Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Field Deployment of an Ambient Vibration-Based Scour Monitoring System at Baildon Bridge, UK

Scour, the loss of material around bridge foundations due to hydraulic action, is the main cause of bridge failures in the United Kingdom and in many other parts of the world. Various techniques have been used to monitor bridge scour, ranging from scuba divers using crude depth measuring instrumentation to high-tech sonar and radar-based systems. In contrast to most other techniques, vibration-based scour monitoring uses accelerometers to provide real-time monitoring whilst also being robust and relatively simple to install. This is an indirect technique that aims to measure changes in the dynamic response of the structure due to the effects of scour, rather than attempting to measure scour directly. To date, research on vibration-based scour monitoring has been limited to laboratory-based experiments and numerical simulations, both of which have indicated that the natural frequencies of bridges should indeed be sensitive to scour. Due to pre-existing scouring, and planned repair work, Baildon Bridge in Shipley, Yorkshire provided a rare opportunity to validate vibration-based scour monitoring in both a scoured and a repaired state. A sensor system was deployed with 10 Epson low-noise, high-sensitivity accelerometers to measure the ambient vibration of the bridge before, during, and after the repair. This paper describes the installation of the accelerometer-based system, the numerical modelling of the bridge and the model updating carried out with the initial findings. Initial operational modal analysis has found two consistent vibration modes of the bridge that were scour sensitive according to the updated numerical model. But the variability of the measured frequencies, compared to the expected scour induced change in frequency, indicates a potential challenge for monitoring scour of small span bridges with vibration-based methods

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Exposure of neonatal rats to maternal cafeteria feeding during suckling alters hepatic gene expression and DNA methylation in the insulin signalling pathway

Nutrition in early life is a determinant of lifelong physiological and metabolic function. Diseases that are associated with ageing may, therefore, have their antecedents in maternal nutrition during pregnancy and lactation. Rat mothers were fed either a standard laboratory chow diet (C) or a cafeteria diet (O) based upon a varied panel of highly palatable human foods, during lactation. Their offspring were then weaned onto chow or cafeteria diet giving four groups of animals (CC, CO, OC, OO n=9-10). Livers were harvested 10 weeks post-weaning for assessment of gene and protein expression, and DNA methylation. Cafeteria feeding post-weaning impaired glucose tolerance and was associated with sex-specific altered mRNA expression of peroxisome proliferator activated receptor gamma (PPARg) and components of the insulin-signalling pathway (Irs2, Akt1 and IrB). Exposure to the cafeteria diet during the suckling period modified the later response to the dietary challenge. Post-weaning cafeteria feeding only down-regulated IrB when associated with cafeteria feeding during suckling (group OO, interaction of diet in weaning and lactation P=0.041). Responses to cafeteria diet during both phases of the experiment varied between males and females. Global DNA methylation was altered in the liver following cafeteria feeding in the post-weaning period, in males but not females. Methylation of the IrB promoter was increased in group OC, but not OO (P=0.036). The findings of this study add to a growing evidence base that suggests tissue function across the lifespan a product of cumulative modifications to the epigenome and transcriptome, which may be both tissue and sex-specific

Locomotor adaptation to a powered ankle-foot orthosis depends on control method

<p>Abstract</p> <p>Background</p> <p>We studied human locomotor adaptation to powered ankle-foot orthoses with the intent of identifying differences between two different orthosis control methods. The first orthosis control method used a footswitch to provide bang-bang control (a kinematic control) and the second orthosis control method used a proportional myoelectric signal from the soleus (a physiological control). Both controllers activated an artificial pneumatic muscle providing plantar flexion torque.</p> <p>Methods</p> <p>Subjects walked on a treadmill for two thirty-minute sessions spaced three days apart under either footswitch control (n = 6) or myoelectric control (n = 6). We recorded lower limb electromyography (EMG), joint kinematics, and orthosis kinetics. We compared stance phase EMG amplitudes, correlation of joint angle patterns, and mechanical work performed by the powered orthosis between the two controllers over time.</p> <p>Results</p> <p>During steady state at the end of the second session, subjects using proportional myoelectric control had much lower soleus and gastrocnemius activation than the subjects using footswitch control. The substantial decrease in triceps surae recruitment allowed the proportional myoelectric control subjects to walk with ankle kinematics close to normal and reduce negative work performed by the orthosis. The footswitch control subjects walked with substantially perturbed ankle kinematics and performed more negative work with the orthosis.</p> <p>Conclusion</p> <p>These results provide evidence that the choice of orthosis control method can greatly alter how humans adapt to powered orthosis assistance during walking. Specifically, proportional myoelectric control results in larger reductions in muscle activation and gait kinematics more similar to normal compared to footswitch control.</p

Breast cancer in systemic lupus

OBJECTIVE: There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. METHODS: We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. RESULTS: There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. CONCLUSIONS: There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted

Age before beauty? Relationships between fertilization success and age-dependent ornaments in barn swallows

When males become more ornamented and reproduce more successfully as they grow older, phenotypic correlations between ornament exaggeration and reproductive success can be confounded with age effects in cross-sectional studies, and thus say relatively little about sexual selection on these traits. This is exemplified here in a correlative study of male fertilization success in a large colony of American barn swallows (Hirundo rustica erythrogaster). Previous studies of this species have indicated that two sexually dimorphic traits, tail length and ventral plumage coloration, are positively correlated with male fertilization success, and a mechanism of sexual selection by female choice has been invoked. However, these studies did not control for potential age-related variation in trait expression. Here, we show that male fertilization success was positively correlated with male tail length but not with plumage coloration. We also show that 1-year-old males had shorter tails and lower fertilization success than older males. This age effect accounted for much of the covariance between tail length and fertilization success. Still, there was a positive relationship between tail length and fertilization success among older males. But as this group consisted of males from different age classes, an age effect may be hidden in this relationship as well. Our data also revealed a longitudinal increase in both tail length and fertilization success for individual males. We argue that age-dependent ornament expression and reproductive performance in males complicate inferences about female preferences and sexual selection