| 1. |
- Dahlin, Paul, 1983-
(author)
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Analysis of sterol metabolism in the pathogenic oomycetes Saprolegnia parasitica and Phytophthora infestans
- 2016
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Doctoral thesis (other academic/artistic)abstract
- The primary objective of this thesis was to investigate the sterol metabolism of two pathogenic oomycetes, specifically the processes of sterol synthesis and sterol acquisition in the fish pathogen Saprolegnia parasitica (Saprolegniales) and the plant pathogen Phytophthora infestans (Peronosporales). Furthermore, the effects of steroidal glycoalkaloids from Solanaceous plants, on P. infestans, were examined. The improved understanding of these processes should help to identify approaches for the identification of new oomycete inhibitors targeting sterol metabolism in agriculture and aquaculture farming systems, and to guide plant-breeding strategies to defend solanaceous plants against oomycetes.For these reasons, the molecular basis of the metabolic pathways of sterol synthesis and/or sterol acquisition was investigated. Sterols are derived from isoprenoids and indispensable in various biological processes. Our biochemical investigation of an oxidosqualene cyclase revealed that sterol synthesis in S. parasitica begins with the formation of lanosterol (Paper I), and a reconstruction of the complete sterol synthesis pathway to the final compound, fucosterol, in S. parasitica was performed using bioinformatics (Paper II). Complementary to this work, the extent to which P. infestans, which is incapable of de novo sterol synthesis, is able to modify exogenously provided sterols was investigated by determining the growth impact of various sterol supplements in the growth media (Paper II). Building on the sterol investigations, the solanaceous sterol derivatives from the glycoalkaloid family were analysed. These compounds contain both a steroidal and a carbohydrate (glycan) moiety. Data obtained by feeding various deuterium-labeled sterols to potato shoots, supported the theory that steroidal glycoalkaloids in Solanum tuberosum are produced from cholesterol (Paper III). Since these steroidal glycoalkaloids are thought to play a role in plant defense, their physiological effects on P. infestans were investigated (Paper IV). Unexpectedly we found that non-glycosylated steroidal alkaloids had a greater inhibitory effect than steroidal glycoalkaloids. Steroidal glycoalkaloids derived from other Solanaceous species exhibited different physiological effects on the growth of P. infestans. This research was conducted on two oomycete species belonging to the Saprolegniales and Peronosporales orders, hence the results presented are likely to be representative of each of these two oomycete orders.
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| 2. |
- Titov, Nickolai, et al.
(author)
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User characteristics and outcomes from a national digital mental health service : an observational study of registrants of the Australian MindSpot Clinic.
- 2020
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In: The Lancet Digital Health. - London, United Kingdom : The Lancet Publishing Group. - 2589-7500. ; 2:11, s. e582-e593
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Journal article (peer-reviewed)abstract
- Background: Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation.Methods: We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment.Outcomes: A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role.Interpretation: Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems.Funding: None.
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| 5. |
- Hinsley, Amy, et al.
(author)
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A review of the trade in orchids and its implications for conservation
- 2018
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In: Botanical journal of the Linnean Society. - : OXFORD UNIV PRESS. - 0024-4074 .- 1095-8339. ; 186:4, s. 435-455
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Research review (peer-reviewed)abstract
- Orchids are one of the largest plant families and are commercially traded for a variety of purposes, including as ornamental plants, medicinal products and food. These markets involve thousands of species, which may be traded legally or illegally, sustainably or unsustainably, and take place at local, national or international scales. In this review, we provide the first overview of commercial orchid trade globally and highlight the main types that involve wild-collected plants. Much of this trade is the result of illegal harvest meaning that it is little documented and is absent from official statistics, at the same time as being of growing conservation concern. We discuss the associated legal-regulatory context, identify key conservation challenges and highlight four key priorities for addressing these challenges. These are to (1) research trade dynamics and the impacts of harvest; (2) strengthen the legal trade of orchids; (3) adopt measures to reduce illegal trade; and (4) raise the profile of orchid trade among policy makers, conservationists and the public.
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| 6. |
- Kaput, J, et al.
(author)
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The case for strategic international alliances to harness nutritional genomics for public and personal health
- 2005
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In: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 94:5, s. 623-632
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Journal article (peer-reviewed)abstract
- Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
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| 7. |
- Klinter, Stefan, 1985-
(author)
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Identification and characterisation of chitin and cellulose synthases in oomycetes : New tools for biochemical studies and structure determination
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Despite resembling ‘true’ fungi in terms of morphological features, oomycetes form a distinct eukaryotic lineage of filamentous microorganisms that belongs to the stramenopiles, a group of protists also comprising the closely-related brown algae and diatoms. Many oomycetes are devastating pathogens of plants and animals, globally causing significant economic losses in the agriculture and aquaculture industries, and posing considerable environmental damage to natural ecosystems. Although the cell wall (CW) is critical for the viability and morphogenesis of the organism it surrounds, our knowledge of oomycete CW architecture and biosynthetic enzymes is limited. Given the vast threat that pathogenic oomycetes pose, uncovering the details of CW biosynthesis and regulation in these pathogens may reveal new opportunities for disease control.To this end, we aimed to elucidate the role of putative membrane-bound glycosyltransferase family 2 enzymes implicated in the biosynthesis of oomycete CW polysaccharides. Suitable gene candidates were identified, and their products analysed, as illustrated by the oomycete-wide discovery and phylogenetic analysis of the chitin synthase gene family (paper I), and the identification of the cellulose synthase genes in Saprolegnia parasitica (paper II) and Phytophthora capsici (paper III). Expression of promising candidate genes was verified using different techniques, including gene expression analysis (papers II and III), and the effect of inhibitors on hyphal growth (papers I and II) and enzymatic activity in in vitro assays (paper II). Single enzymes representing putative chitin synthases from various organisms (unpublished data) and cellulose synthases from S. parasitica (extended data for paper II), and P. capsici cellulose synthase 1 (paper III) were produced, and partly enriched or even purified, in yeast strains specifically engineered to facilitate the biochemical characterisation of the recombinant proteins in in vitro enzyme assays. To advance functional investigations and structure determination of integral membrane proteins, we developed DirectMX, a method that allows the reconstitution of target proteins with their surrounding lipids directly from crude cell membranes into Salipro nanoparticles (paper IV).
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| 8. |
- Middleton, Anna, et al.
(author)
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Attitudes of publics who are unwilling to donate DNA data for research.
- 2019
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In: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 62:5, s. 316-323
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Journal article (peer-reviewed)abstract
- With the use of genetic technology, researchers have the potential to inform medical diagnoses and treatment in actionable ways. Accurate variant interpretation is a necessary condition for the utility of genetic technology to unfold. This relies on the ability to access large genomic datasets so that comparisons can be made between variants of interest. This can only be successful if DNA and medical data are donated by large numbers of people to 'research', including clinical, non-profit and for-profit research initiatives, in order to be accessed by scientists and clinicians worldwide. The objective of the 'Your DNA, Your Say' global survey is to explore public attitudes, values and opinions towards willingness to donate and concerns regarding the donation of one's personal data for use by others. Using a representative sample of 8967 English-speaking publics from the UK, the USA, Canada and Australia, we explore the characteristics of people who are unwilling (n = 1426) to donate their DNA and medical information, together with an exploration of their reasons. Understanding this perspective is important for making sense of the interaction between science and society. It also helps to focus engagement initiatives on the issues of concern to some publics.
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| 9. |
- Middleton, Anna, et al.
(author)
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Global Public Perceptions of Genomic Data Sharing : What Shapes the Willingness to Donate DNA and Health Data?
- 2020
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:4, s. 743-752
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Journal article (peer-reviewed)abstract
- Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.
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| 10. |
- Middleton, Anna, et al.
(author)
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Members of the public in the USA, UK, Canada and Australia expressing genetic exceptionalism say they are more willing to donate genomic data
- 2020
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28:4, s. 424-434
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Journal article (peer-reviewed)abstract
- Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held 'exceptionalist' views about genetics (i.e., believed DNA is different or 'special' compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research.
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| 11. |
- Middleton, Anna, et al.
(author)
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'Your DNA, Your Say': global survey gathering attitudes toward genomics : design, delivery and methods
- 2018
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In: Personalized Medicine. - : Future Medicine Ltd. - 1741-0541 .- 1744-828X. ; 15:4, s. 311-318
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Journal article (peer-reviewed)abstract
- Our international study, 'Your DNA, Your Say', uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics. In order to understand the significance of a genomic result, researchers and clinicians alike use external databases containing DNA and medical information from thousands of people. We ask how publics would like their 'anonymous' data to be used (or not to be used) and whether they are concerned by the potential risks of reidentification; the results will be used to inform policy.
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| 12. |
- Milne, Richard, et al.
(author)
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Demonstrating trustworthiness when collecting and sharing genomic data : public views across 22 countries
- 2021
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 13:1
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Journal article (peer-reviewed)abstract
- BackgroundPublic trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.MethodsWe analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.ResultsProviding transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.ConclusionsOur findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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| 13. |
- Milne, Richard, et al.
(author)
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Trust in genomic data sharing among members of the general public in the UK, USA, Canada and Australia
- 2019
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 138:11-12, s. 1237-1246
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Journal article (peer-reviewed)abstract
- Trust may be important in shaping public attitudes to genetics and intentions to participate in genomics research and big data initiatives. As such, we examined trust in data sharing among the general public. A cross-sectional online survey collected responses from representative publics in the USA, Canada, UK and Australia (n = 8967). Participants were most likely to trust their medical doctor and less likely to trust other entities named. Company researchers were least likely to be trusted. Low, Variable and High Trust classes were defined using latent class analysis. Members of the High Trust class were more likely to be under 50 years, male, with children, hold religious beliefs, have personal experience of genetics and be from the USA. They were most likely to be willing to donate their genomic and health data for clinical and research uses. The Low Trust class were less reassured than other respondents by laws preventing exploitation of donated information. Variation in trust, its relation to areas of concern about the use of genomic data and potential of legislation are considered. These findings have relevance for efforts to expand genomic medicine and data sharing beyond those with personal experience of genetics or research participants.
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| 14. |
- Mullin, Lauren Gayle, 1984-
(author)
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Advances in Mass Spectrometry for the Analysis of Emerging Persistent Organic Pollutants
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Mass spectrometry (MS) is a technique widely implemented for the measurement of environmental pollutants. A critical tool for the analysis of persistent organic pollutants (POPs) over several decades, MS as coupled with liquid and gas chromatography (LC and GC) techniques enables the analysis of emerging POPs. The aim of this thesis was to investigate the use of alternative MS-based techniques to assist specific analytical challenges including separation of stereoisomers using supercritical fluid chromatography (SFC), reduced ionization competition with appropriate mobile phase additives, and applied rotationally averaged collision-cross section (CCS) of ions via ion mobility measurements of emerging POPs.Chromatographic efficiency improvements for the brominated flame retardant, hexabromocyclododecane (HBCDD), were implemented through the development of two supercritical fluid chromatography (SFC) methods. Based on the inherent qualities of supercritical fluids, separation of both predominant diastereomers and respective enantiomers was performed in a shorter time with wider chromatographic resolution using SFC than existing LC methods.Turning next to MS ionization considerations, the emerging perfluoroalkyl substance hexafluoropropylene oxide-dimer acid (HFPO-DA) was investigated. Following a survey of analytical methodologies for HFPO-DA, the challenge of extreme dimer formation, in-source fragmentation and very low [M-H]- production was described. Method development using alternative mobile phase additives in currently used LC-MS acquisition techniques was deployed.Finally, ion mobility spectrometry (IMS) was implemented in a non-targeted acquisition study of indoor dust samples. This study used IMS coupled with quadrupole time-of-flight MS to identify a wide range of contaminant classes, including emerging POPs. Identification confidence is a challenge currently facing non-targeted studies, and the use of prediction mechanisms of analyte IMS gas-phase separations was explored.Through applying diverse alternative techniques, increased method performance was explored for emerging POPs analyses.
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