The factors driving evolved herbicide resistance at a national scale

Repeated use of xenobiotic chemicals has selected for the rapid evolution of resistance threatening health and food security at a global scale. Strategies for preventing the evolution of resistance include cycling and mixtures of chemicals and diversification of management. We currently lack large-scale studies that evaluate the efficacy of these different strategies for minimizing the evolution of resistance. Here we use a national scale dataset of occurrence of the weed Alopecurus myosuroides (Blackgrass) in the UK to address this. Weed densities are correlated with assays of evolved resistance, supporting the hypothesis that resistance is driving weed abundance at a national scale. Resistance was correlated with the frequency of historical herbicide applications suggesting that evolution of resistance is primarily driven by intensity of exposure to herbicides, but was unrelated directly to other cultural techniques. We find that populations resistant to one herbicide are likely to show resistance to multiple herbicide classes. Finally, we show that the economic costs of evolved resistance are considerable: loss of control through resistance can double the economic costs of weeds. This research highlights the importance of managing threats to food production and healthcare systems using an evolutionarily informed approach in a proactive not reactive manner

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

Background: reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. Methods: to test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Results: correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. Conclusions: in summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue

Rotating Stars in Relativity

Rotating relativistic stars have been studied extensively in recent years, both theoretically and observationally, because of the information one could obtain about the equation of state of matter at extremely high densities and because they are considered to be promising sources of gravitational waves. The latest theoretical understanding of rotating stars in relativity is reviewed in this updated article. The sections on the equilibrium properties and on the nonaxisymmetric instabilities in f-modes and r-modes have been updated and several new sections have been added on analytic solutions for the exterior spacetime, rotating stars in LMXBs, rotating strange stars, and on rotating stars in numerical relativity.Comment: 101 pages, 18 figures. The full online-readable version of this article, including several animations, will be published in Living Reviews in Relativity at http://www.livingreviews.org

Results of a UK survey on methods for compensating for unscheduled treatment interruptions and errors in treatment delivery.

In order to obtain a preliminary overview of the current national status regarding the management of both unintentional interruptions to radiotherapy treatments and inadvertent errors in treatment delivery, a short questionnaire was sent to 60 UK radiotherapy departments, of which 35 (58%) responded. The study was initiated by the authors and was not commissioned by any professional body. Amongst the centres which responded the majority (86%) currently have standardized protocols in place for dealing with treatment interruptions and many have extended the enactment of compensation methods to cover a wider range of tumour types than are encompassed within the Royal College of Radiologists (RCR)-defined Categories 1 and 2. Fewer of the respondents (60%) have standardized methods for dealing with treatment errors. Given that 42% of centres did not respond it is difficult to assess the fuller national picture. Some smaller departments may seek protocols or advice from larger adjacent centres, but the overall percentage of centres with systems in place may be lower than indicated from the survey results. The desirability of providing training in the radiobiological methods pertaining to treatment compensation was raised by a number of respondents