Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine.

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.

The structure of turbulence in a rapid tidal flow.

The structure of turbulence in a rapid tidal flow is characterized through new observations of fundamental statistical properties at a site in the UK which has a simple geometry and sedate surface wave action. The mean flow at the Sound of Islay exceeded 2.5 m s-1 and the turbulent boundary layer occupied the majority of the water column, with an approximately logarithmic mean velocity profile identifiable close to the seabed. The anisotropic ratios, spectral scales and higher-order statistics of the turbulence generally agree well with values reported for two-dimensional open channels in the laboratory and other tidal channels, therefore providing further support for the application of universal models. The results of the study can assist in developing numerical models of turbulence in rapid tidal flows such as those proposed for tidal energy generation.

Rhubarb (Rheum species): the role of Edinburgh in its cultivation and development.

Rhubarb was grown and used throughout China for thousands of years. It then found its way to St Petersburg where the Romanovs developed a flourishing trade in the plant to the rest of Europe. James Mounsey, a physician to the Tsar, brought back seeds from Russia to Scotland at considerable risk to himself. He passed some of the seeds to Alexander Dick and John Hope. Both these physicians then grew rhubarb at Prestonfield and the Botanic Garden (both in Edinburgh), respectively. Eventually rhubarb, in the form of Gregory's powder, became a common and popular medicine throughout the UK.

Phytoplankton community responses in a shallow lake following lanthanum-bentonite application.

The release of phosphorus (P) from bed sediments to the overlying water can delay the recovery of lakes for decades following reductions in catchment contributions, preventing water quality targets being met within timeframes set out by environmental legislation (e.g. EU Water Framework Directive: WFD). Therefore supplementary solutions for restoring lakes have been explored, including the capping of sediment P sources using a lanthanum (La)-modified bentonite clay to reduce internal P loading and enhance the recovery process. Here we present results from Loch Flemington where the first long-term field trial documenting responses of phytoplankton community structure and abundance, and the UK WFD phytoplankton metric to a La-bentonite application was performed. A Before-After-Control-Impact (BACI) analysis was used to distinguish natural variability from treatment effect and confirmed significant reductions in the magnitude of summer cyanobacterial blooms in Loch Flemington, relative to the control site, following La-bentonite application. However this initial cyanobacterial response was not sustained beyond two years after application, which implied that the reduction in internal P loading was short-lived; several possible explanations for this are discussed. One reason is that this ecological quality indicator is sensitive to inter-annual variability in weather patterns, particularly summer rainfall and water temperature. Over the monitoring period, the phytoplankton community structure of Loch Flemington became less dominated by cyanobacteria and more functionally diverse. This resulted in continual improvements in the phytoplankton compositional and abundance metrics, which were not observed at the control site, and may suggest an ecological response to the sustained reduction in filterable reactive phosphorus (FRP) concentration following La-bentonite application. Overall, phytoplankton classification indicated that the lake moved from poor to moderate ecological status but did not reach the proxy water quality target (i.e. WFD Good Ecological Status) within four years of the application. As for many other shallow lakes, the effective control of internal P loading in Loch Flemington will require further implementation of both in-lake and catchment-based measures. Our work emphasizes the need for appropriate experimental design and long-term monitoring programmes, to ascertain the efficacy of intervention measures in delivering environmental improvements at the field scale.

Tuberculin manufacturing source and breakdown incidence rate of bovine tuberculosis in British cattle, 2005-2009.

The single intradermal comparative cervical tuberculin (SICCT) test is the primary test used for surveillance for bovine tuberculosis (bTB) in cattle in Great Britain (GB). The tuberculin used can, with other factors, influence test accuracy. In this analysis, the detection of infected cattle in GB 2005-2009 was compared between SICCT tests using tuberculins manufacturered by different manufacturers. Higher rates of reactors (adjusted rate 209 vs 186 per 100,000 tests, P = 0.003) and herd bTB incidents (adjusted total breakdown rate 5.1 vs 4.5 per 100 herd-years at risk, P < 0.001) were detected using tuberculin manufactured at Weybridge compared with Lelystad. However, confirmation of infection in reactors by postmortem evidence was higher with Lelystad tuberculin (adjusted percent 44.1 vs 47.1, P = 0.018). The findings, overall, suggest slightly higher test sensitivity and lower test specificity associated with Weybridge tuberculin compared with Lelystad. Assuming effective adjustment for confounding, the overall impact of tuberculin manufacturing source (2007-2009), was calculated to range somewhere between 315 false positive breakdowns, and 1086 bTB breakdowns missed (624 confirmed) as a result of using Weybridge and Lelystad tuberculin, respectively. However, animals that tested negative to the SICCT were not slaughtered at the time of the tests, so definitive conclusions are not possible.

Characteristics of the turbulence in the flow at a tidal stream power site.

This paper analyses a set of velocity time histories which were obtained at a fixed point in the bottom boundary layer of a tidal stream, 5 m from the seabed, and where the mean flow reached 2.5 m s(-1). Considering two complete tidal cycles near spring tide, the streamwise turbulence intensity during non-slack flow was found to be approximately 12-13%, varying slightly between flood and ebb tides. The ratio of the streamwise turbulence intensity to that of the transverse and vertical intensities is typically 1 : 0.75 : 0.56, respectively. Velocity autospectra computed near maximum flood tidal flow conditions exhibit an f(-2/3) inertial subrange and conform reasonably well to atmospheric turbulence spectral models. Local isotropy is observed between the streamwise and transverse spectra at reduced frequencies of f>0.5. The streamwise integral time scales and length scales of turbulence at maximum flow are approximately 6 s and 11-14 m, respectively, and exhibit a relatively large degree of scatter. They are also typically much greater in magnitude than the transverse and vertical components. The findings are intended to increase the levels of confidence within the tidal energy industry of the characteristics of the higher frequency components of the onset flow, and subsequently lead to more realistic performance and loading predictions.

Effects of ascertainment bias and marker number on estimations of barley diversity from high-throughput SNP genotype data.

The capability of molecular markers to provide information of genetic structure is influenced by their number and the way they are chosen. This study evaluates the effects of single nucleotide polymorphism (SNP) number and selection strategy on estimates of germplasm diversity and population structure for different types of barley germplasm, namely cultivar and landrace. One hundred and sixty-nine barley landraces from Syria and Jordan and 171 European barley cultivars were genotyped with 1536 SNPs. Different subsets of 384 and 96 SNPs were selected from the 1536 set, based on their ability to detect diversity in landraces or cultivated barley in addition to corresponding randomly chosen subsets. All SNP sets except the landrace-optimised subsets underestimated the diversity present in the landrace germplasm, and all subsets of SNP gave similar estimates for cultivar germplasm. All marker subsets gave qualitatively similar estimates of the population structure in both germplasm sets, but the 96 SNP sets showed much lower data resolution values than the larger SNP sets. From these data we deduce that pre-selecting markers for their diversity in a germplasm set is very worthwhile in terms of the quality of data obtained. Second, we suggest that a properly chosen 384 SNP subset gives a good combination of power and economy for germplasm characterization, whereas the rather modest gain from using 1536 SNPs does not justify the increased cost and 96 markers give unacceptably low performance. Lastly, we propose a specific 384 SNP subset as a standard genotyping tool for middle-eastern landrace barley.

The James Lind Library: explaining and illustrating the evolution of fair tests of medical treatments.

The James Lind Library (www.jameslindlibrary.org) has been established to improve public and professional general knowledge about fair tests of treatments in healthcare and their history. Its foundation was laid ten years ago at the Royal College of Physicians of Edinburgh, and its administrative centre is in the College's Sibbald Library, one of the most important collections of historic medical manuscripts, papers and books in the world. The James Lind Library is a website that introduces visitors to the principles of fair tests of treatments, with a series of short, illustrated essays, which are currently available in English, Arabic, Chinese, French, Portuguese, Russian and Spanish. A 100-page book-- Testing Treatments--is now available free through the website, both in English and in Arabic and Spanish translations. To illustrate the evolution of ideas related to fair tests of treatments from 2000 BC to the present, the James Lind Library contains key passages and images from manuscripts, books and journal articles, many of them accompanied by commentaries, biographies, portraits and other relevant documents and images, including audio and video files. New material is being added to the website continuously, as relevant new records are identified and as methods for testing treatments evolve. A multinational, multilingual editorial team oversees the development of the website, which currently receives tens of thousands of visitors every month.

The effect of alpha 2 macroglobulin in commercial cytokine assays.

alpha 2 macroglobulin (alpha 2M), a 725 kDa plasma protein, has been reported to bind a range of cytokines. We have therefore investigated its effect on a number of commercial cytokine assays. The methylamine converted fast form of the molecule was found to reproducibly depress, by 26% or more, the standard curves obtained with certain commercial assays for IL-2 and for tumor necrosis factor alpha, and had a small inhibitory effect on some IL-4 assays. In contrast it slightly enhanced or had no effect on ELISAs for IL-1 beta and IL-6. The inhibition observed was directly proportional to the concentration of alpha 2 M used in the range 0.5-5 mg/ml. Studies in the IL-2 system also revealed that it was largely attributable to the fast form of alpha 2M. Preliminary evidence suggests that the effects observed may be dependent on the assay source. These findings may be relevant to the assay of biological fluids in which alpha 2 M is present.

A two-site immunoradiometric assay for PTH(1-84) using N and C terminal specific monoclonal antibodies.

We report the development of a two-site immunoradiometric assay for PTH(1-84) based on two site-specific monoclonal antibodies--3B3 (radiolabelled antibody) specific for PTH(1-34) and ESQ1 (on solid phase) specific for PTH(74-84). Antibody 3B3 is sensitive to the oxidation of the methionine residues in PTH(1-34) therefore hydrogen peroxide (0.1 M) is added to the incubation mixture. Validation studies confirm quantitative recovery of both oxidized and reduced PTH(1-84). The assay has a minimum detection limit of 0.5 pmol/L and a range of 1.5-250 pmol/L with an intra-assay CV of less than 10% (2.8-250 pmol/L less than 5% CV). Studies on clinical samples indicate good discrimination between normal subjects (mean 2.21; range 1.0-5.0 pmol/L) and patients with primary hyperparathyroidism (mean 21.0; range 5.8-100 pmol/L) who in turn are well separated from patients with hypercalcaemia of malignancy (14/18 less than 0.5 pmol/L).

Antibodies to normal and Alzheimer human brain structures from non-immunised mice of various ages.

Supernatants from mouse spleen hybridoma lines established without previous immunisation were screened immunohistochemically against cryostat sections of human temporal cortex and found to stain a variety of brain structures, including Alzheimer plaques and tangles. The age of the mice had no effect on antibody production.