Comparative population genetics of the German shepherd dog in South Africa

Modern breeding practices strive to achieve distinctive phenotypic uniformity in breeds of dogs, but these strategies are associated with the inevitable loss of genetic diversity. Thus, in parallel with the morphological variation displayed by breeds, purebred dogs commonly express genetic defects as a result of the inbreeding associated with artificial selection and the reduction of selection against disease phenotypes. Microsatellite marker analyses of 15 polymorphic canine loci were used to investigate measures of genetic diversity and population differentiation within and between German-bred and South African-bred German shepherd dogs. These data were quantified by comparison with typically outbred mongrel or crossbred dogs. Both the imported and locally-bred German shepherd dogs exhibited similar levels of genetic diversity. The breed is characterised by only a moderate loss of genetic diversity relative to outbred dogs, despite originating from a single founding sire and experiencing extensive levels of inbreeding throughout the history of the breed. Non-significant population differentiation between the ancestral German and derived South African populations indicates sufficient contemporary gene flow between these populations, suggesting that migration resulting from the importation of breeding stock has mitigated the effects of random genetic drift and a population bottleneck caused by the original founder event in South Africa. Significant differentiation between the combined German shepherd dog population and the outbred dogs illustrates the effects of selection and genetic drift on the breed since its establishment just over 100 years ago

Measuring vertebrate telomeres: applications and limitations

Telomeres are short tandem repeated sequences of DNA found at the ends of eukaryotic chromosomes that function in stabilizing chromosomal end integrity. In vivo studies of somatic tissue of mammals and birds have shown a correlation between telomere length and organismal age within species, and correlations between telomere shortening rate and lifespan among species. This result presents the tantalizing possibility that telomere length could be used to provide much needed information on age, ageing and survival in natural populations where longitudinal studies are lacking. Here we review methods available for measuring telomere length and discuss the potential uses and limitations of telomeres as age and ageing estimators in the fields of vertebrate ecology, evolution and conservation

Using a Service Oriented Architecture Approach to Clinical Decision Support: Performance Results from Two CDS Consortium Demonstrations

The Clinical Decision Support Consortium has completed two demonstration trials involving a web service for the execution of clinical decision support (CDS) rules in one or more electronic health record (EHR) systems. The initial trial ran in a local EHR at Partners HealthCare. A second EHR site, associated with Wishard Memorial Hospital, Indianapolis, IN, was added in the second trial. Data were gathered during each 6 month period and analyzed to assess performance, reliability, and response time in the form of means and standard deviations for all technical components of the service, including assembling and preparation of input data. The mean service call time for each period was just over 2 seconds. In this paper we report on the findings and analysis to date while describing the areas for further analysis and optimization as we continue to expand our use of a Services Oriented Architecture approach for CDS across multiple institutions

Identification of Differentially Expressed Proteins in Murine Embryonic and Postnatal Cortical Neural Progenitors

BACKGROUND: The central nervous system (CNS) develops from a heterogeneous pool of neural stem and progenitor cells (NSPC), the underlying differences among which are poorly understood. The study of NSPC would be greatly facilitated by the identification of additional proteins that mediate their function and that would distinguish amongst different progenitor populations. METHODOLOGY/PRINCIPAL FINDINGS: To identify membrane and membrane-associated proteins expressed by NSPC, we used a proteomics approach to profile NSPC cultured as neurospheres (NS) isolated from the murine cortex during a period of neurogenesis (embryonic day 11.5, E11.5), as compared to NSPC isolated at a peak of gliogenesis (postnatal day 1, P0) and to differentiated E11.5 NS. 54 proteins were identified with high expression in E11.5 NS, including the TrkC receptor, several heterotrimeric G proteins, and the Neogenin receptor. 24 proteins were identified with similar expression in E11.5 and P0 NS over differentiated E11.5 NS, and 13 proteins were identified with high expression specifically in P0 NS compared to E11.5 NS. To illustrate the potential relevance of these identified proteins to neural stem cell biology, the function of Neogenin was further studied. Using Fluorescence Activated Cell Sorting (FACS) analysis, expression of Neogenin was associated with a self-renewing population present in both E11.5 and adult subventricular zone (SVZ) NS but not in P0 NS. E11.5 NS expressed a putative Neogenin ligand, RGMa, and underwent apoptosis when exposed to a ligand-blocking antibody. CONCLUSIONS/SIGNIFICANCE: There are fundamental differences between the continuously self-renewing and more limited progenitors of the developing cortex. We identified a subset of differentially expressed proteins that serve not only as a set of functionally important proteins, but as a useful set of markers for the subsequent analysis of NSPC. Neogenin is associated with the continuously self-renewing and neurogenic cells present in E11.5 cortical and adult SVZ NS, and the Neogenin/RGMa receptor/ligand pair may regulate cell survival during development

The Effect of Gradations in Mineral Content, Matrix Alignment, and Applied Strain on Human Mesenchymal Stem Cell Morphology within Collagen Biomaterials

The tendon-bone junction (TBJ) is a unique, mechanically dynamic, structurally graded anatomical zone which transmits tensile loads between tendon and bone. Current surgical repair techniques rely on mechanical fixation and can result in high re-failure rates. We have recently described a new class of collagen biomaterial that contains discrete mineralized and structurally aligned regions linked by a continuous interface to mimic the graded osteotendinous insertion. Here we report the combined influence of graded biomaterial environment and increasing levels of applied strain (0 – 20%) on MSC orientation and alignment. In osteotendinous scaffolds, which contain opposing gradients of mineral content and structural alignment characteristic of the native osteotendinous interface, MSC nuclear and actin alignment was initially dictated by the local pore architecture, while applied tensile strain enhanced cell alignment in the direction of strain. Comparatively, in layered scaffolds that did not contain any structural alignment cues, MSCs were randomly oriented in the unstrained condition, then became oriented in a direction perpendicular to applied strain. These findings provide an initial understanding of how scaffold architecture can provide significant, potentially competitive, feedback influencing MSC orientation under applied strain, and forms the basis for future tissue engineering efforts to regenerate the osteotendinous enthesis