76 research outputs found

    Is the attentional SNARC effect truly attentional? : Using temporal order judgements to differentiate attention from response

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    Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided in part by a Natural Science and Engineering Research Council of Canada Discovery Grant (2016-06359) awarded to Jay Pratt. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.Peer reviewe

    The transcriptional programme of Salmonella enterica serovar Typhimurium reveals a key role for tryptophan metabolism in biofilms

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    <p>Abstract</p> <p>Background</p> <p>Biofilm formation enhances the capacity of pathogenic <it>Salmonella </it>bacteria to survive stresses that are commonly encountered within food processing and during host infection. The persistence of <it>Salmonella </it>within the food chain has become a major health concern, as biofilms can serve as a reservoir for the contamination of food products. While the molecular mechanisms required for the survival of bacteria on surfaces are not fully understood, transcriptional studies of other bacteria have demonstrated that biofilm growth triggers the expression of specific sets of genes, compared with planktonic cells. Until now, most gene expression studies of <it>Salmonella </it>have focused on the effect of infection-relevant stressors on virulence or the comparison of mutant and wild-type bacteria. However little is known about the physiological responses taking place inside a <it>Salmonella </it>biofilm.</p> <p>Results</p> <p>We have determined the transcriptomic and proteomic profiles of biofilms of <it>Salmonella enterica </it>serovar Typhimurium. We discovered that 124 detectable proteins were differentially expressed in the biofilm compared with planktonic cells, and that 10% of the <it>S</it>. Typhimurium genome (433 genes) showed a 2-fold or more change in the biofilm compared with planktonic cells. The genes that were significantly up-regulated implicated certain cellular processes in biofilm development including amino acid metabolism, cell motility, global regulation and tolerance to stress. We found that the most highly down-regulated genes in the biofilm were located on <it>Salmonella </it>Pathogenicity Island 2 (SPI2), and that a functional SPI2 secretion system regulator (<it>ssrA</it>) was required for <it>S</it>. Typhimurium biofilm formation. We identified STM0341 as a gene of unknown function that was needed for biofilm growth. Genes involved in tryptophan (<it>trp</it>) biosynthesis and transport were up-regulated in the biofilm. Deletion of <it>trpE </it>led to decreased bacterial attachment and this biofilm defect was restored by exogenous tryptophan or indole.</p> <p>Conclusions</p> <p>Biofilm growth of <it>S</it>. Typhimurium causes distinct changes in gene and protein expression. Our results show that aromatic amino acids make an important contribution to biofilm formation and reveal a link between SPI2 expression and surface-associated growth in <it>S</it>. Typhimurium.</p

    Forest fire management, climate change, and the risk of catastrophic carbon losses

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    Approaches to management of fireprone forests are undergoing rapid change, driven by recognition that technological attempts to subdue fire at large scales (fire suppression) are ecologically and economically unsustainable. However, our current framework for intervention excludes the full scope of the fire management problem within the broader context of fire−vegetation−climate interactions. Climate change may already be causing unprecedented fire activity, and even if current fires are within the historical range of variability, models predict that current fire management problems will be compounded by more frequent extreme fire-conducive weather conditions (eg Fried et al. 2004)

    Functional impact of global rare copy number variation in autism spectrum disorders

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    The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviors1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability (ID)2. While ASDs are known to be highly heritable (~90%)3, the underlying genetic determinants are still largely unknown. Here, we analyzed the genome-wide characteristics of rare (<1% frequency) copy number variation (CNV) in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic CNVs (1.19 fold, P= 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P= 3.4×10−4). Among the CNVs, there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes like SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene-sets involved in cellular proliferation, projection and motility, and GTPase/Ras signaling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways

    Pressure UlceR Programme Of reSEarch (PURPOSE): using mixed methods (systematic reviews, prospective cohort, case study, consensus and psychometrics) to identify patient and organisational risk, develop a risk assessment tool and patient-reported outcome Quality of Life and Health Utility measures

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    Background: The Pressure UlceR Programme Of reSEarch (PURPOSE) consisted of two themes. Theme 1 focused on improving our understanding of individuals’ and organisational risk factors and on improving the quality of risk assessments (work packages 1–3) and theme 2 focused on developing patient-reported outcome measures (work packages 4 and 5). Methods: The programme comprised 21 individual pieces of work. Pain: (1) multicentre pain prevalence study in acute hospitals, (2) multicentre pain prevalence study in community localities incorporating (3) a comparison of case-finding methods, and (4) multicentre, prospective cohort study. Severe pressure ulcers: (5) retrospective case study, (6) patient involvement workshop with the Pressure Ulcer Research Service User Network for the UK (PURSUN UK) and (7) development of root cause analysis methodology. Risk assessment: (8) systematic review, (9) consensus study, (10) conceptual framework development and theoretical causal pathway, (11) design and pretesting of draft Risk Assessment Framework and (12) field test to assess reliability, validity, data completeness and clinical usability. Quality of life: (13) conceptual framework development (systematic review, patient interviews), (14 and 15) provisional instrument development, with items generated from patient interviews [from (1) above] two systematic reviews and experts, (16) pretesting of the provisional Pressure Ulcer Quality of Life (PU-QOL) instrument using mixed methods, (17) field test 1 including (18) optimal mode of administration substudy and item reduction with testing of scale formation, acceptability, scaling assumptions, reliability and validity, and (19) field test 2 – final psychometric evaluation to test scale targeting, item response categories, item fit, response bias, acceptability, scaling assumptions, reliability and validity. Cost–utility: (20) time trade-off task valuations of health states derived from selected PU-QOL items, and (21) validation of the items selected and psychometric properties of the new Pressure Ulcer Quality of Life Utility Index (PUQOL-UI). Key findings:Pain: prevalence studies – hospital and community patients experience both pressure area-related and pressure ulcer pain; pain cohort study – indicates that pain is independently predictive of category 2 (and above) pressure ulcer development. Severe pressure ulcers: these were more likely to develop in contexts in which clinicians failed to listen to patients/carers or recognise/respond to high risk or the presence of an existing pressure ulcer and services were not effectively co-ordinated; service users found the interactive workshop format valuable; including novel components (interviews with patients and carers) in root cause analysis improves the quality of the insights captured. Risk assessment: we developed a Pressure Ulcer Risk Assessment Framework, the PURPOSE-T, incorporating the Minimum Data Set, a screening stage, a full assessment stage, use of colour to support decision-making, and decision pathways that make a clear distinction between patients with an existing pressure ulcer(s) (or scarring from previous ulcers) who require secondary prevention and treatment and those at risk who require primary prevention (http://medhealth.leeds.ac.uk/accesspurposet). Quality of life: the final PU-QOL instrument consists of 10 scales to measure pain, exudate, odour, sleep, vitality, mobility/movement, daily activities, emotional well-being, self-consciousness and appearance, and participation (http://medhealth.leeds.ac.uk/puqol-ques). Cost–utility: seven items were selected from the PU-QOL instrument for inclusion in the PUQOL-UI (http://medhealth.leeds.ac.uk/puqol-ui); secondary study analysis indicated that item selection for the PUQOL-UI was appropriate and that the index was acceptable to patients and had adequate levels of validity. Conclusions: The PURPOSE programme has provided important insights for pressure ulcer prevention and treatment and involvement of service users in research and development, with implications for patient and public involvement, clinical practice, quality/safety/health service management and research including replication of the pain risk factor study, work exploring ‘best practice’ settings, the impact of including skin status as an indicator for escalation of preventative interventions, further psychometric evaluation of PU-QOL and PUQOL-UI the measurement of ‘disease attribution.’ Funding: The National Institute for Health Research Programme Grants for Applied Research programme

    A proteomic analysis of the osmotic shock response in 'Salmonella enterica' serovar Typhimurium

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    A proteomic analysis of the osmotic shock response in Salmonella enterica serovar Typhimurium

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    A reliable 2-dimensional gel electrophoresis methodology for the analysis of the Salmonella Typhimurium proteome was established and combined with mss spectrometry to detect and identify proteins that were differentially expressed when Salmonella was exposed to hyper-osmotic stress.  In wild type S. Typhimurium 24 proteins were differentially expressed, 13 were up-regulated and 11 down-regulated.  The proteins identified were involved in a range of bacterial systems including protein handling, protein synthesis, detoxification, metabolism and cell morphogenesis.  In addition, an ompR- mutant was used to determine which of these differentially expressed proteins were regulated by or independent of the OmpR/EnvZ regulatory system.  Generally, a similar set of components were differentially expressed in the ompR- mutant.  However, the degree of induction or repression tended to be exaggerated.  Additional analyses using the non-gel LC/MS based Protein Expression SystemTM strongly supported these results, further highlighting the up-regulation of proteins involved in cell morphogenesis, and also suggesting a subtle down-regulation of TCA cycle components. Two of the proteins that were highly induced by hyper-osmotic stress, and implicated in determining cell shape, where MreB and YgaU (the later was the most strongly induced protein, as detected by 2-D gel analyses, in both Salmonella strains).  Further mRNA analyses indicated that YgaU is transcriptionally up-regulated under hyper-osmotic stress, whereas MreB appears to be post-transcriptionally controlled.  Mutational analysis also confirmed that MreB is involved in cell morphology in Salmonella.</p

    Data from: Prescribed burning protects endangered tropical heathlands of the Arnhem Plateau, northern Australia

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    1. There are concerns that frequent intense fires are reducing biodiversity on the Arnhem Plateau within Kakadu National Park, northern Australia. Since the 1980s, prescribed burning in the early dry season has aimed to reduce the extent of late dry season wildfires. A programme of more strategic prescribed burning has been undertaken since 2007, aiming to increase intervals between fires affecting heathland and rain forest communities. 2. We assess the effectiveness of prescribed burning in Kakadu's Stone Country using a Landsat satellite-derived fire history (1980–2011), in terms of achieving ‘tolerable fire intervals’ for dominant plant communities. 3. Our analysis indicates that fire regimes have become substantially more favourable for biodiversity since the early 1980s. Although annual extent of burning has remained unchanged, two significant changes in fire regimes have occurred over the long term: (i) a switch from late dry season dominance to early dry season dominance and (ii) an increase in the abundance of long-unburnt vegetation, both of which are likely to benefit biodiversity. Demonstrating the statistical significance of changes associated with recent, more strategic fire management (2007–2011) is limited by the short duration of this management approach, although there is evidence of increasing abundance of long-unburnt vegetation during this time. 4. The view that the Arnhem Plateau's fire regimes are increasingly driving biodiversity loss (due to frequent late dry season wildfires) is erroneous; they are in a more benign state now than at any time over the last three decades, most likely due to extensive use of prescribed burning. 5. Synthesis and applications. In highly fire-prone landscapes, such as savannas, prescribed burning can be an effective means of: (i) bringing forward peak fire activity to the time of year when fire conditions are relatively mild and (ii) increasing abundance of long-unburnt vegetation. These changes are likely to favour persistence of a range of fire-sensitive communities. Our case study supports the strategic use of prescribed burning to protect fire-sensitive biota within highly fire-prone landscapes throughout the world
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