Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer

Background: Risk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities—such as radiation pneumonitis—during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors. Methods: We performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines. Results: miRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation. Conclusions: miR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help predict unexpected responses to radiation therapy, such as toxicity. Electronic supplementary material The online version of this article (doi:10.1186/s13014-016-0636-4) contains supplementary material, which is available to authorized users

Evidence gaps and biodiversity threats facing the marine environment of the United Kingdom’s Overseas Territories

Understanding the evidence base and identifying threats to the marine environment is critical to ensure cost-effective management and to identify priorities for future research. The United Kingdom (UK) government is responsible for approximately 2% of the world’s oceans, most of which belongs to its 14 Overseas Territories (UKOTs). Containing biodiversity of global significance, and far in excess of the UK mainland’s domestic species, there has recently been a strong desire from many of the UKOTs, the UK Government, and NGOs to improve marine management in these places. Implementing evidence-based marine policy is, however, challenged by the disparate nature of scientific research in the UKOTs and knowledge gaps about the threats they face. Here, we address these issues by systematically searching for scientific literature which has examined UKOT marine biodiversity and by exploring publicly available spatial threat data. We find that UKOT marine biodiversity has received consistent, but largely low, levels of scientific interest, and there is considerable geographical and subject bias in research effort. Of particular concern is the lack of research focus on management or threats to biodiversity. The extent and intensity of threats vary amongst and within the UKOTs but unsurprisingly, climate change associated threats affect them all and direct human stressors are more prevalent in those with higher human populations. To meet global goals for effective conservation and management, there is an urgent need for additional and continued investment in research and management in the Overseas Territories, particularly those that have been of lesser focus

FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair

BRCA1/2 proteins function in homologous recombination (HR)-mediated DNA repair and cooperate with Fanconi anemia (FA) proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2-deficient tumors upregulate Polθ-mediated alternative end-joining (alt-EJ) repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Polθ recruitment at sites of damage and alt-EJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork

Presentation_1_Linking electromagnetic induction data to soil properties at field scale aided by neural network clustering.pptx

IntroductionThe mapping of soil properties, such as soil texture, at the field scale is important Q6 in the context of national agricultural planning/policy and precision agriculture. Electromagnetic Induction (EMI) surveys are commonly used to measure soil apparent electrical conductivity and can provide valuable insights into such subsurface properties. MethodsMulti-receiver or multi-frequency instruments provide a vertical distribution of apparent conductivity beneath the instrument, while the mobility of such instruments allows for spatial coverage. Clustering is the grouping together of similar multi-dimensional data, such as the processed EMI data over a field. A neural network clustering process, where the number of clusters can be objectively determined, results in a set of one-dimensional apparent electrical conductivity cluster centers, which are representative of the entire three-dimensional dataset. These cluster centers are used to guide inversions of apparent conductivity data to give an estimate of the true electrical conductivity distribution at a site.Results and discussionThe method is applied to two sites and the results demonstrate a correlation between (true) electrical conductivity with soil texture (sampled prior to the EMI surveys) which is superior to correlations where no clustering is included. The method has the potential to be developed further, with the aim of improving the prediction of soil properties at cluster scale, such as texture, from EMI data. A particularly important conclusion from this initial study is that EMI data should be acquired prior to a focused soil sampling campaign to calibrate the electrical conductivity – soil property correlations.</p

An assessment of the surface ozone trend in ireland relevant to air pollution and environmental protection

Hourly data (1994-2009) of surface ozone concentrations at eight monitoring sites have been investigated to assess target level and long-term objective exceedances and their trends. The European Union (EU) ozone target value for human health (60 ppb-maximum daily 8-hour running mean) has been exceeded for a number of years for almost all sites but never exceeded the set limit of 25 exceedances in one year. Second highest annual hourly and 4th highest annual 8-hourly mean ozone concentrations have shown a statistically significant negative trend for in-land sites of Cork-Glashaboy, Monaghan and Lough Navar and no significant trend for the Mace Head site. Peak afternoon ozone concentrations averaged over a three year period from 2007 to 2009 have been found to be lower than corresponding values over a three-year period from 1996 to 1998 for two sites: Cork-Glashaboy and Lough Navar sites. The EU long-term objective value of AOT40 (Accumulated Ozone Exposure over a threshold of 40 ppb) for protection of vegetation (3 ppm-hour, calculated from May to July) has been exceeded, on an individual year basis, for two sites: Mace Head and Valentia. The critical level for the protection of forest (10 ppm-hour from April to September) has not been exceeded for any site except at Valentia in the year 2003. AOT40-Vegetation shows a significant negative trend for a 3-year running average at Cork-Glashaboy (-0.13 +/- 0.02 ppm-hour per year), at Lough Navar (-0.05 +/- 0.02 ppm-hour per year) and at Monaghan (-0.03 +/- 0.03 ppm-hour per year-not statistically significant) sites. No statistically significant trend was observed for the coastal site of Mace head. Overall, with the exception of the Mace Head and Monaghan sites, ozone measurement records at Irish sites show a downward negative trend in peak values that affect human health and vegetation. (c) Author(s) 2012. This work is distributed under the Creative Commons Attribution 3.0 License

Time to recovery of VICC to an INR <2 comparing patients receiving and initial antivenom dose of one vial (N = 18, blue line), two vials (N = 43, green line), or three or more vials (N = 43, red line).

<p>Time to recovery of VICC to an INR <2 comparing patients receiving and initial antivenom dose of one vial (N = 18, blue line), two vials (N = 43, green line), or three or more vials (N = 43, red line).</p