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

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

Explanatory pluralism in the medical sciences: theory and practice

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise

Population Genetic Analysis of Plasmodium falciparum Parasites Using a Customized Illumina GoldenGate Genotyping Assay

The diversity in the Plasmodium falciparum genome can be used to explore parasite population dynamics, with practical applications to malaria control. The ability to identify the geographic origin and trace the migratory patterns of parasites with clinically important phenotypes such as drug resistance is particularly relevant. With increasing single-nucleotide polymorphism (SNP) discovery from ongoing Plasmodium genome sequencing projects, a demand for high SNP and sample throughput genotyping platforms for large-scale population genetic studies is required. Low parasitaemias and multiple clone infections present a number of challenges to genotyping P. falciparum. We addressed some of these issues using a custom 384-SNP Illumina GoldenGate assay on P. falciparum DNA from laboratory clones (long-term cultured adapted parasite clones), short-term cultured parasite isolates and clinical (non-cultured isolates) samples from East and West Africa, Southeast Asia and Oceania. Eighty percent of the SNPs (n = 306) produced reliable genotype calls on samples containing as little as 2 ng of total genomic DNA and on whole genome amplified DNA. Analysis of artificial mixtures of laboratory clones demonstrated high genotype calling specificity and moderate sensitivity to call minor frequency alleles. Clear resolution of geographically distinct populations was demonstrated using Principal Components Analysis (PCA), and global patterns of population genetic diversity were consistent with previous reports. These results validate the utility of the platform in performing population genetic studies of P. falciparum

Convergence or Divergence? Life Expectancy Patterns in Post-communist Countries, 1959–2010

In the 1960s and 1970s, the countries of Central and Eastern Europe and the Soviet Union experienced an unanticipated stagnation in the process of mortality reduction that was accelerating in the west. This was followed by even starker fluctuations and overall declines in life expectancy during the 1980s and 1990s. We identify statistically the extent to which, since the 1990s, the countries of the post-communist region have converged as a group towards other regional or cross-regional geopolitical blocks, or whether there are now multiple steady emerging among these countries. We apply a complex convergence club methodology, including a recursive analysis, to data on 30 OECD countries (including 11 post-communist countries) drawn from the Human Mortality Database and spanning the period 1959-2010. We find that, rather than converging uniformly on western life expectancy levels, the post-communist countries have diverged into multiple clubs, with the lowest seemingly stuck in low-level equilibria, while the best performers (e.g. Czech Republic) show signs of catching-up with the leading OECD countries. As the post-communist period has progressed, the group of transition countries themselves has become more heterogeneous and it is noticeable that distinctive gender and age patterns have emerged. We are the first to employ an empirical convergence club methodology to help understand the complex long-run patterns of life expectancy within the post-communist region, one of very few papers to situate such an analysis in the context of the OECD countries, and one of relatively few to interpret the dynamics over the long-term

Communicating Climate Change: Lessons Learned from a Researcher-Museum Collaboration

The need for science education and outreach is great. However, despite the ever-growing body of available scientific information, facts are often misrepresented to or misunderstood by the general public. This can result in uninformed decisions that negatively impact society at both individual and community levels. One solution to this problem is to make scientific information more available to the public through outreach programs. Most outreach programs, however, focus on health initiatives, STEM programs, or young audiences exclusively. This article describes a collaboration between the Research and Learning Center at the Fort Worth Museum of Science and History and an interdisciplinary team of researchers from the Dallas–Fort Worth (DFW) metroplex area. The collaboration was a pilot effort of a science communication fellowship and was designed to train researchers to effectively convey current science information to the public with a focus on lifelong learning. We focus on the broader idea of a university-museum collaboration that bridges the science communication gap as we outline the process of forming this collaboration, lessons we learned from the process, and directions that can support future collaborations.   

Microsatellite DNA variation indicates low levels of genetic differentiation among cuttlefish (Sepia officinalis L.) populations in the English Channel and the Bay of Biscay

Population substructure of the cuttlefish Sepia officinalis (Mollusca: Cephalopoda), as investigated by genetic variation of microsatellite loci, has been reported to be significantly extensive around the Iberian Peninsula with FST = 0.061 (Pérez-Losada et al. 2002) and panmictic in the semi-enclosed Adriatic Sea with FST = 0.011 (Garoia et al. 2004). Yet, no verified genetic information on population substructure existed for the northern distribution range of this species in the English Channel and Bay of Biscay.So far, reproductive and migration behaviour and in-vitro oxygen binding properties of haemocyanin have suggested existence of separate populations in the English Channel and the Bay of Biscay. Examination of genetic variation at seven microsatellite loci within samples from the Bay of Biscay, the English Channel and the southern North Sea indicated low levels of genetic differentiation in this area but also a breakdown of free gene flow at highly significant average FST = 0.018. Although there is a considerable genetic exchange between populations of S. officinalis in the English Channel and the Bay of Biscay, they cannot be regarded as a single, freely interbreeding population. Earlier reported biological differences might thus be due to genetic variability between the populations