Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations

Impact of grassland burning on soil organic matter as revealed by a synchrotron- and pyrolysis-mass spectrometry-based multi-methodological approach.

Although the continuum of pyrolysed OM is an important part of soil OM (SOM) and therefore involved in global cycles, its formation and structural composition are not sufficiently known. Gaps in knowledge originate from methodological difficulties in detecting compounds formed via heating during vegetation burning. We therefore investigated soil samples (0-4 cm depth) from 33 yr treatments of periodic vegetation burning, mulching and natural succession at two grassland sites in Germany. Samples were investigated by way of X-ray absorption near edge structure (XANES) spectroscopy at the carbon (C) and nitrogen (N) K-edges, pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), Py-single photon ionisation-MS (Py-SPI-MS) and Py-field ionisation MS (Py-FIMS). The XANES spectra differentiated the sites and indicated a relative enrichment in unsaturated C for the burned treatment at one site and substituted aromatic C and non-peptide N (nitriles and/or N in aromatic systems) at both sites. All three Py-MS methods distinguished the sampling sites via variation in content of polysaccharides, N-containing compounds and lignin derived substances. Vegetation burning depleted low molecular weight compounds (Py-SPI-MS and Py-FIMS) and formed high molecular substances (Py-SPI-MS and Py-FIMS) and some N-heterocyclic aromatic products (Py-GC-MS), which were only found in the burned samples. Furthermore, Py-FIMS revealed reaction products from m/z 614 to m/z 619 for both burned treatments. In general, all methods indicated the formation of N-heterocyclics and/or more recalcitrant SOM at almost equal total organic C and N content from periodic vegetation burning

Pain control with paracetamol from a sustained release formulation and a standard release formulation after third molar surgery: a randomised control trial

Objective To compare the analgesic efficacy and safety of a sustained release (SR) paracetamol formulation (Panadol Extend) with a standard immediate release (IR) formulation (Panadol) after third molar surgery. Design A multi-centre, double-blind, randomised clinical trial. Methods Patients received either a single oral dose of SR paracetamol or IR paracetamol for pain after the removal of at least one impacted third molar requiring bone removal under general anaesthesia. Post-operative pain and pain relief assessments were undertaken at time intervals up to 8 hours. Global assessments of effectiveness were made at 4 and 8 hours. Any adverse events were also recorded. Results Of 627 randomised patients, 314 were treated with SR paracetamol and 313 with IR paracetamol. In the per protocol population at 4 hours, 35.1% of the 252 patients on SR paracetamol rated the study medication as very good or excellent compared with 27.7% of the 258 patients on IR paracetamol. There were few statistically significant differences among the secondary parameters but where they did occur they favoured SR paracetamol. Trends in favour of SR paracetamol were observed among the secondary parameters and these tended to emerge at the later time points. For example, while there was no statistically significant difference in time to re-medication between the treatment groups, the estimated time to re-medication was longer for patients treated with SR paracetamol (4 hr 5 min) compared with IR paracetamol (3 hr 10 min). The high rate of re-medication observed is consistent with that reported for IR paracetamol using the post-operative dental pain model4, 6. No difference was observed between the SR paracetamol and IR paracetamol treatment groups in distribution, incidence or severity of adverse events. Conclusions SR paracetamol and IR paracetamol are clinically and statistically equivalent. While SR paracetamol and IR paracetamol were similar in terms of both onset of analgesia and peak analgesic effect, SR paracetamol had a longer duration of activity than IR paracetamol. The safety profiles of SR paracetamol and IR paracetamol were found to be very similar