β-catenin negatively regulates expression of the prostaglandin transporter PGT in the normal intestinal epithelium and colorectal tumour cells: A role in the chemopreventive efficacy of aspirin

Background: Levels of the pro-tumorigenic prostaglandin PGE 2 are increased in colorectal cancer, previously attributed to increased synthesis through COX-2 upregulation and, more recently, to decreased catabolism. The functionally linked genes 15-prostaglandin dehydrogenase (15-PGDH) and the prostaglandin transporter PGT co-operate in prostaglandin degradation and are downregulated in colorectal cancer. We previously reported repression of 15-PGDH expression by the Wnt/β-catenin pathway, commonly deregulated during early colorectal neoplasia. Here we asked whether β-catenin also regulates PGT expression. Methods: The effect of β-catenin deletion in vivo was addressed by PGT immunostaining of β-catenin/lox-villin-cre-ERT2 mouse tissue. The effect of siRNA-mediated β-catenin knockdown and dnTCF4 induction in vitro was addressed by semi-quantitative and quantitative real-time RT-PCR and immunoblotting. Results: This study shows for the first time that deletion of β-catenin in murine intestinal epithelium in vivo upregulates PGT protein, especially in the crypt epithelium. Furthermore, β-catenin knockdown in vitro increases PGT expression in both colorectal adenoma-and carcinoma-derived cell lines, as does dnTCF4 induction in LS174T cells.Conclusions:These data suggest that β-catenin employs a two-pronged approach to inhibiting prostaglandin turnover during colorectal neoplasia by repressing PGT expression in addition to 15-PGDH. Furthermore, our data highlight a potential mechanism that may contribute to the non-selective NSAID aspirins chemopreventive efficacy. © 2012 Cancer Research UK All rights reserved

The use of scenarios and models to evaluate the future of nature values and ecosystem services in Mediterranean forests

Science and society are increasingly interested in predicting the effects of global change and socio-economic development on natural systems, to ensure maintenance of both ecosystems and human well-being. The Intergovernmental Platform on Biodiversity and Ecosystem Services has identified the combination of ecological modelling and scenario forecasting as key to improving our understanding of those effects, by evaluating the relationships and feedbacks between direct and indirect drivers of change, biodiversity, and ecosystem services. Using as case study the forests of the Mediterranean basin (complex socio-ecological systems of high social and conservation value), we reviewed the literature to assess (1) what are the modelling approaches most commonly used to predict the condition and trends of biodiversity and ecosystem services under future scenarios of global change, (2) what are the drivers of change considered in future scenarios and at what scales, and (3) what are the nature and ecosystem service indicators most commonly evaluated. Our review shows that forecasting studies make relatively little use of modelling approaches accounting for actual ecological processes and feedbacks between different socio-ecological sectors; predictions are generally made on the basis of a single (mainly climate) or a few drivers of change. In general, there is a bias in the set of nature and ecosystem service indicators assessed. In particular, cultural services and human well-being are greatly underrepresented in the literature. We argue that these shortfalls hamper our capacity to make the best use of predictive tools to inform decision-making in the context of global change.This work was supported by the Spanish Government through the INMODES project (grant number CGL2017-89999-C2-2-R), the ERA-NET FORESTERRA project INFORMED (grant number 29183), and the project Boscos Sans per a una Societat Saludable funded by Obra Social la Caixa (https://obrasociallacaixa.org/). AMO and AA were supported by Spanish Government through the “Juan de la Cierva” fellowship program (IJCI-2016-30349 and IJCI-2016-30049, respectively). JVRD was supported by the Government of Asturias and the FP7-Marie Curie-COFUND program of the European Commission (Grant “Clarín” ACA17-02)

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer

SPROUTY2 (SPRY2) is an intracellular regulator of receptor tyrosine kinase signaling involved in cell growth, differentiation and tumorigenesis. Here, we show that SPRY2 is a target gene of the Wnt/β-catenin pathway that is abnormally activated in more than 90% of colon carcinomas. In human colon cancer cells, SPRY2 expression is induced by β-catenin in co-operation with the transcription factor FOXO3a instead of lymphoid enhancer factor/T-cell factor proteins. We found binding of β-catenin to the SPRY2 promoter at FOXO3a response elements. In vivo, cells marked by nuclear β-catenin and FOXO3a express SPRY2 in proliferative epithelial tissues, such as intestinal mucosa and epidermis. Consistently, inducible β-catenin deletion in mice reduced Spry2 expression in the small intestine. Moreover, SPRY2 protein expression correlated with nuclear β-catenin and FOXO3a colocalization in human colon carcinomas. Importantly, the amount of SPRY2 protein correlated with shorter overall survival of colon cancer patients. Our data reveal SPRY2 as a novel Wnt/β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer

Data from: Patterns and drivers of aquatic invertebrate diversity across an arid biome

Managing and restoring faunal diversity across large areas requires an understanding of the roles of connectivity and dispersal in driving community patterns. We sought to determine the influence of connectivity, water regime, water source, geographical location, and dispersal traits on patterns of aquatic invertebrate diversity across a continent-wide arid biome. We compiled data on freshwater invertebrate assemblages from sites spanning the breadth of arid Australia. Univariate analyses (analysis of variance and rarefaction) revealed that alpha and gamma diversity across sites decreased as latitude increased. Multivariate analyses (ordination and analysis of similarity) revealed that community composition had considerable fidelity to geographic regions. Hydrological connectivity was strongly associated with riverine community composition although water rarely flowed (often less than annually). Hydrologically isolated sites (springs and rockholes) supported communities that were markedly dissimilar to hydrologically connected sites, and to each other. We investigated the influence of dispersal on diversity patterns by examining Distance Decay Relationships for each of four dispersal trait groups (obligate aquatic and passive, weak, and strong aerial dispersers) on the basis of geodesic (shortest path) distances between pairs of sites and Mantel tests. We did not detect clear differences between dispersal traits and distance decay relationships at the continental scale, even for the two groups with the lowest dispersal ability (obligate aquatics and passive dispersers.) Our results suggest that the loss of hydrological connectivity from water developments in arid lands (for example, the impoundment of intermittent rivers) is likely to affect macroinvertebrates. However, the exact flow mechanisms underlying such changes remain to be determined