92 research outputs found
Genetic Variants in Hormone-Related Genes and Risk of Breast Cancer
Abstract Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk
Shape resonances in nested diffraction gratings
The diffraction problem of a plane wave impinging on a grating formed by
nested cavities is solved by means of the modal method, for and
polarization modes. The cavities are formed by perfectly conducting sheets that
describe rectangular profiles. The electromagnetic response of the grating is
analyzed, paying particular attention to the generation of resonances within
the structure. The dependence of the resonances on the geometrical parameters
of the grating is studied, and results of far and near field are shown. The
results are checked and compared with those available in the literature for
certain limit cases.Comment: 18 pages, 8 figure
Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>
Molecular and morphometric variation within and between population samples of the articulate brachiopod <i>Terebratulina</i> spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation
Development and characterization of polyclonal antibodies against the aryl hydrocarbon receptor protein family (AHR1, AHR2, and AHR repressor) of Atlantic killifish Fundulus heteroclitus
Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 142 (2006): 85-94, doi:10.1016/j.cbpc.2005.10.013.The aryl hydrocarbon receptor (AHR) and AHR repressor (AHRR) proteins regulate gene expression in response to some halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons. The Atlantic killifish is a valuable model of the AHR signaling pathway, but antibodies are not available to fully characterize AHR and AHRR proteins. Using bacterially expressed AHRs, we developed specific and sensitive polyclonal antisera against the killifish AHR1, AHR2, and AHRR. In immunoblots, these antibodies recognized full-length killifish AHR and AHRR proteins synthesized in rabbit reticulocyte lysate, proteins expressed in mammalian cells transfected with killifish AHR and AHRR constructs, and AHR proteins in cytosol preparations from killifish tissues. Killifish AHR1 and AHR2 proteins were detected in brain, gill, kidney, heart, liver, and spleen. Antisera specifically precipitated their respective target proteins in immunoprecipitation experiments with in vitro-expressed proteins. Killifish ARNT2 co-precipitated with AHR1 and AHR2. These sensitive, specific, and versatile antibodies will be valuable to researchers investigating AHR signaling and other physiological processes involving AHR and AHRR proteins.Funding for this research was provided by National Institutes of Health, National Research Service Award (F32 ES05935) from the National Institute of Environmental Health Sciences (RRM), NIEHS Superfund Basic Research Program Grant P42 ES007381 at Boston University (MEH), and the Oliver S. and Jennie R. Donaldson Charitable Trust (MEH and RRM)
Directional genetic selection by pulp mill effluent on multiple natural populations of three-spined stickleback (Gasterosteus aculeatus)
Contamination can cause a rapid environmental change which may require populations to respond with evolutionary changes. To evaluate the effects of pulp mill effluents on population genetics, we sampled three-spined sticklebacks (Gasterosteus aculeatus) near four pulp mills and four adjacent reference sites and analyzed Amplified Fragment Length Polymorphism (AFLP) to compare genetic variability. A fine scale genetic structure was detected and samples from polluted sites separated from reference sites in multidimensional scaling plots (P < 0.005, 1000 permutations) and locus-by-locus Analysis of Molecular Variance (AMOVA) further confirmed that habitats are significantly separated (FST = 0.021, P < 0.01, 1023 permutations). The amount of genetic variation between populations did not differ between habitats, and populations from both habitats had similar levels of heterozygosity (polluted sites Nei’s Hs = 0.11, reference sites Nei’s Hs = 0.11). Still, pairwise FST: s between three, out of four, pairs of polluted-reference sites were significant. A FST-outlier analysis showed that 21 (8.4%) loci were statistically different from a neutral distribution at the P < 0.05 level and therefore indicated to be under divergent selection. When removing 13 FST-outlier loci, significant at the P < 0.01 level, differentiation between habitats disappeared in a multidimensional scaling plot. In conclusion, pulp mill effluence has acted as a selective agent on natural populations of G. aculeatus, causing a convergence in genotype composition change at multiple sites in an open environment
AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish
The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses
Molecular analysis of phylogeographic subspecies in three Ponto-Caspian sturgeon species
- …