Computational analysis of pathogen-borne metallo β-lactamases reveals discriminating structural features between B1 types

<p>Abstract</p> <p>Background</p> <p>Genes conferring antibiotic resistance to groups of bacterial pathogens are cause for considerable concern, as many once-reliable antibiotics continue to see a reduction in efficacy. The recent discovery of the metallo β-lactamase <it>blaNDM-1 </it>gene, which appears to grant antibiotic resistance to a variety of Enterobacteriaceae <it>via </it>a mobile plasmid, is one example of this distressing trend. The following work describes a computational analysis of pathogen-borne MBLs that focuses on the structural aspects of characterized proteins.</p> <p>Results</p> <p>Using both sequence and structural analyses, we examine residues and structural features specific to various pathogen-borne MBL types. This analysis identifies a linker region within MBL-like folds that may act as a discriminating structural feature between these proteins, and specifically resistance-associated acquirable MBLs. Recently released crystal structures of the newly emerged NDM-1 protein were aligned against related MBL structures using a variety of global and local structural alignment methods, and the overall fold conformation is examined for structural conservation. Conservation appears to be present in most areas of the protein, yet is strikingly absent within a linker region, making NDM-1 unique with respect to a linker-based classification scheme. Variability analysis of the NDM-1 crystal structure highlights unique residues in key regions as well as identifying several characteristics shared with other transferable MBLs.</p> <p>Conclusions</p> <p>A discriminating linker region identified in MBL proteins is highlighted and examined in the context of NDM-1 and primarily three other MBL types: IMP-1, VIM-2 and ccrA. The presence of an unusual linker region variant and uncommon amino acid composition at specific structurally important sites may help to explain the unusually broad kinetic profile of NDM-1 and may aid in directing research attention to areas of this protein, and possibly other MBLs, that may be targeted for inactivation or attenuation of enzymatic activity.</p

Evaluation of Aeromagnetic Data of Ilesha Area of Oyo State Nigeria using Analytical Signal (ASM) and Local wavenumber (LWN)

This paper presents the analysis and interpretation of an aeromagnetic data of Ilesha area, (Sheet 243) sourced from Nigeria Geological Survey Agency. The area is located between 7.5oN and 8.0oN of latitude and longitude 4.5oE to 5.0oE. Two methods: Analytic Signal Method (ASM) and Local wavenumber (LWN) were used. These methods were used to process and analyse the data so as to generate the depth to magnetic sources as well as the source locations. The results obtained showed a shallower depth range limit for ASM between 0.348 km and 1.28 km, which is less than the result of LWN within the range of 0.478 km-1.51 km. The results also revealed more source locations in ASM result in comparison with LWN. The overall results of the methods have revealed the prospect of the lithology of the area for magnetic mineral exploration in the field of applied geophysics.Keywords: Aeromagnetic survey, Analytic signal, Magnetic Anomaly, Local wave number, litholog

New Pool of Cortical Interneuron Precursors in the Early Postnatal Dorsal White Matter

The migration of cortical γ-aminobutyric acidergic interneurons has been extensively studied in rodent embryos, whereas few studies have documented their postnatal migration. Combining in vivo analysis together with time-lapse imaging on cortical slices, we explored the origin and migration of cortical interneurons during the first weeks of postnatal life. Strikingly, we observed that a large pool of GAD65-GFP-positive cells accumulate in the dorsal white matter region during the first postnatal week. Part of these cells divides and expresses the transcription factor paired box 6 indicating the presence of local transient amplifying precursors. The vast majority of these cells are immature interneurons expressing the neuronal marker doublecortin and partly the calcium-binding protein calretinin. Time-lapse imaging reveals that GAD65-GFP-positive neurons migrate from the white matter pool into the overlying anterior cingulate cortex (aCC). Some interneurons in the postnatal aCC express the same immature neuronal markers suggesting ongoing migration of calretinin-positive interneurons. Finally, bromodeoxyuridine incorporation experiments confirm that a small fraction of interneurons located in the aCC are generated during the early postnatal period. These results altogether reveal that at postnatal ages, the dorsal white matter contains a pool of interneuron precursors that divide and migrate into the aC

New pool of cortical interneuron precursors in the early postnatal dorsal white matter.

The migration of cortical γ-aminobutyric acidergic interneurons has been extensively studied in rodent embryos, whereas few studies have documented their postnatal migration. Combining in vivo analysis together with time-lapse imaging on cortical slices, we explored the origin and migration of cortical interneurons during the first weeks of postnatal life. Strikingly, we observed that a large pool of GAD65-GFP-positive cells accumulate in the dorsal white matter region during the first postnatal week. Part of these cells divides and expresses the transcription factor paired box 6 indicating the presence of local transient amplifying precursors. The vast majority of these cells are immature interneurons expressing the neuronal marker doublecortin and partly the calcium-binding protein calretinin. Time-lapse imaging reveals that GAD65-GFP-positive neurons migrate from the white matter pool into the overlying anterior cingulate cortex (aCC). Some interneurons in the postnatal aCC express the same immature neuronal markers suggesting ongoing migration of calretinin-positive interneurons. Finally, bromodeoxyuridine incorporation experiments confirm that a small fraction of interneurons located in the aCC are generated during the early postnatal period. These results altogether reveal that at postnatal ages, the dorsal white matter contains a pool of interneuron precursors that divide and migrate into the aCC

Genome scan of Diabrotica virgifera virgifera for genetic variation associated with crop rotation tolerance

Crop rotation has been a valuable technique for control of Diabrotica virgifera virgifera for almost a century. However, during the last two decades, crop rotation has ceased to be effective in an expanding area of the US corn belt. This failure appears to be due to a change in the insect's oviposition behaviour, which, in all probability, has an underlying genetic basis. A preliminary genome scan using 253 amplified fragment-length polymorphism (AFLP) markers sought to identify genetic variation associated with the circumvention of crop rotation. Samples of D. v. virgifera from east-central Illinois, where crop rotation is ineffective, were compared with samples from Iowa at locations that the behavioural variant has yet to reach. A single AFLP marker showed signs of having been influenced by selection for the circumvention of crop rotation. However, this marker was not diagnostic. The lack of markers strongly associated with the trait may be due to an insufficient density of marker coverage throughout the genome. A weak but significant general heterogeneity was observed between the Illinois and Iowa samples at microsatellite loci and AFLP markers. This has not been detected in previous population genetic studies of D. v. virgifera and may indicate a reduction in gene flow between variant and wild-type beetles

MannDB – A microbial database of automated protein sequence analyses and evidence integration for protein characterization

BACKGROUND: MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data. DESCRIPTION: MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins) are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO. CONCLUSION: MannDB comprises a large number of genomes and comprehensive protein sequence analyses representing organisms listed as high-priority agents on the websites of several governmental organizations concerned with bio-terrorism. MannDB provides the user with a BLAST interface for comparison of native and non-native sequences and a query tool for conveniently selecting proteins of interest. In addition, the user has access to a web-based browser that compiles comprehensive and extensive reports. Access to MannDB is freely available at

The lacuna of capital, the state and war? The lost global history and theory of Eastern agency

In this article I seek to constructively engage Alex Anievas’s seminal book that is deservedly the subject of this forum. For Anievas has become a key figure in the revival of Trotskyism in IR and his is one of the first book-length treatments of the New Trotskyist theory of the international. My critique is meant merely as a constructive effort to push his excellent scholarship further in terms of developing his non-Eurocentric approach. In the first section I argue that his book represents a giant leap forward for the New Trotskyist IR. However, in the following sections I argue that although undeniably a brave attempt nevertheless, in the last instance, Anievas falls a few steps short in realising a genuinely non-Eurocentric account of world politics. This is because while he certainly restores or brings in ‘the lost theory and history of IR’ that elevates class forces to a central role in shaping world politics, nevertheless he fails to bring in ‘the lost global theory and history of Eastern agency’ that constitutes, in my view, the key ingredient of a non-Eurocentric approach to world politics. I also argue that while his anti-reductionist ontological credentials are for the most part extremely impressive, nevertheless, I argue that these are compromised in his analysis of Hitler’s racism. Finally, in the conclusion I ask whether the theoretical architecture of the New Trotskyism in IR is capable of developing a non-Eurocentric approach before concluding in the affirmative with respect to its modern revisionist incarnation of which Anievas is in the vanguard

LOSITAN: A workbench to detect molecular adaptation based on a Fst-outlier method

<p>Abstract</p> <p>Background</p> <p>Testing for selection is becoming one of the most important steps in the analysis of multilocus population genetics data sets. Existing applications are difficult to use, leaving many non-trivial, error-prone tasks to the user.</p> <p>Results</p> <p>Here we present LOSITAN, a selection detection workbench based on a well evaluated <it>F</it>_<it>st</it>-outlier detection method. LOSITAN greatly facilitates correct approximation of model parameters (e.g., genome-wide average, neutral <it>F</it>_<it>st</it>), provides data import and export functions, iterative contour smoothing and generation of graphics in a easy to use graphical user interface. LOSITAN is able to use modern multi-core processor architectures by locally parallelizing fdist, reducing computation time by half in current dual core machines and with almost linear performance gains in machines with more cores.</p> <p>Conclusion</p> <p>LOSITAN makes selection detection feasible to a much wider range of users, even for large population genomic datasets, by both providing an easy to use interface and essential functionality to complete the whole selection detection process.</p

LAVA: An Open-Source Approach To Designing LAMP (Loop-Mediated Isothermal Amplification) DNA Signatures

<p>Abstract</p> <p>Background</p> <p>We developed an extendable open-source Loop-mediated isothermal AMPlification (LAMP) signature design program called LAVA (LAMP Assay Versatile Analysis). LAVA was created in response to limitations of existing LAMP signature programs.</p> <p>Results</p> <p>LAVA identifies combinations of six primer regions for basic LAMP signatures, or combinations of eight primer regions for LAMP signatures with loop primers, which can be used as LAMP signatures. The identified primers are conserved among target organism sequences. Primer combinations are optimized based on lengths, melting temperatures, and spacing among primer sites. We compare LAMP signature candidates for <it>Staphylococcus aureus </it>created both by LAVA and by PrimerExplorer. We also include signatures from a sample run targeting all strains of <it>Mycobacterium tuberculosis</it>.</p> <p>Conclusions</p> <p>We have designed and demonstrated new software for identifying signature candidates appropriate for LAMP assays. The software is available for download at <url>http://lava-dna.googlecode.com/</url>.</p

Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?

Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections.<0.001, OR:2.02) by Cox-regression analysis.The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies