Development and characterisation of a novel three-dimensional inter-kingdom wound biofilm model

Chronic diabetic foot ulcers are frequently colonised and infected by polymicrobial biofilms that ultimately prevent healing. This study aimed to create a novel in vitro inter-kingdom wound biofilm model on complex hydrogel-based cellulose substrata to test commonly used topical wound treatments. Inter-kingdom triadic biofilms composed of Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus were shown to be quantitatively greater in this model compared to a simple substratum when assessed by conventional culture, metabolic dye and live dead qPCR. These biofilms were both structurally complex and compositionally dynamic in response to topical therapy, so when treated with either chlorhexidine or povidone iodine, principal component analysis revealed that the 3-D cellulose model was minimally impacted compared to the simple substratum model. This study highlights the importance of biofilm substratum and inclusion of relevant polymicrobial and inter-kingdom components, as these impact penetration and efficacy of topical antiseptics

Part-time learners in open and distance learning: revisiting the critical importance of choice, flexibility and employability

In this article, we argue that, if open learning seeks to (re)assert a social justice mission, issues of openness and flexibility are more critical than ever. Drawing on qualitative data from a National Union of Students Wales/Open University study, which explored, in the voices of Welsh students, the identity, motivation and barriers faced by part-time distance learners, three key findings emerged. First, the chimaera of ‘choice’ – for part-time distance learners whose personal circumstances prevent any other mode of study; second, the vacuity of policy assertions around ‘flexibility’ in HE – what personalised learning means for part-time distance learners should be contested and re-examined; third, the mantra of ‘employability’ – for part-time distance learners, employability is a conundrum which needs to be understood in a far more inclusively nuanced way. We conclude that the voices of part-time distance learners need to be heard by policy makers and should inform open universities’ continuing efforts to enable vulnerable and marginalised learners to access HE

Implications of antimicrobial combinations in complex wound biofilms containing fungi

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while mono-treatment approaches influenced biofilm composition it had no discernible effect on overall quantity. Only by combining bacterial and fungal specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition

The blue channel of the Keck low-resolution imaging spectrometer

This paper summarizes the optical, mechanical, electrical, and software design of LRIS-B, the blue channel of the Keck Low Resolution and Imaging Spectrograph. The LRIS-B project will shortly be completing the existing LRIS instrument through the addition of dichroic beamsplitters, grisms to disperse light on the blue channel, broad-band u, B, and V photometric filters, a blue and near-UV transmitting camera lens, and a large format blue-sensitive CCD detector. LRIS-B will also introduce piezoelectric xy-actuation of the CCD detector inside its Dewar, in order to compensate for flexure in the existing instrument; ultimately the red-side CCD detector will be similarly equipped, its PZT xy-stage being independently programmed. The optical design of the LRIS-B camera uses only fused silica and calcium fluoride elements, and includes a decentered meniscus element to compensate for coma introduced by the LRIS off-axis paraboloid collimator. The design of the blue channel grisms have been optimized for maximum blaze efficiency, the highest dispersion grism having a groove density of 1200 gr/mm. Optical elements not in use at any given time will be stowed in carousels externally mounted to the instrument sidewalls. The entire instrument is designed to permit remote operation

Nitric oxide-mediated posttranslational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability.

Nitric oxide (NO) regulates neuronal function and thus is critical for tuning neuronal communication. Mechanisms by which NO modulates protein function and interaction include posttranslational modifications (PTMs) such as S-nitrosylation. Importantly, cross signaling between S-nitrosylation and prenylation can have major regulatory potential. However, the exact protein targets and resulting changes in function remain elusive. Here, we interrogated the role of NO-dependent PTMs and farnesylation in synaptic transmission. We found that NO compromises synaptic function at the Drosophila neuromuscular junction (NMJ) in a cGMP-independent manner. NO suppressed release and reduced the size of available vesicle pools, which was reversed by glutathione (GSH) and occluded by genetic up-regulation of GSH-generating and de-nitrosylating glutamate-cysteine-ligase and S-nitroso-glutathione reductase activities. Enhanced nitrergic activity led to S-nitrosylation of the fusion-clamp protein complexin (cpx) and altered its membrane association and interactions with active zone (AZ) and soluble N-ethyl-maleimide-sensitive fusion protein Attachment Protein Receptor (SNARE) proteins. Furthermore, genetic and pharmacological suppression of farnesylation and a nitrosylation mimetic mutant of cpx induced identical physiological and localization phenotypes as caused by NO. Together, our data provide evidence for a novel physiological nitrergic molecular switch involving S-nitrosylation, which reversibly suppresses farnesylation and thereby enhances the net-clamping function of cpx. These data illustrate a new mechanistic signaling pathway by which regulation of farnesylation can fine-tune synaptic release

Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

Objective: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). Methods: A pre-specified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents vs. placebo or intensive vs. guideline BP-lowering targets for adults 6ml) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with pre-specified covariables and trial as a random effect. Results: Of 7094 studies identified, 50 trials involving 11,494 patients were eligible and 16 (32.0%) shared patient-level data from 6,221 (54.1%) patients (mean age 64.2 [SD 12.9], 2,266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6−5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared to placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% confidence interval 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute and relative haematoma growth. Interpretation: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent

Interactive analysis of systems biology molecular expression data

Peer reviewedPublisher PD

Estimating the Worldwide Extent of Illegal Fishing

Illegal and unreported fishing contributes to overexploitation of fish stocks and is a hindrance to the recovery of fish populations and ecosystems. This study is the first to undertake a world-wide analysis of illegal and unreported fishing. Reviewing the situation in 54 countries and on the high seas, we estimate that lower and upper estimates of the total value of current illegal and unreported fishing losses worldwide are between $10 bn and$23.5 bn annually, representing between 11 and 26 million tonnes. Our data are of sufficient resolution to detect regional differences in the level and trend of illegal fishing over the last 20 years, and we can report a significant correlation between governance and the level of illegal fishing. Developing countries are most at risk from illegal fishing, with total estimated catches in West Africa being 40% higher than reported catches. Such levels of exploitation severely hamper the sustainable management of marine ecosystems. Although there have been some successes in reducing the level of illegal fishing in some areas, these developments are relatively recent and follow growing international focus on the problem. This paper provides the baseline against which successful action to curb illegal fishing can be judged

The blue channel of the Keck low-resolution imaging spectrometer

This paper summarizes the optical, mechanical, electrical, and software design of LRIS-B, the blue channel of the Keck Low Resolution and Imaging Spectrograph. The LRIS-B project will shortly be completing the existing LRIS instrument through the addition of dichroic beamsplitters, grisms to disperse light on the blue channel, broad-band u, B, and V photometric filters, a blue and near-UV transmitting camera lens, and a large format blue-sensitive CCD detector. LRIS-B will also introduce piezoelectric xy-actuation of the CCD detector inside its Dewar, in order to compensate for flexure in the existing instrument; ultimately the red-side CCD detector will be similarly equipped, its PZT xy-stage being independently programmed. The optical design of the LRIS-B camera uses only fused silica and calcium fluoride elements, and includes a decentered meniscus element to compensate for coma introduced by the LRIS off-axis paraboloid collimator. The design of the blue channel grisms have been optimized for maximum blaze efficiency, the highest dispersion grism having a groove density of 1200 gr/mm. Optical elements not in use at any given time will be stowed in carousels externally mounted to the instrument sidewalls. The entire instrument is designed to permit remote operation

Carbonate-Templated Self-Assembly of an Alkylthiolate-Bridged Cadmium Macrocycle

In the presence of Cd(ClO4)2 and a base, a new mixed N,S-donor alkylthiolate ligand supported both carbonate formation from atmospheric CO2 and the self-assembly of a novel bicapped puckered (CdS)6 molecular wheel. The remarkable stability of the complex was demonstrated by slow intermolecular ligand exchange on the 2J(HH) and J(111/113Cd1H) time scales at elevated temperature. Both CO2 and the base were required to convert amorphous “CdLClO4” precipitated in the absence of air to the carbonate complex. The complex shares structural features with the ζ-carbonic anhydrase class associating cadmium(II) with the biogeochemical cycling of carbon and is the first structurally characterized carbonate complex of any metal involving an alkylthiolate ligand