1,103 research outputs found
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
Facial expression, size, and clutter: Inferences from movie structure to emotion judgments and back
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
of a Fisher-von Mises-Langevin distribution on the -dimensional
unit hypersphere is equal to a given direction . After a reduction
through invariance arguments, we derive local asymptotic normality (LAN)
results in a general high-dimensional framework where the dimension goes
to infinity at an arbitrary rate with the sample size , and where the
concentration behaves in a completely free way with , 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 , that yield different
contiguity rates and different limiting experiments. In each regime, we derive
Le Cam optimal tests under specified 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 . 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
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