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Background and Objectives Cochlear dead region (CDR) is a region in the cochlear where hearing loss has occurred due to damage to the inner hair cells and/or neurons. Recently, a subjective test involving a pure-tone test in the presence of threshold-equalizing noise (TEN) was introduced to identify CDR. However, for uncooperative patients, such a subjective method would be unsuitable and objective methods would be needed instead to detect CDR. The acoustic change complex (ACC) is an evoked potential elicited by changes in the ongoing sound. In this study, we developed an objective method of identifying CDR by combining ACC response with a TEN test, namely the TEN-ACC test, and investigated its feasibility in normal-hearing listeners. Subjects and Method Ten normal-hearing subjects participated in this study. All subjects underwent both behavioral TEN test and electrophysiological TEN-ACC test. The stimuli for the TEN-ACC test consisted of TEN and embedded pure tones with different frequencies/signals to noise ratios (SNRs). To identify the thresholds, the range SNR of stimulation was varied from 0 to 20 dB, in stages of 4 dB. Results The ACC responses of all subjects who participated in this study were well elicited by stimuli developed for the TEN-ACC test. We confirm that the pure-tones embedded in TEN elicited the objective ACC response. Conclusion The results of this study suggest that the novel TEN-ACC test can be applied to evoke ACC in normal-hearing listeners. Future research should incorporate hearing-impaired listeners to determine the feasibility of the TEN-ACC test as an objective method to identify CDR.

Plasma membrane repair defects cause human muscle and heart diseases. In the early stage of membrane repair, TRIM72/MG53 nucleates vesicles to the damaged site within seconds. Despite the therapeutic potential of TRIM72/MG53, the molecular mechanisms are poorly understood. Here, we present the structure of TRIM72, the first complete model of a TRIM E3 ligase. Structure-guided functional analysis revealed a unique phospholipid recognition mode in which a pair of PRYSPRY domains interacts with negatively charged membranes. In subsequent biochemical analyses, the interaction between TRIM72 and the phosphatidylserine-enriched membrane was shown to be critical for both the oligomeric assembly and ubiquitination activity of TRIM72. We elucidated a higher-order model of TRIM72 assembly on the phospholipid bilayer using cryogenic electron tomography followed by subtomogram averaging. We developed a working molecular model of TRIM72 through integrated structural and biochemical techniques. The findings provide a fundamental basis for the study of TRIM E3 ligases, which share a conserved molecular architecture, and provide further insights into the general regulation of RING-type E3 ligases through the cooperation of multiple domains like those in higher-order assemblies.