Researching the lives of disabled children and young people

Why a Special Issue of Children & Society dedicated to disabled children and young people? The simple answer to that question is ‘because disabled children are children first and foremost’. The vast majority of disabled children and young people in the western world live at home with their families, most attending mainstream schools, and disabled children and young people worldwide have rights to inclusion and equal treatment enshrined in national legislation and international conventions. Yet they often remain left out – from generic children’s research, from policy-making about children’s services and, in their everyday lives, from inclusion in friendship groups and social and sporting activities

Mid-infrared resonant cavity light emitting diodes operating at 4.5 μm

We report on a mid-infrared resonant cavity light emitting diode (RCLED) operating at the wavelength of 4.5 μm with narrow spectral linewidth at room temperature. Compared to a reference LED without a resonant cavity our RCLED exhibits (85x) higher peak intensity, (13x) higher integrated output power, (16x) narrower spectral linewidth and (7x) superior temperature stability. The device consists of a one-wavelength thick micro-cavity containing an Al0.12In0.88As/InAs0.85Sb0.15 quantum well active region sandwiched between two high contrast AlAs0.08Sb0.92/GaSb distributed Bragg reflector mirrors, grown lattice–matched on GaSb by molecular beam epitaxy. The high spectral brightness, narrow linewidth and superior temperature stability, are attractive features, enabling these devices to be used for detection of N2O at 4.5 μm. We show that with only minor adjustments the gases CO2 (4.2 μm) and CO (4.6 μm) are also readily accessible

Use of XAS for the elucidation of metal structure and function: applications to nickel biochemistry, molecular toxicology, and carcinogenesis.

Nickel has been shown to be an essential trace element involved in the metabolism of several species of bacteria, archea, and plants. In these organisms, nickel is involved in enzymes that catalyze both non-redox (e.g., urease, glyoxalase I) and redox (e.g., hydrogenase, carbon monoxide dehydrogenase, superoxide dismutase) reactions, and proteins involved in the transport, storage, metallocenter assembly, and regulation of nickel concentration have evolved. Studies of structure/function relationships in nickel biochemistry reveal that cysteine ligands are used to stabilize the Ni(III/II) redox couple. Certain nickel compounds have also been shown to be potent human carcinogens. A likely target for carcinogenic nickel is nuclear histone proteins. Here we present X-ray absorption spectroscopic studies of a model Ni peptide designed to help characterize the structure of the nickel complexes formed with histones and place them in the context of nickel structure/function relationships, to gain insights into the molecular mechanism of nickel carcinogenesis

Inevitability and containment of replication errors for eukaryotic genome lengths spanning Megabase to Gigabase

The replication of DNA is initiated at particular sites on the genome called replication origins (ROs). Understanding the constraints that regulate the distribution of ROs across different organisms is fundamental for quantifying the degree of replication errors and their downstream consequences. Using a simple probabilistic model, we generate a set of predictions on the extreme sensitivity of error rates to the distribution of ROs, and how this distribution must therefore be tuned for genomes of vastly different sizes. As genome size changes from megabases to gigabases, we predict that regularity of RO spacing is lost, that large gaps between ROs dominate error rates but are heavily constrained by the mean stalling distance of replication forks, and that, for genomes spanning ∼100 megabases to ∼10 gigabases, errors become increasingly inevitable but their number remains very small (three or less). Our theory predicts that the number of errors becomes significantly higher for genome sizes greater than ∼10 gigabases. We test these predictions against datasets in yeast, Arabidopsis, Drosophila, and human, and also through direct experimentation on two different human cell lines. Agreement of theoretical predictions with experiment and datasets is found in all cases, resulting in a picture of great simplicity, whereby the density and positioning of ROs explain the replication error rates for the entire range of eukaryotes for which data are available. The theory highlights three domains of error rates: negligible (yeast), tolerable (metazoan), and high (some plants), with the human genome at the extreme end of the middle domain

Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>HIV-1 infection is associated with profound dysfunction of myeloid dendritic cells, for reasons that remain ill-defined. Soluble HLA class I molecules can have important inhibitory effects on T cells and NK cells, but may also contribute to reduced functional properties of professional antigen-presenting cells. Here, we investigated the expression of soluble HLA class I isoforms during HIV-1 infection and assessed their functional impact on antigen-presenting characteristics of dendritic cells.</p> <p>Results</p> <p>Soluble HLA class I molecules were highly upregulated in progressive HIV-1 infection as determined by quantitative Western blots. This was associated with strong increases of intracellular expression of HLA class I isoforms in dendritic cells and monocytes. Using mixed lymphocyte reactions, we found that soluble HLA class I molecules effectively inhibited the antigen-presenting properties of dendritic cells, however, there was no significant influence of HLA class I molecules on the cytokine-secretion properties of these cells. The immunomodulatory effects of soluble HLA class I molecules were mediated by interactions with inhibitory myelomonocytic MHC class I receptors from the Leukocyte Immunoglobulin Like Receptor (LILR) family.</p> <p>Conclusions</p> <p>During progressive HIV-1 infection, soluble HLA class I molecules can contribute to systemic immune dysfunction by inhibiting the antigen-presenting properties of myeloid dendritic cells through interactions with inhibitory myelomonocytic HLA class I receptors.</p

A comparative study of free oligosaccharides in the milk of domestic animals

This study was conducted to provide a comprehensive analysis of the oligosaccharides in the milk of a variety of important domestic animals including cow, goat, sheep, pig, horse, and dromedary camel. Using an analytical workflow which included ultra-performance hydrophilic interaction liquid chromatography with fluorescence detection (UPLC-HILIC-FLD) and coupling to a quadrupole time of flight (qTOF) mass spectrometer (MS), detailed oligosaccharide libraries were established. The partial or full characterization of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar- specific exoglycosidases. Relative peak quantification of the 2-AB labelled oligosaccharides provided additional information. Milks from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed and thirteen of these structures were previously identified in human milk. The direct comparison of the oligosaccharide mixtures could contribute to a better understanding of possible differences in their biological effects and highlight the potential value of animal milks for commercial oligosaccharide extraction.Fil: Albrecht, Simone. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; IrlandaFil: Lane, Jonathan A.. Teagasc Food Research Centre; IrlandaFil: Mariño, Karina Valeria. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Al Busadah, Khalid A.. King Faisal University. Camel Research Center; Arabia SauditaFil: Carrington, Stephen D.. University College Dublin. Veterinary Sciences Centre; IrlandaFil: Hickey, Rita M.. Teagasc Food Research Centre; IrlandaFil: Rudd, Pauline M.. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irland

Modeling atmospheric effects of the September 1859 Solar Flare

We have modeled atmospheric effects, especially ozone depletion, due to a solar proton event which probably accompanied the extreme magnetic storm of 1-2 September 1859. We use an inferred proton fluence for this event as estimated from nitrate levels in Greenland ice cores. We present results showing production of odd nitrogen compounds and their impact on ozone. We also compute rainout of nitrate in our model and compare to values from ice core data.Comment: Revised version including improved figures; Accepted for publication in Geophys. Res. Lett, chosen to be highlighted by AG