Metalliferous Biosignatures for Deep Subsurface Microbial Activity

Acknowledgments We thank the British Geological Survey (BGS) for the provision of samples and the Science & Technology Facilities Council (STFC) grant (ST/L001233/1) for PhD funding which aided this project. Research on selenium in reduction spheroids was also supported by NERC grants (NE/L001764/1 and NE/ M010953/1). The University of Aberdeen Raman facility was funded by the BBSRC. We also thank John Still for invaluable technical assistance.Peer reviewedPublisher PD

Tellurium and selenium in Mesoproterozoic red beds

Acknowledgements This work was supported by the NERC under Grant NE/L001764/1. We are grateful to Martin Bregman, Philip Fralick, and Phyllis Hargrave for provision of samples. David Fox and Monica leGras (CSIRO), John Still and Dave Bellis (University of Aberdeen) provided specialised technical assistance. We are grateful for three critical reviews that helped to improve the manuscript.Peer reviewedPublisher PD

Methane in sulphides from gold-bearing deposits, Britain and Ireland

We are grateful to J. Armstrong and C. Rice for provision of samples. J. Johnston is thanked for skilled technical support.Peer reviewedPostprin

Contrasting microfossil preservation and lake chemistries within the 1200–1000 Ma Torridonian Supergroup of NW Scotland

We acknowledge the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Governments. DW acknowledges funding from the European Commission and the Australian Research Council. This is publication number 838 from the Australian Research Council Centre of Excellence for Core to Crust Fluid Systems.Publisher PD

Gold in irish coal : Palaeo-concentration from metalliferous groundwaters

Peer reviewedPublisher PD

A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years