Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

<p>Abstract</p> <p>Background</p> <p>A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β₆-/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin α_vβ₆, i.e. <it>ITGB6 </it>and <it>ITGAV</it>, were considered candidate genes for this trait.</p> <p>Results</p> <p>The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of <it>musculi arrectores pili</it>, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine <it>ITGB6 </it>and<it>ITGAV </it>orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine <it>ITGB6 </it>and <it>ITGAV </it>in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the <it>ITGB6 </it>and <it>ITGAV </it>coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the <it>ITGB6 </it>pre-mRNA was detected. For both <it>ITGB6 </it>and <it>ITGAV </it>quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin α_vβ₆monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β₆antibody showed immunoreaction in both normal and affected pigs.</p> <p>Conclusion</p> <p>A phenotype resembling the integrin β₆-/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular and functional analyses have excluded that the mutated phenotype is caused by structural mutations in or ablation of any of the two candidate genes.</p

Pseudorapidity distributions of charged particles from Au+Au collisions at the maximum RHIC energy, Sqrt(s_NN) = 200 GeV

We present charged particle densities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at Sqrt{s_NN}=200 GeV. For the 5% most central events we obtain dN_ch/deta(eta=0) = 625 +/- 55 and N_ch(-4.7<= eta <= 4.7) = 4630+-370, i.e. 14% and 21% increases, respectively, relative to Sqrt{s_NN}=130 GeV collisions. Charged-particle production per pair of participant nucleons is found to increase from peripheral to central collisions around mid-rapidity. These results constrain current models of particle production at the highest RHIC energy.Comment: 4 pages, 5 figures; fixed fig. 5 caption; revised text and figures to show corrected calculation of and ; final version accepted for publicatio

Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro.

Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro data provide an insight into mucosal immune modulation during Ascaris infection, and show that A. suum profoundly suppresses immune and inflammatory pathways