Khurram Naik

Patent sales are an underappreciated means of monetizing patents. Recent blockbuster patent sales indicate heightened demand for patent acquisitions. There is evidence that such patent sales transfer patents to parties more skilled in patent enforcement, reducing litigation. Patent sales also move capital to innovators, which enhance incentives to innovate. But crucially, C corporations do not benefit from advantaged tax treatment. Efforts by other nations to encourage patent use and sales by… Show more

Patent sales are an underappreciated means of monetizing patents. Recent blockbuster patent sales indicate heightened demand for patent acquisitions. There is evidence that such patent sales transfer patents to parties more skilled in patent enforcement, reducing litigation. Patent sales also move capital to innovators, which enhance incentives to innovate. But crucially, C corporations do not benefit from advantaged tax treatment. Efforts by other nations to encourage patent use and sales by providing “patent box” preferential tax regimes may provide some guidance for remedying this gap in the tax code. Show less

The cochlear microphonic (CM) can be a useful analytical tool, but many investigators may not be fully familiar with its unique properties to interpret it accurately in mouse models of hearing. The purpose of this report is to develop a model for generation of the CM in wild-type (WT) and prestin knockout mice. Data and modeling results indicate that in the majority of cases, the CM is a passive response, and in the absence of outer hair cell (OHC) damage, mice lacking amplification are… Show more

The cochlear microphonic (CM) can be a useful analytical tool, but many investigators may not be fully familiar with its unique properties to interpret it accurately in mouse models of hearing. The purpose of this report is to develop a model for generation of the CM in wild-type (WT) and prestin knockout mice. Data and modeling results indicate that in the majority of cases, the CM is a passive response, and in the absence of outer hair cell (OHC) damage, mice lacking amplification are expected to generate WT levels of CM for inputs less than ~30 kHz. Hence, this cochlear potential is not a useful metric to estimate changes in amplifier gain. This modeling analysis may explain much of the paradoxical data in the literature.
For example, various manipulations, including the application of salicylate and activation of the crossed olivocochlear bundle, reduce the compound action potential but increase or do not change the CM. Based on this current evaluation, CM measurements are consistent with early descriptions where this AC cochlear potential is dominated by basal OHCs, when recorded at the round window. Show less

A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) and prestin knock-out (KO) genotypes are present in a single… Show more

A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) and prestin knock-out (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases; i.e., genotype ratio and phenotype are closely related. Show less

Cadherin 23 (CDH23), a transmembrane protein localized near the tips of hair cell stereocilia in the mammalian inner ear, is important for delivering mechanical signals to the mechanoelectric transducer channels. To identify CDH23-interacting proteins, a membrane-based yeast two-hybrid screen of an outer hair cell (OHC) cDNA library was performed. EHD4, a member of the C-terminal EH domain containing a protein family involved in endocytic recycling, was identified as a potential interactor. To… Show more

Cadherin 23 (CDH23), a transmembrane protein localized near the tips of hair cell stereocilia in the mammalian inner ear, is important for delivering mechanical signals to the mechanoelectric transducer channels. To identify CDH23-interacting proteins, a membrane-based yeast two-hybrid screen of an outer hair cell (OHC) cDNA library was performed. EHD4, a member of the C-terminal EH domain containing a protein family involved in endocytic recycling, was identified as a potential interactor. To confirm the interaction, we first demonstrated the EHD4 mRNA expression in hair cells using in situ hybridization.
Next, we showed that EHD4 co-localizes and co-immunoprecipitates with CDH23 in mammalian cells. Interestingly, the co- immunoprecipitation was found to be calcium-sensitive. To investigate the role of EHD4 in hearing, compound action potentials were measured in EHD4 knockout (KO) mice. Although EHD4 KO mice have normal hearing sensitivity, analysis of mouse cochlear lysates revealed a 2-fold increase in EHD1, but no increase in EHD2 or EHD3, in EHD4 KO cochleae compared with wild type, suggesting that a compensatory increase in EHD1 levels may account for the absence of a hearing defect in EHD4 KO mice. Taken together, these data indicate that EHD4 is a novel CDH23- interacting protein that could regulate CDH23 trafficking/localization in a calcium-sensitive manner. Show less