TRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca(2)

The cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here, we show that in vivo expression of a neuropathy-causing TRPV4 mutant (TRPV4(R269C)) causes dose-dependent neuronal dysfunction and axonal degeneration, which are rescued by genetic or pharmacological blockade of TRPV4 channel activity. TRPV4(R269C) triggers increased intracellular Ca(2+) through a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated mechanism, and CaMKII inhibition prevents both increased intracellular Ca(2+) and neurotoxicity in Drosophila and cultured primary mouse neurons. Importantly, TRPV4 activity impairs axonal mitochondrial transport, and TRPV4-mediated neurotoxicity is modulated by the Ca(2+)-binding mitochondrial GTPase Miro. Our data highlight an integral role for CaMKII in neuronal TRPV4-associated Ca(2+) responses, the importance of tightly regulated Ca(2+) dynamics for mitochondrial axonal transport, and the therapeutic promise of TRPV4 antagonists for patients with TRPV4-related neurodegenerative diseases

Conceptual and Scaling Evaluation of Vehicle Traffic Thermal Effects on Snow/Ice-Covered Roads*

The potential thermal effects of traffic on road surface thermal energy balance under frost/snow cover conditions have been largely ignored in meteorological evaluations of road ice deposit conditions. Preliminary exploration of these effects, particularly for heavy traffic scenarios with calm wind conditions and an ambient temperature of 0°C, is provided in this study using a conceptual model. Observational data were used to constrain the model, and parameterizations were employed to estimate the various heat transfer processes involved. The results indicate that, for heavy traffic situations, as well as for stopped traffic at intersections, the traffic thermal flux contribution at the surface is noticeable in a wide range of possible frost/snow-covered road conditions. The sensitivity to variation in traffic density, speed, and the emissivity of vehicle radiative surfaces, among others, is evaluated. Simple quantification of these traffic thermal effects, which might be considered in operational meteorological model forecasting of icy road conditions, is offered

Climate change projections of the North American Regional Climate Change Assessment Program (NARCCAP)

We investigate major results of the NARCCAP multiple regional climate model (RCM) experiments driven by multiple global climate models (GCMs) regarding climate change for seasonal temperature and precipitation over North America. We focus on two major questions: How do the RCM simulated climate changes differ from those of the parent GCMs and thus affect our perception of climate change over North America, and how important are the relative contributions of RCMs and GCMs to the uncertainty (variance explained) for different seasons and variables? The RCMs tend to produce stronger climate changes for precipitation: larger increases in the northern part of the domain in winter and greater decreases across a swath of the central part in summer, compared to the four GCMs driving the regional models as well as to the full set of CMIP3 GCM results. We pose some possible process-level mechanisms for the difference in intensity of change, particularly for summer. Detailed process-level studies will be necessary to establish mechanisms and credibility of these results. The GCMs explain more variance for winter temperature and the RCMs for summer temperature. The same is true for precipitation patterns. Thus, we recommend that future RCM-GCM experiments over this region include a balanced number of GCMs and RCMs

The role of connected diagnostics in strengthening regional, national and continental African disease surveillance

No abstract available