SUMMARY Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor, HTR7, as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 displayed reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch, and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.

We use a regional coupled chemistry-transport model to assess changes in surface ozone over the summertime U.S. between present and a 2050 future time period at high spatial resolution under the A2 climate and Representative Concentration Pathway (RCP) 8.5 anthropogenic precursor emission scenarios. Predicted changes in regional climate and globally enhanced ozone are estimated to increase surface ozone over most of the U.S.; the 95th percentile for daily 8 h maximum surface ozone increases from 79 ppb to 87 ppb. The analysis suggests that changes in meteorological drivers likely will add to increasing ozone, but the simulations do not allow separating meteorological feedbacks from that due to enhanced global ozone. Stringent emission controls can counteract these feedbacks; if implemented as in RCP8.5, the 95th percentile for surface ozone is reduced to 55 ppb. A comparison of regional to global model projections shows that the global model is biased high in surface ozone compared to the regional model and compared to observations. On average, both the global and the regional model predict similar future changes but reveal pronounced differences in urban and rural regimes that cannot be resolved at the coarse resolution of the considered global model. This study confirms the key role of emission control strategies in future air quality projections and demonstrates the need for considering degradation of air quality with future climate change in policy making. It also illustrates the need for high-resolution modeling when the objective is to address regional and local air quality or establish links to human health and society.

Abstract. The Price and Rind lightning parameterization based on cloud-top height is a commonly used method for predicting flash rate in global chemistry models. As mesoscale simulations begin to implement flash rate predictions at resolutions that partially resolve convection, it is necessary to validate and understand the behavior of this method within such a regime. In this study, we tested the flash rate parameterization, intra-cloud/cloud-to-ground (IC : CG) partitioning parameterization, and the associated resolution dependency "calibration factor" by Price and Rind using the Weather Research and Forecasting (WRF) model running at 36 km, 12 km, and 4 km grid spacings within the continental United States. Our results show that while the integrated flash count is consistent with observations when model biases in convection are taken into account, an erroneous frequency distribution is simulated. When the spectral characteristics of lightning flash rate are a concern, we recommend the use of prescribed IC : CG values. In addition, using cloud-top from convective parameterization, the "calibration factor" is also shown to be insufficient in reconciling the resolution dependency at the tested grid spacing used in this study. We recommend scaling by areal ratio relative to a base-case grid spacing determined by convective core density.