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

A discourse analysis of trainee teacher identity in online discussion forums

Teacher education involves an identity transformation for trainees from being a student to being a teacher. This discourse analysis examined the online discussion board communications of a cohort of trainee teachers to better understand the situated identities of the trainees and how they were presented online. Their discussion board posts were the primary method of communication during placement periods and, as such, provided insight into how the trainees situated their identities in terms of being a student or being a teacher. During the analysis, the community boundaries, language and culture were explored along with the tutor's power and role in the identity transformation process. This involved looking at the lexis used by the students, the use of pronouns to refer to themselves and others such as teachers and pupils, the types of messages allowed in the community and the effect of the tutor's messages on their communication. The research found that the trainees felt comfortable with teaching but did not feel like teachers during the course. Tutors and school teachers need to develop an awareness of the dual nature of trainees' identities and help promote the transition from student to teacher. In the beginning of the course, trainees should be familiarised with teacher vocabulary and practical concepts in addition to pedagogical theory. Towards the end of the course, trainee identity as teachers could be promoted through the use of authentic assessments that mirror real teacher tasks and requirements

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

In-Space Propulsion: Connectivity to In-Space Fabrication and Repair

The connectivity between new in-space propulsion technologies and the ultimate development of an in-space fabrication and repair infrastructure are described in this Technical Memorandum. A number of advanced in-space propulsion technologies are being developed by NASA, many of which are directly relevant to the establishment of such an in-space infrastructure. These include aerocapture, advanced solar-electric propulsion, solar-thermal propulsion, advanced chemical propulsion, tethers, and solar photon sails. Other, further-term technologies have also been studied to assess their utility to the development of such an infrastructure

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

A window on reality: perceiving edited moving images

Edited moving images entertain, inform, and coerce us throughout our daily lives, yet until recently, the way people perceive movies has received little psychological attention. We review the history of empirical investigations into movie perception and the recent explosion of new research on the subject using methods such as behavioral experiments, functional magnetic resonance imagery (fMRI) eye tracking, and statistical corpus analysis. The Hollywood style of moviemaking, which permeates a wide range of visual media, has evolved formal conventions that are compatible with the natural dynamics of attention and humans’ assumptions about continuity of space, time, and action. Identifying how people overcome the sensory differences between movies and reality provides an insight into how the same cognitive processes are used to perceive continuity in the real world

Tuberculosis in children in India-II: Chemotherapy for tuberculosis

Tubercle bacilli readily become resistant to the common drugs, and resistant bacilli are more likely to proliferate if they are present in the patient at the start of treatment. So always use more than one drug. The only possible exception is prophylaxis for an asymptomatic case with a normal X-ray. CAUTION! (1) Never give intermittent (twice or thrice weekly) treatment unless every dose can be supervised by a health worker. Daily treatment is usually mandatory. (2) When you give more than one drug, give them both at the same time, so that high blood levels coincide; do not give one drug daily and the other drug less often. THE DOSES of the commonly used drugs for daily and intermittent treatment in children and adults are: lsoniazid (H) 5 mg/kg/24 hours if he is moderately ill and 10 mg/kg/24 hours if he is severely ill. The dose for a twice weekly course is 15 mg/kg. CAUTION! Opinions on the dose of isoniazid vary. Some consider 10 mg/kg/24 hours too much for an Indian child and always give 5 mg. Rifampicin (R) 10 mg/kg/24 hours, or 10 mg/kg twice weekly. Pyrazinamide (Z) 35 mg/kg/24 hours, 75 mg/kg twice weekly or 50 mg/kg thrice weekly, is an important drug for short course treatment, so try to include it whenever it is mentioned in the regimes below. Streptomycin (S) 10-20 mg/kg/24 hours, or 40 mg/kg twice weekly, to a total of not more than 0.75 g. Streptomycin is painful, so avoid it if you can. If you give it, inject in different places each day, because repeated injections into the same site are painful. Ethambutol (E) 25 mg/kg/24 hours for 2 months, then 15 mg/kg/24 hours. Avoid ethambutol in younger children (under 12); they are unable to complain of the early symptoms of retrobulbar neuritis (blindness). Thiacetazone (T) 4 mg/kg/24 hours to a maximum Of 150 mg; unsuitable for intermittent treatment

Identifying the mechanisms underpinning recognition of structured sequences of action

© 2012 The Experimental Psychology SocietyWe present three experiments to identify the specific information sources that skilled participants use to make recognition judgements when presented with dynamic, structured stimuli. A group of less skilled participants acted as controls. In all experiments, participants were presented with filmed stimuli containing structured action sequences. In a subsequent recognition phase, participants were presented with new and previously seen stimuli and were required to make judgements as to whether or not each sequence had been presented earlier (or were edited versions of earlier sequences). In Experiment 1, skilled participants demonstrated superior sensitivity in recognition when viewing dynamic clips compared with static images and clips where the frames were presented in a nonsequential, randomized manner, implicating the importance of motion information when identifying familiar or unfamiliar sequences. In Experiment 2, we presented normal and mirror-reversed sequences in order to distort access to absolute motion information. Skilled participants demonstrated superior recognition sensitivity, but no significant differences were observed across viewing conditions, leading to the suggestion that skilled participants are more likely to extract relative rather than absolute motion when making such judgements. In Experiment 3, we manipulated relative motion information by occluding several display features for the duration of each film sequence. A significant decrement in performance was reported when centrally located features were occluded compared to those located in more peripheral positions. Findings indicate that skilled participants are particularly sensitive to relative motion information when attempting to identify familiarity in dynamic, visual displays involving interaction between numerous features

Protecting Cultural Property Through Provenance

This Comment recommends that Congress take action to bring consistency to the treatment of cultural property in two ways. First, ownership disputes should be settled based on the quality of provenance between competing claimants, a system similar to land title registration. Provenance is the history of a piece of cultural property that shows where it came from and where it has been. Second, to ensure provenance is a complete guide to title all cultural objects, both illegally exported and stolen cultural property should receive the same treatment. Part II of this Comment discusses the history of cultural property regulation. Next, Part III addresses the current state of the law protecting cultural objects within the United States and explains the inconsistencies created under the current statutory scheme. Finally, Part IV proposes a solution that will protect interested parties