Sfp1 and Rtg3 reciprocally modulate carbon source-conditional stress adaptation in the pathogenic yeast Candida albicans

Acknowledgements We thank Aaron Mitchell, Dominique Sanglard and Suzanne Noble for their generosity in providing mutant collections, and Linghuo Jiang for generously providing strains. We also thank Susan Budge for her support and excellent technical assistance. We also thank the qPCR Facility in the Institute of Medical Sciences, and particularly Fiona Saunders for her great advice and help. SLK was supported by a PhD scholarship from the University of Aberdeen. AJPB was supported by the UK Biotechnology and Biological Research Council (BB/F00513X/1; BB/K017365/1), by the European Research Council (STRIFE Advanced Grant; ERC-2009-AdG-249793), and by the UK Medical Research Council (MR/M026663/1). AJPB and CAM were also supported by the Wellcome Trust (088858; 097377), and by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

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

Implementation and reporting of causal mediation analysis in 2015: a systematic review in epidemiological studies

BACKGROUND: Causal mediation analysis is often used to understand the impact of variables along the causal pathway of an occurrence relation. How well studies apply and report the elements of causal mediation analysis remains unknown. METHODS: We systematically reviewed epidemiological studies published in 2015 that employed causal mediation analysis to estimate direct and indirect effects of observed associations between an exposure on an outcome. We identified potential epidemiological studies through conducting a citation search within Web of Science and a keyword search within PubMed. Two reviewers independently screened studies for eligibility. For eligible studies, one reviewer performed data extraction, and a senior epidemiologist confirmed the extracted information. Empirical application and methodological details of the technique were extracted and summarized. RESULTS: Thirteen studies were eligible for data extraction. While the majority of studies reported and identified the effects of measures, most studies lacked sufficient details on the extent to which identifiability assumptions were satisfied. Although most studies addressed issues of unmeasured confounders either from empirical approaches or sensitivity analyses, the majority did not examine the potential bias arising from the measurement error of the mediator. Some studies allowed for exposure-mediator interaction and only a few presented results from models both with and without interactions. Power calculations were scarce. CONCLUSIONS: Reporting of causal mediation analysis is varied and suboptimal. Given that the application of causal mediation analysis will likely continue to increase, developing standards of reporting of causal mediation analysis in epidemiological research would be prudent

Empowering young people who experienced domestic violence and abuse: The development of a group therapy intervention

This article describes the development of a group-based therapeutic intervention for young people (YP) who have lived with domestic violence and abuse. The intervention was informed by interviews with 107 YP, focused on their experiences of coping, resilience and agency. The intervention draws on resources from systemic, creative and narrative approaches to group work, and aims to facilitate YP's expression of distress in a way that recognizes that it is embodied, contextual and relational. The intervention also explores YP's existing strategies for coping and maintaining a sense of agency, and works to harness, enhance and further develop those skills. We report on the pilot of this intervention, and its development and application across four European countries (the United Kingdom, Greece, Italy and Spain). We outline the goals, strengths and limitations of this group intervention, as well as the main challenges, hindrances and ethical dilemmas experienced by the research and intervention team. Implications for therapeutic practice and training are addressed

Autotransporters but not pAA are critical for rabbit colonization by Shiga toxin-producing Escherichia coli O104:H4

The outbreak of diarrhea and hemolytic uremic syndrome that occurred in Germany in 2011 was caused by a Shiga toxin-producing enteroaggregative Escherichia coli (EAEC) strain. The strain was classified as EAEC due to the presence of a plasmid (pAA) that mediates a characteristic pattern of aggregative adherence on cultured cells, the defining feature of EAEC that has classically been associated with virulence. Here, we describe an infant rabbit-based model of intestinal colonization and diarrhea caused by the outbreak strain, which we use to decipher the factors that mediate the pathogen’s virulence. Shiga toxin is the key factor required for diarrhea. Unexpectedly, we observe that pAA is dispensable for intestinal colonization and development of intestinal pathology. Instead, chromosome-encoded autotransporters are critical for robust colonization and diarrheal disease in this model. Our findings suggest that conventional wisdom linking aggregative adherence to EAEC intestinal colonization is false for at least a subset of strains

Part of the Family:Children’s Experiences with Their Companion Animals in the Context of Domestic Violence and Abuse

Purpose: Children who experience Domestic Violence and Abuse (DVA) draw on a range of strategies to manage the complex dynamics of family life. This article explored children’s experiences of their relationships with pets and other animals, considering how children understood these relationships.Methods: This qualitative study is based on semi-structured interviews and visual methods-based research with 22 children (aged 9–17), drawn from a larger study on how children cope with DVA. The data were analysed using reflexive thematic analysis.Findings: Five themes are discussed: Part of the family explores how children positioned animals as relational beings who occupied an important place in their lives; caring for animals considers the reciprocal caring relationship children described; listening and support details how children interacted with animals to allow themselves to feel more heard and supported; in the theme control and abuse, we consider children’s experiences of perpetrators’ use of companion animals as part of a pattern of abuse and control; and in disruption, uncertainty and loss, we discuss how children feel and relate to their animals when leaving situations of domestic abuse.Conclusions: The implications of our analysis are considered in relation to providing support for children impacted by domestic abuse, and the importance of ensuring companion animals are provided for in housing policy and planning for domestic abuse survivors

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donorA multicenter analysis

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Effective stress regime around a jacked steel pile during installation ageing and load testing in chalk

This paper reports experiments with 102 mm diameter closed-ended instrumented Imperial College piles (ICPs) jacked into low- to medium-density chalk at a well-characterized UK test site. The “ICP” instruments allowed the effective stress regime surrounding the pile shaft to be tracked during pile installation, equalization periods of up to 2.5 months, and load testing under static tension and one-way axial cyclic loading. Installation resistances are shown to be dominated by the pile tip loads. Low installation shaft stresses and radial effective stresses were measured that correlated with local cone penetration test (CPT) tip resistances. Marked shaft total stress reductions and steep stress gradients are demonstrated in the vicinity of the pile tip. The local interface shaft effective stress paths developed during static and cyclic loading displayed trends that resemble those seen in comparable tests in sands. Shaft failure followed the Coulomb law and constrained interface dilation was apparent as the pile experienced drained loading to failure, although with a lesser degree of radial expansion than with sands. Radial effective stresses were also found to fall with time after installation, leading to reductions in shaft capacity as proven by subsequent static tension testing. The jacked, closed-ended, piles’ ageing trends contrast sharply with those found with open piles driven at the same site, indicating that ageing is affected by pile tip geometry and (or) installation method

Acetyl Cholinesterase Inhibitors and Cell-Derived Peripheral Inflammatory Cytokines in Early Stages of Alzheimer's Disease

Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response.Funding was received from a program co-financed by the European Social Fund and the Greek State (GSRT LS5-3808)info:eu-repo/semantics/publishedVersio