Characterisation of the 3' region of the PSG11 gene : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Genetics at Massey University, Palmerston North, New Zealand

Appendix : Content removed due to copyright restrictions. 1. Bichimica et Biophysica Acta l2l9 (1994) 195-t97 Sequence of a novel pregnancy-specific B,-glycoprotein C-terminal domain Terence W. Joe, Patricia A. McLenachan. Brian C. Mansfield 2. GENOMICS 22, 356-363 (1994) Characterization of the PSG11 Gene P. A. McLenachan,* K. J Rutherfurd* K. T. Beggs S.E. Sims,* B. C. Mansfield 3. Evolutionary Analysis of the Multi-gene Pregnancy-specific B1-glycoprotein Family: Separation of Historical and Non-historical Signals. Patricia A. McLenachan*, Peter J. Lockhart, H. Rick Faber*, Mansfield [accepted manuscript]The pregnancy-specific beta-1 glycoproteins (PSG) are a family of abundant proteins essential to pregnancy that are encoded by 11 genes located on chromosome 19q 13.1-13.3. The genes can be divided into three subgroups based on the organisation of their 3' coding regions. In 1989, our group isolated cosmid hC3.11, which contained most of the PSG11 gene, but which did not include the 3' coding region. This thesis reports subsequent work to characterise two further cosmids which span the PSG11 locus and which do include the 3' coding region. These cosmids were mapped and partially sequenced Three exons encoding potential alternative C-terminal domains were identified: Cw, Cr and Cs. The Cs domain lies 4.6kb from the end of the B2 domain. This is the first report of genomic sequence for this particular domain and for a functional PSG subgroup 3 gene. Downstream from this exon are sequences homologous to the C-termini of subgroup 1 PSG genes This finding suggests that subgroup 1,2 and 3 genes are related via insertion/deletion events. Data from seven PSG genes from all three subgroups and from four different regions were used to construct evolutionary trees. Variability patterns in the data were examined and these showed that the mechanism of sequence evolution for the N-terminal domain, the A1 domain, and to a certain extent, the B2 domain was not neutral Sequences from these regions were shown to be unsuitable for determining historical relationships between PSG genes. In contrast, the data from the C-terminal region showed a better fit with the assumptions of sequence evolution (e.g. all changes are independent and identically distributed) required by currently implemented analysis methods. Evolutionary tree reconstruction using this region gave a phylogeny that was consistent with one based on the genomic organisation of the genes

Ventricular Arrhythmias in Hypertensive Left Ventricular Hypertrophy

Abstract Not Provided

Truth is Stranger than Science Fiction: The Quest for Knowledge in Andrei Tarkovskii’s Solaris and Stalker

This article explores Andrei Tarkovskii’s conception of truth in Solaris (1972) and Stalker (1979) as part of his wider philosophical project concerning knowledge. The director’s epistemological views form a core dimension of his life and aesthetic as he strives towards what he considers a higher, spiritual ‘idea of knowing’. In his search for this idealised notion of truth, Tarkovskii uses the medium of film to address what he perceives as a profound imbalance in modern civilization between scientific rationalism and spiritual/aesthetic ‘truth’. This is nowhere more prominent than in his two science fiction films, Solaris and Stalker, as he uses the genre as a battleground to discuss key debates in epistemology. Comparisons will be made with the Russian author and thinker Tarkovskii most revered, Fyodor Dostoevskii, and the Soviet-period science fiction authors whose works he adapted, Stanisław Lem and the Strugatskii brothers, in order to elucidate how the director came to cinematically represent his philosophy

mRNA transfection of mouse and human neural stem cell cultures

The use of synthetic mRNA as an alternative gene delivery vector to traditional DNA-based constructs provides an effective method for inducing transient gene expression in cell cultures without genetic modification. Delivery of mRNA has been proposed as a safer alternative to viral vectors in the induction of pluripotent cells for regenerative therapies. Although mRNA transfection of fibroblasts, dendritic and embryonic stem cells has been described, mRNA delivery to neurosphere cultures has not been previously reported. Here we sought to establish an efficient method for delivering mRNA to primary neurosphere cultures. Neurospheres derived from the subventricular zone of adult mice or from human embryonic stem cells were transfected with EGFP mRNA by lipofection and electroporation. Transfection efficiency and expression levels were monitored by flow cytometry. Cell survival following transfection was examined using live cell counting and the MTT assay. Both lipofection and electroporation provided high efficiency transfection of neurospheres. In comparison with lipofection, electroporation resulted in increased transfection efficiencies, but lower expression per cell and shorter durations of expression. Additional rounds of lipofection renewed EGFP expression in neurospheres, suggesting this method may be suitable for reprogramming applications. In summary, we have developed a protocol for achieving high efficiency transfection rates in mouse and human neurosphere cell culture that can be applied for future studies of gene function studies in neural stem cells, such as defining efficient differentiation protocols for glial and neuronal linages

P2519: The Impact of Transcatheter Aortic Valve Implantation on Quality of Life: A Mixed Methods Study

Objective: To provide an in-depth understanding of patients' views about the impact of transcatheter aortic valve implantation on self-reported quality of life. Background: Transcatheter aortic valve implantation is considered to be the gold standard of care for inoperable patients diagnosed with severe symptomatic aortic stenosis. Mid- to long-term clinical outcomes are favourable and questionnaire data indicates improvements in quality of life but an in-depth understanding of how quality of life is altered by the intervention is missing. Methods: A mixed methods study design with a total of 89 in-depth qualitative interviews conducted with participants (39% male; mean age 81.7 years), 1 and 3 months post TAVI, recruited from a regional centre in England. Data were triangulated with questionnaire data (SF-36 and EQ5D-VAS) collected, pre, 1 and 3 months post implantation. Results: Participants' accounts were characterised by four key themes; shortened life, extended life, limited life and changed life. Quality of life was changed through two mechanisms. Most participants reported a reduced symptom burden and all explained that their life expectancy was improved. Questionnaire data supported interview data with gradual improvements in mean EQ-5D scores and SF-36 physical and mental domain scores at 1 and 3 months compared to baseline. Conclusion: Findings suggest that TAVI was of variable benefit, producing considerable improvements in either mental or physical health in many participants, while a smaller proportion continued to deteriorate

Incidence and mortality of conjunctival melanoma in Australia (1982 to 2014)

Purpose: The purpose of this study was to estimate the incidence and mortality of conjunctival melanoma in Australia from 1982 to 2014. Methods: De-identified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1982 to 2014. Conjunctival melanoma cases were extracted, and the incidence and mortality were analyzed. Incidence rates were age-standardized against the 2001 Australian Standard Population. Mortality was assessed using log-rank and Cox regression. Results: From 1982 to 2014, there were 299 cases of conjunctival melanoma. The age-standardized incidence rate was 0.48 (95% confidence interval [CI] = 0.41 to 0.54) per million per year. Women (0.52, 95% CI = 0.42 to 0.62) had a higher incidence than men (0.42, 95% CI = 0.33 to 0.51). The incidence of conjunctival melanoma increased in men (+1.46%) and significantly women (+1.41%, P = 0.023) over the study period. The mean 5-, 10-, and 15-year disease-specific survival were 90%, 82%, and 80%, respectively, during the 33-year interval. Comparisons of survival among age, sex, and state revealed no significant differences when tested using log-rank or Cox regression. Conclusions: In conclusion, we found an increase in the rate of conjunctival melanoma diagnoses in Australia from 1982 to 2014. Over the same period, disease survival remained unchanged at a mean of 90%

Incidence and mortality of uveal melanoma in Australia (1982–2014)

Aims: We aimed to estimate the incidence and mortality of uveal melanoma (UM) in Australia from 1982 to 2014. Methods: Deidentified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1 January 1982 to 31 December 2014. UM cases were extracted and trends in incidence and disease-specific mortality were calculated. Incidence rates were age-standardised against the 2001 Australian Standard Population. Mortality was assessed using Cox regression. Results: From 1982 to 2014, there were 5087 cases of ocular melanoma in Australia, of which 4617 were classified as UM. The average age-standardised incidence rate of UM was 7.6 (95% CI 7.3 to 7.9) per million. There was an increase (p=0.0502) in the incidence of UM from 1982 to 1993 with an annual percent change (APC) of +2.5%, followed by a significant decrease in the incidence of UM from 1993 to 2014 (APC −1.2%). The average 5-year survival from 1982 to 2011 did not significantly change from an average of 81%, with an average APC (AAPC) of +0.1%. A multivariate Cox regression revealed that residence in Western Australia (p=0.001) or Tasmania (p=0.05), age ≥60 years (p \u3c 0.001) and histological classification as mixed (p \u3c 0.001) or epithelioid cells (p \u3c 0.001) were significantly associated with reduced survival. Conclusion: In conclusion, we found that the incidence of UM peaked in the 1990s. Although treatment for primary UM has improved in the last 30 years, overall survival did not change significantly in the last 30 years