Evolutionarily conserved function of the even-skipped ortholog in insects revealed by gene knock-out analyses in Gryllus bimaculatus.

Comparing the developmental mechanisms of segmentation among insects with different modes of embryogenesis provides insights on how the function of segmentation genes evolved. Functional analysis of eve by genetic mutants shows that the Drosophila pair-rule gene, even-skipped (eve), contributes to initial segmental patterning. However, eve orthologs tends to have diverse functions in other insects.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

Introduction: The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog.

Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds.

Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (β-TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose effects of β-TCP nanoparticles on biocompatibility and bone forming ability were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% β-TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25, respectively.

PCTK3/CDK18 regulates cell migration and adhesion by negatively modulating FAK activity.

PCTAIRE kinase 3 (PCTK3) is a member of the cyclin dependent kinase family, but its physiological function remains unknown. We previously reported that PCTK3-knockdown HEK293T cells showed actin accumulation at the leading edge, suggesting that PCTK3 is involved in the regulation of actin reorganization. In this study, we investigated the physiological function and downstream signal transduction molecules of PCTK3.

Sebaceous carcinoma of the parotid gland: a case report.

Background: Primary sebaceous carcinoma of the parotid gland is extremely rare, and because of its rarity, clinicopathological characteristics and histogenesis are not fully understood.

Methods: Here, we report a patient who presented with a left infra-auricular painless mass. We present the histological features and discuss possible optimal treatments based on previous literature.

Downregulation of N-methyl-D-aspartate receptor ζ1 subunit (GluN1) gene in inferior colliculus with aging.

Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern.

Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity.

Whereas most epithelial tissues turn-over and regenerate after a traumatic lesion, this restorative ability is diminished in the sensory epithelia of the inner ear; it is absent in the cochlea and exists only in a limited capacity in the vestibular epithelium. The extent of regeneration in vestibular hair cells has been characterized for several mammalian species including guinea pig, rat, and chinchilla, but not yet in mouse. As the fundamental model species for investigating hereditary disease, the mouse can be studied using a wide variety of genetic and molecular tools.

Gene transfer into guinea pig cochlea using adeno-associated virus vectors.

Background: Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects.

Methods: Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear.

Manipulating cell cycle regulation in the mature cochlea.

Sensorineural hearing loss, which is often caused by degeneration of hair cells in the auditory epithelium, is permanent because lost hair cells are not replaced. Several conceptual approaches can be used to place new hair cells in the auditory epithelium. One possibility is to enhance proliferation of non-sensory cells that remain in the deaf ear and induce transdifferentiation of some of these cells into the hair cell phenotype.

Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction.

Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies.

Electromotile hearing: acoustic tones mask psychophysical response to high-frequency electrical stimulation of intact guinea pig cochleae.

When sinusoidal electric stimulation is applied to the intact cochlea, a frequency-specific acoustic emission can be recorded in the ear canal. Acoustic emissions are produced by basilar membrane motion, and have been used to suggest a corresponding acoustic sensation termed "electromotile hearing." Electromotile hearing has been specifically attributed to electric stimulation of outer hair cells in the intact organ of Corti.

Transfer of accelerated presbycusis by transplantation of bone marrow cells from senescence-accelerated mice.

Until now, there has been no effective therapy for chronic sensorineural hearing impairment. This study investigated the role of bone marrow cells (BMCs) in cochlear dysfunction. BALB/c mice (2 months of age), a non-presbycusis-prone mouse strain, were lethally irradiated and then transplanted with BMCs from SAMP1 mice (2 months of age), a presbycusis-prone mouse strain.

p27(Kip1) deficiency causes organ of Corti pathology and hearing loss.

p27(Kip1) (p27) has been shown to inhibit several cyclin-dependent kinase molecules and to play a central role in regulating entry into the cell cycle. Once hair cells in the cochlea are formed, p27 is expressed in non-sensory cells of the organ of Corti and prevents their re-entry into the cell cycle. In one line of p27 deficient mice (p27(-/-)), cell division in the organ of Corti continues past its normal embryonic time, leading to continual production of cells in the organ of Corti.

Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals.

In the mammalian auditory system, sensory cell loss resulting from aging, ototoxic drugs, infections, overstimulation and other causes is irreversible and leads to permanent sensorineural hearing loss. To restore hearing, it is necessary to generate new functional hair cells. One potential way to regenerate hair cells is to induce a phenotypic transdifferentiation of nonsensory cells that remain in the deaf cochlea.

Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions.

Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration.

Strategies for replacing lost cochlear hair cells.

The auditory sensory epithelium is a mosaic composed of sensory (hair) cells and several types of non-sensory (supporting) cells. All these cells are highly differentiated in their structure and function. Mosaic epithelia (and other complex tissues) are generally formed by differentiation of distinct and specialized cell types from common progenitors.

Adenovirus-mediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage.

Hair cell loss, the most common cause of deafness, is often associated with auditory nerve degeneration. Our goal was to determine the influence of combined ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) gene therapy on the survival of spiral ganglion neurons (SGNs) after elimination of inner hair cells in the mature guinea pig ear. Seven days after bilateral deafening, a 5-microl suspension of CNTF and/or BDNF adenovirus vectors was injected into the left scala tympani through the round window.

Antioxidant gene therapy can protect hearing and hair cells from ototoxicity.

Aminoglycosides are commonly used antibiotics that often induce ototoxicity leading to permanent hair cell loss and hearing impairment. The ototoxic effects of aminoglycosides have been linked to oxidative stress. To determine the feasibility of antioxidant gene therapy for protecting the inner ear against aminoglycoside-induced oxidative stress, we used adenoviral vectors for overexpression of catalase, Cu/Zn superoxide dismutase (SOD1), and Mn superoxide dismutase (SOD2).

Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration.

Tight junctions (TJs) create ion-selective paracellular permeability barriers between extracellular compartments. In the organ of Corti of the inner ear, TJs of the reticular lamina separate K(+)-rich endolymph and Na(+)-rich perilymph. In humans, mutations of the gene encoding claudin 14 TJ protein cause profound deafness but the underlying pathogenesis is unknown.

Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo.

Hair cell loss in the mammalian cochlea is irreversible and results in permanent hearing loss. Math1, the basic helix-loop-helix transcription factor homolog of the Drosophila atonal gene, is a positive regulator of hair cell differentiation during cochlear development. Developing hair cells express Math1, and nonsensory cells do not.

Hearing and hair cells are protected by adenoviral gene therapy with TGF-beta1 and GDNF.

Glial cell line-derived neurotrophic factor (GDNF) overexpression in the inner ear can protect hair cells against degeneration induced by aminoglycoside ototoxicity. The protective efficiency of GDNF increases when it is combined with co-factors such as transforming growth factor beta1 (TGF-beta1), a ubiquitous cytokine. The aim of this study was to determine whether TGF-beta1 receptors are expressed in the inner ear and whether a cocktail of GDNF and TGF-beta1 transgenes provides enhanced protection of the inner ear against ototoxic trauma.

Gene-based therapy for inner ear disease.

Environmental inner ear insults often lead to hair cell injury and loss. Therapeutic measures for the prevention of hair cell loss are currently limited. Several reports have demonstrated the applicability of growth factors for hair cell protection.

A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea.

Gene transfer using a recombinant adenovirus is a powerful tool for research and clinical applications, but its cytotoxicity and immune response limit its use, especially when repeated application of the vector is necessary. This study investigated the effects of dexamethasone (DEX)-induced immunosuppression on the outcome of adenovirus gene transfer in guinea pig inner ears. Animals received DEX for 29 days.