Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen-Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs

Data availability. The RNA sequencing dataset is available at EBI (www.ebi.ac.uk/arrayexpress/) under accession number E-MTAB-5990. Other data that support the findings of this study are available from the corresponding author upon reasonable request. ACKNOWLEDGMENTS We thank Debbie Smith for constructing the strains JC41 and JC310, Arnab Pradhan for help with DHE control experiments, and our colleagues in the Aberdeen Fungal Group and Newcastle Yeast Group for insightful discussions. We are also grateful to Mike Gustin for his advice. We are grateful to the Centre for Genome Enabled Biology and Medicine, Aberdeen Proteomics, the Iain Fraser Cytometry Centre, the Microscopy and Histology Facility, and the qPCR facility at the University of Aberdeen for their help, advice, and support. This work was funded by the UK Biotechnology and Biological Research Council (http://www.bbsrc.ac.uk) (grants BB/K017365/1 and BB/F00513X/1 to A.J.P.B. and grant BB/K016393/1 to J.Q.). This work was also supported by the European Research Council (http://erc.europa.eu/) (STRIFE advanced grant C-2009-AdG-249793 to A.J.P.B.), the UK Medical Research Council (http://www.mrc.ac.uk) (grant MR/M026663/1 to A.J.P.B. and grant MR/M000923/1 to P.S.S.), the Wellcome Trust (https://wellcome.ac.uk) (grant 097377 to A.J.P.B. and J.Q.), the MRC Centre for Medical Mycology and the University of Aberdeen (grant MR/M026663/1 to A.J.P.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The Evolutionary Rewiring of Ubiquitination Targets Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast \u3ci\u3eCandida albicans\u3c/i\u3e

Microbes must assimilate carbon to grow and colonize their niches. Transcript profiling has suggested that Candida albicans, a major pathogen of humans, regulates its carbon assimilation in an analogous fashion to the model yeast Saccharomyces cerevisiae, repressing metabolic pathways required for the use of alterative nonpreferred carbon sources when sugars are available. However, we show that there is significant dislocation between the proteome and transcriptome in C. albicans. Glucose triggers the degradation of the ICL1 and PCK1 transcripts in C. albicans, yet isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are stable and are retained. Indeed, numerous enzymes required for the assimilation of carboxylic and fatty acids are not degraded in response to glucose. However, when expressed in C. albicans, S. cerevisiae Icl1 (ScIcl1) is subjected to glucose-accelerated degradation, indicating that like S. cerevisiae, this pathogen has the molecular apparatus required to execute ubiquitin-dependent catabolite inactivation. C. albicans Icl1 (CaIcl1) lacks analogous ubiquitination sites and is stable under these conditions, but the addition of a ubiquitination site programs glucose-accelerated degradation of CaIcl1. Also, catabolite inactivation is slowed in C. albicans ubi4 cells. Ubiquitination sites are present in gluconeogenic and glyoxylate cycle enzymes from S. cerevisiae but absent from their C. albicans homologues. We conclude that evolutionary rewiring of ubiquitination targets has meant that following glucose exposure, C. albicans retains key metabolic functions, allowing it to continue to assimilate alternative carbon sources. This metabolic flexibility may be critical during infection, facilitating the rapid colonization of dynamic host niches containing complex arrays of nutrients

Infrastructural Speculations: Tactics for Designing and Interrogating Lifeworlds

This paper introduces “infrastructural speculations,” an orientation toward speculative design that considers the complex and long-lived relationships of technologies with broader systems, beyond moments of immediate invention and design. As modes of speculation are increasingly used to interrogate questions of broad societal concern, it is pertinent to develop an orientation that foregrounds the “lifeworld” of artifacts—the social, perceptual, and political environment in which they exist. While speculative designs often imply a lifeworld, infrastructural speculations place lifeworlds at the center of design concern, calling attention to the cultural, regulatory, environmental, and repair conditions that enable and surround particular future visions. By articulating connections and affinities between speculative design and infrastructure studies research, we contribute a set of design tactics for producing infrastructural speculations. These tactics help design researchers interrogate the complex and ongoing entanglements among technologies, institutions, practices, and systems of power when gauging the stakes of alternate lifeworlds

Protocol for the proactive or reactive telephone smoking cessation support (PORTSSS) trial

Background: Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts. Smoking cessation counselling provided via telephone can either be reactive (i.e. primarily involving the provision of evidence-based information), or proactive (i.e. primarily involving repeated, sequenced calls from and interaction with trained cessation counsellors). Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation, delivered through the National Health Service (NHS) Smoking Helpline is more effective or cost-effective than reactive support. It will also investigate whether or not providing nicotine replacement therapy (NRT), in addition to telephone counselling, has an adjunctive impact on smoking cessation rates and whether or not this is cost effective. Methods: This will be a parallel group, factorial design RCT, conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow. Participants will be smokers who call the helpline from any location in England and who wish to stop smoking. If 644 participants are recruited to four equally-sized trial groups (total sample size = 2576), the trial will have 90% power for detecting a treatment effect (Odds Ratio) of 1.5 for each of the two interventions: i) proactive versus reactive support and ii) the offer of NRT versus no offer. The primary outcome measure for the study is self-reported, prolonged abstinence from smoking for at least six months following an agreed quit date. A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline. Discussion: The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation. Trial Registration: (clinicaltrials.gov): NCT0077594

E-cigarette marketing in the UK: evidence from adult and youth surveys and policy compliance studies

Electronic cigarettes (e-cigarettes) are battery-powered devices that heat a liquid, usually containing nicotine, to allow users to inhale the vapour. The evidence so far suggests they are far less harmful than smoking and can help people to quit smoking. However, as e-cigarettes are a relatively new product and their long-term effects are unknown, they should not be used by people who have never smoked, particularly young people. In 2016 and 2017, regulations were introduced to help ensure that e-cigarette advertising is socially responsible. This means protecting young people, minimising conflation between e-cigarettes and tobacco, and preventing uptake of e-cigarettes amongst people who don’t smoke or use nicotine. The Tobacco and Related Products Regulations 2016 (TRPR) set rules on how e-cigarettes can be advertised and prohibited marketing in specific media channels. Subsequently, the UK Advertising Standards Authority (ASA), Committee of Advertising Practice (CAP) Code and Broadcast Committee of Advertising Practice (BCAP) Code, updated in 2017, set out further advertising regulations in CAP Code Rule 22 and BCAP Code Rule 33. The overall aim of this report was to assess compliance with and the impact of the current UK e-cigarette marketing regulations. The UK Government is obliged to review and deliver a report on the TRPR within five years of the legislation being enacted, by May 2021. This report will help to inform the Government’s review. This report brings together two complementary studies to provide a description of e-cigarette advertising spend, advertising content, compliance with advertising regulations, and reported noticing and appeal of e-cigarette marketing. Study A (by the Institute for Social Marketing & Health) consisted of an analysis of e-cigarette advertising expenditure in the UK in 2019 and a detailed content analysis of a sample of advertising taken from the same year. Study B consisted of an analysis of survey data from the International Tobacco Control Policy Evaluation Project (ITC Project), which measured reported noticing of e-cigarette marketing by young people (16 to 19-year-olds) between 2017 and 2019, and adults (aged 18 and older) between 2016 and 2018 in a broad range of marketing channels.Additional co-authors: James F Thrasher, Yoo Jin Cho, Catherine Cowell, Tim Coker, Sarah Bullock, Alizee Froguel, Jyotsna Vohr

E-cigarette marketing in the UK: evidence from adult and youth surveys and policy compliance studies

Electronic cigarettes (e-cigarettes) are battery-powered devices that heat a liquid, usually containing nicotine, to allow users to inhale the vapour. The evidence so far suggests they are far less harmful than smoking and can help people to quit smoking. However, as e-cigarettes are a relatively new product and their long-term effects are unknown, they should not be used by people who have never smoked, particularly young people. In 2016 and 2017, regulations were introduced to help ensure that e-cigarette advertising is socially responsible. This means protecting young people, minimising conflation between e-cigarettes and tobacco, and preventing uptake of e-cigarettes amongst people who don’t smoke or use nicotine. The Tobacco and Related Products Regulations 2016 (TRPR) set rules on how e-cigarettes can be advertised and prohibited marketing in specific media channels. Subsequently, the UK Advertising Standards Authority (ASA), Committee of Advertising Practice (CAP) Code and Broadcast Committee of Advertising Practice (BCAP) Code, updated in 2017, set out further advertising regulations in CAP Code Rule 22 and BCAP Code Rule 33. The overall aim of this report was to assess compliance with and the impact of the current UK e-cigarette marketing regulations. The UK Government is obliged to review and deliver a report on the TRPR within five years of the legislation being enacted, by May 2021. This report will help to inform the Government’s review. This report brings together two complementary studies to provide a description of e-cigarette advertising spend, advertising content, compliance with advertising regulations, and reported noticing and appeal of e-cigarette marketing. Study A (by the Institute for Social Marketing & Health) consisted of an analysis of e-cigarette advertising expenditure in the UK in 2019 and a detailed content analysis of a sample of advertising taken from the same year. Study B consisted of an analysis of survey data from the International Tobacco Control Policy Evaluation Project (ITC Project), which measured reported noticing of e-cigarette marketing by young people (16 to 19-year-olds) between 2017 and 2019, and adults (aged 18 and older) between 2016 and 2018 in a broad range of marketing channels

Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

Background: most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients' preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial.Methods: patients aged 60-74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared.Results: two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population.Conclusion: this study has demonstrated the difficulties involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors