The Benthic Geoecology Model Within The Modular System For Shelves And Coasts (MOSSCO)

The Modular System for Shelves and Coasts (MOSSCO) integrates physical, biological, chemical and geological models of shelves and coasts for the North Sea and Baltic Sea in an exchangeable way. The MOSSCO software forms a coupling framework for exchanging data and models, which distinguishes between physical domains (Earth System compartments such as the benthic and pelagic zone) and processes (such as benthic geochemistry, physical erosion and biological stabilization). Information exchange across physical domains with different grids and time steps are managed using the ESMF (Earth System Modelling Framework), whereas coupling of processes within individual modules is achieved using FABM (Framework for Aquatic Biogeochemical Models). This paper reports coupling of a newly developed benthic geoecology model to the MOSSCO framework. This new model incorporates the biological effects of macrofauna (the bivalve Tellina fabula is taken as an example) and microphytobenthos on erodibility and critical bed shear stress. The model is implemented in an object-oriented generic modular way so that it can be extended to any number of biological effects on the sediment transport for an arbitrary number of species. Finally, the application of the coupled model is demonstrated in simulation of a1D setup

Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor

Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to α-, β-, and γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA–induced reduction of PCDHG@ encoded proteins leads to elevated β-catenin protein, increased β-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses β-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

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