A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants

KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong dominant-negative effect on potassium currents by reducing the channel expression at the cell surface representing the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2. Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4 mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry. Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4 protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality control in the ER but does not reach the cell surface at normal levels. Currently we are investigating the trafficking behaviour and electrophysiological properties of several KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the common mechanism underlying DFNA2

Triple-junction solar cell performance under Fresnel-based concentrators taking into account chromatic aberration and off-axis operation

Concentration photovoltaic (CPV) systems might produce quite uneven irradiance distributions (both on their level and on their spectral distribution) on the solar cell. This effect can be even more evident when the CPV system is slightly off-axis, since they are often designed to assure good uniformity only at normal incidence. The non-uniformities both in absolute irradiance and spectral content produced by the CPV systems, can originate electrical losses in multi-junction solar cells (MJSC). This works is focused on the integration of ray-tracing methods for simulating the irradiance and spectrum maps produced by different optic systems throughout the solar cell surface, with a 3D fully distributed circuit model which simulates the electrical behavior of a state-of-the-art triple-junction solar cell under the different light distributions obtained with ray-tracing. In this study four different CPV system (SILO, XTP, RTP, and FK) comprising Fresnel lenses concentrating sunlight onto the same solar cell are modeled when working on-axis and 0.6 degrees off-axis. In this study the impact of non-uniformities on a CPV system behavior is revealed. The FK outperforms other Fresnel-based CPV systems in both on-axis and off-axis conditions.