A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.     

Embryological and molecular investigations of parental imprinting on mouse chromosome 7

Mouse embryos with duplications of whole maternal (parthenogenetic and gynogenetic) or paternal (androgenetic) genomes show reciprocal phenotypes and do not develop to term. Genetic complementation has identified the distal region of chromosome 7 (Chr 7) as one of the regions for which both a maternal and paternal chromosome copy are essential for normal development, presumably because of the presence of imprinted genes whose expression is dependent on their parental origin. Embryos with the maternal duplication and paternal deficiency of distal Chr 7 are growth retarded and die around day 16 of gestation; the reciprocal paternal duplication embryos die at an unidentified earlier stage. We report here the incorporation of cells with the paternal duplication into chimaeras, resulting in a striking growth enhancement of the embryos. One gene located on mouse distal Chr 7 (ref. 5) is the insulin-like growth factor 2 (Igf2) gene, an embryonic mitogen. In embryos with the maternal duplication of distal Chr 7, the two maternal alleles of the Igf2 gene are repressed. The presence of two paternal alleles of this gene in many cells is probably responsible for the growth enhancement observed in chimaeras. We propose that there are other imprinted genes in this Chr 7 region. We also compare the imprinting of this subgenomic region with phenotypes resulting from the duplication of the whole parental genome in parthenogenones and androgenones.     

The Moxee City (Washington) mammoth: morphostratigraphic, taphonomic, and taxonomic considerations

A nearly complete, but highly fractured, proboscidean tusk was unearthed during parking lot construction near Moxee City in central Washington in May 2001. Schreger angle analysis revealed that the tusk was from a mammoth. AMS radiocarbon dating of the tusk established that the mammoth died 14,570 14C yr BP. The age, combined with the biogeography of proboscidean finds in the Pacific Northwest, suggests the tusk is from a Columbian mammoth ( Mammuthus columbi ). The condition of the tusk and its association with basalt and crystalline erratics suggest that a locally derived tusk was swept up in the advancing flood and transported to ～320 m elevation, where it was deposited in the sediments of the 3rd of 3 Missoula Floods that are preserved in the area. The tusk's weathering indicates subaerial exposure prior to burial in the slackwater sediments. Slackwater deposits at the site are pale, ～30-100 cm thick, calcareous, fine-textured strata that include occasional coarse basalt and crystalline sand and gravel. They are intruded by numerous clastic dikes. The sediments encapsulating the tusk lack rhythmites because of their deposition in the nearshore zone of an ephemeral slackwater lake. The first 2 floods inundated the site between 15,300 14 C yr BP and 14,570 14 C yr BP, stripping the A horizon from a well-developed soil formed in alluvial fan sediments sitting above an Ellensburg Formation pediment. The last flood to reach the site occurred later than 14,570 14 C yr BP, as indicated by the presence of the dated tusk. Post-flood and post-MSH S tephra loess derived from the Yakima River floodplain mantles these slackwater deposits. The Warden soil is forming in the now-stable loess parent material.     

Freshwater sponges (Porifera: Spongillidae) of western Montana

Between May 1992 and April 1996, freshwater sponges (Porifera: Spongillidae) were collected at 24 sites, distributed among 6 sub-major drainage basins in western Montana, to determine the species present. Water samples also were analyzed from 16 of these sites and from 9 sites at which no sponges were detected to characterized sponge habitats chemically. Three species of sponges were identified: Ephydatia muelleri (Em), Eunapius fragilis (Ef), and Spongilla lacustris (Sl). A 4th type of specimen was present at 2 sites but could not be identified because of the absence of gemmules and gemmoscleres. At 46% of the sites containing sponges, more than 1 specimen type was present. Sponges were most commonly found near outlets of lakes, attached to sides or undersides of submerged rocks and logs. They appeared as encrusting (Em, Ef, Sl), lobate (Em), and fingerlike (Sl) growths, varying in color from light tan to green. Dimensions of the spicules varied greatly within each species and expanded previously recorded ranges. No factors limiting sponge distribution were identified, but ranges of conductivity (Em) and of silica (Em, Sl), calcium (Em), and magnesium (Em) concentrations were expanded beyond those reported previously.     

Transgenes as probes for active chromosomal domains in mouse development

Embryonic development entails a well defined temporal and spatial programme of gene expression, which may be influenced by active chromosomal domains. These chromosomal domains can be detected using transgenes which integrate randomly throughout the genome, as their expression can be affected by chromosomal position. Position effects are probably exerted most strongly on transgenes that do not contain strong promoters, enhancers or other modulating sequences. Here we have systematically explored position effects using a transgene with the weak herpes-simplex-virus thymidine-kinase promoter, linked to the readily visualized lacZ indicator gene (HSV-TK-lacZ). Each transgenic fetus with detectable expression displayed a unique lacZ staining pattern. Thus expression of this construct is apparently dictated entirely by its chromosomal position, without any construct specificity. Furthermore the transgene is faithfully transmitted to subsequent generations, allowing for systematic mapping of changes in expression during development and in adult life. These results demonstrate that transgenes can indeed be powerful tools to probe the genome for active chromosomal regions, with the potential for identifying endogenous genes involved in organogenesis and pattern formation.     

Psychology: red enhances human performance in contests

Red coloration is a sexually selected, testosterone-dependent signal of male quality in a variety of animals, and in some non-human species a male's dominance can be experimentally increased by attaching artificial red stimuli. Here we show that a similar effect can influence the outcome of physical contests in humans--across a range of sports, we find that wearing red is consistently associated with a higher probability of winning. These results indicate not only that sexual selection may have influenced the evolution of human response to colours, but also that the colour of sportswear needs to be taken into account to ensure a level playing field in sport.     

Influence of parental chromosomes on spatial specificity in androgenetic----parthenogenetic chimaeras in the mouse

The presence of both parental genomes is essential for development to term in the mouse embryo probably because of germline-specific modifications of homologous chromosomes. Neither androgenetic nor parthenogenetic embryos can by themselves develop to term; any post-implantation embryos they produce have opposite phenotypes, which reflects the presence of complementary information in parental chromosomes. The development of androgenetic----parthenogenetic chimaeras is of considerable interest because in this case both parental chromosomes are available even though they are in separate cells. We demonstrate here that in post-implantation chimaeric fetuses, the expression of parental information results in spatial specificity so that parthenogenetic cells are confined to the embryo but the trophoblast consists almost entirely of androgenetic cells. The yolk sac contains both cell types. However, there is incomplete functional complementation because the chimaeras do not reach term. Although failure to reach term may occur partly because of inadequate intermingling and interactions between embryonic cells, it is more likely that further control of mouse development depends on the presence of both sets of chromosomes within the same cells.     

Effect of dipyridamole and adenosine monophosphate on cell proliferation in the hemopoietic tissue of normal and gamma-irradiated mice

Combined treatment with dipyridamole and adenosine monophosphate enhances cell proliferation in the hemopoietic tissue of normal and gamma-irradiated mice. This effect can be explained by the elevation of extracellular adenosine, and the receptor-mediated activation of the cell adenylate cyclase system.