Hypoxia Promotes Immune Evasion by Triggering β-glucan Masking on the Candida albicans Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling

We are very grateful to the members of our Iain Fraser Cytometry Centre and Microscopy and Histology Core Facility for their superb help, advice and support. We also thank our generous colleagues in the Candida community, and in particular Ana Traven, Jan Quinn, Guanghua Huang, Suzanne Noble, Donna MacCallum, Liz Johnson, Karl Kuchler, Patrick van Dijck, Rich Calderone and Malcolm Whiteway for providing strains used in this study. This work was funded by grants from the UK Medical Research Council [www.mrc.ac.uk], to AJPB, NARG, LPE, MN (MR/M026663/1), and by PhD studentships from the University of Aberdeen to AP, DL. The work was also supported by the Wellcome Trust [www.wellcome.ac.uk], NARG, GDB, AJPB (097377) and GDB (102705); and by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion

Data Availability The authors declare that the data supporting the findings of this study are available within the paper (and its supplementary information files). Acknowledgements We are grateful to Raif Yuecel, Linda Duncan, Kimberley Sim and Ailsa Laird in the Iain Fraser Cytometry Centre, and to Kevin MacKenzie, Debbie Wilkinson, Gillian Milne and Lucy Wight in our Microscopy and Histology Core Facility for their superb support. We thank Katja Schafer and Angela Lopez for help with the design of primers and for providing CRISPR-Cas9 protocols for mutant construction. We also thank our colleagues in the Candida community, and in particular Jan Quinn, Guanghua Huang, Suzanne Noble, Karl Kuchler, Patrick van Dijck, Rich Calderone and Malcolm Whiteway for providing strains used in this study. This work was funded by a programme grant from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1], and by PhD studentships from the University of Aberdeen to AP, DL. The work was also supported by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen [MR/N006364/1], by the European Commission [FunHoMic: H2020-MSCA-ITN-2018-812969], and by the Wellcome Trust via Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards [www.wellcome.ac.uk: 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

High-Resolution Ice Cores from US ITASE (West Antarctica): Development and Validation of Chronologies and Determination of Precision and Accuracy

Shallow ice cores were obtained from widely distributed sites across the West Antarctic ice sheet, as part of the United States portion of the International Trans-Antarctic Scientific Expedition (US ITASE) program. The US ITASE cores have been dated by annual-layer counting, primarily through the identification of summer peaks in non-sea-salt sulfate (nssSO(4)(2-)) concentration. Absolute dating accuracy of better than 2 years and relative dating accuracy better than 1 year is demonstrated by the identification of multiple volcanic marker horizons in each of the cores, Tambora, Indonesia (1815), being the most prominent. Independent validation is provided by the tracing of isochronal layers from site to site using high-frequency ice-penetrating radar observations, and by the timing of mid-winter warming events in stable-isotope ratios, which demonstrate significantly better than 1 year accuracy in the last 20 years. Dating precision to 1 month is demonstrated by the occurrence of summer nitrate peaks and stable-isotope ratios in phase with nssSO(4)(2-), and winter-time sea-salt peaks out of phase, with phase variation of \u3c 1 month. Dating precision and accuracy are uniform with depth, for at least the last 100 years

Impact of changes at the Candida albicans cell surface upon immunogenicity and colonisation in the gastrointestinal tract

Acknowledgements This work was supported by a programme grant from the UK Medical Research Council (MR/M026663/1; MR/M026663/2) and by the Medical Research Council Centre for Medical Mycology (MR/N006364/1; MR/N006364/2). NARG acknowledges Wellcome support for a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z; 215599/Z/19/Z) and Strategic Awards (097377/Z11/Z). LR, SHD and AWW received core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. MGN was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research.Peer reviewedPublisher PD

Glucose-enhanced oxidative stress resistance-A protective anticipatory response that enhances the fitness of Candida albicans during systemic infection

Acknowledgments We thank Carol Munro for her generosity in providing the plasmids for barcoding C. albicans, and Victoria Brown, Gerry Fink, Bill Fonzi, Guanghua Huang, Joachim Morschauser, Suzanne Noble, Jesus Pla, Patrick Van Dijck, Reinhard Würzner and Oscar Zaragoza for providing strains. We thank our colleagues in the MRC Centre for Medical Mycology and the Aberdeen Fungal Group for insightful discussions. We are grateful to the following Research Facilities for their advice and support: the Centre for Genome Enabled Biology at the University of Aberdeen, and the Sequencing Facility at the University of Exeter for help with the barcode sequencing. Funding: This work was funded by a programme grant to AJPB, NARG, LEP and MGN from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1, MR/M026663/2] and by PhD studentships to DEL from the Universities of Aberdeen and Exeter. The work was also supported by the Medical Research Council Centre for Medical Mycology (MR/N006364/1, MR/N006364/2). NARG acknowledges Wellcome support of Senior Investigator (101873/Z/13/Z, 224323/Z/21/Z) and Collaborative (200208/A/15/Z, 215599/Z/19/Z) Awards. MGN was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research. The barcode sequencing performed by the Exeter Sequencing Facility utilised equipment funded by Wellcome (218247/Z/19/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

A CO2 sensing module modulates β-1,3-glucan exposure in Candida albicans.

This work was funded by a program grant to A.J.P.B., N.A.R.G., L.P.E., and M.G.N. from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1, MR/M026663/2]. The work was also supported by the Medical Research Council Centre for Medical Mycology [MR/N006364/1, MR/N006364/2], by a grant to C.d.E. from the European Commission [FunHoMic: H2020-MSCA-ITN-2018–812969], and by the Wellcome Trust via Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards [www.wellcome.ac.uk: 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208, 217163, 224323]. Work in the d’Enfert laboratory was supported by grants from the Agence Nationale de Recherche (ANR-10-LABX-62-IBEID) and the Swiss National Science Foundation (Sinergia CRSII5_173863/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Asymmetric rolling of interstitial-free steel using differential roll diameters. Part II : microstructure and annealing effects

The effects of annealing on the microstructure, texture, tensile properties, and R value evolution of an IF steel sheet after room-temperature symmetric and asymmetric rolling were examined. Simulations were carried out to obtain R values from the experimental textures using the viscoplastic self-consistent polycrystal plasticity model. The investigation revealed the variations in the textures due to annealing and symmetric/asymmetric rolling and showed that the R values correlate strongly with the evolution of the texture. An optimum heat treatment for the balance of strength, ductility, and deep drawability was found to be at 873 K (600 _C) for 30 minutes

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Claudin-1 Is a p63 Target Gene with a Crucial Role in Epithelial Development

The epidermis of the skin is a self-renewing, stratified epithelium that functions as the interface between the human body and the outer environment, and acts as a barrier to water loss. Components of intercellular junctions, such as Claudins, are critical to maintain tissue integrity and water retention. p63 is a transcription factor essential for proliferation of stem cells and for stratification in epithelia, mutated in human hereditary syndromes characterized by ectodermal dysplasia. Both p63 and Claudin-1 null mice die within few hours from birth due to dehydration from severe skin abnormalities. These observations suggested the possibility that these two genes might be linked in one regulatory pathway with p63 possibly regulating Claudin-1 expression. Here we show that silencing of ΔNp63 in primary mouse keratinocytes results in a marked down-regulation of Claudin-1 expression (−80%). ΔNp63α binds in vivo to the Claudin-1 promoter and activates both the endogenous Claudin-1 gene and a reporter vector containing a –1.4 Kb promoter fragment of the Claudin-1 gene. Accordingly, Claudin-1 expression was absent in the skin of E15.5 p63 null mice and natural p63 mutant proteins, specifically those found in Ankyloblepharon–Ectodermal dysplasia–Clefting (AEC) patients, were indeed altered in their capacity to regulate Claudin-1 transcription. This correlates with deficient Claudin-1 expression in the epidermis of an AEC patient carrying the I537T p63 mutation. Notably, AEC patients display skin fragility similar to what observed in the epidermis of Claudin-1 and p63 null mice. These findings reinforce the hypothesis that these two genes might be linked in a common regulatory pathway and that Claudin-1 may is an important p63 target gene involved in the pathogenesis of ectodermal dysplasias

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy