Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen-specific IgE in Ugandan communities.

BACKGROUND: Serum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries. METHODS: Among community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma. RESULTS: Total IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE. CONCLUSIONS AND CLINICAL RELEVANCE: Our immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics

An active-radio-frequency-identification system capable of identifying co-locations and social-structure: Validation with a wild free-ranging animal

Abstract Behavioural events that are important for understanding sociobiology and movement ecology are often rare, transient and localised, but can occur at spatially distant sites e.g. territorial incursions and co‐locating individuals. Existing animal tracking technologies, capable of detecting such events, are limited by one or more of: battery life; data resolution; location accuracy; data security; ability to co‐locate individuals both spatially and temporally. Technology that at least partly resolves these limitations would be advantageous. European badgers (Meles meles L.), present a challenging test‐bed, with extra‐group paternity (apparent from genotyping) contradicting established views on rigid group territoriality with little social‐group mixing. In a proof of concept study we assess the utility of a fully automated active‐radio‐frequency‐identification (aRFID) system combining badger‐borne aRFID‐tags with static, wirelessly‐networked, aRFID‐detector base‐stations to record badger co‐locations at setts (burrows) and near notional border latrines. We summarise the time badgers spent co‐locating within and between social‐groups, applying network analysis to provide evidence of co‐location based community structure, at both these scales. The aRFID system co‐located animals within 31.5 m (adjustable) of base‐stations. Efficient radio transmission between aRFIDs and base‐stations enables a 20 g tag to last for 2–5 years (depending on transmission interval). Data security was high (data stored off tag), with remote access capability. Badgers spent most co‐location time with members of their own social‐groups at setts; remaining co‐location time was divided evenly between intra‐ and inter‐social‐group co‐locations near latrines and inter‐social‐group co‐locations at setts. Network analysis showed that 20–100% of tracked badgers engaged in inter‐social‐group mixing per week, with evidence of trans‐border super‐groups, that is, badgers frequently transgressed notional territorial borders. aRFID occupies a distinct niche amongst established tracking technologies. We validated the utility of aRFID to identify co‐locations, social‐structure and inter‐group mixing within a wild badger population, leading us to refute the conventional view that badgers (social‐groups) are territorial and to question management strategies, for controlling bovine TB, based on this model. Ultimately aRFID proved a versatile system capable of identifying social‐structure at the landscape scale, operating for years and suitable for use with a range of species. EPSRC WILDSENSING projec

Silica burial enhanced by iron limitation in oceanic upwelling margins

In large swaths of the ocean, primary production by diatoms may be limited by the availability of silica, which in turn limits the biological uptake of carbon dioxide. The burial of biogenic silica in the form of opal is the main sink of marine silicon. Opal burial occurs in equal parts in iron-limited open-ocean provinces and upwelling margins, especially the eastern Pacific upwelling zone. However, it is unclear why opal burial is so efficient in this margin. Here we measure fluxes of biogenic material, concentrations of diatom-bound iron and silicon isotope ratios using sediment traps and a sediment core from the Gulf of California upwelling margin. In the sediment trap material, we find that periods of intense upwelling are associated with transient iron limitation that results in a high export of silica relative to organic carbon. A similar correlation between enhanced silica burial and iron limitation is evident in the sediment core, which spans the past 26,000 years. A global compilation also indicates that hotspots of silicon burial in the ocean are all characterized by high silica to organic carbon export ratios, a diagnostic trait for diatoms growing under iron stress. We therefore propose that prevailing conditions of silica limitation in the ocean are largely caused by iron deficiency imposing an indirect constraint on oceanic carbon uptake

The Global Health System: Actors, Norms, and Expectations in Transition

In the first in a series of four articles highlighting the changing nature of global health institutions, Nicole Szlezák and colleagues outline the origin and aim of the series

Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis

The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are responsible for the ability of MYC to initiate and/or maintain tumorigenesis is not clear. Previously, we have shown that upon brief MYC inactivation, some tumors undergo sustained regression. Here we demonstrate that upon MYC inactivation there are global permanent changes in gene expression detected by microarray analysis. By applying StepMiner analysis, we identified genes whose expression most strongly correlated with the ability of MYC to induce a neoplastic state. Notably, genes were identified that exhibited permanent changes in mRNA expression upon MYC inactivation. Importantly, permanent changes in gene expression could be shown by chromatin immunoprecipitation (ChIP) to be associated with permanent changes in the ability of MYC to bind to the promoter regions. Our list of candidate genes associated with tumor maintenance was further refined by comparing our analysis with other published results to generate a gene signature associated with MYC-induced tumorigenesis in mice. To validate the role of gene signatures associated with MYC in human tumorigenesis, we examined the expression of human homologs in 273 published human lymphoma microarray datasets in Affymetrix U133A format. One large functional group of these genes included the ribosomal structural proteins. In addition, we identified a group of genes involved in a diverse array of cellular functions including: BZW2, H2AFY, SFRS3, NAP1L1, NOLA2, UBE2D2, CCNG1, LIFR, FABP3, and EDG1. Hence, through our analysis of gene expression in murine tumor models and human lymphomas, we have identified a novel gene signature correlated with the ability of MYC to maintain tumorigenesis

Predicting sulfotyrosine sites using the random forest algorithm with significantly improved prediction accuracy

addresses: School of Biosciences, University of Exeter, Exeter EX4 5DE, UK. [email protected]: PMCID: PMC2777180types: Journal Article; Research Support, Non-U.S. Gov't© 2009 Yang; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tyrosine sulfation is one of the most important posttranslational modifications. Due to its relevance to various disease developments, tyrosine sulfation has become the target for drug design. In order to facilitate efficient drug design, accurate prediction of sulfotyrosine sites is desirable. A predictor published seven years ago has been very successful with claimed prediction accuracy of 98%. However, it has a particularly low sensitivity when predicting sulfotyrosine sites in some newly sequenced proteins

A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

We propose a biophysical model of Escherichia coli that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that E. coli is in a state of balanced exponential steadystate growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven E. coli strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside E. coli is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type E. coli cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity

The history of Quaker employers A deconstruction

SIGLEAvailable from British Library Document Supply Centre-DSC:3597.811(98/3) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Revealing the hidden lives of underground animals using magneto-inductive tracking.

Currently, there is no existing method for automatically tracking the location of burrowing animals when they are underground, consequently zoologists only have a partial view of their subterranean behaviour and habits. Conventional RF based methods of localization are unsuitable because electromagnetic waves are severely attenuated by soil and moisture. Here, we use an as yet unexploited method of localization, namely magneto-inductive (MI) localization. Magnetic fields are not affected by soil or water, and thus have virtually unattenuated ground penetration. In this paper, we present a method that allows the position of an animal to be determined through soil. Not only does this enable the study of behaviour, it also allows the structure of the tunnel to be automatically mapped as the animal moves through it. We describe the application for tracking wild European Badgers (Meles meles) within their burrows, providing experimental data from a two month deployment. Copyright 2010 ACM