Numerical modelling of climate change impacts on freshwater lenses on the North Sea Island of Borkum using hydrological and geophysical methods

A numerical, density dependent groundwater model is set up for the North Sea Island of Borkum to estimate climate change impacts on coastal aquifers and especially the situation of barrier islands in the Wadden Sea. The database includes information from boreholes, a seismic survey, a helicopter-borne electromagnetic (HEM) survey, monitoring of the freshwater-saltwater boundary by vertical electrode chains in two boreholes, measurements of groundwater table, pumping and slug tests, as well as water samples. Based on a statistical analysis of borehole columns, seismic sections and HEM, a hydrogeological model is set up. The groundwater model is developed using the finite-element programme FEFLOW. The density dependent groundwater model is calibrated on the basis of hydraulic, hydrological and geophysical data, in particular spatial HEM and local monitoring data. Verification runs with the calibrated model show good agreement between measured and computed hydraulic heads. A good agreement is also obtained between measured and computed density or total dissolved solids data for both the entire freshwater lens on a large scale and in the area of the well fields on a small scale. For simulating future changes in this coastal groundwater system until the end of the current century, we use the climate scenario A2, specified by the Intergovernmental Panel on Climate Change and, in particular, the data for the German North Sea coast. Simulation runs show proceeding salinisation with time beneath the well fields of the two waterworks Waterdelle and Ostland. The modelling study shows that the spreading of well fields is an appropriate protection measure against excessive salinisation of the water supply until the end of the current century

Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells

Differentiation and lineage specification are controlled by cooperation of growth factor signalling. The involvement of epigenetic regulators in lineage specification remains largely elusive. Here, we show that the histone methyltransferase Mll1 prevents intestinal progenitor cells from differentiation, whereas it is also involved in secretory lineage specification of Paneth and goblet cells. Using conditional mutagenesis in mice and intestinal organoids, we demonstrate that loss of Mll1 renders intestinal progenitor cells permissive for Wnt-driven secretory differentiation. However, Mll1-deficient crypt cells fail to segregate Paneth and goblet cell fates. Mll1 deficiency causes Paneth cell-determined crypt progenitors to exhibit goblet cell features by unleashing Mapk signalling, resulting in increased numbers of mixed Paneth/goblet cells. We show that loss of Mll1 abolishes the pro-proliferative effect of Mapk signalling in intestinal progenitor cells and promotes Mapk-induced goblet cell differentiation. Our data uncover Mll1 and its downstream targets Gata4/6 as a regulatory hub of Wnt and Mapk signalling in the control of lineage specification of intestinal secretory Paneth and goblet cells

Numerical modelling of climate change impacts on freshwater lenses on the North Sea Island of Borkum using hydrological and geophysical methods

A numerical, density dependent groundwater model is set up for the North Sea Island of Borkum to estimate climate change impacts on coastal aquifers and especially the situation of barrier islands in the Wadden Sea. The database includes information from boreholes, a seismic survey, a helicopter-borne electromagnetic (HEM) survey, monitoring of the freshwater-saltwater boundary by vertical electrode chains in two boreholes, measurements of groundwater table, pumping and slug tests, as well as water samples. Based on a statistical analysis of borehole columns, seismic sections and HEM, a hydrogeological model is set up. The groundwater model is developed using the finite-element programme FEFLOW. The density dependent groundwater model is calibrated on the basis of hydraulic, hydrological and geophysical data, in particular spatial HEM and local monitoring data. Verification runs with the calibrated model show good agreement between measured and computed hydraulic heads. A good agreement is also obtained between measured and computed density or total dissolved solids data for both the entire freshwater lens on a large scale and in the area of the well fields on a small scale. <br><br> For simulating future changes in this coastal groundwater system until the end of the current century, we use the climate scenario A2, specified by the Intergovernmental Panel on Climate Change and, in particular, the data for the German North Sea coast. Simulation runs show proceeding salinisation with time beneath the well fields of the two waterworks Waterdelle and Ostland. <br><br> The modelling study shows that the spreading of well fields is an appropriate protection measure against excessive salinisation of the water supply until the end of the current century

The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness

Wnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5(+) stem cells and human colon carcinomas with increased nuclear β-catenin. High levels of MLL1 are associated with poor survival of colon cancer patients. The genetic ablation of Mll1 in mice prevents Wnt/β-catenin-driven adenoma formation from Lgr5(+) intestinal stem cells. Ablation of Mll1 decreases the self-renewal of human colon cancer spheres and halts tumor growth of xenografts. Mll1 controls the expression of stem cell genes including the Wnt/β-catenin target gene Lgr5. Upon the loss of Mll1, histone methylation at the stem cell promoters switches from activating H3K4 tri-methylation to repressive H3K27 tri-methylation, indicating that Mll1 sustains stem cell gene expression by antagonizing gene silencing through polycomb repressive complex 2 (PRC2)-mediated H3K27 tri-methylation. Transcriptome profiling of Wnt-mutated intestinal tumor-initiating cells reveals that Mll1 regulates Gata4/6 transcription factors, known to sustain cancer stemness and to control goblet cell differentiation. Our results demonstrate that Mll1 is an essential epigenetic regulator of Wnt/β-catenin-induced intestinal tumorigenesis and cancer stemness

Numerical modelling of climate change impacts on freshwater lenses on the North Sea Island of Borkum using hydrological and geophysical methods

A numerical, density dependent groundwater model is set up for the North Sea Island of Borkum to estimate climate change impacts on coastal aquifers and especially the situation of barrier islands in the Wadden Sea. The database includes information from boreholes, a seismic survey, a helicopter-borne electromagnetic (HEM) survey, monitoring of the freshwater-saltwater boundary by vertical electrode chains in two boreholes, measurements of groundwater table, pumping and slug tests, as well as water samples. Based on a statistical analysis of borehole columns, seismic sections and HEM, a hydrogeological model is set up. The groundwater model is developed using the finite-element programme FEFLOW. The density dependent groundwater model is calibrated on the basis of hydraulic, hydrological and geophysical data, in particular spatial HEM and local monitoring data. Verification runs with the calibrated model show good agreement between measured and computed hydraulic heads. A good agreement is also obtained between measured and computed density or total dissolved solids data for both the entire freshwater lens on a large scale and in the area of the well fields on a small scale. <br><br> For simulating future changes in this coastal groundwater system until the end of the current century, we use the climate scenario A2, specified by the Intergovernmental Panel on Climate Change and, in particular, the data for the German North Sea coast. Simulation runs show proceeding salinisation with time beneath the well fields of the two waterworks Waterdelle and Ostland. <br><br> The modelling study shows that the spreading of well fields is an appropriate protection measure against excessive salinisation of the water supply until the end of the current century

High Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53

Specified intestinal epithelial cells reprogram and contribute to the regeneration and renewal of the epithelium upon injury. Mutations that deregulate such renewal processes may contribute to tumorigenesis. Using intestinal organoids, we show that concomitant activation of Notch signaling and ablation of p53 induce a highly proliferative and regenerative cell state, which is associated with increased levels of Yap and the histone methyltransferase Mll1. The induced signaling system orchestrates high proliferation, self-renewal, and niche-factor-independent growth, and elevates the trimethylation of histone 3 at lysine 4 (H3K4me3). We demonstrate that Yap and Mll1 are also elevated in patient-derived colorectal cancer (CRC) organoids and control growth and viability. Our data suggest that Notch activation and p53 ablation induce a signaling circuitry involving Yap and the epigenetic regulator Mll1, which locks cells in a proliferative and regenerative state that renders them susceptible for tumorigenesis