116 research outputs found

    The PPCD1 Mouse: Characterization of a Mouse Model for Posterior Polymorphous Corneal Dystrophy and Identification of a Candidate Gene

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    The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is characterized by an enlarged anterior chamber resulting from metaplasia of the corneal endothelium and blockage of the iridocorneal angle by epithelialized corneal endothelial cells. The presence of stratified multilayered corneal endothelial cells with abnormal patterns of cytokeratin expression are remarkably similar to those observed in human posterior polymorphous corneal dystrophy (PPCD) and the sporadic condition, iridocorneal endothelial syndrome. Affected eyes exhibit epithelialized corneal endothelial cells, with inappropriate cytokeratin expression and proliferation over the iridocorneal angle and posterior cornea. We have termed this the “mouse PPCD1” phenotype and mapped the mouse locus for this phenotype, designated “Ppcd1”, to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval. Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete penetrance on the sensitive DBA/2J background and decreased penetrance on the C57BL/6J background. Comparative genome hybridization has identified a hemizygous 78 Kbp duplication in the mapped interval. The endpoints of the duplication are located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase-PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased in eyes of PPCD1 mice. Based on the observations of decreased gene expression levels, association with ZEB1-related pathways, and the report of corneal opacities in Csrp2bptm1a(KOMP)Wtsi heterozygotes and embryonic lethality in nulls, we postulate that duplication of the 78 Kbp segment leading to haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype. Similarly, CSRP2BP haploinsufficiency may lead to human PPCD

    Invited Commentary: Broadening the Evidence for Adolescent Sexual and Reproductive Health and Education in the United States

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    Correspondence

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    Islands in the stream: revisiting methodological nationalism under conditions of globalization

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    Reference to the sovereign nation-state has traditionally been held to lie at the heart of the conceptualisation of inter-state relations in social scientific discourse. Recent debates have sought to problematise the centrality of this concept, particularly under the banner of globalisation. Specifically, it has been argued that contemporary practices have weakened national boundaries thereby undermining the effectiveness of state actors and the relevance and explanatory value of the national. In this paper we examine the maritime industry as a ‘critical case’, and demonstrate how in an extensively globalised context the national understood as legitimate authority, grounded in territory, is still necessary to understand certain key processes. We present a series of cases in which the normal, smooth operation of shipping is disturbed, in order to reveal operative practice. Our claim is that methodological nationalism continues to be a legitimate perspective even in an extensively globalised context
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