280 research outputs found

    Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation.

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    Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation

    Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

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    BACKGROUND: Prostate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value. METHODOLOGY/PRINCIPAL FINDINGS: We first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7-8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men. CONCLUSION/SIGNIFICANCE: SPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA

    Amputation-free survival in 17,353 people at high risk for foot ulceration in diabetes:a national observational study

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    Acknowledgements Some of the data were presented as an abstract at the Diabetes UK Professional Conference in 2017. Diabetes data for Scotland are available for analysis by members of the Scottish Diabetes Research Network (SDRN) thanks to the hard work and dedication of NHS staff across Scotland who enter the data and people and organisations (the Scottish Care Information –Diabetes Collaboration (SCI-DC) Steering Group, the Scottish Diabetes Group, the Scottish Diabetes Survey Group, the managed clinical network managers and staff in each Health Board) involved in setting up, maintaining and overseeing SCI-DC. The SDRN receives core support from the Chief Scientist’s Office at the Scottish Government Health Department. Members of the Scottish Diabetes Research Network Epidemiology Group who do not qualify for authorship but who contributed to data collection include R. Lindsay (Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK); J. McKnight (Western General Hospital, Edinburgh, UK); S. Philip (Institute of Applied Health Sciences, University of Aberdeen, UK); Members of the Scottish Diabetes Research Network Epidemiology Group who do not qualify for authorship but who contributed to data management include L. Blackbourn (Institute of Genetics and Molecular Medicine, University of Edinburgh, UK); B. Farran (Institute of Genetics and Molecular Medicine, University of Edinburgh, UK); D. McAllister (Institute of Health and Wellbeing, University of Glasgow, UK); P. McKeigue (Usher Institute of Population Health Sciences, University of Edinburgh, UK); S. Read (Usher Institute of Population Health Sciences, University of Edinburgh, UK).Peer reviewedPublisher PD

    Conservation prioritization can resolve the flagship species conundrum

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    Conservation strategies based on charismatic flagship species, such as tigers, lions, and elephants, successfully attract funding from individuals and corporate donors. However, critics of this species-focused approach argue it wastes resources and often does not benefit broader biodiversity. If true, then the best way of raising conservation funds excludes the best way of spending it. Here we show that this conundrum can be resolved, and that the flagship species approach does not impede cost-effective conservation. Through a tailored prioritization approach, we identify places containing flagship species while also maximizing global biodiversity representation (based on 19,616 terrestrial and freshwater species). We then compare these results to scenarios that only maximized biodiversity representation, and demonstrate that our flagship-based approach achieves 79−89% of our objective. This provides strong evidence that prudently selected flagships can both raise funds for conservation and help target where these resources are best spent to conserve biodiversity

    Sodium Selenide Toxicity Is Mediated by O2-Dependent DNA Breaks

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    Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few experiments studied the direct link between this toxic agent and cell death. To address this question, we first screened a systematic collection of Saccharomyces cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor for hydrogen selenide (H2Se/HSe−/Se2−). Among the genes whose deletion caused hypresensitivity, homologous recombination and DNA damage checkpoint genes were over-represented, suggesting that DNA double-strand breaks are a dominant cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly induced DNA phosphodiester-bond breaks via an O2-dependent reaction. The reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl radicals and ruling out participations of superoxide anions or hydrogen peroxide. The •OH signature could indeed be detected by electron spin resonance upon exposure of a solution of sodium selenide to O2. Finally we showed that, in vivo, toxicity strictly depended on the presence of O2. Therefore, by combining genome-wide and biochemical approaches, we demonstrated that, in yeast cells, hydrogen selenide induces toxic DNA breaks through an O2-dependent radical-based mechanism

    An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles

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    Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences

    The Effect of Carbon Credits on Savanna Land Management and Priorities for Biodiversity Conservation

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    Carbon finance offers the potential to change land management and conservation planning priorities. We develop a novel approach to planning for improved land management to conserve biodiversity while utilizing potential revenue from carbon biosequestration. We apply our approach in northern Australia's tropical savanna, a region of global significance for biodiversity and carbon storage, both of which are threatened by current fire and grazing regimes. Our approach aims to identify priority locations for protecting species and vegetation communities by retaining existing vegetation and managing fire and grazing regimes at a minimum cost. We explore the impact of accounting for potential carbon revenue (using a carbon price of US14pertonneofcarbondioxideequivalent)onpriorityareasforconservationandtheimpactofexplicitlyprotectingcarbonstocksinadditiontobiodiversity.OurresultsshowthatimprovedmanagementcanpotentiallyraiseapproximatelyUS14 per tonne of carbon dioxide equivalent) on priority areas for conservation and the impact of explicitly protecting carbon stocks in addition to biodiversity. Our results show that improved management can potentially raise approximately US5 per hectare per year in carbon revenue and prevent the release of 1–2 billion tonnes of carbon dioxide equivalent over approximately 90 years. This revenue could be used to reduce the costs of improved land management by three quarters or double the number of biodiversity targets achieved and meet carbon storage targets for the same cost. These results are based on generalised cost and carbon data; more comprehensive applications will rely on fine scale, site-specific data and a supportive policy environment. Our research illustrates that the duel objective of conserving biodiversity and reducing the release of greenhouse gases offers important opportunities for cost-effective land management investments
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