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

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

Niche shifts and energetic condition of songbirds in response to phenology of food-resource availability in a high-elevation sagebrush ecosystem

Seasonal fluctuations in food availability can affect diets of consumers, which in turn may influence the physiological state of individuals and shape intra- and inter-specific patterns of resource use. High-elevation ecosystems often exhibit a pronounced seasonal “pulse” in productivity, although few studies document how resource use and energetic condition by avian consumers change in relation to food-resource availability in these ecosystems. We tested the hypothesis that seasonal increases (pulses) in food resources in high-elevation sagebrush ecosystems result in 2 changes after the pulse, relative to the before-pulse period: (1) reduced diet breadth of, and overlap between, 2 sympatric sparrow species; and (2) enhanced energetic condition in both species. We tracked breeding-season diets using stable isotopes and energetic condition using plasma metabolites of Brewer\u27s Sparrows (Spizella breweri), Vesper Sparrows (Pooecetes gramineus), and their food resources during 2011, and of only Brewer\u27s Sparrows and their food resources during 2013. We quantify diet breadth and overlap between both species, along with coincident physiological consequences of temporal changes in resource use. After invertebrate biomass increased following periods of rainfall in 2011, dietary breadth decreased by 35% in Brewer\u27s Sparrows and by 48% in Vesper Sparrows, while dietary overlap decreased by 88%. Energetic condition of both species increased when dietary overlap was lower and diet breadth decreased, after the rapid rise of food-resource availability. However, energetic condition of Brewer\u27s Sparrows remained constant in 2013, a year with low precipitation and lack of a strong pulse in food resources, even though the species\u27 dietary breadth again decreased that year. Our results indicate that diet breadth and overlap in these sparrow species inhabiting sagebrush ecosystems generally varied as predicted in relation to intra- and interannual changes in food resources, and this difference in diet was associated with improved energetic condition of sparrows at least in one year

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

The Microbiome in Pediatric Cystic Fibrosis Patients: The Role of Shared Environment Suggests a Window of Intervention

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the role that genetics plays in their evolution. We found that the microbial communities in sputum from pediatric patients living together were much more alike than those from pediatric individuals living apart, regardless of whether samples were taken from monozygous twins or from nontwin CF siblings living together, which we used as a proxy for dizygous twins. In contrast, adult communities were comparatively monolithic and much less diverse than the microbiome of pediatric patients

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Crystal structures of the GH18 domain of the bifunctional peroxiredoxin-chitinase CotE from Clostridium difficile

CotE is a coat protein that is present in the spores of Clostridium difficile, an obligate anaerobic bacterium and a pathogen that is a leading cause of antibiotic-associated diarrhoea in hospital patients. Spores serve as the agents of disease transmission, and CotE has been implicated in their attachment to the gut epithelium and subsequent colonization of the host. CotE consists of an N-terminal peroxiredoxin domain and a C-terminal chitinase domain. Here, a C-terminal fragment of CotE comprising residues 349-712 has been crystallized and its structure has been determined to reveal a core eight-stranded β-barrel fold with a neighbouring subdomain containing a five-stranded β-sheet. A prominent groove running across the top of the barrel is lined by residues that are conserved in family 18 glycosyl hydrolases and which participate in catalysis. Electron density identified in the groove defines the pentapeptide Gly-Pro-Ala-Met-Lys derived from the N-terminus of the protein following proteolytic cleavage to remove an affinity-purification tag. These observations suggest the possibility of designing peptidomimetics to block C. difficile transmission

Extraction of bodily features for gait recognition and gait attractiveness evaluation

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-012-1319-2. Copyright @ 2012 Springer.Although there has been much previous research on which bodily features are most important in gait analysis, the questions of which features should be extracted from gait, and why these features in particular should be extracted, have not been convincingly answered. The primary goal of the study reported here was to take an analytical approach to answering these questions, in the context of identifying the features that are most important for gait recognition and gait attractiveness evaluation. Using precise 3D gait motion data obtained from motion capture, we analyzed the relative motions from different body segments to a root marker (located on the lower back) of 30 males by the fixed root method, and compared them with the original motions without fixing root. Some particular features were obtained by principal component analysis (PCA). The left lower arm, lower legs and hips were identified as important features for gait recognition. For gait attractiveness evaluation, the lower legs were recognized as important features.Dorothy Hodgkin Postgraduate Award and HEFCE

Education for Sustainable Development: Towards the Sustainable University

We  planned  this  conference  in  anticipation  of  the  end  of  the  UN  Decade  of  Education  for  Sustainable   Development  (DESD),  and  the  start  of  the  next  phase  for  those  involved  in  ESD  here  and   internationally.    At  Plymouth  University,  2015  marks  ten  year  anniversary  since  cross-­‐institutional   work  on  sustainability  and  sustainability  education  was  spearheaded  by  the  founding  of  the  Centre  for   Sustainable  Futures  (CSF).    Coincidentally,  2015  also  marks  a  ten  years  since  the  influential  HEFCE   policy  document  ‘Sustainable  Development  in  Higher  Education’  was  released.   Holding  the  conference  in  January  –  named  after  the  Roman  god  of  doorways,  of  endings  and   beginnings  –  we  sought  to  look  at  some  of  what  has  been  achieved  in  sustainability  education  to  date   and  explore  its  prospects  as  we  move  forward.   Following  an  enthusiastic  response  to  the  call  for  abstracts,  the  conference  featured  a  diverse  range   of  research  papers,  posters,  and  roundtable  presentations  from  academics  and  practitioners  across   the  UK  and  beyond.  The  conference  was  arranged  around  three  overarching  themes:     ESD  Pedagogy:  Criticality,  Creativity,  and  Collaboration   What  are  the  teaching  and  learning  processes  that  enable  students  to  develop  their  own  capacity  to   think  critically  and  creatively  in  the  face  of  global  sustainability  challenges  and,  secondly,  to  act   collaboratively  in  ways  that  pursue  more  hopeful  and  sustainable  futures?   Innovative  Learning  Spaces  for  ESD   What  are  the  physical  environments  that  provide  opportunities  for  new  forms  of  sustainability   education  to  flourish?  What  lies  beyond  the  lecture  hall  that  is  conducive  to  student  learning  through   inquiry-­‐based,  active,  participatory,  interdisciplinary  and  experiential  methods?   Towards  the  Sustainable  University   What  are  effective  approaches  for  leading  institutional  change,  organisational  learning,  and  staff  CPD   towards  sustainability?  This  publication  focuses  on  the  last  theme  –  Towards  the  Sustainable  University.    The  previous   PedRIO  Occasional  Paper  8  looks  at  the  first  theme  ESD  Pedagogy:  Criticality,  Creativity,  and   Collaboration