146 research outputs found

    Stability monitoring of a rail slope using acoustic emission

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    The paper details the use of acoustic emission generated by active waveguide subsurface instrumentation to monitor the stability of a rail soil cutting slope failure. Operation of the active waveguide, unitary battery-operated acoustic emission sensor and warning communication system are described. Previous field trials reported by the authors demonstrate that acoustic emission rates generated by active waveguides are proportional to the velocity of slope movement, and can therefore be used to detect changes in rates of movement in response to destabilising and stabilising effects, such as rainfall and remediation, respectively. The paper presents a field trial of the acoustic emission monitoring system at a reactivated rail-cutting slope failure at Players Crescent, Totton, Southampton, UK. The results of the monitoring are compared with both periodic and continuous deformation measurements. The study demonstrated that acoustic emission monitoring can provide continuous information on displacement rates, with high temporal resolution. The ability of the monitoring system to detect slope movements and disseminate warnings by way of text messages is presented. The monitoring approach is shown to provide real-time information that could be used by operators to make decisions on traffic safety

    Hypoxia-responsive microRNAs and trans-acting small interfering RNAs in Arabidopsis

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    Low-oxygen (hypoxia) stress associated with natural phenomena such as waterlogging, results in widespread transcriptome changes and a metabolic switch from aerobic respiration to anaerobic fermentation. High-throughput sequencing of small RNA libraries obtained from hypoxia-treated and control root tissue identified a total of 65 unique microRNA (miRNA) sequences from 46 families, and 14 trans-acting small interfering RNA (tasiRNA) from three families. Hypoxia resulted in changes to the abundance of 46 miRNAs from 19 families, and all three tasiRNA families. Chemical inhibition of mitochondrial respiration caused similar changes in expression in a majority of the hypoxia-responsive small RNAs analysed. Our data indicate that miRNAs and tasiRNAs play a role in gene regulation and possibly developmental responses to hypoxia, and that a major signal for these responses is likely to be dependent on mitochondrial function

    eIF4A Inhibition Allows Translational Regulation of mRNAs Encoding Proteins Involved in Alzheimer's Disease

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    Alzheimer's disease (AD) is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta), a cleavage product of amyloid precursor protein (APP). Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective

    The human insulin receptor mRNA contains a functional internal ribosome entry segment.

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    Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5'-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective

    PRAME Is a Golgi-Targeted Protein That Associates with the Elongin BC Complex and Is Upregulated by Interferon-Gamma and Bacterial PAMPs

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    Preferentially expressed antigen in melanoma (PRAME) has been described as a cancer-testis antigen and is associated with leukaemias and solid tumours. Here we show that PRAME gene transcription in leukaemic cell lines is rapidly induced by exposure of cells to bacterial PAMPs (pathogen associated molecular patterns) in combination with type 2 interferon (IFNγ). Treatment of HL60 cells with lipopolysaccharide or peptidoglycan in combination with IFNγ resulted in a rapid and transient induction of PRAME transcription, and increased association of PRAME transcripts with polysomes. Moreover, treatment with PAMPs/IFNγ also modulated the subcellular localisation of PRAME proteins in HL60 and U937 cells, resulting in targeting of cytoplasmic PRAME to the Golgi. Affinity purification studies revealed that PRAME associates with Elongin B and Elongin C, components of Cullin E3 ubiquitin ligase complexes. This occurs via direct interaction of PRAME with Elongin C, and PRAME colocalises with Elongins in the Golgi after PAMP/IFNγ treatment. PRAME was also found to co-immunoprecipitate core histones, consistent with its partial localisation to the nucleus, and was found to bind directly to histone H3 in vitro. Thus, PRAME is upregulated by signalling pathways that are activated in response to infection/inflammation, and its product may have dual functions as a histone-binding protein, and in directing ubiquitylation of target proteins for processing in the Golgi

    Identification and characterisation of seed storage protein transcripts from Lupinus angustifolius

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    <p>Abstract</p> <p>Background</p> <p>In legumes, seed storage proteins are important for the developing seedling and are an important source of protein for humans and animals. <it>Lupinus angustifolius </it>(L.), also known as narrow-leaf lupin (NLL) is a grain legume crop that is gaining recognition as a potential human health food as the grain is high in protein and dietary fibre, gluten-free and low in fat and starch.</p> <p>Results</p> <p>Genes encoding the seed storage proteins of NLL were characterised by sequencing cDNA clones derived from developing seeds. Four families of seed storage proteins were identified and comprised three unique α, seven β, two γ and four δ conglutins. This study added eleven new expressed storage protein genes for the species. A comparison of the deduced amino acid sequences of NLL conglutins with those available for the storage proteins of <it>Lupinus albus </it>(L.), <it>Pisum sativum </it>(L.), <it>Medicago truncatula </it>(L.), <it>Arachis hypogaea </it>(L.) and <it>Glycine max </it>(L.) permitted the analysis of a phylogenetic relationships between proteins and demonstrated, in general, that the strongest conservation occurred within species. In the case of 7S globulin (β conglutins) and 2S sulphur-rich albumin (δ conglutins), the analysis suggests that gene duplication occurred after legume speciation. This contrasted with 11S globulin (α conglutin) and basic 7S (γ conglutin) sequences where some of these sequences appear to have diverged prior to speciation. The most abundant NLL conglutin family was β (56%), followed by α (24%), δ (15%) and γ (6%) and the transcript levels of these genes increased 10<sup>3 </sup>to 10<sup>6 </sup>fold during seed development. We used the 16 NLL conglutin sequences identified here to determine that for individuals specifically allergic to lupin, all seven members of the β conglutin family were potential allergens.</p> <p>Conclusion</p> <p>This study has characterised 16 seed storage protein genes in NLL including 11 newly-identified members. It has helped lay the foundation for efforts to use molecular breeding approaches to improve lupins, for example by reducing allergens or increasing the expression of specific seed storage protein(s) with desirable nutritional properties.</p

    Human Sensory LTP Predicts Memory Performance and Is Modulated by the BDNF Val66Met Polymorphism

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    Background: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val66Met; a single-nucleotide polymorphism (SNP) implicated in memory function.Methods: Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory.Results: The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance.Conclusions: The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function

    Humanising the interview process: an evaluation of Service User/Carers contribution to value based recruitment in a Pre-registration Adult Nursing Programme.

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    Within the UK there has been move towards value based recruitment (VBR) as a response to some highly publicised poor standards of care with the National Health Service (Francis 2013). In 2014, Health Education England (HEE) published their VBR Framework which articulated how recruitment of healthcare practitioners needed to focus on how applicants’ individual values/behaviours aligned with core values of the NHS Constitution (DoH 2013). Higher Education Institutes were expected to comply as 50% of student nurse programmes are based in healthcare settings. During 2014-2015 the pre-registration adult nursing team redesigned the interview process to increase a focus on VBR: integral to this, we felt was the inclusion of Service Users/Carers within the interview process. Following training SU/Carers graded applicants in a group activity alongside academic and practice partners. There have been few research studies published evaluating SU/Carers engagement in Pre-registration Adult Nursing interviews probably due to the challenges of implementing SU/Carer engagement in the large cohort numbers that adult nursing attracts. This mixed-method evaluation analysed the perspectives of differing stakeholders (Candidates, SU/Carers, Academics and Practice Partners) regarding the role SU/Carer engagement in Adult Nursing Pre-registration interviews. Early findings from candidates have highlighted they value the involvement of SU/Carers in the interview process, SU/Carers add a “human dimension” ensuring a focus on the heart of nursing and its value base rather than the role of nursing and associated nursing tasks. This paper will present the full evaluation identifying areas of good practice, some of the challenges as well recommendations for future work. References Department of Health. (2013) NHS Constitution. Department of Health: London. Francis, R. (2013) Report of the Mid Staffordshire NHS Foundation Trust Public Inquiry; Executive Summary. London. Health Education England. (2014) Value Based Recruitment Framework. Available from: http://hee.nhs.uk/wp-content/blogs.dir/321/files/2014/10/VBR-Framework.pdf (accessed 07/02/15

    The Astropy Problem

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    The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software
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