overlapping sub-populations that are organised hierarchically within the tumour. The lack of CD133 expression in OTSCC tumour cells brings into question the utility of this protein as a CSC marker. The findings demonstrate a unique expression signature for the CSC population within the OTSCC samples investigated and support a hierarchical CSC model of carcinogenesis, while the novel findings provide interesting avenues for further research.

    View record details
  • The role of retromer in the epithelial sodium channel trafficking pathway

    Geda, Anna Caterina (2015)

    Undergraduate thesis
    University of Otago

    The epithelial sodium channel (ENaC) is a protein located at the apical membrane of polarised epithelial cells, primarily expressed in the epithelia of the gastrointestinal tract, lungs and kidney. ENaC's main function is that of absorbing sodium and it is strongly involved in regulating and maintaining total-body salt and water homeostasis, acting as the rate-limiting step for sodium reabsorption into the body. Its activity, therefore, is crucial for determining blood volume and, as a consequence, blood pressure. The sorting and trafficking of ENaC to the apical membrane is a tightly controlled process, requiring the interaction of multiple proteins and organelles. Although ENaC has been well-characterised, there are certain aspects about its trafficking which need to be clarified, such as defining the many proteins involved in the recycling of the channel to and from the apical membrane. A potential, novel candidate involved in ENaC recycling is the retromer complex. This endosome-associated protein complex has been shown to have a role in protein recycling, as well as maintaining cell polarity by assisting in the transport of proteins to and from their appropriate membrane. The aim of this study was to investigate whether retromer is involved in the recycling of ENaC in polarised epithelia, focusing on three specific proteins, namely ccdc22, Snx4 and KIBRA. Whilst ccdc22 is an established component of the retromer complex, Snx4 and KIBRA were hypothesised to be part of retromer, a plausible concept given their cellular localisation and proposed function. To test whether ccdc22, Snx4 and KIBRA were involved in ENaC recycling, their function was altered (via protein knockdown or overexpression) and the effects on ENaC trafficking were measured. Using transiently transfected HEK293 (human embryonic kidney) and FRT (Fischer rat thyroid) cells, semi-quantitative analysis was carried out with Western blots to visualise whether the knockdowns/overexpression of the proteins of interest were occurring. Then, Ussing chamber experiments were conducted to detect any changes in the ENaC channel’s activity at the apical membrane when a retromer protein was knocked down or over-expressed. Finally, GST-pulldown assays were performed to visualise whether the ENaC channel interacted with retromer through the protein KIBRA. Significant knockdowns were obtained of both Snx4 (ps blood pressure.

    View record details
  • Predictors of Referral Delay and Treatment Response to Intravitreal Bevacizumab for Wet Age-Related Macular Degeneration

    Ang, Wee Choen (Sebastian) (2017)

    Undergraduate thesis
    University of Otago

    Background: Recent years have seen anti-vascular endothelial growth factor (VEGF) agents revolutionize the treatment of wet age-related macular degeneration (AMD). To ensure optimal outcomes for this time-sensitive disease, current guidelines recommend that patients should be seen in clinic within two weeks of referral and treated with a loading phase of three injections, followed by a follow-up visit for reassessment. However, meeting these guidelines is challenging due to the increasing global prevalence of wet AMD and the accumulating cohort of patients requiring treatment. In addition, services with inefficient referral pathways and limited treatment capacities have been shown to threaten patient access to prompt treatment and increase adverse patient outcomes. Aims and Methods: This project is a two-year retrospective audit conducted at the Eye Department in Dunedin Public Hospital with the aims to (1) assess the efficiency of the current wet AMD referral pathway against contemporary guidelines and (2) identify any risk factors that are predictive of referral delay and treatment outcome. Relevant patient, referrer, referral and clinical characteristics were retrieved from retrospective analysis of clinical records and OCT scans of 113 patients. The outcome measures were referral delay (i.e. duration from point of referral to first assessment clinic); and treatment response measured by changes in visual acuity, changes in central macular thickness (CMT) and clearance of macular fluid. All potential predictors of these outcome measures were analysed via multivariable binomial logistic regression. Results: Only 49% of patients at Dunedin Public Hospital met referral guidelines, but 85% met treatment guidelines. Overall median time from point of referral to first treatment was 10 days. A loading phase of three bevacizumab injections significantly improved mean visual acuity by 5 ± 24 letters (p=0.03) and reduced mean central macular thickness (CMT) by 55μm (p85 years) were associated with an increased likelihood of CMT reduction (OR 9.157; 95% CI 2.6, 31.747; p<0.001 and OR 4.79; 95% CI 1.11, 20.7; p=0.036 respectively), whereas patients with longer duration of symptoms (1 to 3 months) were significantly associated with a decreased likelihood of CMT reduction compared to patients with symptoms of less than one month (OR 1.65; 95% CI 0.044, 0.616, p value = 0.007). Thicker baseline CMT was also found to be significantly associated with a greater reduction of macular fluid (OR 1.475; 95% CI 0.75, 4.578; p=0.017) after treatment, and so were females compared to males (OR 3.9; 95% CI 1.2, 12.58; p=0.02). Conclusion: This study identified that the current wet AMD referral pathway at Dunedin Public Hospital can and should be more efficient, and quality improvement work is warranted to improve compliance to contemporary guidelines.

    View record details
  • Mineralogy and geochemistry of paralavas in Otago and Southland, New Zealand

    Rait, Rachel Jane (1992)

    Undergraduate thesis
    University of Otago

    74 leaves :ill., 1 map ; 30 cm. Bibliography: leaves 71-74. Errata note on t.p. University of Otago department: Geology.

    View record details
  • Access to irrigation water : private property rights applied to water

    Milmine, Craig A. (2000)

    Undergraduate thesis
    University of Otago

    58 leaves, [3] leaves of plates :ill., maps ; 27 cm. University of Otago department: Geography.

    View record details
  • Investigation into the business and operations of Carlton Party Hire Limited.

    Hart, Graeme Richard (1988)

    Undergraduate thesis
    University of Otago

    107 leaves. University of Otago programme: MBA. From title page: "Project 660".

    View record details
  • Why did so many babies die? : infant mortality and causes of death in Dunedin, 1900-1920

    Schumacher, Conrad (1998)

    Undergraduate thesis
    University of Otago

    ix, 93 leaves :ill., maps ; 30 cm. Includes bibliographical references. Typescript (photocopy).

    View record details
  • Groundwater modelling of the Omaha aquifer system

    Martin, G. A. (1994)

    Undergraduate thesis
    University of Otago

    55 p. ; 27 cm. Bibliography: p.53-55. University of Otago department : Surveying

    View record details
  • Trichosurus vulpecula and rattus norvegious in the epidemiology of two arboviruses.

    Dempster, Alexander George (1964)

    Undergraduate thesis
    University of Otago

    v, 70 leaves ; 30 cm. Includes bibliographical references.

    View record details
  • Stir, bustle and whir! : a history of the New Zealand Clothing Factory, 1873-1905

    Isaac, Penelope Sheila (1996)

    Undergraduate thesis
    University of Otago

    74 leaves :ill., map, port. ; 30 cm. Includes bibliographical references (leaves 71-74). Typescript (photocopy).

    View record details
  • Potions, pills and poisons : quackery in New Zealand, circa 1900-1915.

    Gray, Jennifer Margaret (1980)

    Undergraduate thesis
    University of Otago

    112 leaves ; 30 cm. Includes bibliographical references (leaves 108-112).

    View record details
  • Jurassic sediments at Chaslands mistake.

    Geary, Geoffrey Clive (1976)

    Undergraduate thesis
    University of Otago

    v, 34 leaves ; 30 cm. Includes bibliographical references. University of Otago department: Geology

    View record details
  • "Unfortunate folk" : a study of the social context of committal to Seacliff Asylum 1928-1937

    Holloway, Judith Anne (1991)

    Undergraduate thesis
    University of Otago

    137 leaves :ill., facsims ; 30 cm. Bibliography: leaves 134-137. Typescript (photocopied)

    View record details
  • The hill of health : aspects of community at Waipiata Sanatorium 1923-1961

    Haugh, Susan Margaret (2005)

    Undergraduate thesis
    University of Otago

    102 leaves, [21] p. of plates :ill., facsim., map, ports. ; 30 cm. Bibliography: leaves 101-102.

    View record details
  • Hydrography and photommetry : tools for artificial surfing reef studies?

    Scarfe, Bradley Edward (1999)

    Undergraduate thesis
    University of Otago

    xi, 104 leaves, [18] leaves of plates :ill., maps (some folded) ; 30 cm. Includes bibliographic references. University of Otago department : Surveying. Cover title. "November 1999."

    View record details
  • Loving our national parks to death

    Mann, Amber (2005)

    Undergraduate thesis
    University of Otago

    iii, 91 leaves :col. ill., plan ; 30 cm. Includes bibliographical references.

    View record details
  • Alpine fault pseudotachylytes

    Ritchie, Samuel David (2009)

    Undergraduate thesis
    University of Otago

    xvii, 171 leaves :col. ill., maps30 cm Includes bibliographical references. "October 2009". University of Otago department: Geology

    View record details