26 research outputs found
Selenium Status of the Australian Population: Effect of Age, Gender and Cardiovascular Disease
No full textGriffith Health, School of Medical ScienceFull Tex
Genetic and biochemical changes of the serotonergic system in migraine pathobiology
No full textMigraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.Office of the Snr Dep Vice Chancellor, Institute for GlycomicsFull Tex
Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk
No full textObjectivesThe aim of this study was to evaluate the role of cardiac K(+) channel gene variants in families with atrial fibrillation (AF).BackgroundThe K(+) channels play a major role in atrial repolarization but single mutations in cardiac K(+) channel genes are infrequently present in AF families. The collective effect of background K(+) channel variants of varying prevalence and effect size on the atrial substrate for AF is largely unexplored.MethodsGenes encoding the major cardiac K(+) channels were resequenced in 80 AF probands. Nonsynonymous coding sequence variants identified in AF probands were evaluated in 240 control subjects. Novel variants were characterized using patch-clamp techniques and in silico modeling was performed using the Courtemanche atrial cell model.ResultsNineteen nonsynonymous variants in 9 genes were found, including 11 rare variants. Rare variants were more frequent in AF probands (18.8% vs. 4.2%, p 30 ms) shortening or lengthening of action potential duration as well as increased dispersion of repolarization.ConclusionsFamilies with AF show an excess of rare functional K(+) channel gene variants of varying phenotypic effect size that may contribute to an atrial arrhythmogenic substrate. Atrial cell modeling is a useful tool to assess epistatic interactions between multiple variants.Stefan A. Mann, Robyn Otway, Guanglan Guo, Magdalena Soka, Lina Karlsdotter, Gunjan Trivedi, Monique Ohanian, Poonam Zodgekar, Robert A. Smith, Merridee A. Wouters, Rajesh Subbiah, Bruce Walker, Dennis Kuchar, Prashanthan Sanders, Lyn Griffiths, Jamie I. Vandenberg, Diane Fatki
A novel multiplex PCR-RFLP method for simultaneous detection of the <it>MTHFR 677 C > T</it>, <it>eNOS +894 G > T</it> and <it>- eNOS -786 T > C</it> variants among Malaysian Malays
No full textAbstract Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS −786 T > C, the allele frequencies were 0.87 (T allele) and 0.13 (C allele). Conclusions Our PCR-RFLP method is a simple, cost-effective and time-saving method. It can be used to successfully genotype subjects for the MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants simultaneously with 100% concordance from DNA sequencing data. This method can be routinely used for rapid investigation of the MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants.</p
Connecting theory and fiction: Margaret Atwood's novels and second wave feminism
No full textThis thesis undertakes an examination of the manner in which a novelist interacts with a contemporary theoretical discourse. I argue that the novelist and the theoretical discourse enter into a symbiotic relationship in which each influences and is influenced by the other. This process, I suggest, is simultaneous and complex. The thesis demonstrates how the prevailing theoretical discourse is absorbed by the contemporary author, is developed and redefined in conjunction with alternative concerns, and comes to permeate the narrative in an altered state. The novelist's new perspectives, frequently problematising theoretical claims, are then disseminated by the novel, promoting further discussion and development of the theoretical discourse. The thesis focuses on the novels of Margaret Atwood, considering them in relation to the history and development of second wave feminism. "Second wave feminism" is understood as an umbrella term that incorporates a wide variety of related but diverse and occasionally contradictory discourses, centring on the subjects of gender, femininity, and sexuality. The focus of the discussion is dual and presented simultaneously. Atwood's novels are analysed chronologically, and within the parameter of this analysis I demonstrate how her work has been influenced by earlier feminist theories, how it comments upon a variety of contemporary feminist ideas, and how it can be seen to anticipate further discussions within feminist discourse. Finally, I identify moments in Atwood's writing when alternative discourses compete with feminism to create new directions for feminist criticism. Examples of these discourses include Canadian nationalism, liberalism, communitarianism and environmentalism. The specificity of the novelist's interests and politics create a unique site of interaction for feminism which, I argue, benefits feminist theory by challenging, broadening and diversifying its focus. The thesis concludes that the symbiotic relationship of the theorist and the novelist is self-perpetuating and is also necessary and beneficial to both parties
Investigation of association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4
No full textPatent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke. © 2011 Moradi Marjaneh et al
Mutations in Cardiac T-Box Factor Gene TBX20 Are Associated with Diverse Cardiac Pathologies, Including Defects of Septation and Valvulogenesis and Cardiomyopathy
No full textThe T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference–mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up
Cultural and gender politics in a neglected archive of Jamaican women's poetry : Una Marson and her Creole contemporaries
No full textThis thesis considers the gender and cultural politics of selected Jamaican
women's poetry published during the first half of the twentieth century and
seeks to establish that an approach to this poetry sensitive to these issues will
illuminate aspects of their work previously neglected by canonical and colonial
modes of interpretation. The central interest of this thesis is the poetry of Una
Marson, a black woman poet whose work has been critically neglected and
devalued to date. My project is to read Marson's work in some detail, and to
explore to what extent her poetry, which often works within colonial models and
with conventional notions of feminine fulfilment, employs received aesthetic
and ideological paradigms both strategically and subversively. In the belief
that critics of Jamaican women's writing should be as attentive to the gender
and cultural politics of their ways of reading, as of the texts they wish to read,
the first chapter of this thesis engages in a sustained analysis of theoretical
positions and attempts to map out the various problems and possibilities
which critical discourses present in relation to this material. The second
chapter examines the various social and literary contexts in which Jamaican
poetry was produced and received during this period, and the third chapter
looks in more detail at contemporary notions of aesthetic and cultural forms.
The fourth and fifth chapters are structured aromd close textual readings
which explore the variety and complexity of Marson's, and her Creole
contemporaries', poetic engagement with the issues of cultural and gender
identities. The thesis concludes that Marson's poetry questions dominant
notions both of identity and of aesthetics, and consequently that her poetry
offers an example of Jamaican literary expression which moves beyond the
nationalization of consciousness which has come to mark the literary
achievement of this period
Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
No full textCorrection to: Nature Communications https://doi.org/10.1038/s41467-023-42320-4, published online 22 December 202
