Mental health selection : common mental disorder and migration between multiple states of deprivation in a UK cohort

Funding Funding for this work was received from Public Health Wales NHS Trust as part of a report on migration and health. Support for the report was also received from the National Centre for Population Health and Wellbeing Research (NCPHWR). The eCATALYsT multiagency dataset and the baseline survey was supported by the Wales Office of Research and Development (SCC99/1/105 and R00/1/017). The follow-up survey was supported by a Welsh Assembly Government/Medical Research Council Health Research Partnership Award (H07-3-030), and the electronic cohort is supported by a National Institute for Social Care and Health Research Welsh Assembly Government Translational Health Research Platform Award (TPR08-020). Data availability statement Data may be obtained from a third party and are not publicly available. The electronic cohort is securely stored and maintained on the Secure Anonymised Information Linkage (SAIL) databank at Swansea University Medical School. The authors welcome general enquiries and ideas for new collaborations. Readers with an interest in further details should contact Professor Shantini Paranjothy, Principal Investigator.Peer reviewedPublisher PD

Acrebol, a novel toxic peptaibol produced by an Acremonium exuviarum indoor isolate

Aims: To identify a toxin and its producer isolated from woody material in a building where the occupants experienced serious ill health symptoms. Methods and Results: Hyphal extracts of an indoor fungus, identified as the cycloheximide-tolerant species Acremonium exuviarum, inhibited motility of boar spermatozoa (EC50 5 ± 2 lg of crude solids ml)1) and caused cytolysis of murine neuroblastoma cells (MNA) and feline fetal lung cells (FL). The responsible substances were purified and identified as two structurally similar, heatstable, novel, toxic peptaibols, 1726 Da and 1740 Da, respectively, with amino acid sequences of Acetyl-Phe-Iva ⁄ Val-Gln-Aib-Ile-Thr-Leu-Aib-Pro-Aib-Gln- Pro-Aib-(X-X-X)-SerOH and Acetyl-Phe-Iva ⁄ Val-Gln-Aib-Ile-Thr-Leu-Val-Pro- Aib-Gln-Pro-Aib-(X-X-X)-SerOH. Purified acrebol inhibited motility of boar sperm, depleted ATP half-content in 1 day (EC50 of 0Æ1 lg ml)1, 60 nmol l)1) depolarised the mitochondria after 2 days, but did not affect the cellular content in NADH. This indicates mitochondrial toxicity. Plate-grown biomass of A. exuviarum BMB4 contained 0Æ1–1% (w ⁄ w) of acrebol, depending on the culture medium. Conclusions: Acrebol paralysed the energy generation of mammalian cells suggesting that mitochondria were its target of action. Significance and Impact of the Study: Acremonium exuviarum, as an indoor fungus, is potentially hazardous to health because of the toxic peptaibols that it produces.Peer reviewe

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine

Landscape genomics and biased FST approaches reveal single nucleotide polymorphisms under selection in goat breeds of North-East Mediterranean

<p>Abstract</p> <p>Background</p> <p>In this study we compare outlier loci detected using a <it>F<smcaps>ST </smcaps></it>based method with those identified by a recently described method based on spatial analysis (SAM). We tested a panel of single nucleotide polymorphisms (SNPs) previously genotyped in individuals of goat breeds of southern areas of the Mediterranean basin (Italy, Greece and Albania). We evaluate how the SAM method performs with SNPs, which are increasingly employed due to their high number, low cost and easy of scoring.</p> <p>Results</p> <p>The combined use of the two outlier detection approaches, never tested before using SNP polymorphisms, resulted in the identification of the same three loci involved in milk and meat quality data by using the two methods, while the <it>F<smcaps>ST </smcaps></it>based method identified 3 more loci as under selection sweep in the breeds examined.</p> <p>Conclusion</p> <p>Data appear congruent by using the two methods for <it>F<smcaps>ST </smcaps></it>values exceeding the 99% confidence limits. The methods of <it>F<smcaps>ST </smcaps></it>and SAM can independently detect signatures of selection and therefore can reduce the probability of finding false positives if employed together. The outlier loci identified in this study could indicate adaptive variation in the analysed species, characterized by a large range of climatic conditions in the rearing areas and by a history of intense trade, that implies plasticity in adapting to new environments.</p

Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately