Vibrio vulnificus Type 6 Secretion System 1 contains anti-Bacterial properties.

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Vibrio vulnificus is a bacterium responsible for severe gastroenteritis, sepsis and wound infections. Gastroenteritis and sepsis are commonly associated with the consumption of raw oysters, whereas wound infection is often associated with the handling of contaminated fish. Although classical virulence factors of this emerging pathogen are well characterised, there remains a paucity of knowledge regarding the general biology of this species. To investigate the presence of previously unreported virulence factors, we applied whole genome sequencing to a panel of ten V. vulnificus strains with varying virulence potentials. This identified two novel type 6 secretion systems (T6SSs), systems that are known to have a role in bacterial virulence and population dynamics. By utilising a range of molecular techniques and assays we have demonstrated the functionality of one of these T6SSs. Furthermore, we have shown that this system is subject to thermoregulation and is negatively regulated by increasing salinity concentrations. This secretion system was also shown to be involved in the killing of V. vulnificus strains that did not possess this system and a model is proposed as to how this interaction may contribute to population dynamics within V. vulnificus strains. In addition to this intra-species killing, this system also contributes to the killing of inter bacterial species and may have a role in the general composition of Vibrio species in the environment.This work was funded by a CEFAS-Exeter University Alliance PhD Studentship awarded to SRC and SLM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Experimental Validation of Plant Peroxisomal Targeting Prediction Algorithms by Systematic Comparison of In Vivo Import Efficiency and In Vitro PTS1 Binding Affinity

Most peroxisomal matrix proteins possess a C-terminal targeting signal type 1 (PTS1). Accurate prediction of functional PTS1 sequences and their relative strength by computational methods is essential for determination of peroxisomal proteomes in silico but has proved challenging due to high levels of sequence variability of non-canonical targeting signals, particularly in higher plants, and low levels of availability of experimentally validated non-canonical examples. In this study, in silico predictions were compared with in vivo targeting analyses and in vitro thermodynamic binding of mutated variants within the context of one model targeting sequence. There was broad agreement between the methods for entire PTS1 domains and position-specific single amino acid residues, including residues upstream of the PTS1 tripeptide. The hierarchy Leu>Met>Ile>Val at the C-terminal position was determined for all methods but both experimental approaches suggest that Tyr is underweighted in the prediction algorithm due to the absence of this residue in the positive training dataset. A combination of methods better defines the score range that discriminates a functional PTS1. In vitro binding to the PEX5 receptor could discriminate among strong targeting signals while in vivo targeting assays were more sensitive, allowing detection of weak functional import signals that were below the limit of detection in the binding assay. Together, the data provide a comprehensive assessment of the factors driving PTS1 efficacy and provide a framework for the more quantitative assessment of the protein import pathway in higher plants

Towards designer organelles by subverting the peroxisomal import pathway

The development of ‘designer’ organelles could be a key strategy to enable foreign pathways to be efficiently controlled within eukaryotic biotechnology. A fundamental component of any such system will be the implementation of a bespoke protein import pathway that can selectively deliver constituent proteins to the new compartment in the presence of existing endogenous trafficking systems. Here we show that the protein–protein interactions that control the peroxisomal protein import pathway can be manipulated to create a pair of interacting partners that still support protein import in moss cells, but are orthogonal to the naturally occurring pathways. In addition to providing a valuable experimental tool to give new insights into peroxisomal protein import, the variant receptor-signal sequence pair forms the basis of a system in which normal peroxisomal function is downregulated and replaced with an alternative pathway, an essential first step in the creation of a designer organelle

Intranasal immunisation with Outer Membrane Vesicles (OMV) protects against airway colonisation and systemic infection with Acinetobacter baumannii.

OBJECTIVES: The multi-drug resistant bacteria Acinetobacter baumannii is a major cause of hospital associated infection; a vaccine could significantly reduce this burden. The aim was to develop a clinically relevant model of A. baumannii respiratory tract infection and to test the impact of different immunisation routes on protective immunity provided by an outer membrane vesicle (OMV) vaccine. METHODS: BALB/c mice were intranasally challenged with isolates of oxa23-positive global clone GC2 A. baumannii from the lungs of patients with ventilator associated pneumonia. Mice were immunised with OMVs by the intramuscular, subcutaneous or intranasal routes; protection was determined by measuring local and systemic bacterial load. RESULTS: Infection with A. baumannii clinical isolates led to a more disseminated infection than the prototype A. baumannii strain ATCC17978; with bacteria detectable in upper and lower airways and the spleen. Intramuscular immunisation induced an antibody response but did not protect against bacterial infection. However, intranasal immunisation significantly reduced airway colonisation and prevented systemic bacterial dissemination. CONCLUSION: Use of clinically relevant isolates of A. baumannii provides stringent model for vaccine development. Intranasal immunisation with OMVs was an effective route for providing protection, demonstrating that local immunity is important in preventing A. baumannii infection

Identifying a human rights–based approach to obesity for States and civil society

Summary Obesity and its comorbidities pose daunting challenges to global health and development in the 21st century. This paper reviews some commonalities between obesity and another global health challenge, the pandemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). International human rights law was an important catalyst for civil society movements that helped to overcome inertia and generate political will for State action in response to HIV and AIDS. Drawing on the HIV experience, the authors propose a conceptual model for a human rights?based response to obesity founded on the twin pillars of State obligations and civil society engagement. Framing States' obligations to address the global obesity pandemic as a matter of international law, informed by the examples of the United Nations ?International Guidelines on HIV/AIDS and Human Rights? and the General Comments of the United Nations human rights treaty bodies on HIV and AIDS, provides a normative framework to guide State actions and opportunities to engage the extensive accountability mechanisms of the United Nations international human rights system. In addition, it provides civil society organizations with the language and tools to demand State action on obesity. The authors call for similar authoritative guidance for States on the application of international human rights law to obesity

Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

The ALMaQUEST survey IX: The nature of the resolved star forming main sequence

We investigate the nature of the scaling relations between the surface density of star formation rate ($\Sigma _{\rm SFR}$), stellar mass ($\Sigma _*$), and molecular gas mass ($\Sigma _{\rm H_2}$), aiming at distinguishing between the relations that are primary, i.e. more fundamental, and those which are instead an indirect by-product of the other relations. We use the ALMaQUEST survey and analyse the data by using both partial correlations and Random Forest regression techniques. We unambiguously find that the strongest intrinsic correlation is between $\Sigma _{\rm SFR}$ and $\Sigma_{\rm H_2}$ (i.e. the resolved Schmidt-Kennicutt relation), followed by the correlation between $\Sigma _{\rm H_2}$ and $\Sigma _*$ (resolved Molecular Gas Main Sequence, rMGMS). Once these two correlations are taken into account, we find that there is no evidence for any intrinsic correlation between $\Sigma _{\rm SFR}$ and $\Sigma _*$, implying that SFR is entirely driven by the amount of molecular gas, while its dependence on stellar mass (i.e. the resolved Star Forming Main Sequence, rSFMS) simply emerges as a consequence of the relationship between molecular gas and stellar mass.Science and Technology Facilities Council (STFC). ERC Advanced Grant 695671 "QUENCH"

The enigmatic monotypic crab plover Dromas ardeola is closely related to pratincoles and coursers (Aves, Charadriiformes, Glareolidae)

The phylogenetic placement of the monotypic crab plover Dromasardeola (Aves, Charadriiformes) remains controversial. Phylogenetic analysis of anatomical and behavioral traits using phenetic and cladistic methods of tree inference have resulted in conflicting tree topologies, suggesting a close association of Dromas to members of different suborders and lineages within Charadriiformes. Here, we revisited the issue by applying Bayesian and parsimony methods of tree inference to 2,012 anatomical and 5,183 molecular characters to a set of 22 shorebird genera (including Turnix). Our results suggest that Bayesian analysis of anatomical characters does not resolve the phylogenetic relationship of shorebirds with strong statistical support. In contrast, Bayesian and parsimony tree inference from molecular data provided much stronger support for the phylogenetic relationships within shorebirds, and support a sister relationship of Dromas to Glareolidae (pratincoles and coursers), in agreement with previously published DNA-DNA hybridization studies

Evolution of the magnetic field distribution of active regions

AIMS: Although the temporal evolution of active regions (ARs) is relatively well understood, the processes involved continue to be the subject of investigation. We study how the magnetic field of a series of ARs evolves with time to better characterise how ARs emerge and disperse. METHODS: We examined the temporal variation in the magnetic field distribution of 37 emerging ARs. A kernel density estimation plot of the field distribution was created on a log-log scale for each AR at each time step. We found that the central portion of the distribution is typically linear, and its slope was used to characterise the evolution of the magnetic field. RESULTS: The slopes were seen to evolve with time, becoming less steep as the fragmented emerging flux coalesces. The slopes reached a maximum value of ∼-1.5 just before the time of maximum flux before becoming steeper during the decay phase towards the quiet-Sun value of ∼-3. This behaviour differs significantly from a classical diffusion model, which produces a slope of -1. These results suggest that simple classical diffusion is not responsible for the observed changes in field distribution, but that other processes play a significant role in flux dispersion. CONCLUSIONS. We propose that the steep negative slope seen during the late-decay phase is due to magnetic flux reprocessing by (super)granular convective cells