Dissection of the Candida albicans class I chitin synthase promoters

We acknowledge financial support from the Biotechnology and Biological Sciences Research Council (10161), Medical Research Council (New Investigator Award to C.A.M.), the European Community FUNGALWALL and SIGNALPATH initiatives and the Wellcome Trust.Peer reviewedPublisher PD

Cell wall stress induces alternative fungal cytokinesis and septation strategies

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Cell wall protection by the Candida albicans class I chitin synthases

Open Access funded by Medical Research Council Acknowledgments We thank Kevin Mackenzie in the Microscopy and Histology Core Facility (Institute of Medical Sciences, University of Aberdeen), and Donna MacCallum for helpful statistical advice. This work was supported by grants from the Wellcome Trust (0868827 and 080088) including a Wellcome Trust Strategic Award (097377) and an Investigator Award to NG (101873), an MRC New Investigator Award to ML (MR/J008230/1) and a PhD scholarship awarded to KP from the Ministry of Sciences and Technology and Chiang Mai University, Thailand. Author contributions are as follows: KP constructed strains, performed the majority of the experiments, analyzed the data and contributed to the preparation of the manuscript. JA produced Fig. S1 using the data from the phosphoproteomic analysis conducted by SP and AB. NG conceived and designed experiments, analyzed data and commented on drafts of the manuscript. ML constructed strains, conceived, designed and performed experiments, analyzed data and wrote the manuscript.Peer reviewedPublisher PD

Intrauterine exposure to preeclampsia does not impair vascular health in children

Background and objectives: Preeclampsia is a serious multisystem blood pressure disorder during pregnancy that is associated with increased long-term risk of cardiovascular disease to the mother and offspring. We investigated the vascular health of children exposed to intrauterine preeclampsia. Materials and methods: This was a cross-sectional study of offspring in a prospective cohort of women with complications during pregnancy. Children aged between 2 and 5 years [median age 4.7 (2.8, 5.1) years] exposed to intrauterine preeclampsia (n = 26) or normotensive controls (n = 34), were recruited between July 2020 and April 2021. Vascular health was assessed by measuring aortic intima-media thickness and pulse wave velocity. Univariate generalized linear regression models were used to explore associations between vascular measurements and explanatory variables. Results: Children exposed to preeclampsia had a lower body mass index at assessment (15.5 vs. 16.2 kg/m2, p = 0.04), birth weight (2.90 vs. 3.34 kg, p = 0.004), gestational age at birth (37.5 vs. 39.4 weeks, p < 0.001) and higher frequency of preterm birth (27% vs. 6%, p = 0.02). There were no differences in vascular health between children exposed to preeclampsia vs. controls (mean aortic intima-media thickness 0.575 mm vs. 0.563 mm, p = 0.51, pulse wave velocity 4.09 vs. 4.18 m/s, p = 0.54) and there were no significant associations in univariate analyses. Conclusions: There were no major adverse differences in vascular health which contrasts with existing studies. This suggests exposure to intrauterine preeclampsia may result in a less severe cardiovascular phenotype in young children. While reassuring, longitudinal studies are required to determine if and when exposure to intrauterine preeclampsia affects vascular health in children

Aortic intima media thickness in children and adolescents with type 1 diabetes : A systematic review

Aims Greater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta-analysis compared aIMT in youth with type 1 diabetes and healthy controls. Methods A systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta-analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection. Results Meta-analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure. Conclusions Type 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559)

Recognition and blocking of innate immunity cells by Candida albicans chitin

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Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation

Funding: JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans

Funding Information: We thank Carol Munro for helpful discussions during the research, Raif Yuecel, Elizabeth Adams, Linda Duncan, Barry Lewis and Kimberley Sim for assistance with FACS at Aberdeen Cytometry Core Facility, and Yang Meng and Dominique Sanglard with help in construction of mutants. We also thank Linghuo Jiang, David Soll, Jes?s Pla, Jan Quinn, Terry Roemer and Joseph Heitman for mutant strains. N.A.R.G. acknowledges support from the Wellcome Trust [Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z and 215599/Z/19/Z) and Strategic (097377/Z11/Z) Awards] and from the Medical Research Council Centre for Medical Mycology (MR/N006364/2). This work was also supported by a Marie Curie FP7-PEOPLE-ITN-2008 grant (MB004 RGE0655 ARIADNE) and by a Wellcome Trust project grant (086827). Open access funding provided by University of Exeter. Deposited in PMC for immediate release.Peer reviewedPublisher PD

The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles

NARG thanks The Wellcome Trust (080088, 086827, 075470, 099215 & 097377) and MRC Centre for Medical Mycology (MR/N006364/1) and acknowledges financial support from Gilead Sciences for a studentship and grant IX-EU-131-0262. Dr. Linda Soo Hoo and Tark Bunch of Gilead provided expert technical assistance in liposomal sample preparations and GF provided gold labelled test articles. JAM is funded in part from a research grant from Gilead Sciences Inc. ML was supported by the MRC (MR/J008230/1). AC was supported in part by 5R01HL059842, 5R01AI033774, 5R37AI033142, and 5R01AI052733. We thank Debbie Wilkinson and Kevin McKenzie at the Imaging Core Facility at the University of Aberdeen for expert assistance with TEM.Peer reviewedPublisher PD