Pathogenicity and other genomic islands in plant pathogenic bacteria

Pathogenicity islands (PAIs) were first described in uropathogenic E. coli. They are now defined as regions of DNA that contain virulence genes and are present in the genome of pathogenic strains, but absent from or only rarely present in non-pathogenic variants of the same or related strains. Other features include a variable G+C content, distinct boundaries from the rest of the genome and the presence of genes related to mobile elements such as insertion sequences, integrases and transposases. Although PAIs have now been described in a wide range of both plant and animal pathogens it has become evident that the general features of PAIs are displayed by a number of regions of DNA with functions other than pathogenicity, such as symbiosis and antibiotic resistance, and the general term genomic islands has been adopted. This review will describe a range of genomic islands in plant pathogenic bacteria including those that carry effector genes, phytotoxins and the type III protein secretion cluster. The review will also consider some medically important bacteria in order to discuss the range, acquisition and stabilization of genomic islands.

Conditional symmetric instability in sting-jet storms

Sting jets are transient mesoscale jets of air that descend from the tip of the cloud head towards the top of the boundary layer in severe extratropical cyclones and can lead to damaging surface wind gusts. This recently identified jet is distinct from the well-documented jets associated with the cold and warm conveyor belts. One mechanism proposed for their development is the release of conditional symmetric instability (CSI). Here the spatial distribution and temporal evolution of several CSI diagnostics in four severe storms are analysed. A sting jet has been identified in three of these storms; for comparison, we also analysed one storm that did not have a sting jet, even though it hadmany of the apparent features of sting-jet storms. The sting-jet storms are distinct from the non-sting-jet storms by having much greater andmore extensive conditional instability (CI) and CSI. CSI is released by ascending air parcels in the cloud head in two of the sting-jet storms and by descending air parcels in the other sting-jet storm. By contrast, only weak CI to ascending air parcels is present at the cloud-head tip in the non-sting-jet storm. CSI released by descending air parcels, as diagnosed by decaying downdraught slantwise convective available potential energy (DSCAPE), is collocated with the sting jets in all three sting-jet storms and has a localisedmaximum in two of them. Consistent evolutions of saturated moist potential vorticity are found.We conclude that CSI release has a role in the generation of the sting jet, that the sting jet may be driven by the release of instability to both ascending and descending parcels, and that DSCAPE could be used as a discriminating diagnostic for the sting jet based on these four case-studies.

Symmetry breaking, mixing, instability, and low frequency variability in a minimal Lorenz-like system

Starting from the classical Saltzman two-dimensional convection equations, we derive via a severe spectral truncation a minimal 10 ODE system which includes the thermal effect of viscous dissipation. Neglecting this process leads to a dynamical system which includes a decoupled generalized Lorenz system. The consideration of this process breaks an important symmetry and couples the dynamics of fast and slow variables, with the ensuing modifications to the structural properties of the attractor and of the spectral features. When the relevant nondimensional number (Eckert number Ec) is different from zero, an additional time scale of O(Ec−1) is introduced in the system, as shown with standard multiscale analysis and made clear by several numerical evidences. Moreover, the system is ergodic and hyperbolic, the slow variables feature long-term memory with 1/f3/2 power spectra, and the fast variables feature amplitude modulation. Increasing the strength of the thermal-viscous feedback has a stabilizing effect, as both the metric entropy and the Kaplan-Yorke attractor dimension decrease monotonically with Ec. The analyzed system features very rich dynamics: it overcomes some of the limitations of the Lorenz system and might have prototypical value in relevant processes in complex systems dynamics, such as the interaction between slow and fast variables, the presence of long-term memory, and the associated extreme value statistics. This analysis shows how neglecting the coupling of slow and fast variables only on the basis of scale analysis can be catastrophic. In fact, this leads to spurious invariances that affect essential dynamical properties (ergodicity, hyperbolicity) and that cause the model losing ability in describing intrinsically multiscale processes.

The Genomic Threading Database: a comprehensive resource for structural annotations of the genomes from key organisms

Currently, the Genomic Threading Database (GTD) contains structural assignments for the proteins encoded within the genomes of nine eukaryotes and 101 prokaryotes. Structural annotations are carried out using a modified version of GenTHREADER, a reliable fold recognition method. The Gen THREADER annotation jobs are distributed across multiple clusters of processors using grid technology and the predictions are deposited in a relational database accessible via a web interface at http://bioinf.cs.ucl.ac.uk/GTD. Using this system, up to 84% of proteins encoded within a genome can be confidently assigned to known folds with 72% of the residues aligned. On average in the GTD, 64% of proteins encoded within a genome are confidently assigned to known folds and 58% of the residues are aligned to structures.

The Genomic Threading Database

The Genomic Threading Database currently contains structural annotations for the genomes of over 100 recently sequenced organisms. Annotations are carried out by using our modified GenTHREADER software and through implementing grid technology.

Improvement of the GenTHREADER method for genomic fold recognition

Motivation: In order to enhance genome annotation, the fully automatic fold recognition method GenTHREADER has been improved and benchmarked. The previous version of GenTHREADER consisted of a simple neural network which was trained to combine sequence alignment score, length information and energy potentials derived from threading into a single score representing the relationship between two proteins, as designated by CATH. The improved version incorporates PSI-BLAST searches, which have been jumpstarted with structural alignment profiles from FSSP, and now also makes use of PSIPRED predicted secondary structure and bi-directional scoring in order to calculate the final alignment score. Pairwise potentials and solvation potentials are calculated from the given sequence alignment which are then used as inputs to a multi-layer, feed-forward neural network, along with the alignment score, alignment length and sequence length. The neural network has also been expanded to accommodate the secondary structure element alignment (SSEA) score as an extra input and it is now trained to learn the FSSP Z-score as a measurement of similarity between two proteins. Results: The improvements made to GenTHREADER increase the number of remote homologues that can be detected with a low error rate, implying higher reliability of score, whilst also increasing the quality of the models produced. We find that up to five times as many true positives can be detected with low error rate per query. Total MaxSub score is doubled at low false positive rates using the improved method.

Accommodative instability: relationship to progression of early onset myopia

Background: In a previous study, we demonstrated that children with early onset myopia had greater instability of accommodation than a group of emmetropic children. Since that study was correlational, we were unable to determine the causal relationship between this and myopic progression. To address this, we examined the children two years later. We predicted that if accommodative instability was causing the myopic progression, instability at Visit 1 should predict the refractive error at Visit 2. Additionally, instability at Visit 1 should predict myopic progression. Methods: Thirteen myopic and 16 emmetropic children were included in the analysis. Dynamic measures of accommodation were made using eccentric photorefraction (PowerRefractor) while children viewed targets set at three distances (accommodative demands), namely, 0.25 metres (4.00 D demand), 0.5 metres (2.00 D demand) and 4.00 metres (0.25 D demand). Results: Both refractive error and accommodative instability at Visit 1 were highly correlated with the same measures at Visit 2. Children with myopia showed greater instability of accommodation (0.38 D) than children with emmetropia (0.26 D) at the 4.00 D target on Visit 1 and this instability of accommodation weakly predicted myopic progression. Conclusions: The results presented in the present study suggest that instability of accommodation accompanies myopic progression, although a casual relationship cannot be established.

Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities

Background and aims: GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GPTCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Materials and methods: Literature studies, opinion polls and discussions among consortium members and stakeholders. Results: By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority to integrative medicine, concerned on the impact of regulation of TCM practitioners and emphasised intersectoral collaborations in funding TCM research, especially clinical trials. Conclusions: The GP-TCM consortium made great efforts to address some fundamental issues in TCM research, including developing guidelines, as well as identifying priorities, challenges and opportunities. These consortium guidelines and consensus will need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. To promote this, a new consortium, known as the GP-TCM Research Association, is being established to succeed the 3-year fixed term FP7 GP-TCM consortium and will be officially launched at the Final GP-TCM Congress in Leiden, the Netherlands, in April 2012.

Comparative genomic indexing reveals the phylogenomics of Escherichia coli pathogens

The Escherichia coli O26 serogroup includes important food-borne pathogens associated with human and animal diarrheal disease. Current typing methods have revealed great genetic heterogeneity within the O26 group; the data are often inconsistent and focus only on verotoxin (VT)-positive O26 isolates. To improve current understanding of diversity within this serogroup, the genomic relatedness of VT-positive and -negative O26 strains was assessed by comparative genomic indexing. Our results clearly demonstrate that irrespective of virulence characteristics and pathotype designation, the O26 strains show greater genomic similarity to each other than to any other strain included in this study. Our data suggest that enteropathogenic and VT-expressing E. coli O26 strains represent the same clonal lineage and that W-expressing E. coli O26 strains have gained additional virulence characteristics. Using this approach, we established the core genes which are central to the E. coli species and identified regions of variation from the E. coli K-12 chromosomal backbone.

On nonlinear symmetric stability and the nonlinear saturation of symmetric instability

A nonlinear symmetric stability theorem is derived in the context of the f-plane Boussinesq equations, recovering an earlier result of Xu within a more general framework. The theorem applies to symmetric disturbances to a baroclinic basic flow, the disturbances having arbitrary structure and magnitude. The criteria for nonlinear stability are virtually identical to those for linear stability. As in Xu, the nonlinear stability theorem can be used to obtain rigorous upper bounds on the saturation amplitude of symmetric instabilities. In a simple example, the bounds are found to compare favorably with heuristic parcel-based estimates in both the hydrostatic and non-hydrostatic limits.

Nonlinear saturation of baroclinic instability: part III: bounds on the energy

Rigorous upper bounds are derived on the saturation amplitude of baroclinic instability in the two-layer model. The bounds apply to the eddy energy and are obtained by appealing to a finite amplitude conservation law for the disturbance pseudoenergy. These bounds are to be distinguished from those derived in Part I of this study, which employed a pseudomomentum conservation law and provided bounds on the eddy potential enstrophy. The bounds apply to conservative (inviscid, unforced) flow, as well as to forced-dissipative flow when the dissipation is proportional to the potential vorticity. Bounds on the eddy energy are worked out for a general class of unstable westerly jets. In the special case of the Phillips model of baroclinic instability, and in the limit of infinitesimal initial eddy amplitude, the bound states that the eddy energy cannot exceed ϵβ2/6F where ϵ = (U − Ucrit)/Ucrit is the relative supercriticality. This bound captures the essential dynamical scalings (i.e., the dependence on ϵ, β, and F) of the saturation amplitudes predicted by weakly nonlinear theory, as well as exhibiting remarkable quantitative agreement with those predictions, and is also consistent with heuristic baroclinic adjustment estimates.

Nonlinear saturation of baroclinic instability: part II: continuously stratified fluid

Rigorous upper bounds are derived that limit the finite-amplitude growth of arbitrary nonzonal disturbances to an unstable baroclinic zonal flow in a continuously stratified, quasi-geostrophic, semi-infinite fluid. Bounds are obtained bath on the depth-integrated eddy potential enstrophy and on the eddy available potential energy (APE) at the ground. The method used to derive the bounds is essentially analogous to that used in Part I of this study for the two-layer model: it relies on the existence of a nonlinear Liapunov (normed) stability theorem, which is a finite-amplitude generalization of the Charney-Stern theorem. As in Part I, the bounds are valid both for conservative (unforced, inviscid) flow, as well as for forced-dissipative flow when the dissipation is proportional to the potential vorticity in the interior, and to the potential temperature at the ground. The character of the results depends on the dimensionless external parameter γ = f02ξ/β0N2H, where ξ is the maximum vertical shear of the zonal wind, H is the density scale height, and the other symbols have their usual meaning. When γ ≫ 1, corresponding to “deep” unstable modes (vertical scale ≈H), the bound on the eddy potential enstrophy is just the total potential enstrophy in the system; but when γ≪1, corresponding to ‘shallow’ unstable modes (vertical scale ≈γH), the eddy potential enstrophy can be bounded well below the total amount available in the system. In neither case can the bound on the eddy APE prevent a complete neutralization of the surface temperature gradient which is in accord with numerical experience. For the special case of the Charney model of baroclinic instability, and in the limit of infinitesimal initial eddy disturbance amplitude, the bound states that the dimensionless eddy potential enstrophy cannot exceed (γ + 1)2/24&gamma2h when γ ≥ 1, or 1/6;&gammah when γ ≤ 1; here h = HN/f0L is the dimensionless scale height and L is the width of the channel. These bounds are very similar to (though of course generally larger than) ad hoc estimates based on baroclinic-adjustment arguments. The possibility of using these kinds of bounds for eddy-amplitude closure in a transient-eddy parameterization scheme is also discussed.

Nonlinear saturation of baroclinic instability: part I: the two-layer model

A rigorous bound is derived which limits the finite-amplitude growth of arbitrary nonzonal disturbances to an unstable baroclinic zonal flow within the context of the two-layer model. The bound is valid for conservative (unforced) flow, as well as for forced-dissipative flow that when the dissipation is proportional to the potential vorticity. The method used to derive the bound relies on the existence of a nonlinear Liapunov (normed) stability theorem for subcritical flows, which is a finite-amplitude generalization of the Charney-Stern theorem. For the special case of the Philips model of baroclinic instability, and in the limit of infinitesimal initial nonzonal disturbance amplitude, an improved form of the bound is possible which states that the potential enstrophy of the nonzonal flow cannot exceed ϵβ2, where ϵ = (U − Ucrit)/Ucrit is the (relative) supereriticality. This upper bound turns out to be extremely similar to the maximum predicted by the weakly nonlinear theory. For unforced flow with ϵ < 1, the bound demonstrates that the nonzonal flow cannot contain all of the potential enstrophy in the system; hence in this range of initial supercriticality the total flow must remain, in a certain sense, “close” to a zonal state.