The contractile segment of the abneural limbus in the gecko cochlea is enriched in vimentin

Previously, we discovered a contractile segment within the cartilaginous abneural limbus of the gecko cochlea, the noncartilaginous abneural limbus (NAL, Ganeshina and Vorobyev, J Comp Neurol 461:539–547, 2003). Here, we demonstrate, by means of SDS-PAGE electrophoresis, the nanoLC-ESI-MSMS technique, immunoblotting, and immunocytochemistry, that the major cytoskeletal protein of the NAL cells is vimentin. Filamentous actin constitutes a minor component of the NAL contractile cell cytoskeleton. Our data indicate that the NAL represents a previously unknown specialization of connective tissue, characterized by the reduction of extracellular matrix and a hypertrophy of the vimentin-based intracellular cytoskeleton. The results are compatible with our hypothesis that the NAL is involved in an adaptation of the cochlear mechanics.     

Listening for males and bats: spectral processing in the hearing organ of <Emphasis Type="Italic">Neoconocephalus bivocatus</Emphasis> (Orthoptera: Tettigoniidae)

Tettigoniids use hearing for mate finding and the avoidance of predators (mainly bats). Using intracellular recordings, we studied the response properties of auditory receptor cells of Neoconocephalus bivocatus to different sound frequencies, with a special focus on the frequency ranges representative of male calls and bat cries. We found several response properties that may represent adaptations for hearing in both contexts. Receptor cells with characteristic frequencies close to the dominant frequency of the communication signal were more broadly tuned, thus extending their range of high sensitivity. This increases the number of cells responding to the dominant frequency of the male call at low signal amplitudes, which should improve long distance call localization. Many cells tuned to audio frequencies had intermediate thresholds for ultrasound. As a consequence, a large number of receptors should be recruited at intermediate amplitudes of bat cries. This collective response of many receptors may function to emphasize predator information in the sensory system, and correlates with the amplitude range at which ultrasound elicits evasive behavior in tettigoniids. We compare our results with spectral processing in crickets, and discuss that both groups evolved different adaptations for the perceptual tasks of mate and predator detection.     

Mutational analysis of the mitochondrial tRNALeu(UUR) gene in Tunisian patients with mitochondrial diseases

The mitochondrial tRNA(Leu(UUR)) gene (MTTL) is a hot spot for pathogenic mutations that are associated with mitochondrial diseases with various clinical features. Among these mutations, the A3243G mutation was associated with various types of mitochondrial multisystem disorders, such as MIDD, MELAS, MERRF, PEO, hypertrophic cardiomyopathy, and a subtype of Leigh syndrome. We screened 128 Tunisian patients for the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. This screening was carried out using PCR-RFLP with the restriction endonuclease ApaI. None of the 128 patients or the 100 controls tested were found to carry the mitochondrial A3243G mutation in the tRNA(Leu(UUR)) gene in homoplasmic or heteroplasmic form. After direct sequencing of the entire mitochondrial tRNA(Leu(UUR)) gene and a part of the mitochondrial NADH dehydrogenase 1, we found neither mutations nor polymorphisms in the MTTL1 gene in the tested patients and controls, and we confirmed the absence of the A3243G mutation in this gene. We also found a T3396C transition in the ND1 gene in one family with NSHL which was absent in the other patients and in 100 controls. Neither polymorphisms nor other mutations were found in the mitochondrial tRNA(Leu(UUR)) gene in the tested patients.     

单侧人工耳蜗植入对学龄前耳聋儿童听觉言语康复的效果影响因素分析

目的:探讨单侧人工耳蜗植入(cochlear implantation,CI)对学龄前耳聋儿童听觉语言康复的治疗效果以及相关影响因素。方法:将我院自2017年1月至2017年12月行CI治疗的学龄前儿童72例行作为研究对象,通过问卷调查手术患儿的相关资料,对可能影响患儿听觉言语康复效果的因素和听觉行为分级(Categories of auditory performance,CAP)以及言语可懂程度分级(Speech intelligibility rating,SIR)结果进行二分类变量的单因素分析,再进行多分类变量的Logistic回归分析评估患儿的治疗效果和影响康复效果的因素。结果:耳聋患儿CI植入年龄、术前平均残余听力、术前佩戴助听器时间、使用人工耳蜗时间和术后语训时间等因素和CAP增长倍数之间有明显的相关性(P0.05),除了上述因素之外还有术前语训时间等因素与治疗后患儿SIR增长倍数存在相关性(P0.05);CI植入年龄、术前平均残余听力和术前佩戴助听器时间对患儿术后CAP的恢复具有影响(P0.05);CI植入年龄、术前佩戴助听器时间、术前语训时间等因素对患儿SIR恢复产生影响(P0.05)。结论:患儿植入人工耳蜗的年龄、术前平均残余听力、术前佩戴助听器时间和术前言语训练时间是影响学龄前耳聋患儿术后听力言语功能恢复的主要因素。     

OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia

Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations, the OSBPL2-disrupted Bama miniature(BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer(SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss(HL) with degeneration/apoptosis of cochlea hair cells(HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet(HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss(NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.     

c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family

We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technology yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement using microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hearing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 variants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal dominant hereditary hearing loss and corresponds to DFNA17. The mutation identified in our study is the same described in the prior report. Thus, although linkage studies suggested a candidate gene in chromosome 14, we concluded that the mutation in chromosome 22 better explains the hearing loss phenotype in the Brazilian family.     

Large Protein Assemblies Formed by Multivalent Interactions between Cadherin23 and Harmonin Suggest a Stable Anchorage Structure at the Tip Link of Stereocilia

Stereocilia tip links of inner ear hair cells are subjected to constant stretching during hair-bundle deflection, and accordingly are well designed to prevent from being broken by mechanical tensions. The roots of tip links, which couple tip links with the cytoskeleton, supposedly play important roles in withstanding large forces under stimulated conditions. The upper root of the tip link is mainly formed by the cytoplasmic tail of cadherin23 and its actin-anchoring protein harmonin. However, the detailed organization mode of the two proteins that gives rise to a strong upper root remains unclear. Here we show that the exon68-encoded peptide of cadherin23 can either interact with the N-terminal domain (NTD) of harmonin or form a homodimer. We demonstrate that the three harmonin binding sites of cadherin23, namely the NTD-binding motif, the exon68 peptide, and the C-terminal PDZ binding motif, do not synergize with each other in binding to harmonin, instead they facilitate formation of polymeric cadherin23/harmonin complexes. The exon68 peptide can promote the cadherin23/harmonin polymer formation via either binding to harmonin NTD or self-dimerization. We propose that the polymeric cadherin23/harmonin complex formed beneath the upper tip link membranes may serve as part of the stable rootlet structure for anchoring the tip links of stereocilia.     

Mitochondrial 12S rRNA susceptibility mutations in aminoglycoside-associated and idiopathic bilateral vestibulopathy

The mitochondrial 12S rRNA is considered a hotspot for mutations associated with nonsyndromic (NSHL) and aminoglycoside-induced hearing loss (AIHL). Although aminoglycoside ototoxicity is the most common cause of bilateral vestibular dysfunction, the conceivable role of 12S rRNA mutations has never been systematically investigated. We sequenced the 12S rRNA of 66 patients with bilateral vestibulopathy (BV) with (n = 15) or without (n = 51) prior exposure to aminoglycosides, as well as 155 healthy controls with intact vestibular function (sport pilots), and compared these to 2704 published sequences (Human Mitochondrial Genome Database). No mutations with a confirmed pathogenicity were found (A1555G, C1494T), but four mutations with a hitherto tentative status were detected (T669C, C960del, C960ins, T961G). Due to their predominant occurrence in patients without aminoglycoside exposure, their detection in controls and a weak evolutionary conservation, their pathogenic role in vestibulocochlear dysfunction remains provisional.     

Electromechanical Models of the Outer Hair Cell Composite Membrane

The outer hair cell (OHC) is an extremely specialized cell and its proper functioning is essential for normal mammalian hearing. This article reviews recent developments in theoretical modeling that have increased our knowledge of the operation of this fascinating cell. The earliest models aimed at capturing experimental observations on voltage-induced cellular length changes and capacitance were based on isotropic elasticity and a two-state Boltzmann function. Recent advances in modeling based on the thermodynamics of orthotropic electroelastic materials better capture the cell’s voltage-dependent stiffness, capacitance, interaction with its environment and ability to generate force at high frequencies. While complete models are crucial, simpler continuum models can be derived that retain fidelity over small changes in transmembrane voltage and strains occurring in vivo. By its function in the cochlea, the OHC behaves like a piezoelectric-like actuator, and the main cellular features can be described by piezoelectric models. However, a finer characterization of the cell’s composite wall requires understanding the local mechanical and electrical fields. One of the key questions is the relative contribution of the in-plane and bending modes of electromechanical strains and forces (moments). The latter mode is associated with the flexoelectric effect in curved membranes. New data, including a novel experiment with tethers pulled from the cell membrane, can help in estimating the role of different modes of electromechanical coupling. Despite considerable progress, many problems still confound modelers. Thus, this article will conclude with a discussion of unanswered questions and highlight directions for future research.     

背景噪声对人感知声音时间信息的影响

对声音时间信息的分辨在人和动物感知声音信息的过程中至关重要.在自然声环境中,声音信息总处于一定的噪声背景下.文章以间隔探测阈值为指标测定了人对纯音和噪声的间隔探测阈值,以及持续噪声背景对间隔探测阈值的影响.声音信号采用1000～10000 Hz的纯音信号和白噪声信号,声音强度为70 dB SPL.背景噪声为持续白噪声,强度分别为45、55、65 dB SPL.结果表明,对纯音信号,随着背景噪声强度增加,间隔探测阈值有升高的趋势.对噪声信号来说,45、55 dB SPL的背景噪声对噪声信号的间隔探测阈值无显著影响,但65 dB SPL的背景噪声使间隔探测阈值显著升高.研究结果提示,背景噪声能够在一定程度上影响人对声音时间信息的感知,影响的程度与背景噪声的强度有关.