The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions

During spore formation in Bacillus subtilis, the SpoIVB protein is a critical component of the sigma (K) regulatory checkpoint. SpoIVB has been shown to be a serine peptidase that is synthesized in the spore chamber and which self-cleaves, releasing active forms. These forms can signal proteolytic processing of the transcription factor sigma (K) in the outer mother cell chamber of the sporulating cell. This forms the basis of the sigma (K) checkpoint and ensures accurate sigma (K)-controlled gene expression. SpoIVB has also been shown to activate a second distinct process, termed the second function, which is essential for the formation of heat-resistant spores. In addition to the serine peptidase domain, SpoIVB contains a PDZ domain. We have altered a number of conserved residues in the PDZ domain by site-directed mutagenesis and assayed the sporulation phenotype and signaling properties of mutant SpoIVB proteins. Our work has revealed that the SpoIVB PDZ domain could be used for up to four distinct processes, (i) targeting of itself for trans proteolysis, (11) binding to the protease inhibitor BofC, (iii) signaling of pro-sigma (K) processing, and (iv) signaling of the second function of SpoIVB

Wound infection, dressings and pain, is there a relationship in the chronic wound?

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management

Using Co-operative Inquiry to embed Education for Sustainable Development (ESD) across all programmes offered by Plymouth Institute of Education (PIoE)

Our aim is to embed Education for Sustainable Development across all of our courses, ensuring that all students benefit from an education where social, economic and environmental sustainability is woven into the very fabric of their learning experience, thereby producing graduates who take this learning forward and embed it in their own teaching. To achieve this, the aims of the projects were: To embed elements of ESD in all PIoE programmes utilising a co-operative inquiry approach (Heron and Reason 2001) • To critically evaluate co-operative inquiry (CI) as an effective mechanism for the implementation of ESD in HE.PedRI

Collagen matrix wound dressings and the treatment of DFUs

Objective: To obtain clinical evidence on the use of a collagen wound dressing in patients with diabetic foot ulcers (DFus).   Method: A convenience sample of patients managed in the podiatry outpatient clinic over an 8-month period were included in the evaluation, if their DFus were not progressing. All participants received traditional adjunctive wound care as part of their treatment. Wound surface-area measurements and imaging of patients was carried out on a regular basis to allow the tracking of wound healing. Results: Six patients, with seven wounds were included in this study. There was an overall decrease in wound surface area over time. Three patients showed a relatively swift reduction in wound area, while one patient showed a slight increase in wound area. The percentage decrease in wound area levelled out quite quickly in three patients, with a mean wound duration of 14 months compared with 7.3 months in the remaining four wounds. one patient died of an unrelated cause. Conclusion: This case series evaluation provides a snapshot of experience at one clinical centre and the treatment of DFus, and suggests that an active biological collagen dressing may support progression to healing by modulating the wound environment. l declaration of interest: S. Haycocks and P. Chadwick received supplies of ProHeal from MedSkin Solutions Dr Suwelack for use on patients in this evaluation. K.F. Cutting is a consultant to MedSkin Solutions Dr Suwelack and received a honorarium for his participation. MedSkin Solutions Dr Suwelack did not have any editorial control over the production of this manuscript

Human recognition based on gait poses

This paper introduces a new approach for gait analysis based on the Gait Energy Image (GEI). The main idea is to segment the gait cycle into some biomechanical poses, and to compute a particular GEI for eachpose. Pose-based GEIs can better represent body parts and dynamics descriptors with respect to the usually blurred depiction provided by a general GEI. Gait classification is carried out by fusing separatedpose-based decisions. Experiments on human identification prove the benefits of this new approach when compared to the original GEI method.Partially supported by projects CSD2007-00018 and CICYT TIN2009-14205-C04-04 from the Spanish Ministry of Innovation and Science, P1-1B2009-04 from Fundació Bancaixa and PREDOC/2008/04 grant from Universitat Jaume I. Portions of the research in this paper use the CASIA Gait Database collected by Institute of Automation, Chinese Academy of Science

Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results

We consider one of the most important problems in directional statistics, namely the problem of testing the null hypothesis that the spike direction $\theta$ of a Fisher-von Mises-Langevin distribution on the $p$-dimensional unit hypersphere is equal to a given direction $\theta_0$. After a reduction through invariance arguments, we derive local asymptotic normality (LAN) results in a general high-dimensional framework where the dimension $p_n$ goes to infinity at an arbitrary rate with the sample size $n$, and where the concentration $\kappa_n$ behaves in a completely free way with $n$, which offers a spectrum of problems ranging from arbitrarily easy to arbitrarily challenging ones. We identify various asymptotic regimes, depending on the convergence/divergence properties of $(\kappa_n)$, that yield different contiguity rates and different limiting experiments. In each regime, we derive Le Cam optimal tests under specified $\kappa_n$ and we compute, from the Le Cam third lemma, asymptotic powers of the classical Watson test under contiguous alternatives. We further establish LAN results with respect to both spike direction and concentration, which allows us to discuss optimality also under unspecified $\kappa_n$. To investigate the non-null behavior of the Watson test outside the parametric framework above, we derive its local asymptotic powers through martingale CLTs in the broader, semiparametric, model of rotationally symmetric distributions. A Monte Carlo study shows that the finite-sample behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

Psychological characteristics of children with visual impairments: learning, memory and imagery

The performance of children (and sometimes adults) with visual impairments (VI) on a range of tasks that reflect learning, memory and mental imagery is considered in this article. Sometimes the evidence suggests that there are impairments in performance in comparison with typically developing children with vision and sometimes some advantages emerge. The author’s aim is to describe some of her own and others’ findings and explore what they tell us about the cognitive characteristics of such children, so that progress with practical interventions can be advanced through understanding. The article starts by focusing on social-cognitive development and in particular considers the potential benefits of language in that development. This is followed by a review of some studies of learning and memory performance which provide a coherent picture of development without vision and finally ends with a consideration of spatial mental imagery