269 research outputs found

    Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

    Get PDF
    A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

    SL(2,R) Chern-Simons, Liouville, and Gauge Theory on Duality Walls

    Full text link
    We propose an equivalence of the partition functions of two different 3d gauge theories. On one side of the correspondence we consider the partition function of 3d SL(2,R) Chern-Simons theory on a 3-manifold, obtained as a punctured Riemann surface times an interval. On the other side we have a partition function of a 3d N=2 superconformal field theory on S^3, which is realized as a duality domain wall in a 4d gauge theory on S^4. We sketch the proof of this conjecture using connections with quantum Liouville theory and quantum Teichmuller theory, and study in detail the example of the once-punctured torus. Motivated by these results we advocate a direct Chern-Simons interpretation of the ingredients of (a generalization of) the Alday-Gaiotto-Tachikawa relation. We also comment on M5-brane realizations as well as on possible generalizations of our proposals.Comment: 53+1 pages, 14 figures; v2: typos corrected, references adde

    Dimer Models and Integrable Systems

    Full text link
    We explore various aspects of the correspondence between dimer models and integrable systems recently introduced by Goncharov and Kenyon. Dimer models give rise to relativistic integrable systems that match those arising from 5d N=1 gauge theories studied by Nekrasov. We apply the correspondence to dimer models associated to the Y^{p,0} geometries, showing that they give rise to the relativistic generalization of the periodic Toda chain originally studied by Ruijsenaars. The correspondence reduces the calculation of all conserved charges to a straightforward combinatorial problem of enumerating non-intersecting paths in the dimer model. We show how the usual periodic Toda chain emerges in the non-relativistic limit and how the Lax operator corresponds to the Kasteleyn matrix of the dimer model. We discuss how the dimer models for general Y^{p,q} manifolds give rise to other relativistic integrable systems, generalizing the periodic Toda chain and construct the integrable systems for general Y^{p,p} explicitly. The impurities introduced in the construction of Y^{p,q} quivers are identified with impurities in twisted sl(2) XXZ spin chains. Finally we discuss how the physical concept of higgsing a dimer model provides an efficient method for producing new integrable systems starting from known ones. We illustrate this idea by constructing the integrable systems for higgsings of Y^{4,0}.Comment: 29 pages, 16 figures. v2: typos fixe

    The Effect of Organisational Factors in Motivating Healthcare Employees: A Systematic Review

    Get PDF
    Healthcare employee motivation is a key concept in the achievement of efficient,effective and good quality healthcare delivery. In this paper a systematic review of primary data from the UK, Europe, Africa and Asia was conducted to consolidate the available evidence on the effect of organisational factors on healthcare employee motivation. Because healthcare delivery is highly labour intensive, it must be acknowledged that human resources are extremely critical in the drive for healthcare organisations to deliver on their organisational goals. The organisational factors which were identified as having a great effect on healthcare employee motivation can be divided into financial and non-financial factors. Remuneration was identified as a strong extrinsic factor, while conducive working conditions, increased responsibilities and appreciation from the communities in which they serve were identified as strong intrinsic factors. Even though there is a cultural aspect to motivation, remuneration, managerial support and career advancement are core factors that affect all healthcare professionals irrespective of country. Many of the factors that were observed in the literature as affecting motivation can be addressed by an overhaul of the reward strategy of healthcare organisations

    Association mapping of stigma and spikelet characteristics in rice (Oryza sativa L.)

    Get PDF
    Stigma and spikelet characteristics play an essential role in hybrid seed production. A mini-core of 90 accessions developed from USDA rice core collection was phenotyped in field grown for nine traits of stigma and spikelet and genotyped with 109 DNA markers, 108 SSRs plus an indel. Three major clusters were built upon Rogers’ genetic distance, indicative of indicas, and temperate and tropical japonicas. A mixed linear model combining PC-matrix and K-matrix was adapted for mapping marker-trait associations. Resulting associations were adjusted using false discovery rate technique. We identified 34 marker-trait associations involving 22 SSR markers for eight traits. Four markers were associated with single stigma exsertion (SStgE), six with dual exsertion (DStgE) and five with total exsertion. RM5_Chr1 played major role indicative of high regression with not only DStgE but also SStgE. Four markers were associated with spikelet length, three with width and seven with L/W ratio. Numerous markers were co-associated with multiple traits that were phenotypically correlated, i.e. RM12521_Chr2 associated with all three correlated spikelet traits. The co-association should improve breeding efficiency because single marker could be used to assist breeding for multiple traits. Indica entry 1032 (cultivar 50638) and japonica entry 671 (cultivar Linia 84 Icar) with 80.65 and 75.17% of TStgE, respectively are recommended to breeder for improving stigma exsertion

    Genetic diversity in cultivated carioca common beans based on molecular marker analysis

    Get PDF
    A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats – SSRs and amplified fragment length polymorphisms – AFLPs) for assessing the genetic diversity of carioca beans. The amount of information provided by Roger’s modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively) than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm
    corecore