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https://www.readbyqxmd.com/read/29140244/subcellular-analysis-of-pigeon-hair-cells-implicates-vesicular-trafficking-in-cuticulosome-formation-and-maintenance
#1
Simon Nimpf, Erich Pascal Malkemper, Mattias Lauwers, Lyubov Ushakova, Gregory Nordmann, Andrea Wenninger-Weinzierl, Thomas R Burkard, Sonja Jacob, Thomas Heuser, Guenter P Resch, David A Keays
Hair cells are specialized sensors located in the inner ear that enable the transduction of sound, motion, and gravity into neuronal impulses. In birds some hair cells contain an iron-rich organelle, the cuticulosome, that has been implicated in the magnetic sense. Here, we exploit histological, transcriptomic and tomographic methods to investigate the development of cuticulosomes, as well as the molecular and subcellular architecture of cuticulosome positive hair cells. We show that this organelle forms rapidly after hatching in a process that involves vesicle fusion and nucleation of ferritin nanoparticles...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29139542/temporal-and-spatial-expression-patterns-of-hedgehog-receptors-in-the-developing-inner-and-middle-ear
#2
Jeong-Oh Shin, Harinarayana Ankamreddy, Naga Mahesh Jakka, Seokwon Lee, Un-Kyung Kim, Jinwoong Bok
The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc)...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29130354/delivery-of-adeno-associated-viral-vectors-in-adult-mammalian-inner-ear-cell-subtypes-without-auditory-dysfunction
#3
Yong Tao, Mingqian Huang, Yilai Shu, Adam Ruprecht, Hongyang Wang, Yong Tang, Luk H Vandenberghe, Qiuju Wang, Guangping Gao, Wei-Jia Kong, Zheng-Yi Chen
Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in human with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to effectively recover auditory functions in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points whereas in human the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether or not AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damages to the inner ear...
November 12, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#4
Alex M Rohacek, Thomas W Bebee, Richard K Tilton, Caleb M Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A Germiller, Ian D Krantz, Russ P Carstens, Douglas J Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1(-/-) mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29105116/a-mitochondrial-targeting-tetrapeptide-bendavia-protects-lateral-line-hair-cells-from-gentamicin-exposure
#5
Xiao Kuang, Yanhui Sun, Zhenjie Wang, Shuang Zhou, Hongzhuo Liu
The hearing loss induced by aminoglycosides is caused by the permanent loss of mechanosensory hair cells of the inner ear. The aim of the present study is therefore to evaluate the protective effect of Bendavia, a novel antioxidant, on gentamicin-induced hair cell damage in zebrafish lateral lines. The results demonstrated the pretreatment of Bendavia exhibited dose-dependent protection against gentamicin in both acute and chronic exposure. We found that Bendavia at 150 μm conferred optimal protection from either acute or chronic exposure with ototoxin...
November 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29104815/a-novel-nano-approach-for-targeted-inner-ear-imaging
#6
M N Kayyali, L Brake, A J Ramsey, A C Wright, B W O'Malley, D Daqing Li
During the last decade, there have been major improvements in imaging modalities and the development of molecular imaging in general. However detailed inner ear imaging still provides very limited information to physicians. This is unsatisfactory as sensorineural hearing loss is the main cause of permanent hearing loss in adults and at least 134 genetic mutations that result in congenital hearing loss have been identified. We are still unable, in most cases where gross anatomical changes are not observed, to determine the exact cause of hearing loss at a cellular or molecular level in patients using non-invasive techniques...
August 2017: Journal of Nanomedicine & Nanotechnology
https://www.readbyqxmd.com/read/29104531/the-repression-of-atoh1-by-neurogenin1-during-inner-ear-development
#7
Héctor Gálvez, Juan J Tena, Fernando Giraldez, Gina Abelló
Atonal homolog 1 (Atoh1) and Neurogenin1 (Neurog1) are basic Helix-Loop-Helix (bHLH) transcription factors crucial for the generation of hair cells (HCs) and neurons in the inner ear. Both genes are induced early in development, but the expression of Atoh1 is counteracted by Neurog1. As a result, HC development is prevented during neurogenesis. This work aimed at understanding the molecular basis of this interaction. Atoh1 regulation depends on a 3'Atoh1-enhancer that is the site for Atoh1 autoregulation. Reporter assays on chick embryos and P19 cells show that Neurog1 hampers the autoactivation of Atoh1, the effect being cell autonomous and independent on Notch activity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29093665/pi3k-and-inhibitor-of-apoptosis-proteins-modulate-gentamicin-induced-hair-cell-death-in-the-zebrafish-lateral-line
#8
Heather Wiedenhoft, Lauren Hayashi, Allison B Coffin
Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29093664/towards-the-prevention-of-aminoglycoside-related-hearing-loss
#9
REVIEW
Mary E O'Sullivan, Adela Perez, Randy Lin, Autefeh Sajjadi, Anthony J Ricci, Alan G Cheng
Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is death of inner ear sensory hair cells selectively triggered by aminoglycosides. For decades, research has sought to unravel the molecular events mediating sensory cell demise, emphasizing the roles of reactive oxygen species and their potentials as therapeutic targets. Studies in recent years have revealed candidate transport pathways including the mechanotransducer channel for drug entry into sensory cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29070485/functions-of-wnt-signaling-pathway-in-hair-cell-differentiation-and-regeneration
#10
Qing-Qing Fan, Fei-Long Meng, Ran Fang, Gao-Peng Li, Xiao-Li Zhao
Wnt signaling pathway plays important roles in the development and homeostasis of multicellular organisms. Through their bindings with the Frizzled receptors, the Wnt ligands regulate a wide range of developmental processes, such as axis patterning, cell division, and cell fate specification. Wnt signaling plays vital roles in the development of inner ear of the mouse. In the early stages of inner ear development, Wnt signaling specifies the size of the placode and the formation of the otic vesicle. In later stages, Wnt signaling mediates hair cell specification and orients the stereociliary bundles in a uniform direction...
October 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29063958/identification-and-characterization-of-a-novel-chemically-induced-allele-at-the-planar-cell-polarity-gene-vangl2
#11
Abdul-Rahman El-Hassan, Vicki Leung, Fares Kharfallah, Marie-Claude Guyot, Redouane Allache, Philippe Gros, Zoha Kibar
Planar cell polarity (PCP) signaling controls a number of morphogenetic processes including convergent extension during gastrulation and neural tube formation. Defects in this pathway cause neural tube defects (NTD), the most common malformations of the central nervous system. The Looptail (Lp) mutant mouse was the first mammalian mutant implicating a PCP gene (Vangl2) in the pathogenesis of NTD. We report on a novel chemically induced mutant allele at Vangl2 called Curly Bob that causes a missense mutation p...
October 24, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29059194/role-of-neuropilin-1-semaphorin-3a-signaling-in-the-functional-and-morphological-integrity-of-the-cochlea
#12
Pezhman Salehi, Marshall X Ge, Usha Gundimeda, Leah Michelle Baum, Homero Lael Cantu, Joel Lavinsky, Litao Tao, Anthony Myint, Charlene Cruz, Juemei Wang, Angeliki Maria Nikolakopoulou, Carolina Abdala, Matthew William Kelley, Takahiro Ohyama, Thomas Matthew Coate, Rick A Friedman
Neuropilin-1 (Nrp1) encodes the transmembrane cellular receptor neuropilin-1, which is associated with cardiovascular and neuronal development and was within the peak SNP interval on chromosome 8 in our prior GWAS study on age-related hearing loss (ARHL) in mice. In this study, we generated and characterized an inner ear-specific Nrp1 conditional knockout (CKO) mouse line because Nrp1 constitutive knockouts are embryonic lethal. In situ hybridization demonstrated weak Nrp1 mRNA expression late in embryonic cochlear development, but increased expression in early postnatal stages when cochlear hair cell innervation patterns have been shown to mature...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29049311/a-kinase-inhibitor-library-screen-identifies-novel-enzymes-involved-in-ototoxic-damage-to-the-murine-organ-of-corti
#13
Matthew Ryals, Kwang Pak, Rahul Jalota, Arwa Kurabi, Allen F Ryan
Ototoxicity is a significant side effect of a number of drugs, including the aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are used to treat life-threatening illnesses. Although much progress has been made, the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs) remains incompletely understood. Given the critical role of protein phosphorylation in intracellular processes, including both damage and survival signaling, we screened a library of kinase inhibitors targeting members of all the major families in the kinome...
2017: PloS One
https://www.readbyqxmd.com/read/29030130/behavioural-and-objective-vestibular-assessment-in-persons-with-osteoporosis-and-osteopenia-a-preliminary-investigation
#14
Aditi Gargeshwari, Raghav Hira Jha, Niraj Kumar Singh, Prawin Kumar
INTRODUCTION: Calcium is vital for the functioning of the inner ear hair cells as well as for the neurotransmitter release that triggers the generation of a nerve impulse. A reduction in calcium level could therefore impair the peripheric vestibular functioning. However, the outcome of balance assessment has rarely been explored in cases with osteopenia and osteoporosis, the medical conditions associated with reduction in calcium levels. OBJECTIVE: The present study aimed to investigate the impact of osteopenia and osteoporosis on the outcomes of behavioural and objective vestibular assessment tests...
September 21, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/28983916/piezo2-as-the-anomalous-mechanotransducer-channel-in-auditory-hair-cells
#15
Maryline Beurg, Robert Fettiplace
Throughout post-natal maturation of the mouse inner ear, cochlear hair cells display at least two types of mechanically-gated ion channel: normal mechanotransducer (MT) channels at the tips of the stereocilia, activated by tension in inter-ciliary tip links; and anomalous mechanosensitive (MS) channels on the top surface of the cells. The anomalous MS channels are responsible for the reverse-polarity current that appears in mutants in which normal transduction is lost. They are also seen in wild-type hair cells around birth, appearing two days earlier than normal MT channels, and being down-regulated with the emergence of the normal channels...
October 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28969522/soft-tissue-conduction-review-mechanisms-and-implications
#16
Haim Sohmer
Soft tissue conduction (STC) is a recently explored mode of auditory stimulation, complementing air (AC) and bone (BC) conduction stimulation. STC can be defined as the hearing induced when vibratory stimuli reach skin and soft tissue sites not directly overlying skull bone such as the head, neck, thorax, and body. Examples of STC include the delivery of vibrations to the skin of parts of the body by a clinical bone vibrator, hearing underwater sounds and free field air sounds, while AC hearing is attenuated by earplugs...
January 2017: Trends in Hearing
https://www.readbyqxmd.com/read/28955205/micrornas-in-hearing-disorders-their-regulation-by-oxidative-stress-inflammation-and-antioxidants
#17
REVIEW
Kedar N Prasad, Stephen C Bondy
MicroRNAs (miRs) are small non-coding single-stranded RNAs that bind to their complimentary sequences in the 3'-untranslated regions (3'-UTRs) of the target mRNAs that prevent their translation into the corresponding proteins. Since miRs are strongly expressed in cells of inner ear and play a role in regulating their differentiation, survival and function, alterations in their expression may be involved in the pathogenesis of hearing disorders. Although increased oxidative stress and inflammation are involved in initiation and progression of hearing disorders, it is unknown whether the mechanisms of damage produced by these biochemical events on inner ear cells are mediated by altering the expression of miRs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28955202/magnetic-nanoparticle-mediated-steroid-delivery-mitigates-cisplatin-induced-hearing-loss
#18
Bharath Ramaswamy, Soumen Roy, Andrea B Apolo, Benjamin Shapiro, Didier A Depireux
Cisplatin (cis-diamminedichloroplatinum) is widely used as a chemotherapeutic drug for genitourinary, breast, lung and head and neck cancers. Though effective in inducing apoptosis in cancer cells, cisplatin treatment causes severe hearing loss among patients. Steroids have been shown to mitigate cisplatin-induced hearing loss. However, steroids may interfere with the anti-cancer properties of cisplatin if administered systemically, or are rapidly cleared from the middle and inner ear and hence lack effectiveness when administered intra-tympanically...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28934520/damage-of-inner-ear-sensory-hair-cells-via-mitochondrial-loss-in-a-murine-model-of-sleep-apnea-with-chronic-intermittent-hypoxia
#19
Young Joon Seo, Hyun Mi Ju, Sun Hee Lee, Sang Hyun Kwak, Min Jung Kang, Joo-Heon Yoon, Chang-Hoon Kim, Hyung-Ju Cho
Study Objectives: Investigating the exact pathophysiology of obstructive sleep apnea syndrome (OSAS)-induced hearing loss is critical. We sought to verify the hypothesis that a correlation exists between mitochondrial dysfunction in inner ear hair cells and the auditory dysfunction induced by chronic intermittent hypoxia (CIH) in a murine model of sleep apnea. Methods: C57BL/6J adult male mice were randomized to 4 weeks of CIH (n = 12) or normoxia (Sham) (n = 12)...
September 1, 2017: Sleep
https://www.readbyqxmd.com/read/28929130/cytoskeletal-stability-in-the-auditory-organ-in-vivo-rhoa-is-dispensable-for-wound-healing-but-essential-for-hair-cell-development
#20
Tommi Anttonen, Ilya Belevich, Maarja Laos, Anni Herranen, Eija Jokitalo, Cord Brakebusch, Ulla Pirvola
Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice in vivo. We show that the thick belts serve as intracellular scaffolds that preserve the positions of surviving cells in the cochlear sensory epithelium...
September 2017: ENeuro
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