PhyloPars: estimation of missing parameter values using phylogeny

A wealth of information on metabolic parameters of a species can be inferred from observations on species that are phylogenetically related. Phylogeny-based information can complement direct empirical evidence, and is particularly valuable if experiments on the species of interest are not feasible. The PhyloPars web server provides a statistically consistent method that combines an incomplete set of empirical observations with the species phylogeny to produce a complete set of parameter estimates for all species. It builds upon a state-of-the-art evolutionary model, extended with the ability to handle missing data. The resulting approach makes optimal use of all available information to produce estimates that can be an order of magnitude more accurate than ad-hoc alternatives. Uploading a phylogeny and incomplete feature matrix suffices to obtain estimates of all missing values, along with a measure of certainty. Real-time cross-validation provides further insight in the accuracy and bias expected for estimated values. The server allows for easy, efficient estimation of metabolic parameters, which can benefit a wide range of fields including systems biology and ecology. PhyloPars is available at: http://www.ibi.vu.nl/programs/phylopars/

Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B) has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD) of NS4B is highly conserved in Hepaciviruses, though its function remains unknown.</p> <p>Results</p> <p>A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH). The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD) of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system.</p> <p>Conclusion</p> <p>Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.</p

Symmetry without Symmetry: Numerical Simulation of Axisymmetric Systems using Cartesian Grids

We present a new technique for the numerical simulation of axisymmetric systems. This technique avoids the coordinate singularities which often arise when cylindrical or polar-spherical coordinate finite difference grids are used, particularly in simulating tensor partial differential equations like those of 3+1 numerical relativity. For a system axisymmetric about the z axis, the basic idea is to use a 3-dimensional Cartesian (x,y,z) coordinate grid which covers (say) the y=0 plane, but is only one finite-difference-molecule--width thick in the y direction. The field variables in the central y=0 grid plane can be updated using normal (x,y,z)--coordinate finite differencing, while those in the y \neq 0 grid planes can be computed from those in the central plane by using the axisymmetry assumption and interpolation. We demonstrate the effectiveness of the approach on a set of fully nonlinear test computations in 3+1 numerical general relativity, involving both black holes and collapsing gravitational waves.Comment: 17 pages, 4 figure

Microbiomes associated with bovine periodontitis and oral health

Periodontitis is an infectious polymicrobial, immuno-inflammatory disease of multifactorial aetiology that has an impact on the health, production and welfare of ruminants. The objective of the present study was to determine the microbial profiles present in the gingival sulcus of cattle considered periodontally healthy and in the periodontal pocket of animals with periodontitis lesions using high-throughput bacterial 16S rRNA gene sequencing. Subgingival biofilm samples were collected from 40 cattle with periodontitis and 38 periodontally healthy animals. In total, 1923 OTUs were identified and classified into 395 genera or higher taxa. Microbial profiles in health differed significantly from periodontitis in their composition (p &lt; 0.0001, F = 5.30; PERMANOVA) but no statistically significant differences were observed in the diversity of healthy and periodontitis microbiomes. The most prevalent taxa in health were Pseudomonas, Burkholderia and Actinobacteria, whereas in disease these were Prevotella, Fusobacterium and Porphyromonas. The most discriminative taxa in health were Gastranaerophilales, Planifilum and Burkholderia, and in disease these were Elusimicrobia, Synergistes and Propionivibrio. In conclusion, statistically significant difference exists between the microbiome in bovine oral health and periodontitis, with populations showing 72.6% dissimilarity. The diversity of the bacteria found in health and periodontitis were similar and bacteria recognised as periodontal pathogens showed increased abundance in disease. In this context, the main components of bacterial homeostasis in the biofilm of healthy sites and of dysbiosis in periodontal lesions provide unprecedented indicators for the evolution of knowledge about bovine periodontitis

Quasi-equilibrium binary black hole sequences for puncture data derived from helical Killing vector conditions

We construct a sequence of binary black hole puncture data derived under the assumptions (i) that the ADM mass of each puncture as measured in the asymptotically flat space at the puncture stays constant along the sequence, and (ii) that the orbits along the sequence are quasi-circular in the sense that several necessary conditions for the existence of a helical Killing vector are satisfied. These conditions are equality of ADM and Komar mass at infinity and equality of the ADM and a rescaled Komar mass at each puncture. In this paper we explicitly give results for the case of an equal mass black hole binary without spin, but our approach can also be applied in the general case. We find that up to numerical accuracy the apparent horizon mass also remains constant along the sequence and that the prediction for the innermost stable circular orbit is similar to what has been found with the effective potential method.Comment: 6 pages, 3 figures, 1 tabl

The 3D Grazing Collision of Two Black Holes

We present results for two colliding black holes (BHs), with angular momentum, spin, and unequal mass. For the first time gravitational waveforms are computed for a grazing collision from a full 3D numerical evolution. The collision can be followed through the merger to form a single BH, and through part of the ringdown period of the final BH. The apparent horizon is tracked and studied, and physical parameters, such as the mass of the final BH, are computed. The total energy radiated in gravitational waves is shown to be consistent with the total mass of the spacetime and the final BH mass. The implication of these simulations for gravitational wave astronomy is discussed.Comment: 4 pages, 7 figures, revte

Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping

This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. We are grateful to microbiology colleagues throughout Scotland for clinical isolates collection.Peer reviewedPublisher PD

Adaptive mesh and geodesically sliced Schwarzschild spacetime in 3+1 dimensions

We present first results obtained with a 3+1 dimensional adaptive mesh code in numerical general relativity. The adaptive mesh is used in conjunction with a standard ADM code for the evolution of a dynamically sliced Schwarzschild spacetime (geodesic slicing). We argue that adaptive mesh is particularly natural in the context of general relativity, where apart from adaptive mesh refinement for numerical efficiency one may want to use the built in flexibility to do numerical relativity on coordinate patches.Comment: 21 pages, LaTeX, 7 figures included with eps

Gauge conditions for long-term numerical black hole evolutions without excision

Numerical relativity has faced the problem that standard 3+1 simulations of black hole spacetimes without singularity excision and with singularity avoiding lapse and vanishing shift fail after an evolution time of around 30-40M due to the so-called slice stretching. We discuss lapse and shift conditions for the non-excision case that effectively cure slice stretching and allow run times of 1000M and more.Comment: 19 pages, 14 figures, REVTeX, Added a missing Acknowledgmen

Microbiome analysis of feline odontoclastic resorptive lesion (FORL) and feline oral health

Introduction. Feline odontoclastic resorptive lesion (FORL) is one of the most common and painful oral diseases of the cat. It is characterised by tooth resorption due to destructive activity of odontoclasts. FORL can result in tooth loss. While the aetiology of FORL is not clearly understood, it is thought to be multifactorial and bacteria are likely to play a major role. Hypothesis. Dysbiosis of the normal feline oral microbiota leads to an alteration in commensal bacteria populations, which results in the development of FORL. Aim. The purpose of the current study was to determine the composition of the microbiomes associated with feline oral health and FORL. Methodology. Supragingival plaque was collected from 25 cats with a healthy oral cavity and 40 cats with FORL. DNA was extracted from each sample, the V4 region of the 16S rRNA gene amplified by polymerase chain reaction and amplicons sequenced. Diversity and species richness analyses were performed, principal component analysis was used to explore differences between the oral microbiomes of healthy cats and those with FORL, and linear discriminant analysis effect size was used to assess differences between the groups. Results. The six most abundant bacterial genera identified were Bergeyella , Capnocytophaga, Lampropedia, Morexella, Porphyromonas and Treponema . Two-step cluster analysis of the data identified two FORL sub-groups (FORL-1, FORL-2). The FORL-2 sub-group was very similar to the healthy group, whilst the FORL-1 sub-group was clearly different from both the FORL-2 sub-group and the healthy groups. In this analysis, Capnocytophaga (P &lt;0.001) and Lampropedia (P &lt;0.01) were found at significantly lower levels and Porphyromonas at a slightly higher level in the FORL-1 sub-group compared to the healthy and FORL-2 sub-groups. Microbial diversity was found to be less in the FORL-1 sub-group than in the healthy group. Lampropedia sp., a phosphate-accumulating oral commensal species, was significantly lower in the FORL-1 sub-group. Conclusion. The oral microbiota associated with the FORL-1 sub-group is distinct from that found in the healthy group and FORL-2 sub-group. Lampropedia species may influence the local calcium-phosphate ratio, which could be a factor in tooth and bone resorption observed in FORL