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"Scott, Ian"
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Role of CYP9E2 and a long non-coding RNA gene in resistance to a spinosad insecticide in the Colorado potato beetle, Leptinotarsa decemlineata
Spinosads are insecticides used to control insect pests, especially in organic farming where limited tools for pest management exist. However, resistance has developed to spinosads in economically important pests, including Colorado potato beetle (CPB), Leptinotarsa decemlineata . In this study, we used bioassays to determine spinosad sensitivity of two field populations of CPB, one from an organic farm exposed exclusively to spinosad and one from a conventional farm exposed to a variety of insecticides, and a reference insecticide naïve population. We found the field populations exhibited significant levels of resistance compared with the sensitive population. Then, we compared transcriptome profiles between the two field populations to identify genes associated primarily with spinosad resistance and found a cytochrome P450, CYP9E2 , and a long non-coding RNA gene, lncRNA-2 , were upregulated in the exclusively spinosad-exposed population. Knock-down of these two genes simultaneously in beetles of the spinosad-exposed population using RNA interference (RNAi) resulted in a significant increase in mortality when gene knock-down was followed by spinosad exposure, whereas single knock-downs of each gene produced smaller effects. In addition, knock-down of the lncRNA-2 gene individually resulted in significant reduction in CYP9E2 transcripts. Finally, in silico analysis using an RNA-RNA interaction tool revealed that CYP9E2 mRNA contains multiple binding sites for the lncRNA-2 transcript. Our results imply that CYP9E2 and lncRNA-2 jointly contribute to spinosad resistance in CPB, and lncRNA-2 is involved in regulation of CYP9E2 expression. These results provide evidence that metabolic resistance, driven by overexpression of CYP and lncRNA genes, contributes to spinosad resistance in CPB.
Journal Article
Access all areas : stories from a hard rock life
Musician Scott Ian shares zany, bizarre, funny, and captivating stories from his more than thirty years in the hard rock scene. -- Adapted from book jacket.
Book
Overexpression of a cytochrome P450 and a UDP-glycosyltransferase is associated with imidacloprid resistance in the Colorado potato beetle, Leptinotarsa decemlineata
Current control of insect pests relies on chemical insecticides, however, insecticide resistance development by pests is a growing concern in pest management. The main mechanisms for insecticide resistance typically involve elevated activity of detoxifying enzymes and xenobiotic transporters that break-down and excrete insecticide molecules. In this study, we investigated the molecular mechanisms of imidacloprid resistance in the Colorado potato beetle,
Leptinotarsa decemlineata
(Say) (Coleoptera: Chrysomelidae), an insect pest notorious for its capacity to develop insecticide resistance rapidly. We compared the transcriptome profiles of imidacloprid-resistant and sensitive beetle strains and identified 102 differentially expressed transcripts encoding detoxifying enzymes and xenobiotic transporters. Of these, 74 were up-regulated and 28 were down-regulated in the resistant strain. We then used RNA interference to knock down the transcript levels of seven up-regulated genes in the resistant beetles. Ingestion of double-stranded RNA successfully knocked down the expression of the genes for three cytochrome P450s (
CYP6BQ15
,
CYP4Q3
and
CYP4Q7
), one ATP binding cassette (ABC) transporter (
ABC-G
), one esterase (
EST1
), and two UDP-glycosyltransferases (
UGT1
and
UGT2
). Further, we demonstrated that silencing of
CYP4Q3
and U
GT2
significantly increased susceptibility of resistant beetles to imidacloprid, indicating that overexpression of these two genes contributes to imidacloprid resistance in this resistant strain.
Journal Article
Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?
Two different Janus kinase (JAK) inhibitors—baricitinib and tofacitinib—are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs). These show some evidence of increased risks of pulmonary thrombosis, though not pulmonary embolism or venous thrombosis. Observational studies suggest in the general population and non-RA controls there are one to four thromboembolic events per 1000 patient years. In RA, thromboembolic risks increase to three to seven per 1000 patient years. The impact of biologics and disease-modifying anti-rheumatic drugs (DMARDs) on disease risk appears minimal, and the number of thromboembolic events is between four and eight per 1000 patient years. In the short term, full details of thromboembolic events in trials of JAK inhibitors need to be published. As the numbers of thromboembolic events will be small and patients enrolled in trials are not representative of all RA patients who may receive JAK inhibitors, this information is unlikely to provide definitive answers. Consequently, in the longer term, large observational studies are needed to accurately quantify thromboembolic risks attributable to JAK inhibitors and other drugs used to treat RA, and differentiate these from risks attributable to RA itself and its comorbidities.
Journal Article
Exploring stakeholder attitudes towards AI in clinical practice
ObjectivesDifferent stakeholders may hold varying attitudes towards artificial intelligence (AI) applications in healthcare, which may constrain their acceptance if AI developers fail to take them into account. We set out to ascertain evidence of the attitudes of clinicians, consumers, managers, researchers, regulators and industry towards AI applications in healthcare.MethodsWe undertook an exploratory analysis of articles whose titles or abstracts contained the terms ‘artificial intelligence’ or ‘AI’ and ‘medical’ or ‘healthcare’ and ‘attitudes’, ‘perceptions’, ‘opinions’, ‘views’, ‘expectations’. Using a snowballing strategy, we searched PubMed and Google Scholar for articles published 1 January 2010 through 31 May 2021. We selected articles relating to non-robotic clinician-facing AI applications used to support healthcare-related tasks or decision-making.ResultsAcross 27 studies, attitudes towards AI applications in healthcare, in general, were positive, more so for those with direct experience of AI, but provided certain safeguards were met. AI applications which automated data interpretation and synthesis were regarded more favourably by clinicians and consumers than those that directly influenced clinical decisions or potentially impacted clinician–patient relationships. Privacy breaches and personal liability for AI-related error worried clinicians, while loss of clinician oversight and inability to fully share in decision-making worried consumers. Both clinicians and consumers wanted AI-generated advice to be trustworthy, while industry groups emphasised AI benefits and wanted more data, funding and regulatory certainty.DiscussionCertain expectations of AI applications were common to many stakeholder groups from which a set of dependencies can be defined.ConclusionStakeholders differ in some but not all of their attitudes towards AI. Those developing and implementing applications should consider policies and processes that bridge attitudinal disconnects between different stakeholders.
Journal Article
Shaping cities for health: complexity and the planning of urban environments in the 21st century
[...]consideration of the value-laden nature of policy interventions and the creation of forums to debate the moral and ethical dimensions of different approaches to urban health and city environments are essential. [...]attention to health inequalities within urban areas should be a key focus of planning the urban environment.
Journal Article