Chemical and physical dynamics of marine pockmarks with insights into the organic carbon cycling on the Malin Shelf and in Dunmanus Bay, Ireland.

Pockmarks are specific type of marine geological setting resembling craters or pits. They are considered surface expression of fluid flow in the marine subsurface. Pockmarks are widespread in the aquatic environment but the understanding of their formation mechanisms, relationship with marine macro- and micro-biota and their geochemistry remains limited. Despite numerous findings of these features in Irish waters they received little attention and remain poorly studied. In this work extensive geophysical data sets collected by the Irish National Seabed Survey and its successor the INFOMAR project as well in situ sediment samples were utilized to provide baseline information on the nature of some of these features, the processes they are fuelled by and their geochemical characteristics. Pockmarks from open shelf (Malin Shelf) and bay, fjord like environment (Dunmanus Bay) are compared and theories of their formation are formulated. Sediment from these features was extensively studied utilizing advanced geotechnical and geochemical tools to describe and quantify processes taking place in the subsurface. Organic matter was characterized on a molecular level by combined biomarker and advanced Nuclear Magnetic Resonance approach

CV10_28 Irish Sea cruise report

Cruise CV10_28 mobilized and demobilized from Howth, Co. Dublin, on the 2nd and 7th June 2010 respectively, and totalled over 112 operational hours. The objectives of this cruise were primarily to investigate and sample previously identified methane-related seepage structures in the Irish Designated Seabed Zone (IDSZ) of the Irish Sea, to carry out sampling grids of Dublin Bay and of the region of the IDSZ from Dublin Bay to Dundalk Bay for multidisciplinary geochemical and microbiological studies, and also to sample the water column for dissolved organic matter studies. A total of 113 sampling stations were successfully sampled: 46 grabs; 55 boxcores (0.25m2); 5 gravity cores (1m); and 7 vibrocores (3m). Gas-related seepage features successfully investigated were methane-derived authigenic carbonates (MDAC) in the Codling Fault Zone (CFZ), the Lambay Deep mud diapir, and also a shallow pockmark in the northen mudbelt region. Four videolines with over six hours of video footage were acquired in the MDAC target sites. Video footage and image stills of clusters of MDAC slabs, nodules and outcroppings, as well as indications enhanced anaerobic oxidation of methane (AOM) were successfully obtained. These features were subsequently successfully ground-truthed, sampled and preliminary geochemical analysis was carried out, thereby proving MDAC mounds in the CFZ are distinct features caused by active sub-surface seepage of methane. The Lambay Deep mud diapir was investigated by videoline deployment, whereby no distinct differences in seabed structure or biodiversity were observed. Fine sandy muds with relatively high macrofaunal biodiversity characterized seabed both inside and outside of Lambay Deep. The feature and surrounding seabed was ground-truthed by vibrocore and boxcore, and results supported the videoline findings. Sub-surface sediment (0-3m) was characterized by homogenous well-sorted fine sandy mud, with low infauna and shell presence, and little or no evidence of sub-surface anoxia. The mudbelt pockmark was investigated by videoline deployment and also subsequently ground-truthed by gravity core and boxcore. Videoline and sampling evidence suggests that the pockmark and reference samples from the surrounding seabed is uniform, and characterized by very fine mud with little sub-surface zonation. Previous sub-bottom profiling of the feature suggests no evidence of gas seepage or accumulations in the vicinity of the pockmark. The weather and sampling conditions were overall favourable throughout the cruise but the lack of dynamic positioning aboard the Celtic Voyager and also the restriction on the vibrocore to slack water and day-time use resulted in some sampling limitations and incomplete secondary objectives. Overall CV10_28 achieved the vast majority of its objectives, and a comprehensive foundation for numerous studies and peer-reviewed publications has been established

Hydrographic controls on marine organic matter fate and microbial diversity in the western Irish Sea

Cycling of organic matter (OM) is the key biological process in the marine environment and knowledge of the sources and the reactivity of OM, in addition to factors controlling its distribution in estuarine, coastal and shelf sediments are of key importance for understanding global biogeochemical cycles. With recent advances in cultivation-independent molecular approaches to microbial ecology, the key role of prokaryotes in global biogeochemical cycling in marine ecosystems has been emphasised. However, spatial studies combining the distribution and fate of OM with microbial community abundance and diversity remain rare. Here, a combined spatial lipid biomarker and 16S rRNA tagged pyrosequencing study was conducted in surface sediments and particulate matter across hydrographically distinct zones associated with the seasonal western Irish Sea gyre. The aim was to assess the spatial variation of, and factors controlling, marine organic cycling and sedimentary microbial communities across these distinct zones. The distribution of phospholipid fatty acids, source-specific sterols, wax esters and C25 highly branched isoprenoids indicate that diatoms, dinoflagellates and green algae were the major contributors of marine organic matter, while the distribution of cholesterol, wax esters and C20 and C22 polyunsaturated fatty acids have highlighted the importance of copepod grazing for mineralizing organic matter in the water column5. This marine OM production and mineralisation was greatest in well-mixed waters compared to offshore stratified waters. Lipid analysis and 16S rRNA PCR-DGGE profiling also suggests that sedimentary bacterial abundance increases while community diversity decreases in offshore stratified waters. The major bacterial classes are the Deltaproteobacteria, Clostridia, Flavobacteriia, Gammaproteobactera and Bacteroiidia. At the family/genus level most groups appear to be associated with organoheterotrophic processing of sedimentary OM, ranging from degradation of complex organic matter (e.g. Tepidibacter sp.) to sulfur-dependent utilisation of simple organic molecules (e.g. Desulfobulbaceae and Desulfuromonadaceae)

Biomarkers reveal the effects of hydrography on the sources and fate of marine and terrestrial organic matter in the western Irish Sea

A suite of lipid biomarkers were investigated from surface sediments and particulatematter across hydrographically distinct zones associated with the western Irish Sea gyre and the seasonal bloom. The aim was to assess the variation of organic matter (OM) composition, production, distribution and fate associated with coastal and southern mixed regions and also the summer stratified region. Based on the distribution of a suite of diagnostic biomarkers, including phospholipid fatty acids, source-specific sterols, wax esters and C25 highly branched isoprenoids, diatoms, dinoflagellates and green algae were identified as major contributors of marine organic matter (MOM) in this setting. The distribution of cholesterol, wax esters and C20 and C22 polyunsaturated fatty acids indicate that copepod grazing represents an important process for mineralising this primary production. Net tow data from 2010 revealed much greater phytoplankton and zooplankton biomass in well-mixed waters compared to stratified waters. This appears to be largely reflected in MOM input to surface sediments. Terrestrial organic matter (TOM), derived from higher plants, was identified as a major source of OM regionally, but was concentrated in proximity to major riverine input at the Boyne Estuary and Dundalk Bay. Near-bottom residual circulation and the seasonal gyre also likely play a role in the fate of TOM in the western Irish Sea

Częstość występowania mutacji somatycznych RAS w raku rdzeniastym tarczycy — analiza populacji polskiej

Introduction: Somatic RET mutations are detectable in two-thirds of sporadic cases of medullary thyroid cancer (MTC). Recent studies reported a high proportion of RAS somatic mutations in RET negative tumours, which may indicate RAS mutation as a possible alternative genetic event in sporadic MTC tumorigenesis. Thus, the aim of the study was to evaluate the frequency of somatic RAS mutations in sporadic medullary thyroid cancer in the Polish population and to relate the obtained data to the presence of somatic RET mutations.Material and methods: Somatic mutations (RET, RAS genes) were evaluated in 78 snap-frozen MTC samples (57 sporadic and 21 hereditary) by direct sequencing. Next, three randomly selected RET-negative MTC samples were analysed by the next generation sequencing.Results: RAS mutation was detected in 26.5% of 49 sporadic MTC tumours. None of all the analysed samples showed N-RAS mutation. When only RET-negative samples were considered, the prevalence of RAS mutation was 68.7%, compared to 6% observed in RET-positive samples. Most of these mutations were located in H-RAS codon 61 (72%). None of 21 hereditary MTC samples showed any RAS mutations.Conclusions: RAS mutations constitute a frequent molecular event in RET-negative sporadic medullary thyroid carcinoma in Polish patients. However, their role in MTC tumorigenesis remains unclear. (Endokrynol Pol 2015; 66 (2): 121–125)Wstęp: Somatyczne mutacje proto-onkogenu RET wykrywane są w trzech czwartych wszystkich sporadycznych raków rdzeniastych tarczycy (MTC). Ostatnie badania wykazały, że mutacja genu RAS jest również częstym wydarzeniem w sporadycznych guzach MTC, co może oznaczać, że mutacje genów z rodziny RAS są alternatywnym wydarzeniem molekularnym w kancerogezie sporadycznej postaci tego raka. Z tego względu celem niniejszej pracy było oszacowanie częstości występowania mutacji genów RAS w sporadycznym raku rdzeniastym tarczycy w populacji polskiej i odniesieniu częstości ich występowania do obecności mutacji somatycznych proto-onkogenu RET.Materiał i metody: Materiał do badań stanowiło 78 fragmentów guza raka rdzeniastego tarczycy (57 próbek postaci sporadycznej i 21 dziedzicznej MTC). Analizowano mutacje genu RET, H-RAS, K-RAS i N-RAS metodą bezpośredniego sekwencjonowania a także 3 próbki raka sporadycznego, wybrane losowo, zostały zeskwencjonowane metodą głębokiego sekwencjonowania (Illumina).Wyniki: Mutację genów RAS wykryto w 26,5% z 49 przeanalizowanych guzów sporadycznej postaci MTC. Natomiast, gdy tylko brano pod uwagę próbki RET-negatywne, częstość występowania mutacji genów RAS wynosiła 68,7% w porównaniu z 6% obserwowanych w guzach RET-pozytywnych. Nie wykryto, w żadnej z próbek, mutacji genu N-RAS. Najczęściej wykrywaną mutacją była zmiana w kodonie 61 genu H-RAS (72%). Nie wykryto mutacji genów RAS w żadnej z próbek dziedzicznego guza raka tarczycy.Wnioski: Mutacje somatyczne genów RAS są częstym wydarzeniem obserwowanym w RET-negatywnych sporadycznych rakach rdzeniastych tarczycy w populacji polskiej. Jednakże rola tych mutacji w rozwoju rdzeniastego raka tarczycy nie jest do końca poznana. (Endokrynol Pol 2015; 66 (2): 121–125

A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations.

Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6-23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.This research was supported by ERC Starting Investigator grant (FP7 - 261213) to T.K. http://erc.europa.eu/. CTS, YX, QA and MS were supported by the Wellcome Trust (098051). TA was supported by The Wellcome Trust (WT100066MA). M.M and R.V. were supported by EU ERDF Centre of Excellence in Genomics to EBC; T.K, M.M and R.V. by Estonian Institutional Research grant (IUT24-1), and M.M by Estonian Science Foundation (grant 8973).This is the accepted manuscript. The final version is available from Cell/Elsevier at http://www.cell.com/ajhg/abstract/S0002-9297%2814%2900422-4

Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD) and JDRF and supported by grant U01 DK062418 from the US National Institutes of Health. Further support was provided by grants from the NIDDK (DK046635 and DK085678) to P.C. and by a joint JDRF and Wellcome Trust grant (WT061858/09115) to the Diabetes and Inflammation Laboratory at Cambridge University, which also received support from the NIHR Cambridge Biomedical Research Centre. ImmunoBase receives support from Eli Lilly and Company. C.W. and H.G. are funded by the Wellcome Trust (089989). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). We gratefully acknowledge the following groups and individuals who provided biological samples or data for this study. We obtained DNA samples from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council and the Wellcome Trust. We acknowledge use of DNA samples from the NIHR Cambridge BioResource. We thank volunteers for their support and participation in the Cambridge BioResource and members of the Cambridge BioResource Scientific Advisory Board (SAB) and Management Committee for their support of our study. We acknowledge the NIHR Cambridge Biomedical Research Centre for funding. Access to Cambridge BioResource volunteers and to their data and samples are governed by the Cambridge BioResource SAB. Documents describing access arrangements and contact details are available at http://www.cambridgebioresource.org.uk/. We thank the Avon Longitudinal Study of Parents and Children laboratory in Bristol, UK, and the British 1958 Birth Cohort team, including S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton, for preparing and providing the control DNA samples. This study makes use of data generated by the Wellcome Trust Case Control Consortium, funded by Wellcome Trust award 076113; a full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/.This is the author accepted manuscript. The final version is available via NPG at http://www.nature.com/ng/journal/v47/n4/full/ng.3245.html

FineMAV: AFR+EAS+EUR

Header:<div><p>CHR, POS, REF_ALLELE, ALT_ALLELE, DER_ALLELE, POP, DAP, DAF_GLOB, DAPxDAF_GLOB, DDAF_AFR_EUR, DDAF_AFR_EAS, DDAF_EAS_EUR, DAF_EUR, DAF_EAS, DAF_AFR, CADD, DAPxDAF_AFR, DAPxDAF_EUR, DAPxDAF_EAS, FineMAV_AFR, FineMAV_EUR, FineMAV_EAS</p></div

FineMAV: AFR+EAS+EUR

Header:<div><p>CHR, POS, REF_ALLELE, ALT_ALLELE, DER_ALLELE, POP, DAP, DAF_GLOB, DAPxDAF_GLOB, DDAF_AFR_EUR, DDAF_AFR_EAS, DDAF_EAS_EUR, DAF_EUR, DAF_EAS, DAF_AFR, CADD, DAPxDAF_AFR, DAPxDAF_EUR, DAPxDAF_EAS, FineMAV_AFR, FineMAV_EUR, FineMAV_EAS</p></div

FineMAV: custom script

Example of FineMAV implementatio