Dendritic spines receive most excitatory inputs in the CNS and compartmentalize calcium. Although the mechanisms of calcium influx into spines have been explored, it is unknown what determines the calcium decay kinetics in spines. With two-photon microscopy we investigate action potential-induced calcium dynamics in spines from rat CA1 pyramidal neurons in slices. The [Ca(2+)](i) in most spines shows two decay kinetics: an initial fast component, during which [Ca(2+)](i) in spines decays to dendritic levels, followed by a slower decay phase in which the spine follows dendritic kinetics. The correlation between [Ca(2+)](i) in spine and dendrite at the breakpoint of the decay kinetics demonstrates diffusional equilibration between spine and dendrite during the slower component. To explain the faster initial decay, we rule out saturation or kinetic effects of endogenous or exogenous buffers and focus instead on (1) active calcium extrusion and (2) buffered diffusion of calcium from spine to dendrite. The presence of an undershoot in most spines indicates that extrusion mechanisms can be intrinsic to the spine. Supporting the two mechanisms, pharmacological blockade of smooth endoplasmic reticulum calcium (SERCA) pumps and the length of the spine neck affect spine decay kinetics. Using a mathematical model, we find that the contribution of calcium pumps and diffusion varies from spine to spine. We conclude that dendritic spines have calcium pumps and that their density and kinetics, together with the morphology of the spine neck, determine the time during which the spine compartmentalizes calcium.

The von Hippel-Lindau disease gene (VHL) is the causative gene for most adult renal cancers. However, the mechanism by which VHL protein functions as a renal tumor suppressor remains largely unknown. To identify low occupancy VHL protein partners with potential relevance to renal cancer, we screened a human kidney library against human VHL p30 using a yeast two-hybrid approach. Jade-1 (gene for Apoptosis and Differentiation in Epithelia) encodes a previously uncharacterized 64-kDa protein that interacts strongly with VHL protein and is most highly expressed in kidney. Jade-1 protein is short-lived and contains a candidate destabilizing (PEST) motif and plant homeodomains that are not required for the VHL interaction. Jade-1 is abundant in proximal tubule cells, which are clear-cell renal cancer precursors, and expression increases with differentiation. Jade-1 is expressed in cytoplasm and the nucleus diffusely and in speckles, where it partly colocalizes with VHL. VHL reintroduction into renal cancer cells increases endogenous Jade-1 protein abundance up to 10-fold. Furthermore, VHL increases Jade-1 protein half-life up to 3-fold. Thus, direct protein stabilization is identified as a new VHL function. Moreover, Jade-1 protein represents a novel candidate regulatory factor in VHL-mediated renal tumor suppression.

Green eco-friendly housing includes approaches to reduce indoor air pollutant sources and to increase energy efficiency. Although sealing/tightening buildings can save energy and reduce the penetration of outdoor pollutants, an adverse outcome can be increased buildup of pollutants with indoor sources. The objective of this study was to determine the differences in the indoor air quality (IAQ) between green and non-green homes in low-income housing complexes. In one housing complex, apartments were renovated using green principles (n=28). Home visits were conducted immediately after the renovation, and subsequently at 6 months and at 12 months following the renovation. Of these homes, eight homes had pre-renovation home visits; this allowed pre- and post-renovation comparisons within the same homes. Parallel visits were conducted in non-green (control) apartments (n=14) in a nearby low-income housing complex. The IAQ assessments included PM2.5, black carbon, ultrafine particles, sulfur, total volatile organic compounds (VOCs), formaldehyde, and air exchange rate. Data were analyzed using linear mixed-effects models. None of the indoor pollutant concentrations were significantly different between green and non-green homes. However, we found differences when comparing the concentrations before and after renovation. Measured immediately after renovation, indoor black carbon concentrations were significantly lower averaging 682 ng/m3 in post-renovation vs. 2,364 ng/m3 in pre-renovation home visits (p=0.01). In contrast, formaldehyde concentrations were significantly higher in post-renovated (0.03 ppm) than in pre-renovated homes (0.01 ppm) (p=0.004). Questionnaire data showed that opening of windows occurred less frequently in homes immediately post-renovation compared to pre-renovation; this factor likely affected the levels of indoor black carbon (from outdoor sources) and formaldehyde (from indoor sources) more than the renovation status itself. To reduce IAQ problems and potentially improve health, careful selection of indoor building materials and ensuring sufficient ventilation are important for green building designs.