G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity.

The alpha 1B-adrenergic receptor (alpha 1B-ADR) is a member of the G-protein-coupled family of transmembrane receptors. When transfected into Rat-1 and NIH 3T3 fibroblasts, this receptor induces focus formation in an agonist-dependent manner. Focus-derived, transformed fibroblasts exhibit high levels of functional alpha 1B-ADR expression, demonstrate a catecholamine-induced enhancement in the rate of cellular proliferation, and are tumorigenic when injected into nude mice. Induction of neoplastic transformation by the alpha 1B-ADR, therefore, identifies this normal cellular gene as a protooncogene. Mutational alteration of this receptor can lead to activation of this protooncogene, resulting in an enhanced ability of agonist to induce focus formation with a decreased latency and quantitative increase in transformed foci. In contrast to cells expressing the wild-type alpha 1B-ADR, focus formation in "oncomutant"-expressing cell lines appears constitutively activated with the generation of foci in unstimulated cells. Further, these cell lines exhibit near-maximal rates of proliferation even in the absence of catecholamine supplementation. They also demonstrate an enhanced ability for tumor generation in nude mice with a decreased period of latency compared with cells expressing the wild-type receptor. Thus, the alpha 1B-ADR gene can, when overexpressed and activated, function as an oncogene inducing neoplastic transformation. Mutational alteration of this receptor gene can result in the activation of this protooncogene, enhancing its oncogenic potential. These findings suggest that analogous spontaneously occurring mutations in this class of receptor proteins could play a key role in the induction or progression of neoplastic transformation and atherosclerosis.

Discharge competence and pattern formation in peatlands: a meta-ecosystem model of the Everglades ridge-slough landscape.

Regular landscape patterning arises from spatially-dependent feedbacks, and can undergo catastrophic loss in response to changing landscape drivers. The central Everglades (Florida, USA) historically exhibited regular, linear, flow-parallel orientation of high-elevation sawgrass ridges and low-elevation sloughs that has degraded due to hydrologic modification. In this study, we use a meta-ecosystem approach to model a mechanism for the establishment, persistence, and loss of this landscape. The discharge competence (or self-organizing canal) hypothesis assumes non-linear relationships between peat accretion and water depth, and describes flow-dependent feedbacks of microtopography on water depth. Closed-form model solutions demonstrate that 1) this mechanism can produce spontaneous divergence of local elevation; 2) divergent and homogenous states can exhibit global bi-stability; and 3) feedbacks that produce divergence act anisotropically. Thus, discharge competence and non-linear peat accretion dynamics may explain the establishment, persistence, and loss of landscape pattern, even in the absence of other spatial feedbacks. Our model provides specific, testable predictions that may allow discrimination between the self-organizing canal hypotheses and competing explanations. The potential for global bi-stability suggested by our model suggests that hydrologic restoration may not re-initiate spontaneous pattern establishment, particularly where distinct soil elevation modes have been lost. As a result, we recommend that management efforts should prioritize maintenance of historic hydroperiods in areas of conserved pattern over restoration of hydrologic regimes in degraded regions. This study illustrates the value of simple meta-ecosystem models for investigation of spatial processes.

Contribution of the North Atlantic subtropical high to regional climate model (RCM) skill in simulating southeastern United States summer precipitation

© 2014, Springer-Verlag Berlin Heidelberg.This study assesses the skill of advanced regional climate models (RCMs) in simulating southeastern United States (SE US) summer precipitation and explores the physical mechanisms responsible for the simulation skill at a process level. Analysis of the RCM output for the North American Regional Climate Change Assessment Program indicates that the RCM simulations of summer precipitation show the largest biases and a remarkable spread over the SE US compared to other regions in the contiguous US. The causes of such a spread are investigated by performing simulations using the Weather Research and Forecasting (WRF) model, a next-generation RCM developed by the US National Center for Atmospheric Research. The results show that the simulated biases in SE US summer precipitation are due mainly to the misrepresentation of the modeled North Atlantic subtropical high (NASH) western ridge. In the WRF simulations, the NASH western ridge shifts 7° northwestward when compared to that in the reanalysis ensemble, leading to a dry bias in the simulated summer precipitation according to the relationship between the NASH western ridge and summer precipitation over the southeast. Experiments utilizing the four dimensional data assimilation technique further suggest that the improved representation of the circulation patterns (i.e., wind fields) associated with the NASH western ridge substantially reduces the bias in the simulated SE US summer precipitation. Our analysis of circulation dynamics indicates that the NASH western ridge in the WRF simulations is significantly influenced by the simulated planetary boundary layer (PBL) processes over the Gulf of Mexico. Specifically, a decrease (increase) in the simulated PBL height tends to stabilize (destabilize) the lower troposphere over the Gulf of Mexico, and thus inhibits (favors) the onset and/or development of convection. Such changes in tropical convection induce a tropical–extratropical teleconnection pattern, which modulates the circulation along the NASH western ridge in the WRF simulations and contributes to the modeled precipitation biases over the SE US. In conclusion, our study demonstrates that the NASH western ridge is an important factor responsible for the RCM skill in simulating SE US summer precipitation. Furthermore, the improvements in the PBL parameterizations for the Gulf of Mexico might help advance RCM skill in representing the NASH western ridge circulation and summer precipitation over the SE US.