A retrospective study of the prevalence of the canine degenerative myelopathy associated superoxide dismutase 1 mutation (SOD1: c. 118G> A) in a referral population of German Shepherd dogs from the UK

BACKGROUND: Canine degenerative myelopathy (CDM) is an adult onset, progressive neurodegenerative disease of the spinal cord. The disease was originally described in the German Shepherd dog (GSD), but it is now known to occur in many other dog breeds. A previous study has identified a mutation in the superoxide dismutase 1 gene (SOD1:c.118G > A) that is associated with susceptibility to CDM. In the present study, restriction fragment length polymorphism (RFLP) analysis was used to genotype GSD for SOD1:c.118G > A in order to estimate the prevalence of the mutation in a referral population of GSD in the UK. RESULTS: This study demonstrated that the RFLP assay, based on use of PCR and subsequent digestion with the Eco571 enzyme, provided a simple genotyping test for the SOD1:c.118G > A mutation. In a young GSD population (i.e. dogs less than 6 years of age, before clinical signs of the disease usually become apparent), 8 of 50 dogs were found to be homozygous and a further 19 were heterozygous for the mutation. In dogs over 8 years of age, 21 of 50 dogs admitted to a tertiary referral hospital with pelvic limb ataxia as a major clinical sign were homozygous for the mutation, compared to none of 50 dogs of similar age, but where no neurological disease was reported on referral. CONCLUSIONS: This data suggests that genotyping for the SOD1:c.118G > A mutation is clinically applicable and that the mutation has a high degree of penetrance. Genotyping might also be useful for screening the GSD population to avoid mating of two carriers, but since the allele frequency is relatively high in the UK population of GSD, care should be taken to avoid reduction in genetic diversity within the breed

Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment

RHIC physics overview

The results from data taken during the last several years at the Relativistic Heavy-Ion Collider (RHIC) will be reviewed in the paper. Several selected topics that further our understanding of constituent quark scaling, jet quenching and color screening effect of heavy quarkonia in the hot dense medium will be presented. Detector upgrades will further probe the properties of Quark Gluon Plasma. Future measurements with upgraded detectors will be presented. The discovery perspectives from future measurements will also be discussed.Comment: 9 pages, 4 figures, invited review article, published by Frontier of Physics in Chin

A doubled discretisation of abelian Chern-Simons theory

A new discretisation of a doubled, i.e. BF, version of the pure abelian Chern-Simons theory is presented. It reproduces the continuum expressions for the topological quantities of interest in the theory, namely the partition function and correlation function of Wilson loops. Similarities with free spinor field theory are discussed which are of interest in connection with lattice fermion doubling.Comment: 5 pages, revtex, 2 ps figures (epsf required). To appear in Phys.Rev.Let

Large-scale structure of brown rat (Rattus norvegicus) populations in England: effects on rodenticide resistance

The brown rat (Rattus norvegicus) is a relatively recent (<300 years) addition to the British fauna, but by association with negative impacts on public health, animal health and agriculture, it is regarded as one of the most important vertebrate pest species. Anticoagulant rodenticides were introduced for brown rat control in the 1950s and are widely used for rat control in the UK, but long-standing resistance has been linked to control failures in some regions. One thus far ignored aspect of resistance biology is the population structure of the brown rat. This paper investigates the role population structure has on the development of anticoagulant resistance. Using mitochondrial and microsatellite DNA, we examined 186 individuals (from 15 counties in England and one location in Wales near the Wales–England border) to investigate the population structure of rural brown rat populations. We also examined individual rats for variations of the VKORC1 gene previously associated with resistance to anticoagulant rodenticides. We show that the populations were structured to some degree, but that this was only apparent in the microsatellite data and not the mtDNA data. We discuss various reasons why this is the case. We show that the population as a whole appears not to be at equilibrium. The relative lack of diversity in the mtDNA sequences examined can be explained by founder effects and a subsequent spatial expansion of a species introduced to the UK relatively recently. We found there was a geographical distribution of resistance mutations, and relatively low rate of gene flow between populations, which has implications for the development and management of anticoagulant resistance

Children's construction task performance and spatial ability: controlling task complexity and predicting mathematics performance.

This paper presents a methodology to control construction task complexity and examined the relationships between construction performance and spatial and mathematical abilities in children. The study included three groups of children (N = 96); ages 7-8, 10-11, and 13-14 years. Each group constructed seven pre-specified objects. The study replicated and extended previous findings that indicated that the extent of component symmetry and variety, and the number of components for each object and available for selection, significantly predicted construction task difficulty. Results showed that this methodology is a valid and reliable technique for assessing and predicting construction play task difficulty. Furthermore, construction play performance predicted mathematical attainment independently of spatial ability

Invertible Dirac operators and handle attachments on manifolds with boundary

For spin manifolds with boundary we consider Riemannian metrics which are product near the boundary and are such that the corresponding Dirac operator is invertible when half-infinite cylinders are attached at the boundary. The main result of this paper is that these properties of a metric can be preserved when the metric is extended over a handle of codimension at least two attached at the boundary. Applications of this result include the construction of non-isotopic metrics with invertible Dirac operator, and a concordance existence and classification theorem.Comment: Accepted for publication in Journal of Topology and Analysi