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*  The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation...
The hair cells of the inner ear seem to be specified properly as they express many of the typical hair cell markers such as myosin VI/VIIa, Math1 and Brn3c. Thus, Gfi1 is not required for the specification of hair cells as they are formed in both the vestibule and the cochlea. However, the loss of Gfi1 seems to affect the vestibular and cochlear hair cells differently. In the vestibule, the hair cells are morphologically abnormal at the earliest stages of hair cell differentiation and at all subsequent stages. In addition, hair cells are not specifically localized to a lumenal monolayer, and are more variable in size and shape. This disorganization of ...
  http://dev.biologists.org/content/130/1/221
*  Channel gating forces govern accuracy of mechano-electrical transduction in hair cells : Sussex Research Online
Sensory hair cells are known for the exquisite displacement sensitivity with which they detect the sound-evoked vibrations in the inner ear. In this article, we determine a stochastically imposed fundamental lower bound on a hair cell's sensitivity to detect mechanically coded information arriving at its hair bundle. Based on measurements of transducer current and its noise in outer hair cells and the application of estimation theory, we show that a hair cell's transducer current carries information that allows the detection of vibrational amplitudes with an accuracy on the order of nanometers. We identify the transducer channel's molecular gating force as the physical factor controlling this accuracy in proportion to the inverse of its magnitude. Further, we show that the ...
  http://sro.sussex.ac.uk/29504/
*  Somatostatin and gentamicin-induced auditory hair cell loss - Zurich Open Repository and Archive
OBJECTIVE/HYPOTHESIS: Hair cells of the mammalian auditory system do not regenerate, and therefore their loss leads to irreversible hearing loss. Aminoglycosides, among other substances, can irreversibly damage hair cells. Somatostatin, a peptide with hormone/neurotransmitter properties, has neuroprotective effects by binding to its receptor. In this study, we tested whether somatostatin can protect hair cells from gentamicin-induced damage in vitro. STUDY DESIGN: This study confirmed the expression of somatostatin receptor mRNA within the cochlea and analyzed the effect of somatostatin on gentamicin-induced hair cell damage and death in vitro. METHODS: Expression of somatostatin receptor mRNA in the rat cochlea was analyzed by reverse transcriptase-polymerase chain reaction ...
  http://www.zora.uzh.ch/id/eprint/18734/
*  Initial characterization of kinocilin, a protein of the hair cell kinocilium : Sussex Research Online
A subtracted library prepared from vestibular sensory areas [Nat. Genet. 26 (2000) 51] was used to identify a 960 bp murine transcript preferentially expressed in the inner ear and testis. The cDNA predicts a basic 124 aa protein that does not share any significant sequence homology with known proteins. Immunofluorescence and immunoelectron microscopy revealed that the protein is located mainly in the kinocilium of sensory cells in the inner ear. The protein was thus named kinocilin. In the mouse, kinocilin is first detected in the kinocilia of vestibular and auditory hair cells at embryonic days 14.5, and 18.5, respectively. In the mature vestibular hair cells, kinocilin is still present in the kinocilium. As the auditory hair cells begin to lose the kinocilium during postnatal development, kinocilin ...
  http://sro.sussex.ac.uk/19553/
*  Delta1 expression during avian hair cell regeneration | Development
Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced ...
  http://dev.biologists.org/content/126/5/961
*  Angelika Doetzlhofer - The Solomon H Snyder Department of Neuroscience
Auditory hair cells, located in the inner ear cochlea are critical for our ability to detect sound.. In mammals, neural innervated hair cells come in two flavors: inner hair cells, which are our primary mechanoreceptor and relay sound information to the brain and the signal amplifying outer hair cells. Inner and outer hair cells are structurally and functionally supported by different types of glial-like supporting cells with which they share a close lineage relationship. Despite their importance for our ability to hear, little is known about how the different hair cell and supporting cell lineages are specified and what molecular cues ...
  http://neuroscience.jhu.edu/research/faculty/22
*  ORBi: Browsing ORBi
in Ear, Nose, & Throat Journal (1998), 77(4), 276280282-5. Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led ... [more ▼]. Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led to new and exciting possibilities in inner ear medicine and surgery; specifically, the treatment or prevention of a variety of types of hearing losses in the foreseeable future. Sensorineural hearing loss in humans is commonly associated with a loss of auditory hair cells. It has been generally accepted ...
  http://orbi.ulg.ac.be/browse?type=author&sort_by=1&order=DESC&rpp=20&etal=3&value=Moonen%2C+Gustave+p000749&offset=200
*  Pairwise coupling of hair cell transducer channels links auditory sensitivity and dynamic range : Sussex Research Online
Hair cells in the inner ear provide the basis for the exquisite hearing capabilities of mammals. These cells transduce sound-induced displacements of their mechanosensitive hair bundle into electrical currents within a fraction of a millisecond and with nanometer fidelity. Excitatory displacements of the hair cell¿s bundle tense tip links that open transducer channels. These channels are located either at one or at both ends of the links, where the latter possibility was thought to compromise sensitivity via negative cooperativity, and discarded for quantitatively describing the transduction process. Here, we show instead that this series mode of activation accurately explains measured transduction in hair cells. It enhances both sensitivity and dynamic range of ...
  http://sro.sussex.ac.uk/25277/
*  Frontiers | Making sense of Wnt signaling-linking hair cell regeneration to development | Frontiers in Cellular Neuroscience
Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, ...
  https://www.frontiersin.org/articles/10.3389/fncel.2015.00066/full
*  JCI - Designer aminoglycosides prevent cochlear hair cell loss and hearing loss
Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat ...
  https://hrhjchina.com.insight.mobile.jci.org/articles/view/77424/figure/1
*  JCI - Designer aminoglycosides prevent cochlear hair cell loss and hearing loss
Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat ...
  https://jci.org/articles/view/77424/pdf
*  Mike Evans - Keele University
In my PhD (Bristol University, 1983) I used ion-sensitive microelectrodes to investigate pH regulation in snail neurones, supervised by Dr RC Thomas. I was awarded a Royal Society Exchange Fellowship to work in Paris (ENS), mainly with Dr Alain Marty on the muscarinic response in rat lacrimal glands, but also did some single channel work and a characterisation of a novel calcium-activated chloride current. I then switched direction towards hearing and the cochlea, doing a postdoc in Denver (UCHSC) with Dr Paul Fuchs following a short period in Bristol. We investigated the electrical resonance mechanism in chick cochlear hair cells. I next investigated the hair cell transduction mechanism in turtles, working with Andrew Crawford and Robert Fettiplace in Cambridge. In 1990 I became a temporary lecturer in Physiology, Bristol, and two years later was awarded a Wellcome Trust postdoctoral fellowship to ...
  https://www.keele.ac.uk/lifesci/people/mikeevans/
*  Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle | The...
In this study, we addressed the developmental role of harmonin in the inner ear sensory cells (hair cells). Mutations in the gene, USH1C, encoding this PDZ domain‐containing protein have been shown to underlie one genetic form of USH1 (Bitner‐Glindzicz et al., 2000; Verpy et al., 2000). Here, we show that harmonin directly interacts with cadherin 23, a protein defective in another genetic form of USH1 (Bolz et al., 2001; Bork et al., 2001). We also show that harmonin b, which thus far has only been detected in the inner ear (Verpy et al., 2000), binds to actin filaments. In addition, cadherin 23 and harmonin b concomitantly appear in the emerging stereocilia and disappear from the adult hair bundle. Together, these results strongly suggest that harmonin b bridges cadherin 23 to the cytoskeletal actin core of the stereocilium. Since Cdh23 mutations result in the disorganization of the ...
  http://emboj.embopress.org/content/21/24/6689
*  Plus it
Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells and in the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by non-traumatic noise levels and as none of the cells showing this activation ...
  http://www.eneuro.org/content/early/2016/04/24/ENEURO.0047-16.2016
*  Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells. - PubMed - NCBI
PLoS Biol. 2013;11(6):e1001583. doi: 10.1371/journal.pbio.1001583. Epub 2013 Jun 11. Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
  https://www.ncbi.nlm.nih.gov/pubmed/23776407
*  Frontiers | Epigenetic DNA Demethylation Causes Inner Ear Stem Cell Differentiation into Hair Cell-Like Cells | Frontiers in...
The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28.57% decrease after treatment, which causes significantly repressed DNMT1 protein expression and DNMT activity. Additionally, FM1-43 permeation assays indicated that the permeability of 5-aza-treated MUCs was similar to that of sensory hair ...
  https://www.frontiersin.org/articles/10.3389/fncel.2016.00185/full
*  Gene Therapy To Treat Deafness ( Replacing lost sensory hair cells in th...)
Health,Replacing lost sensory hair cells in the inner ear may restore partial... Scientists are of the opinion that viral vector found in a dev...Deafness is often associated with loss of sensory hairs in the coc...Tested on guinea pigs with a positive result the procedure shows ...,Gene,Therapy,To,Treat,Deafness,,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
  http://www.bio-medicine.org/medicine-news/Gene-Therapy-To-Treat-Deafness--3398-1/
*  Human Hair Cell Regeneration Clinical Trial Using Stem Cells Begins
by Neil Bauman, Ph.D.. Research into regenerating human hair cells in the inner ear, with the aim of restoring hearing, has been ongoing for a number of years. Researchers have been trying, with varying degrees of success, to get hair cells to regenerate in animals-but there are still many hurdles to overcome. Consequently, human trials appear to still be a number of years away.. However, one method has just leapfrogged the competition and has already begun a Phase I clinical trial. (Note: a Phase I clinical trial is done on a very small group of people [in this case 10] to see if the proposed treatment will be safe and identify any resulting side effects. It's not till Phase II trials that researchers primarily determine just how effective the treatment will be, although preliminary results hopefully will come out of the Phase I trials.). This Phase I clinical trial is very limited in scope-just for ...
  http://hearinglosshelp.com/blog/human-hair-cell-regeneration-clinical-trial-using-stem-cells-begins/
*  Plus it
To many animals, including humans, some of the best things in life are mechanical. Not only courtship and sex but also simple movements such as walking depend on the ability to transform mechanical energy in the form of touch, sound, and muscle tension into ionic currents. This ability is also essential for control of osmotic balance, bladder function, and blood pressure in mammals. To meet these diverse needs, animals bear numerous sensory organs that contain either ciliated or nonciliated mechanoreceptor cells. Vertebrate hair cells and insect chordotonal neurons are examples of ciliated mechanoreceptor cells; mechanoreceptive neurons that innervate the body surface of nematodes, insects, and mammals are examples of nonciliated mechanoreceptor cells. All of these cells share the ability to signal the presence of mechanical stimuli by opening ion channels. ...
  http://www.jneurosci.org/content/24/42/9220
*  Search
The inner ear contains the auditory and vestibular organs, which are sensory neuroepithelia composed of mechanosensory hair cells and glia-like supporting cells. The mammalian auditory sensory epithelium, the organ of Corti, is responsible for transduction of sound stimuli into electrical signals for hearing function. Hair ...
  https://digital.lib.washington.edu/researchworks/handle/1773/4897/discover?filtertype=author&filter_relational_operator=equals&filter=Hartman%2C+Byron+H.
*  Thingumbobesquire -- Abandon All Axioms Ye Who Enter Here: The Essence of Change
The cochlea is a spiral-shaped tunnel in the bony labyrinth of the inner ear. Its principal component is a strip of sensory tissue (red) called the organ of Corti. The organ of Corti is lined with rows of auditory hair cells. Hair bundles that project from the hair cells are deflected in response to sound-induced vibrations in the basilar membrane. This bending opens mechanically gated ion channels, initiating the conversation of the sound-induced mechanical stimulus into an electrical transmission ...
  http://thingumbobesquire.blogspot.com/2011/10/essence-of-change.html
*  Ush1c - Harmonin - Mus musculus (Mouse) - Ush1c gene & protein
Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (PubMed:19447093). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018).
  http://www.uniprot.org/uniprot/Q9ES64
*  Recent Articles | Regenerative Medicine | The Scientist Magazine®| Page 1
Researchers isolate stem cells from the mouse cochlea and convert them into auditory hair cells, potentially paving the way for therapies to treat hearing loss.. 0 Comments. ...
  http://www.the-scientist.com/?articles.list/tagNo/49/tags/regenerative-medicine/pageNo/1/
*  The roles of F-actin belts and tension in hair cell regeneration - Joseph Burns
A study of data collected from 2001-2004 estimated 35.4% of adults aged 40 and older have balance problems, with odds of dysfunction increasing significantly wi...
  http://grantome.com/grant/NIH/F31-DC010519-02