Threonine 57 is required for the post-translational activation of Escherichia coli aspartate α-decarboxylase.

Aspartate α-decarboxylase is a pyruvoyl-dependent decarboxylase required for the production of β-alanine in the bacterial pantothenate (vitamin B5) biosynthesis pathway. The pyruvoyl group is formed via the intramolecular rearrangement of a serine residue to generate a backbone ester intermediate which is cleaved to generate an N-terminal pyruvoyl group. Site-directed mutagenesis of residues adjacent to the active site, including Tyr22, Thr57 and Tyr58, reveals that only mutation of Thr57 leads to changes in the degree of post-translational activation. The crystal structure of the site-directed mutant T57V is consistent with a non-rearranged backbone, supporting the hypothesis that Thr57 is required for the formation of the ester intermediate in activation

Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation.

Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN-γ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes

The variation of G in a negatively curved space-time

Scalar-tensor (ST) gravity theories provide an appropriate theoretical framework for the variation of Newton's fundamental constant, conveyed by the dynamics of a scalar-field non-minimally coupled to the space-time geometry. The experimental scrutiny of scalar-tensor gravity theories has led to a detailed analysis of their post-newtonian features, and is encapsulated into the so-called parametrised post-newtonian formalism (PPN). Of course this approach can only be applied whenever there is a newtonian limit, and the latter is related to the GR solution that is generalized by a given ST solution under consideration. This procedure thus assumes two hypothesis: On the one hand, that there should be a weak field limit of the GR solution; On the other hand that the latter corresponds to the limit case of given ST solution. In the present work we consider a ST solution with negative spatial curvature. It generalizes a general relativistic solution known as being of a degenerate class (A) for its unusual properties. In particular, the GR solution does not exhibit the usual weak field limit in the region where the gravitational field is static. The absence of a weak field limit for the hyperbolic GR solution means that such limit is also absent for comparison with the ST solution, and thus one cannot barely apply the PPN formalism. We therefore analyse the properties of the hyperbolic ST solution, and discuss the question o defining a generalised newtonian limit both for the GR solution and for the purpose of contrasting it with the ST solution. This contributes a basic framework to build up a parametrised pseudo-newtonian formalism adequate to test ST negatively curved space-times.Comment: 7 pages, 5 figures. Contribution to the Joint European and National Astronomy Meeting (JENAM) 2010; based on a talk given by JPM in the "From Varying Couplings to Fundamental Physics" Symposiu

Searching for motifs in the behaviour of larval Drosophila melanogaster and Caenorhabditis elegans reveals continuity between behavioural states

We present a novel method for the unsupervised discovery of behavioural motifs in larval Drosophila melanogaster and Caenorhabditis elegans. A motif is defined as a particular sequence of postures that recurs frequently. The animal's changing posture is represented by an eigenshape time series, and we look for motifs in this time series. To find motifs, the eigenshape time series is segmented, and the segments clustered using spline regression. Unlike previous approaches, our method can classify sequences of unequal duration as the same motif. The behavioural motifs are used as the basis of a probabilistic behavioural annotator, the eigenshape annotator (ESA). Probabilistic annotation avoids rigid threshold values and allows classification uncertainty to be quantified. We apply eigenshape annotation to both larval Drosophila and C. elegans and produce a good match to hand annotation of behavioural states. However, we find many behavioural events cannot be unambiguously classified. By comparing the results with ESA of an artificial agent's behaviour, we argue that the ambiguity is due to greater continuity between behavioural states than is generally assumed for these organisms

A Computational Approach for Designing Tiger Corridors in India

Wildlife corridors are components of landscapes, which facilitate the movement of organisms and processes between intact habitat areas, and thus provide connectivity between the habitats within the landscapes. Corridors are thus regions within a given landscape that connect fragmented habitat patches within the landscape. The major concern of designing corridors as a conservation strategy is primarily to counter, and to the extent possible, mitigate the effects of habitat fragmentation and loss on the biodiversity of the landscape, as well as support continuance of land use for essential local and global economic activities in the region of reference. In this paper, we use game theory, graph theory, membership functions and chain code algorithm to model and design a set of wildlife corridors with tiger (Panthera tigris tigris) as the focal species. We identify the parameters which would affect the tiger population in a landscape complex and using the presence of these identified parameters construct a graph using the habitat patches supporting tiger presence in the landscape complex as vertices and the possible paths between them as edges. The passage of tigers through the possible paths have been modelled as an Assurance game, with tigers as an individual player. The game is played recursively as the tiger passes through each grid considered for the model. The iteration causes the tiger to choose the most suitable path signifying the emergence of adaptability. As a formal explanation of the game, we model this interaction of tiger with the parameters as deterministic finite automata, whose transition function is obtained by the game payoff.Comment: 12 pages, 5 figures, 6 tables, NGCT conference 201

Physicochemical property distributions for accurate and rapid pairwise protein homology detection

<p>Abstract</p> <p>Background</p> <p>The challenge of remote homology detection is that many evolutionarily related sequences have very little similarity at the amino acid level. Kernel-based discriminative methods, such as support vector machines (SVMs), that use vector representations of sequences derived from sequence properties have been shown to have superior accuracy when compared to traditional approaches for the task of remote homology detection.</p> <p>Results</p> <p>We introduce a new method for feature vector representation based on the physicochemical properties of the primary protein sequence. A distribution of physicochemical property scores are assembled from 4-mers of the sequence and normalized based on the null distribution of the property over all possible 4-mers. With this approach there is little computational cost associated with the transformation of the protein into feature space, and overall performance in terms of remote homology detection is comparable with current state-of-the-art methods. We demonstrate that the features can be used for the task of pairwise remote homology detection with improved accuracy versus sequence-based methods such as BLAST and other feature-based methods of similar computational cost.</p> <p>Conclusions</p> <p>A protein feature method based on physicochemical properties is a viable approach for extracting features in a computationally inexpensive manner while retaining the sensitivity of SVM protein homology detection. Furthermore, identifying features that can be used for generic pairwise homology detection in lieu of family-based homology detection is important for applications such as large database searches and comparative genomics.</p

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

Neural models that convince: Model hierarchies and other strategies to bridge the gap between behavior and the brain.

Computational modeling of the brain holds great promise as a bridge from brain to behavior. To fulfill this promise, however, it is not enough for models to be &apos;biologically plausible&apos;: models must be structurally accurate. Here, we analyze what this entails for so-called psychobiological models, models that address behavior as well as brain function in some detail. Structural accuracy may be supported by (1) a model&apos;s a priori plausibility, which comes from a reliance on evidence-based assumptions, (2) fitting existing data, and (3) the derivation of new predictions. All three sources of support require modelers to be explicit about the ontology of the model, and require the existence of data constraining the modeling. For situations in which such data are only sparsely available, we suggest a new approach. If several models are constructed that together form a hierarchy of models, higher-level models can be constrained by lower-level models, and low-level models can be constrained by behavioral features of the higher-level models. Modeling the same substrate at different levels of representation, as proposed here, thus has benefits that exceed the merits of each model in the hierarchy on its own