Impact of secreted glucanases upon the cell surface and fitness of Candida albicans during colonisation and infection.

Acknowledgements We thank Raif Yuecel and Attila Bebes in the Exeter Centre for Cytomics for their help with the cytometry, and Annie Phillips-Brookes, Jamie Harvey and the BSU staff for their support with the animal experimentation. We are grateful to Karen Moore, Paul O’Neill and Jemima Onime in the University of Exeter Sequencing Facility University of Exeter Sequencing Facility for their help with the barcode sequencing. We also thank Paulina Cherek in the Bioimaging Facility in Exeter Biosciences for her help with the transmission electron microscopy, and Darren Thomson in the MRC Centre for Medical Mycology for his support for our the DeltaVision imaging. 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 reviewe

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

Constraining mid to late Holocene relative sea level change in the southern equatorial Pacific Ocean relative to the Society Islands, French Polynesia

Precisely quantifying the current climate-related sea level change requires accurate knowledge of long-term geological processes known as Glacial Isostatic Adjustments (GIA). Although the major postglacial melting phase is likely to have ended ∼6–4 ka BP (before present), GIA is still significantly affecting the present-day vertical position of the mean sea surface and the sea bottom. Here we present empirical rsl (relative sea level) data based on U/Th dated fossil corals from reef platforms of the Society Islands, French Polynesia, together with the corresponding GIA-modeling. Fossil coral data constrain the timing and amplitude of rsl variations after the Holocene sea level maximum (HSLM). Upon correction for isostatic island subsidence, we find that local rsl was at least ∼1.5 ± 0.4 m higher than present at ∼5.4 ka. Later, minor amplitude variations occurred until ∼2 ka, when the rsl started dropping to its present position with a rate of ∼0.4 mm/yr. The data match with predicted rsl curves based on global ice-sheet chronologies confirming the role of GIA-induced ocean siphoning effect throughout the mid to late Holocene. A long lasting Late Holocene highstand superimposed with second-order amplitudinal fluctuations as seen from our data suggest that the theoretical predicted timing of rsl change can still be refined pending future calibration

Isolated oculomotor nerve palsy secondary to acute sinusitis.

Sinusitis is a common condition, but only very rarely accompanied by isolated cranial nerve palsies. We describe a case of a 64-year-old male with a two-day history of left-sided ptosis associated with one week of nasal congestion and frontal sinus pain. Examination revealed ptosis with left pupil mydriasis. Uncontrasted computed tomography and angiography of the head demonstrated neither intracranial vascular abnormalities nor acute lesions; however, it did show mucosal thickening in the left frontal sinus, ethmoid air cells and left maxillary sinus, indicating potential obstruction of the left ostiomeatal complex. The sinusitis was treated with intranasal steroids, xylomethazoline and nasal douching. The patient reported resolution of all symptoms, including left ptosis, within one week of therapy. This rare case of sinusitis causing ptosis is presented due to its infrequent nature, such that awareness of the differential diagnosis of cranial nerve palsy and complications of sinusitis may be improved

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

The immunogenicity of Candida albicans cells is influenced by changes in the exposure of microbe-associated molecular patterns (MAMPs) on the fungal cell surface. Previously, the degree of exposure on the C. albicans cell surface of the immunoinflammatory MAMP β-(1,3)-glucan was shown to correlate inversely with colonisation levels in the gastrointestinal (GI) tract. This is important because life-threatening systemic candidiasis in critically ill patients often arises from translocation of C. albicans strains present in the patient's GI tract. Therefore, using a murine model, we have examined the impact of gut-related factors upon β-glucan exposure and colonisation levels in the GI tract. The degree of β-glucan exposure was examined by imaging flow cytometry of C. albicans cells taken directly from GI compartments, and compared with colonisation levels. Fungal β-glucan exposure was lower in the cecum than the small intestine, and fungal burdens were correspondingly higher in the cecum. This inverse correlation did not hold for the large intestine. The gut fermentation acid, lactate, triggers β-glucan masking in vitro, leading to attenuated anti-Candida immune responses. Additional fermentation acids are present in the GI tract, including acetate, propionate, and butyrate. We show that these acids also influence β-glucan exposure on C. albicans cells in vitro and, like lactate, they influence β-glucan exposure via Gpr1/Gpa2-mediated signalling. Significantly, C. albicans gpr1Δ gpa2Δ cells displayed elevated β-glucan exposure in the large intestine and a corresponding decrease in fungal burden, consistent with the idea that Gpr1/Gpa2-mediated β-glucan masking influences colonisation of this GI compartment. Finally, extracts from the murine gut and culture supernatants from the mannan grazing gut anaerobe Bacteroides thetaiotaomicron promote β-glucan exposure at the C. albicans cell surface. Therefore, the local microbiota influences β-glucan exposure levels directly (via mannan grazing) and indirectly (via fermentation acids), whilst β-glucan masking appears to promote C. albicans colonisation of the murine large intestine

House dust mite induced lung inflammation does not alter circulating vitamin D levels

© 2014 Chen et al. Low circulating levels of 25-hydroxyvitamin D [25(OH)D] are associated with chronic lung diseases such as asthma. However, it is unclear whether vitamin D is involved in disease pathogenesis or is modified by the inflammation associated with the disease process. We hypothesized that allergic inflammation decreases the level of circulating 25(OH)D and tested this using a mice model of house dust mite (HDM) induced allergic airway inflammation. Cellular influx was measured in bronchoalvelar lavage (BAL) fluid, and allergic sensitization and 25(OH)D levels were measured in serum. Exposure to HDM caused a robust inflammatory response in the lung that was enhanced by prior influenza infection. These responses were not associated with any change in circulating levels of 25(OH)D. These data suggest that alterations in circulating 25(OH)D levels induced by Th-2 driven inflammation are unlikely to explain the cross-sectional epidemiological association between vitamin D deficiency and asthma