A C-terminally truncated human parathyroid hormone receptor is functional and activates multiple G proteins

AbstractWe have investigated the role of the C-terminal cytoplasmic domain of the human PTH receptor in effector coupling. Following transient expression in COS-1 cells, coupling to both AC and PI-PLC was observed with the full-length receptor. Progressive C-terminal truncations did not dissociate activation of the two signalling systems. In stably transfected 293 cells, however, the full-length receptor as well as the majority of truncated constructs stimulated AC exclusively but failed to activate PI-PLC. Activation of both signalling systems was again observed following stable expression of a severely truncated receptor (R483) in 293 cells. In this case, pertussis toxin was also found to potentiate the cAMP response to hPTH-(1–38) significantly, indicating functional coupling of R483 to Gi proteins. Our results suggest that a core region of the human PTH receptor (first, second, third intracellular loop) can interact promiscuously with different G proteins and that the C-terminus of the full-length receptor directs the receptor towards an interaction with G

Modeling of Nitrogen in River Water Using a Detailed and a Simplified Model

To model catchment surface water quantity and quality, different model types are available. They vary from detailed physically based models to simplified conceptual and empirical models. The most appropriate model type for a certain application depends on the project objectives and the data availability. The detailed models are very useful for short-term simulations of representative events. They cannot be used for long-term statistical information or as a management tool. For those purposes, more simplified (conceptual or meta-) models must be used. In this study, nitrogen dynamics are modeled in a river in Flanders. Nitrogen sources from agricultural leaching and domestic point sources are considered. Based on this input, concentrations of ammonium (NH4-N) and nitrate (NO3-N) in the river water are modeled in MIKE 11 by taking into consideration advection and dispersion and the most important biological and chemical processes. Model calibration was done on the basis of available measured water quality data. To this detailed model, a more simplified model was calibrated with the objective to more easily yield long-term simulation results that can be used in a statistical analysis. The results show that the conceptual simplified model is 1800 times faster than the MIKE 11 model. Moreover the two models have almost the same accuracy. The detailed models are recommended for short-term simulations unless there are enough data for model input and model parameters. The conceptual simplified model is recommended for long-term simulations

Amphiregulin Is a Novel Growth Factor Involved in Normal Bone Development and in the Cellular Response to Parathyroid Hormone Stimulation

Parathyroid hormone (PTH) is the major mediator of calcium homeostasis and bone remodeling and is now known to be an effective drug for osteoporosis treatment. Yet the mechanisms responsible for its functions in bone are largely unknown. Here we report that the expression of amphiregulin (AR), a member of the epidermal growth factor (EGF) family, is rapidly and highly up-regulated by PTH in several osteoblastic cell lines and bone tissues. Other osteotropic hormones (1{alpha},25-dihydroxyvitamin D3 and prostaglandin E2) also strongly stimulate AR expression. We found all EGF-like ligands and their receptors are expressed in osteoblasts, but AR is the only member that is highly regulated by PTH. Functional studies demonstrated that although AR is a potent growth factor for preosteoblasts, it completely inhibits further differentiation. AR also strongly and quickly stimulated Akt and ERK phosphorylation and c-fos and c-jun expression in an EGF receptor-dependent manner. Moreover, AR null mice displayed significantly less tibial trabecular bone than wild-type mice. Taken together, we have identified a novel growth factor that is PTH-regulated and appears to have an important role in bone metabolism

Global long-term observations of coastal erosion and accretion

Changes in coastal morphology have broad consequences for the sustainability of coastal communities, structures and ecosystems. Although coasts are monitored locally in many places, understanding long-term changes at a global scale remains a challenge. Here we present a global and consistent evaluation of coastal morphodynamics over 32 years (1984–2015) based on satellite observations. Land losses and gains were estimated from the changes in water presence along more than 2 million virtual transects. We find that the overall surface of eroded land is about 28,000 km2, twice the surface of gained land, and that often the extent of erosion and accretion is in the order of km. Anthropogenic factors clearly emerge as the dominant driver of change, both as planned exploitation of coastal resources, such as building coastal structures, and as unforeseen side effects of human activities, for example the installment of dams, irrigation systems and structures that modify the flux of sediments, or the clearing of coastal ecosystems, such as mangrove forests. Another important driver is the occurrence of natural disasters such as tsunamis and extreme storms. The observed global trend in coastal erosion could be enhanced by Sea Level Rise and more frequent extreme events under a changing climate.JRC.E.1-Disaster Risk Managemen

The Combination of PlGF Inhibition and MMC as a Novel Anti-Scarring Strategy for Glaucoma Filtration Surgery

The complementary effects of mitomycin-C (MMC) and anti-placental growth factor (PlGF) therapy were explored and compared to the combined administration of MMC and aflibercept. Additionally, the effect of PlGF (inhibition) on IOP was investigated, since aqueous PlGF is known to be upregulated in glaucoma patients.status: publishe