191 research outputs found

    Feed-Forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

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    SummaryWe compared transcriptomes of terminally differentiated mouse 3T3-L1 and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3-L1. It is interesting that AR induction corresponded with dexamethasone activation of the glucocorticoid receptor (GR); however, when exposed to the differentiation cocktail required for adipocyte maturation, AR adopted an antagonist conformation and was transcriptionally repressed. To further explore effectors within the cocktail, we applied an image-based support vector machine (SVM) classification scheme to show that adipocyte differentiation components inhibit AR action. The results demonstrate human adipocyte differentiation, via GR activation, upregulates AR but also inhibits AR transcriptional activity

    Septic Arthritis of the Temporomandibular Joint: Case Reports and Review of the Literature

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    Septic arthritis of the temporomandibular (TM) joint is rare, but it is associated with high risk for significant morbidity

    Burning behaviour of rainscreen façades

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    Four reduced-height (5 m) BS 8414-1 façade flammability tests were conducted, three having mineral-filled aluminium composite material (ACM-A2) with polyisocyanurate (PIR) and phenolic (PF) foam and stone wool (SW) insulation, the fourth having polyethylene-filled ACM (ACM-PE) with PIR insulation. Each façade was constructed from a commercial façade engineer’s design, and built by practising façade installers. The ACM-PE/PIR façade burnt so ferociously it was extinguished after 13.5 min, for safety. The three ACM-A2 cladding panels lost their structural integrity, and melted away from the test wall, whereupon around 40% of both the combustible PIR and PF insulation burnt and contributed to the fire spread. This demonstrates why all façade products must be non-combustible, not just the outer panels. For the three ACM-A2 tests, while the temperature in front of the cavity was independent of the insulation, the temperatures within it varied greatly, depending on the insulation. The system using PF/A2 allowed fire to break through to the cavity first, as seen by a sharp increase in temperature after 17 min. For PIR/A2, the temperature increased sharply at 22 minutes, as the panel started to fall away from the wall. For SW/A2, no rapid temperature rise was observed

    Flame retardants in UK furniture increase smoke toxicity more than they reduce fire growth rate

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    This paper uses fire statistics to show the importance of fire toxicity on fire deaths and injuries, and the importance of upholstered furniture and bedding on fatalities from unwanted fires. The aim was to compare the fire hazards (fire growth and smoke toxicity) using different upholstery materials. Four compositions of sofa-bed were compared: three meeting UK Furniture Flammability Regulations (FFR), and one using materials without flame retardants intended for the mainland European market. Two of the UK sofa-beds relied on chemical flame retardants to meet the FFR, the third used natural materials and a technical weave in order to pass the test. Each composition was tested in the bench-scale cone calorimeter (ISO 5660) and burnt as a whole sofa-bed in a sofa configuration in a 3.4 × 2.25 × 2.4 m3 test room. All of the sofas were ignited with a No. 7 wood crib; the temperatures and yields of toxic products are reported. The sofa-beds containing flame retardants burnt somewhat more slowly than the non-flame retarded EU sofa-bed, but in doing so produced significantly greater quantities of the main fire toxicants, carbon monoxide and hydrogen cyanide. Assessment of the effluents' potential to incapacitate and kill is provided showing the two UK flame retardant sofa-beds to be the most dangerous, followed by the sofa-bed made with European materials. The UK sofa-bed made only from natural materials (Cottonsafe®) burnt very slowly and produced very low concentrations of toxic gases. Including fire toxicity in the FFR would reduce the chemical flame retardants and improve fire safety. [Abstract copyright: Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

    Fire behaviour of modern façade materials – Understanding the Grenfell Tower fire

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    The 2017 Grenfell Tower fire spread rapidly around the combustible façade system on the outside of the building, killing 72 people. We used a range of micro- and bench-scale methods to understand the fire behaviour of different types of façade product, including those used on the Tower, in order to explain the speed, ferocity and lethality of the fire. Compared to the least flammable panels, polyethylene-aluminium composites showed 55x greater peak heat release rates (pHRR) and 70x greater total heat release (THR), while widely-used high-pressure laminate panels showed 25x greater pHRR and 115x greater THR. Compared to the least combustible insulation products, polyisocyanurate foam showed 16x greater pHRR and 35x greater THR, while phenolic foam showed 9x greater pHRR and 48x greater THR. A few burning drips of polyethylene from the panelling are enough to ignite the foam insulation, providing a novel explanation for rapid flame-spread within the facade. Smoke from polyisocyanurates was 15x, and phenolics 5x more toxic than from mineral wool insulation. 1kg of burning polyisocyanurate insulation is sufficient to fill a 50m3 room with an incapacitating and ultimately lethal effluent. Simple, additive models are proposed, which provide the same rank order as BS8414 large-scale regulatory tests

    Impact of the structural integrity of the three-way junction of adenovirus VAI RNA on PKR inhibition

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    Sherpa Romeo green journal. Open access article. Creative Commons Attribution License applies.Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2αand attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem. Recent studies have highlighted the potential importance of the tertiary structure of the three-way junction to PKR inhibition by enabling interaction between regions of the central and terminal stems. To further investigate the role of the three-way junction, we characterized the binding affinity and inhibitory potential of central stem mutants designed to introduce subtle alterations. These results were then correlated with small-angle X-ray scattering solution studies and computational tertiary structural models. Our results demonstrate that while mutations to the central stem have no observable effect on binding affinity to PKR, mutations that appear to disrupt the structure of the three-way junction prevent inhibition of PKR. Therefore, we propose that instead of simply sequestering PKR, a specific structural conformation of the PKR-VAI complex may be required for inhibition
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