Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

El "Análisis de Correspondencias Múltiples" como herramienta metodológica de síntesis teórica y empírica : Su aporte al estudio del locus universitario privado argentino (1955-1983)

El Análisis de Correspondencias Múltiples (ACM), recurso metodológico utilizado por Bourdieu y su equipo en un nivel avanzado de síntesis teórico-empírica, constituye una herramienta fundamental para la construcción analítica de espacios relacionales. Permite posicionar relacionalmente unidades de análisis en función de un conjunto determinado de variables y plasmar la multiplicidad resultante tanto gráfica como analíticamente. Comenzando por una reflexión general sobre las potencialidades de la herramienta, este artículo analiza la configuración del espacio universitario privado en Argentina (1955-1983) a partir del ACM, que permitió determinar las relaciones de homología y principios de diferenciación existentes entre las instituciones que lo componen.

(Table 2) Radiocarbon ages on Arctic box and multicores

Paleo-sea-ice history in the Arctic Ocean was reconstructed using the sea-ice dwelling ostracode Acetabulastoma arcticum from late Quaternary sediments from the Mendeleyev, Lomonosov, and Gakkel Ridges, the Morris Jesup Rise and the Yermak Plateau. Results suggest intermittently high levels of perennial sea ice in the central Arctic Ocean during Marine Isotope Stage (MIS) 3 (25-45 ka), minimal sea ice during the last deglacial (16-11 ka) and early Holocene thermal maximum (11-5 ka) and increasing sea ice during the mid-to-late Holocene (5-0 ka). Sediment core records from the Iceland and Rockall Plateaus show that perennial sea ice existed in these regions only during glacial intervals MIS 2, 4, and 6. These results show that sea ice exhibits complex temporal and spatial variability during different climatic regimes and that the development of modern perennial sea ice may be a relatively recent phenomenon.

Abyssal community analysis from replicate box cores in the central North Pacific

A 0.25 m**2 United States Naval Electronics Laboratory box corer was used to take replicate samples from an oligotrophic bottom under the North Pacific Central Water Mass (~28°N, 155°W). The bottom is a red clay with manganese nodules at a depth of 5500-5800 m. Macrofaunal density ranges from 84 to 160 individuals per m**2 and is therefore much the same as in Northwest Atlantic Gyre waters. Of the macrofaunal taxa, polychaetes dominate (55 %), followed by tanaids (18 %), bivalves (7 %), and isopods (6 %). Meiofaunal taxa were only partially retained by the 297 µm screen used in washing. Even then, they are 1.5-3.9 times as abundant as the macrofaunal taxa, with nematodes being numerically dominant by far. Foraminifera seem to comprise an important portion of the community, but could not be assessed accurately because of the inability to discriminate living and dead tests. Remains of what are probably xenophyophoridans are also very important, but offer the same problem. Faunal diversity is extremely high, with deposit feeders comprising the overwhelming majority. Most species are rare, being encountered only once. The distributions of only three species show any significant deviation from randomness. The polychaete fauna from box cores collected from 90 miles to the north was not significantly different from that of the principal study locality. Concordance appeared at several taxonomic levels, from species through macrofaunal/meiofaunal relationships. As a result, the variation in total animal abundance shows aggregation among cores. We discuss Sokolova's concept of a deep-sea oligotrophic zone dominated by suspension feeders, and reconcile it with our present findings. The high diversity of the fauna combined with the low food level contradict theories that relate diversity directly with productivity.

Table 1. Radiocarbon dates from TPC522 and box core surface samples from BC521 and BC523

Recent intensification of wind-driven upwelling of warm upper circumpolar deep water (UCDW) has been linked to accelerated melting of West Antarctic ice shelves and glaciers. To better assess the long term relationship between UCDWupwelling and the stability of theWest Antarctic Ice Sheet, we present a multi-proxy reconstruction of surface and bottom water conditions in Marguerite Bay, West Antarctic Peninsula (WAP), through the Holocene. A combination of sedimentological, diatom and foraminiferal records are, for the first time, presented together to infer a decline in UCDW influence within Marguerite Bay through the early to mid Holocene and the dominance of cyclic forcing in the late Holocene. Extensive glacial melt, limited sea ice and enhanced primary productivity between 9.7 and 7.0 ka BP is considered to be most consistent with persistent incursions of UCDW through Marguerite Trough. From 7.0 ka BP sea ice seasons increased and productivity decreased, suggesting that UCDW influence within Marguerite Bay waned, coincident with the equatorward migration of the Southern Hemisphere Westerly Winds (SWW). UCDW influence continued through the mid Holocene, and by 4.2 ka BP lengthy sea ice seasons persisted within Marguerite Bay. Intermittent melting and reforming of this sea ice within the late Holocene may be indicative of episodic incursions of UCDW into Marguerite Bay during this period. The cyclical changes in the oceanography within Marguerite Bay during the late Holocene is consistent with enhanced sensitively to ENSO forcing as opposed to the SWW-forcing that appears to have dominated the early to mid Holocene. Current measurements of the oceanography of the WAP continental shelf suggest that the system has now returned to the early Holocene-like oceanographic configuration reported here, which in both cases has been associated with rapid deglaciation.