Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.     

Greenhouse Effects in Global Warming based on Analogical Reasoning

Using an analogy in science and everyday life is a double-edged sword because they are accompanied by alternative ideas, in addition to scientific concepts. Schools and public education explain global warming by making a common analogy between this phenomenon and greenhouse effects (Chen in Philos Cogn Sci 105–114, 2012). Unfortunately, this analogy sometimes produces various incorrect explanatory mental models. To construct a correct understanding of global warming, it is necessary: first, to investigate the attributes of analogical reasoning; second, to understand these features by restructuring the greenhouse analogy; and third, to explore the problems and benefits of the greenhouse analogy. The characteristics of relations, rather than objects, must be mapped according to the principle of systematicity, but the public tends to preserve the attributes of the base domain, which is mapped relatively easily. In conclusion, certain facets of the prevailing greenhouse analogy cause a distorted public view of climate change. We must use the greenhouse analogy and yet simultaneously emphasize the relations and attributes highlighted and hidden in the analogy during evaluation.     

The genome of the extremophile crucifer Thellungiella parvula

Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a number of tandem duplications that, by the nature of the duplicated genes, suggest a possible basis for T. parvula's extremophile lifestyle. Our results provide essential background for developing genomically influenced testable hypotheses for the evolution of environmental stress tolerance.     

Distribution of sculpins in the Clearwater River Basin, Idaho

The distributions of Cottus bairdi, C. rhotheus, and C. beldingi exhibited a highly significant positive degree of association. Conversely, the distribution of C. confusus exhibited a highly significant negative association with the distributional complex, C. bairdi, C. rhotheus, and C. beldingi. These species of sculpins can be grouped into two assemblages; one based on the distribution of C. confusus and the other based on the combined distributions of the other three species. The factor or factors limiting the downstream distribution of C. confusus or the upstream distribution of the other three species could not be positively identified. However, we hypothesize that competition between C. confusus and one or more members of the C. bairdi, C. rhotheus and C. beldingi complex is involved. In the area of overlapping distributions among C. bairdi, C. rhotheus, and C. bairdi we hypothesize that resource partitioning is occurring. However, the data did not allow evaluation of this hypothesis.        

Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy

The molecular complexity of tissues and the inaccessibility of most cells within a tissue limit the discovery of key targets for tissue-specific delivery of therapeutic and imaging agents in vivo. Here, we describe a hypothesis-driven, systems biology approach to identifying a small subset of proteins induced at the tissue-blood interface that are inherently accessible to antibodies injected intravenously. We use subcellular fractionation, subtractive proteomics and bioinformatics to identify endothelial cell surface proteins exhibiting restricted tissue distribution and apparent tissue modulation. Expression profiling and gamma-scintigraphic imaging with antibodies establishes two of these proteins, aminopeptidase-P and annexin A1, as selective in vivo targets for antibodies in lungs and solid tumours, respectively. Radio-immunotherapy to annexin A1 destroys tumours and increases animal survival. This analytical strategy can map tissue- and disease-specific expression of endothelial cell surface proteins to uncover novel accessible targets useful for imaging and therapy.