Common Polymorphisms at the <i>CYP17A1 </i>Locus Associate With Steroid Phenotype:Support for Blood Pressure Genome-Wide Association Study Signals at This Locus

Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency &gt;0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects

A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.This research was conducted as part of C.S.B.’s Ph.D dissertation, which was funded by the University of Southampton and NERC (NE/L50161X/1), and through a NERC Grant-in-Kind from the Life Sciences Mass Spectrometry Facility (LSMSF; EK267-03/16). We thank A. Bates, D. Sims, F. Neat, R. McGill and J. Newton for their analytical contributions and comments on the manuscripts.Peer reviewe

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

A benthic bioindicator reveals distinct land and ocean-Based influences in an urbanized coastal embayment.

Biogeochemical maps of coastal regions can be used to identify important influences and inputs that define nearshore environments and biota. Biogeochemical tracers can also track animal movement and their diet, monitor human coastal development, and evaluate the condition of habitats and species. However, the beneficial applications of spatial biogeochemical analysis are hindered by a limited understanding of how tracer distribution is affected by different land and ocean-based influences. To help address these knowledge gaps, we determined the spatial trends of three stable isotopes (δ13C-carbon, δ15N-nitrogen, δ34S-sulfur) and 13 major and trace elements in an urbanized coastal embayment (Moreton Bay, Australia), as incorporated into the muscle tissue of a marine consumer, the eastern king prawn Melicertus plebejus. Results were used to identify unique biochemical regions within the bay and to discuss how spatial patterns in tracers could be used to indicate the relative importance of catchment, urban and offshore drivers in coastal bays. Discriminant analysis identified seven biogeochemical regions that were likely distinguished by variation in catchment, urban, and offshore input, and habitat type. δ13C and δ15N patterns suggested nearshore areas could be distinguished by increased sediment resuspension and higher wastewater inputs from catchments. High inshore lead (Pb) and copper (Cu) concentrations were likely the result of urban input. Arsenic (As) and cadmium (Cd) increased further from shore. This trend implied oceanic influences were a significant control over As and Cd bioavailability. Cobalt (Co) and rare earths were also used to differentiate some nearshore areas, but incongruent distribution patterns in Co suggested it may be less reliable. Overall, results indicated that δ15N, δ13C, Cd, Cu, Pb and rare earth elements were the most reliable tracers to differentiate nearshore and offshore environments, and catchment-based effects. We encourage future studies to consider using a similar multivariate approach in coastal spatial analysis, and to include unrelated tracers that reflect distinct coastal influences

Feeding ecology of common demersal elasmobranch species in the Pacific coast of Costa Rica inferred from stable isotope and stomach content analyses

Knowledge of the feeding ecology and trophic interactions of marine species is essential to understanding food web dynamics and developing ecosystem-based management approaches. Given that many top predatory fishes have experienced large population declines from coastal ecosystems, it is critical to understand the role of smaller, mesopredators in coastal food webs. This study used stomach content (SCA) and stable isotope analyses (SIA) of muscle tissue (δ13C, δ15N) to examine the feeding ecology of four common demersal elasmobranchs (Mustelus henlei, Raja velezi, Zapteryx xyster and Torpedo peruana) from the Pacific coast of Costa Rica, Central America. Specifically, we investigated: (i) size- and sex-related changes in diet; (ii) dietary changes between seasons; (iii) dietary changes across depth and latitudinal gradients; and (iv) the degree of diet overlap among species. SCA showed that M. henlei, R. velezi and Z. xyster were feeding on a wide range of teleost and decapod species, whereas teleosts dominated the diet of T. peruana. Torpedo peruana had a lower prey diversity and dietary breath than the other species. Interestingly, SIA revealed a significantly larger isotopic niche breath in Z. xyster, indicating that SIA can provide a broader perspective of diet than SCA. Both SCA and SIA showed relatively low dietary overlap among species, except between R. velezi and Z. xyster which have a similar size, mouth morphology and potentially feeding behaviour. Latitude and size were identified as important drivers of the feeding ecology of elasmobranchs; however, their effect varied considerably among species and was often influenced by other factors such as sex and depth. Season had little influence on elasmobranch diet, but our data suggested that isotopic baseline values differ between geographic regions due to differences in local biogeochemical processes and/or prey availability, and possibly in response to seasonal nutrient fluctuations. This may also indicate that some of these elasmobranchs tend to use more localized habitats along the coast. The present study increased our understanding of the feeding ecology of common demersal elasmobranch species. Moreover, trophic information of elasmobranchs provided an important baseline record to understanding how trawling fisheries may impact demersal ecosystems in Costa Rica and the Central American region.Consejo Nacional de Ciencia y Tecnología de Costa Rica/[FI-449-10]/CONICIT/Costa RicaUniversidad de Costa Rica/[808-B0-536]/UCR/Costa RicaUniversidad de Costa Rica/[808-B1-547]/UCR/Costa RicaUniversidad de Costa Rica/[808-B1-537]/UCR/Costa RicaUniversidad de Costa Rica/[111-A4-508]/UCR/Costa RicaConservation International and MarViva/[]//Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches

County child poverty rates in the US: a spatial regression approach

We apply methods of exploratory spatial data analysis (ESDA) and spatial regression analysis to examine intercounty variation in child poverty rates in the US. Such spatial analyses are important because regression models that exclude explicit specification of spatial effects, when they exist, can lead to inaccurate inferences about predictor variables. Using county-level data for 1990, we re-examine earlier published results [Friedman and Lichter (Popul Res Policy Rev 17:91–109, 1998)]. We find that formal tests for spatial autocorrelation among county child poverty rates confirm and quantify what is obvious from simple maps of such rates: the risk of a child living in poverty is not (spatially) a randomly distributed risk at the county level. Explicit acknowledgment of spatial effects in an explanatory regression model improves considerably the earlier published regression results, which did not take account of spatial autocorrelation. These improvements include: (1) the shifting of “wrong sign” parameters in the direction originally hypothesized by the authors, (2) a reduction of residual squared error, and (3) the elimination of any substantive residual spatial autocorrelation. While not without its own problems and some remaining ambiguities, this reanalysis is a convincing demonstration of the need for demographers and other social scientists to examine spatial autocorrelation in their data and to explicitly correct for spatial externalities, if indicated, when performing multiple regression analyses on variables that are spatially referenced. Substantively, the analysis improves the estimates of the joint effects of place-influences and family-influences on child poverty. Copyright Springer Science+Business Media B.V. 2006Child poverty, Exploratory spatial data analysis, Spatial error models, Spatial lag models, Spatial regression,

Data from: A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30&deg; and 50&deg; of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches. </span