203 research outputs found

    State-of-the-art glycosaminoglycan characterization

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    Glycosaminoglycans (GAGs) are heterogeneous acidic polysaccharides involved in a range of biological functions. They have a significant influence on the regulation of cellular processes and the development of various diseases and infections. To fully understand the functional roles that GAGs play in mammalian systems, including disease processes, it is essential to understand their structural features. Despite having a linear structure and a repetitive disaccharide backbone, their structural analysis is challenging and requires elaborate preparative and analytical techniques. In particular, the extent to which GAGs are sulfated, as well as variation in sulfate position across the entire oligosaccharide or on individual monosaccharides, represents a major obstacle. Here, we summarize the current state-of-the-art methodologies used for GAG sample preparation and analysis, discussing in detail liquid chromatograpy and mass spectrometry-based approaches, including advanced ion activation methods, ion mobility separations and infrared action spectroscopy of mass-selected species

    Recall and awareness of gambling advertising and sponsorship in sport in the UK: a study of young people and adults

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    Background: The impact of gambling advertisements shown during sporting events on young people is an important public health issue. While extensive research has taken place in Australia, there is still only a limited understanding of this issue in the United Kingdom (UK). Method: A mixed methods study was conducted with 71 family groups comprised of 99 young people (8–16 years) and 71 adults recruited at six sites across South London, England (May–July 2018). Interviewer-assisted surveys investigated recall and awareness of sports betting brands using interviews and a magnet placement board activity developed in Australia. Quantitative data were analysed using descriptive statistics, with qualitative data interpreted using thematic analysis techniques. Results: Just under half of young people (n = 46, 46%) and more than two thirds of adults (n = 49, 71%) were able, unprompted, to name at least one gambling brand. Boys had a significantly higher recall of brands than girls, as did young people who watched a lot of football on television. Almost two thirds of young people (n = 63, 63%) correctly placed one or more shirt sponsor magnets next to the corresponding football team, and 30% (n = 30) correctly placed three or more sponsors magnets next to the corresponding football team. Just under two thirds of adults (n = 44, 62%) correctly placed one or more shirt sponsors magnets next to the corresponding football team. Young people recalled seeing gambling advertising on television (n = 78), technology/screens (n = 49), and in association with sports teams (n = 43). Adults recalled seeing advertising on television (n = 56), on technology/screens (n = 37), in sports stadiums (n = 34), and in betting venues (n = 34). Over three quarters of young people (n = 74 out of 95 responses, 78%) and 86% of adults (n = 59 out of 69 responses) thought that betting had become a normal part of sport. Conclusion: In order to reduce the exposure of young people to gambling advertising, policymakers in the UK should consider comprehensive approaches, similar to those applied in tobacco control, which cover all forms of advertising, including promotion and sponsorship

    ‘Occasionally there are moments of light’: the challenges of primary school teaching in England, and the factors that motivate teachers to stay in the profession

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    This research, exploring the health and well-being of education professionals, was carried out at the behest of a Multi-Academy Trust of five primary schools. The intention was to assess the needs of educators, before designing a programme to support them. Data were collected through anonymous online survey from 244 staff in primary schools in England. Similar to previous literature, respondents reported feeling stressed and overwhelmed with their workload; as well as feeling undervalued, lacking autonomy and experiencing low morale. Our data suggest that these factors damaged educators’ health and well-being and, for some, impacted negatively upon their home lives. The general negativity of responses was tempered by mentions of the more intrinsically rewarding aspects of the role. This research highlights significant changes that are needed to education funding and policy, whilst suggesting approaches that schools can take, in the meantime, to protect the health and wellbeing of their staff

    Water Enables Efficient CO2 Capture from Natural Gas Flue Emissions in an Oxidation-Resistant Diamine-Appended Metal-Organic Framework.

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    Supported by increasingly available reserves, natural gas is achieving greater adoption as a cleaner-burning alternative to coal in the power sector. As a result, carbon capture and sequestration from natural gas-fired power plants is an attractive strategy to mitigate global anthropogenic CO2 emissions. However, the separation of CO2 from other components in the flue streams of gas-fired power plants is particularly challenging due to the low CO2 partial pressure (∼40 mbar), which necessitates that candidate separation materials bind CO2 strongly at low partial pressures (≤4 mbar) to capture ≥90% of the emitted CO2. High partial pressures of O2 (120 mbar) and water (80 mbar) in these flue streams have also presented significant barriers to the deployment of new technologies for CO2 capture from gas-fired power plants. Here, we demonstrate that functionalization of the metal-organic framework Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) with the cyclic diamine 2-(aminomethyl)piperidine (2-ampd) produces an adsorbent that is capable of ≥90% CO2 capture from a humid natural gas flue emission stream, as confirmed by breakthrough measurements. This material captures CO2 by a cooperative mechanism that enables access to a large CO2 cycling capacity with a small temperature swing (2.4 mmol CO2/g with ΔT = 100 °C). Significantly, multicomponent adsorption experiments, infrared spectroscopy, magic angle spinning solid-state NMR spectroscopy, and van der Waals-corrected density functional theory studies suggest that water enhances CO2 capture in 2-ampd-Mg2(dobpdc) through hydrogen-bonding interactions with the carbamate groups of the ammonium carbamate chains formed upon CO2 adsorption, thereby increasing the thermodynamic driving force for CO2 binding. In light of the exceptional thermal and oxidative stability of 2-ampd-Mg2(dobpdc), its high CO2 adsorption capacity, and its high CO2 capture rate from a simulated natural gas flue emission stream, this material is one of the most promising adsorbents to date for this important separation

    Context-Dependent Medicinal Effects of Anabasine and Infection-Dependent Toxicity in Bumble Bees

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    Background Floral phytochemicals are ubiquitous in nature, and can function both as antimicrobials and as insecticides. Although many phytochemicals act as toxins and deterrents to consumers, the same chemicals may counteract disease and be preferred by infected individuals. The roles of nectar and pollen phytochemicals in pollinator ecology and conservation are complex, with evidence for both toxicity and medicinal effects against parasites. However, it remains unclear how consistent the effects of phytochemicals are across different parasite lineages and environmental conditions, and whether pollinators actively self-medicate with these compounds when infected. Approach Here, we test effects of the nectar alkaloid anabasine, found in Nicotiana, on infection intensity, dietary preference, and survival and performance of bumble bees (Bombus impatiens). We examined variation in the effects of anabasine on infection with different lineages of the intestinal parasite Crithidia under pollen-fed and pollen-starved conditions. Results We found that anabasine did not reduce infection intensity in individual bees infected with any of four Crithidia lineages that were tested in parallel, nor did anabasine reduce infection intensity in microcolonies of queenless workers. In addition, neither anabasine nor its isomer, nicotine, was preferred by infected bees in choice experiments, and infected bees consumed less anabasine than did uninfected bees under no-choice conditions. Furthermore, anabasine exacerbated the negative effects of infection on bee survival and microcolony performance. Anabasine reduced infection in only one experiment, in which bees were deprived of pollen and post-pupal contact with nestmates. In this experiment, anabasine had antiparasitic effects in bees from only two of four colonies, and infected bees exhibited reduced—rather than increased—phytochemical consumption relative to uninfected bees. Conclusions Variation in the effect of anabasine on infection suggests potential modulation of tritrophic interactions by both host genotype and environmental variables. Overall, our results demonstrate that Bombus impatiens prefer diets without nicotine and anabasine, and suggest that the medicinal effects and toxicity of anabasine may be context dependent. Future research should identify the specific environmental and genotypic factors that determine whether nectar phytochemicals have medicinal or deleterious effects on pollinators

    Expressed sequence tags from Peromyscus testis and placenta tissue: Analysis, annotation, and utility for mapping

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    <p>Abstract</p> <p>Background</p> <p>Mice of the genus <it>Peromyscus </it>are found in nearly every habitat from Alaska to Central America and from the Atlantic to the Pacific. They provide an evolutionary outgroup to the <it>Mus/Rattus </it>lineage and serve as an intermediary between that lineage and humans. Although <it>Peromyscus </it>has been studied extensively under both field and laboratory conditions, research has been limited by the lack of molecular resources. Genes associated with reproduction typically evolve rapidly and thus are excellent sources of evolutionary information. In this study we describe the generation of two cDNA libraries, one from placenta and one from testis, characterize the resulting ESTs, and describe their utility for mapping the <it>Peromyscus </it>genome.</p> <p>Results</p> <p>The 5' ends of 1,510 placenta and 4,798 testis clones were sequenced. Low quality sequences were removed and after clustering and contig assembly, 904 unique placenta and 2,002 unique testis sequences remained. Average lengths of placenta and testis ESTs were 711 bp and 826 bp, respectively. Approximately 82% of all ESTs were identified using the BLASTX algorithm to <it>Mus </it>and <it>Rattus</it>, and 34 – 54% of all ESTs could be assigned to a biological process gene ontology category in either <it>Mus </it>or <it>Rattus</it>. Because the <it>Peromyscus </it>genome organization resembles the <it>Rattus </it>genome more closely than <it>Mus </it>we examined the distribution of the <it>Peromyscus </it>ESTs across the rat genome finding markers on all rat chromosomes except the Y. Approximately 40% of all ESTs were specific to only one location in the <it>Mus </it>genome and spanned introns of an appropriate size for sequencing and SNP detection. Of the primers that were tried 54% provided useful assays for genotyping on interspecific backcross and whole-genome radiation hybrid cell panels.</p> <p>Conclusion</p> <p>The 2,906 <it>Peromyscus </it>placenta and testis ESTs described here significantly expands the molecular resources available for the genus. These ESTs allow for specific PCR amplification and broad coverage across the genome, creating an excellent genetic marker resource for the generation of a medium-density genomic map. Thus, this resource will significantly aid research of a genus that is uniquely well-suited to both laboratory and field research.</p

    Multisite Binding of a General Anesthetic to the Prokaryotic Pentameric Erwinia chrysanthemi Ligand-gated Ion Channel (ELIC)

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    Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABAA/C receptors, and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anesthetics. Here, we report the x-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore and equates with a noncompetitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7–β10 strands. Together, these results extend our understanding of pLGIC modulation and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multisite model of allosteric modulation in this family of ion channels

    Optogenetic Apoptosis: Light-Triggered Cell Death

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    An optogenetic Bax has been designed that facilitates light-induced apoptosis. We demonstrate that mitochondrial recruitment of a genetically encoded light-responsive Bax results in the release of mitochondrial proteins, downstream caspase 3 cleavage, changes in cellular morphology, and ultimately cell death. Mutagenesis of a key phosphorylatable residue or modification of the C-terminus mitigates background levels (dark) of apoptosis due to Bax overexpression. The mechanism of optogenetic Bax-mediated apoptosis was explored using a series of small molecules known to interfere with various steps in programmed cell death. Optogenetic Bax appears to form a mitochondrial apoptosis-induced channel analogous to that of endogenous Bax
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