High levels of fluctuating asymmetry in populations of Apodemus flavicollis from the most contaminated areas in Chornobyl

Random deviations from the perfect symmetry of normally bilaterally symmetrical characters for an individual with a given genotype occur during individual development due to the influence of multiple environmental factors. Fluctuating asymmetry (FA) is often used as a measure of developmental instability, and can be estimated as the variance of the distribution of differences between the left and right sides. We addressed the question of whether levels of FA were elevated in radioactively contaminated populations living around Chornobyl compared to those in reference populations of the yellow-necked mouse (Apodemus flavicollis). In addition, we studied amounts of directional asymmetry (DA) when one side is larger than the other on average. There was a significant difference among populations, including reference populations, in the amount of both FA and DA. A higher level of FA was documented for the contaminated populations in close proximity to the failed Chornobyl reactor for both the asymmetry of size and shape. The FAs of size and shape were highest in populations from the most contaminated locations in the Chornobyl exclusion zone. Although the directional asymmetry of shape was also highest in the contaminated populations, it was not significantly different from those in most of the reference populations. Populations from less contaminated areas inside the Chornobyl exclusion zone did not express FA values different from those of the reference populations outside the affected area

Problems with developmental stability in two rodent species from Chornobyl

Changes in developmental patterns are some of the most important effects that may be observed at radioactively contaminated sites like those at Chornobyl. Developmental instability may arise from the interactions between an organism\u27s genotype and its environment and be manifested as deviant morphology. Fluctuating asymmetry (FA) is a measure of deviations from the expected bilateral symmetry of the body. Our objective was to test for differences in FA in two rodent species (Apodemus flavicollis and Clethrionomys glareolus) that live in habitats suirounding the failed Chornobyl reactor. Rodents were collected from four different locations (two contaminated and two reference sites), and a series of adult skulls were photographed and 24 landmarks on each skull were located on digital images from photographed skulls. FA was calculated from the differences in these landmarks on the right and left side of the skull. Significantly more asymmetry (~2X) was observed in mice and voles living around Chornobyl compared to those living at the uncontaminated reference sites. These are relatively large effects in comparison to those previously found for plants and swallows. FA can be a cheap, easily determined and sensitive indicator of radiation-induced stress in small mammals. FA can be used to prioritize environments for remediation efforts and to efficiently evaluate the effectiveness of the remediation efforts

Problems with developmental stability in two rodent species from Chornobyl

Changes in developmental patterns are some of the most important effects that may be observed at radioactively contaminated sites like those at Chornobyl. Developmental instability may arise from the interactions between an organism\u27s genotype and its environment and be manifested as deviant morphology. Fluctuating asymmetry (FA) is a measure of deviations from the expected bilateral symmetry of the body. Our objective was to test for differences in FA in two rodent species (Apodemus flavicollis and Clethrionomys glareolus) that live in habitats suirounding the failed Chornobyl reactor. Rodents were collected from four different locations (two contaminated and two reference sites), and a series of adult skulls were photographed and 24 landmarks on each skull were located on digital images from photographed skulls. FA was calculated from the differences in these landmarks on the right and left side of the skull. Significantly more asymmetry (~2X) was observed in mice and voles living around Chornobyl compared to those living at the uncontaminated reference sites. These are relatively large effects in comparison to those previously found for plants and swallows. FA can be a cheap, easily determined and sensitive indicator of radiation-induced stress in small mammals. FA can be used to prioritize environments for remediation efforts and to efficiently evaluate the effectiveness of the remediation efforts

Genetic heterogeneity of white-tailed deer: management lessons from a long-term study

Genetic data from a long-term (16-year) study of white-tailed deer (Odocoileus virginianus) on the U.S. Department of Energy\u27s Savannah River Site (SRS) were examined to evaluate spatial and temporal genetic heterogeneity in this species. Based on our analyses of the long-term data set, three major findings emerged, all of which have important implications for management of white-tailed deer: (1) There exists significant spatial genetic heterogeneity in white-tailed deer based on analyses of allozyme frequencies and mtDNA haplotypes. This heterogeneity exists on a much smaller spatial scale than would be expected for such a large and potentially mobile species as 0. virginianus. (2) The genetic structure of white-tailed deer at SRS is temporally dynamic and significant heterogeneity exists within demographic units such as age and sex classes. (3) Levels of genetic variation, as measured by multilocus heterozygosity, are frequently correlated to characteristics that are important determinants of ecological function in white-tailed deer populations. These findings are evaluated in the context of a general management model for 0. virginianus that is also applicable to other wildlife species

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response

Common Gene Variants in the Tumor Necrosis Factor (TNF) and TNF Receptor Superfamilies and NF-kB Transcription Factors and Non-Hodgkin Lymphoma Risk

BACKGROUND:A promoter polymorphism in the pro-inflammatory cytokine tumor necrosis factor (TNF) (TNF G-308A) is associated with increased non-Hodgkin lymphoma (NHL) risk. The protein product, TNF-alpha, activates the nuclear factor kappa beta (NF-kappaB) transcription factor, and is critical for inflammatory and apoptotic responses in cancer progression. We hypothesized that the TNF and NF-kappaB pathways are important for NHL and that gene variations across the pathways may alter NHL risk. METHODOLOGY/PRINCIPAL FINDINGS:We genotyped 500 tag single nucleotide polymorphisms (SNPs) from 48 candidate gene regions (defined as 20 kb 5', 10 kb 3') in the TNF and TNF receptor superfamilies and the NF-kappaB and related transcription factors, in 1946 NHL cases and 1808 controls pooled from three independent population-based case-control studies. We obtained a gene region-level summary of association by computing the minimum p-value ("minP test"). We used logistic regression to compute odds ratios and 95% confidence intervals for NHL and four major NHL subtypes in relation to SNP genotypes and haplotypes. For NHL, the tail strength statistic supported an overall relationship between the TNF/NF-kappaB pathway and NHL (p = 0.02). We confirmed the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA rs2844484 SNP most significantly and specifically associated with the major subtype, diffuse large B-cell lymphoma (DLBCL) (p-trend = 0.001). We also implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3, associated with NHL. Other gene regions identified as statistically significantly associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C. Accordingly, the single most significant SNPs associated with NHL were FAS rs4934436 (p-trend = 0.0024), IRF4 rs12211228 (p-trend = 0.0026), TNFSF13B rs2582869 (p-trend = 0.0055), TANK rs1921310 (p-trend = 0.0025), TNFSF7 rs16994592 (p-trend = 0.0024), and TNFRSF13C rs6002551 (p-trend = 0.0074). All associations were consistent in each study with no apparent specificity for NHL subtype. CONCLUSIONS/SIGNIFICANCE:Our results provide consistent evidence that variation in the TNF superfamily of genes and specifically within chromosome 6p21.3 impacts lymphomagenesis. Further characterization of these susceptibility loci and identification of functional variants are warranted