Structural and Mechanical Analysis of Tectorial Membrane Tecta Mutants

AbstractThe tectorial membrane (TM) is an extracellular matrix of the cochlea whose prominent role in hearing has been demonstrated through mutation studies. The C1509G mutation of the Tecta gene, which encodes for the α-tectorin protein, leads to hearing loss. The heterozygote TM only attaches to the first row of outer hair cells (OHCs), and the homozygote TM does not attach to any OHCs. Here we measured the morphology and mechanical properties of wild-type, heterozygous, and homozygous Tecta TMs. Morphological analyses conducted with second- and third-harmonic imaging, scanning electron microscopy, and immunolabeling revealed marked changes in the collagen architecture and stereocilin-labeling patterns of the mutant TMs. The mechanical properties of the mutant TM were measured by force spectroscopy. Whereas the axial Young's modulus of the low-frequency (apical) region of Tecta mutant TM samples was similar to that of wild-type TMs, it significantly decreased in the basal region to a value approaching that found at the apex. Modeling simulations suggest that a reduced TM Young's modulus is likely to reduce OHC stereociliary deflection. These findings argue that the heterozygote C1509G mutation results in a lack of attachment of the TM to the OHCs, which in turn reduces both the overall number of OHCs that are involved in mechanotransduction and the degree of mechanotransduction exhibited by the OHCs that remain attached to the TM

In vivo vibrometry inside the apex of the mouse cochlea using spectral domain optical coherence tomography

Sound transduction within the auditory portion of the inner ear, the cochlea, is a complex nonlinear process. The study of cochlear mechanics in large rodents has provided important insights into cochlear function. However, technological and experimental limitations have restricted studies in mice due to their smaller cochlea. These challenges are important to overcome because of the wide variety of transgenic mouse strains with hearing loss mutations that are available for study. To accomplish this goal, we used spectral domain optical coherence tomography to visualize and measure sound-induced vibrations of intracochlear tissues. We present, to our knowledge, the first vibration measurements from the apex of an unopened mouse cochlea

Hair cell force generation does not amplify or tune vibrations within the chicken basilar papilla

Frequency tuning within the auditory papilla of most non-mammalian species is electrical, deriving from ion-channel resonance within their sensory hair cells. In contrast, tuning within the mammalian cochlea is mechanical, stemming from active mechanisms within outer hair cells that amplify the basilar membrane travelling wave. Interestingly, hair cells in the avian basilar papilla demonstrate both electrical resonance and force-generation, making it unclear which mechanism creates sharp frequency tuning. Here, we measured sound-induced vibrations within the apical half of the chicken basilar papilla in vivo and found broadly-tuned travelling waves that were not amplified. However, distortion products were found in live but not dead chickens. These findings support the idea that avian hair cells do produce force, but that their effects on vibration are small and do not sharpen tuning. Therefore, frequency tuning within the apical avian basilar papilla is not mechanical, and likely derives from hair cell electrical resonance

High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss

BACKGROUND: Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. METHODS: To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. RESULTS: The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. CONCLUSION: These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which expression of prestin might be maintained in cells carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5 transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant

Mechanisms of Hearing Loss after Blast Injury to the Ear

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the bodyﾒs most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

Anti-periodic boundary value problems with Riesz–Caputo derivative

Abstract This paper is concerned with a class of anti-periodic boundary value problems for fractional differential equations with the Riesz–Caputo derivative, which can reflected both the past and the future nonlocal memory effects. By means of new fractional Gronwall inequalities and some fixed point theorems, we obtain some existence results of solutions under the Lipschitz condition, the sublinear growth condition, the nonlinear growth condition and the comparison condition. Three examples are given to illustrate the results

NUMERICAL NUMERICAL NUMERICAL NUMERICAL RESEARCH RESEARCH RESEARCH RESEARCH ON ON ON ON FORCED FORCED FORCED FORCED RESPONSE RESPONSE RESPONSE RESPONSE OF OF OF OF A A A A COMPRESSOR COMPRESSOR COMPRESSOR COMPRESSOR ROTOR ROTOR ROTOR ROTOR ROW ROW ROW ROW

ABSTRACT ABSTRACT ABSTRACT ABSTRACT Under inlet total pressure distortion, forced response of compressor blades poses a threat to aircraft propulsion system. Research on blade dynamic response is premise and basis for high-cycle fatigue life analysis. Blades of a compressor first rotor row are studied with three dimensional numerical simulation in fluid-structure coupling methods. The inlet distortion's influence on blade aeroelastic dynamic response and flow field characteristics are analyzed. The results demonstrate that circumferential and radial total pressure distortion should be considered together in the phenomenon of actual inlet distortion induced blade vibration response. At the condition of low angle of attacks, radial distortion intensity is weak, the relation between vibration response level of rotor blades and circumferential distortion intensity is proportional. With the angle of attack increases, the vibratory stress under aerodynamic forces grows sufficiently. The radial total pressure distortion near hub increases dynamic response severity of rotor blades

Dynamic System Modeling of a Hybrid Neural Network with Phase Space Reconstruction and a Stability Identification Strategy

Focusing on the identification of dynamic system stability, a hybrid neural network model is proposed in this research for the rotating stall phenomenon in an axial compressor. Based on the data fusion of the amplitude of the spatial mode, the nonlinear property is well characterized in the feature extraction of the rotating stall. This method of data processing can effectively avoid the inaccurate recognition of single or multiple measuring sensors only depending on pressure. With the analysis on the spatial mode, a chaotic characteristic was shown in the development of the amplitude with the first-order spatial mode. With the prerequisite of revealing the essence of this dynamic system, a hybrid radial basis function (RBF) neural network was adopted to represent the properties of the system by artificial intelligence learning. Combining the advantages of the methods of K-means and Gradient Descent (GD), the Chaos–K-means–GD–RBF fusion model was established based on the phase space reconstruction of the chaotic sequence. Compared with the two methods mentioned above, the calculation accuracy was significantly improved in the hybrid neural network model. By taking the strategy of global sample entropy and difference quotient criterion identification, a warning of inception can be suggested in advance of 12.3 revolutions (296 ms) with a multi-step prediction before the stall arrival