A5091556749- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Acoustic Wave Phenomena Research
- Force Microscopy Techniques and Applications
- Electrochemical Analysis and Applications
- Analytical Chemistry and Sensors
- Connexins and lens biology
- Ion Channels and Receptors
- Ear Surgery and Otitis Media
- Biochemical Analysis and Sensing Techniques
- Congenital heart defects research
- Heart Rate Variability and Autonomic Control
- Cancer-related molecular mechanisms research
- Neurobiology and Insect Physiology Research
- Animal Vocal Communication and Behavior
- Muscle Physiology and Disorders
- Cell Adhesion Molecules Research
- Neuroscience and Neural Engineering
- Adipose Tissue and Metabolism
- Lipid Membrane Structure and Behavior
- Plant Molecular Biology Research
- Mechanical and Optical Resonators
- Pain Mechanisms and Treatments
- Bacterial Genetics and Biotechnology
University of Kentucky
2016-2025
Cytoskeleton (United States)
2017
Albert B. Chandler Hospital
2005-2016
National Institutes of Health
1997-2009
National Institute on Deafness and Other Communication Disorders
1998-2009
Gene Therapy Laboratory
2006
Medical Research Council
2005
University of Cambridge
2005
Newcastle University
2005
Imperial College London
2003-2005
The long-term average speech spectrum (LTASS) and some dynamic characteristics of were determined for 12 languages: English (several dialects), Swedish, Danish, German, French (Canadian), Japanese, Cantonese, Mandarin, Russian, Welsh, Singhalese, Vietnamese. LTASS only was also measured Arabic. Speech samples (18) recorded, using standardized equipment procedures, in 15 localities (usually) ten male female talkers. All analyses conducted at the National Acoustic Laboratories, Sydney. similar...
Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows graded heights. Calcium and integrin-binding protein 2 is essential for hearing localizes to but its exact function unknown. Here, we have characterized two mutant mouse lines, one lacking calcium carrying a human deafness-related Cib2 mutation, show both deaf exhibit no mechanotransduction auditory cells, despite presence tip links gate mechanotransducer channels....
Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of cells in inner ear. The different elements bundle, stereocilia a kinocilium, interconnected variety link types. One these links, tip link, connects top shorter stereocilium with lateral membrane an adjacent taller may gate mechanotransducer channel cell. Mass spectrometric Western blot analyses identify tip-link antigen, hitherto unidentified antigen specifically associated kinocilial...
Electromotility, i.e., the ability of cochlear outer hair cells (OHCs) to contract and elongate at acoustic frequencies, is presumed depend on voltage-driven conformational changes "motor" proteins present in OHC lateral plasma membrane. Recently, two membrane have been proposed as candidates for motor. A sugar transporter, GLUT-5, was based its localization OHCs observation that transport alters voltage sensitivity motor mechanism. Another candidate, "prestin," identified from a subtracted...
Generation of a strong electrical potential in the cochlea is uniquely mammalian and may reflect recent evolutionary advances cellular voltage-dependent amplifiers. This endocochlear hypothesized to dramatically improve hearing sensitivity, concept that difficult explore experimentally, because manipulating cochlear function frequently causes rapid degenerative changes early development. Here, we examine deafness phenotype adult Claudin 11-null mice, which lack basal cell tight junctions...
Do not touch! The surface of a living cell is soft and responsive therefore high-resolution imaging the membrane has been possible to date. Now noncontact protein complexes in plasma cells demonstrated (see picture) used follow cells' structural reorganization. This breakthrough opens up wealth new experiments biology. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503915_s.pdf or from author. Please note: publisher responsible...
The S1P(2) receptor is a member of family G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. widely expressed and linked to multiple protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated expression essential for proper functioning auditory vestibular systems. Auditory brainstem response analysis revealed receptor-null mice were deaf by one month age. These null...
Beta(cyto)-actin and gamma(cyto)-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that null mice (Actg1(-/-)) viable. However, they suffer increased mortality progressive hearing loss during adulthood despite compensatory up-regulation beta(cyto)-actin. The surprising viability normal young Actg1(-/-) means beta(cyto)-actin can likely build actin-based cytoskeletal structures...
Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate current stem cell gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little known about postnatal maturating HCs. Here we apply type-specific functional genomic analysis to transcriptomes auditory vestibular sensory epithelia from early mice. We...
Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the link, with protocadherin 15 (PCDH15) at lower cadherin 23 (CDH23) upper end link. In terminally differentiated mammalian auditory cells, are subjected sound-induced forces throughout an organism's life. Although can regenerate disrupted restore hearing, molecular details this...
Mechanotransducer channels at the tips of sensory stereocilia inner ear hair cells are gated by tension 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links tensioned rest, resulting in a continuous influx Ca2+ into cell. Here, we show that this constitutive influx, usually considered as potentially deleterious for cells, is fact essential stability. In auditory young postnatal mice and rats, reduction mechanotransducer current, via pharmacological channel...
Although the dynamics of cell membranes and associated structures is vital for function, little known due to lack suitable methods. We found, using scanning ion conductance microscopy, that microvilli, membrane projections supported by internal actin bundles, undergo a life cycle: fast height-dependent growth, relatively short steady state, slow height-independent retraction. The microvilli can aggregate into stable where state extended. suggest intrinsic combined with their ability make...
The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular junction protein tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated knockin mouse carries mutation orthologous coding linked DFNB49 humans. Tricellulin was absent from inner ear epithelia of mutant animals, developed rapidly progressing...
The precise assembly of inner ear hair cell stereocilia into rows increasing height is critical for mechanotransduction and the sense hearing. Yet, how lengths actin-based are regulated remains poorly understood. Mutations molecular motor myosin 15 stunt growth cause deafness. We found that cells express two isoforms differ by inclusion an 133-kDa N-terminal domain, these can selectively traffic to different rows. Using isoform-specific knockout mouse, we show expressing only small isoform...
Hearing loss is a complex disorder caused by both genetic and environmental factors. Previously, mutations in CIB2 have been identified as common cause of hearing Pakistani Turkish populations. Here we report novel (c.556C>T; p.(Arg186Trp)) transition mutation the gene through whole exome sequencing (WES) Caribbean Hispanic family with non-syndromic loss. belongs to calcium-and integrin-binding (CIB) proteins. The carboxy-termini CIB proteins are associated calcium binding intracellular...
ABSTRACT Cochlear hair cells transduce sound using stereocilia, and disruption to these delicate mechanosensors is a significant cause of hearing loss. Stereocilia architecture dependent upon the nanomotor myosin 15. A short isoform (MYO15A-2) drives stereocilia development by delivering an elongation-promoting complex (EC) tips, alternatively spliced long (MYO15A-1) tunes postnatal size in shorter which possess mechanosensitive ion channels. Disruption functions causes two distinct...