Two-dimensional distribution of Gi2α in the plasma membrane: a critical evaluation by immunocytochemistry

AbstractCaveolae have been postulated as a center for signal transduction, because many signaling molecules are concentrated in caveolin-rich fractions. We took Gi2α as an example and examined whether it is constitutively concentrated in caveolae. First, the behavior of caveolin and Gi2α in density-equilibrium ultracentrifugation was reexamined. By collecting fractions efficiently, caveolin and Gi2α were found to distribute differently. Secondly, by novel immunocytochemical methods it was found that the labeling density of Gi2α was 2.29 times higher in caveolae than in the non-caveolar plasma membrane. The results indicate that the concentration of Gi2α in caveolae is lower than deduced from most biochemical studies

Aging Is a Risk Factor for Utricular Dysfunction in Idiopathic Benign Paroxysmal Positional Vertigo

Benign paroxysmal positional vertigo (BPPV) is the most common cause of balance disorders in the elderly. Dislodgement of the otoconia in BPPV might have an association with damage to the otolith organs. The aim of this study was to investigate whether aging is a risk factor for otolith organ dysfunction in idiopathic BPPV. We retrospectively reviewed the medical records of 112 consecutive idiopathic BPPV patients who underwent cervical VEMP testing to air-conducted sound (ACS cVEMP), ocular VEMP testing to bone-conducted vibration (BCV oVEMP), and caloric testing. We performed binomial logistic regression analyses to see whether age, the side affected by BPPV or the canal affected by BPPV have an association with the presence of peripheral vestibular dysfunction in idiopathic BPPV patients. The elderly group (aged ≥65 years) had a significantly positive association with abnormalities in BCV oVEMPs (p = 0.0109), while the side affected by BPPV (p = 0.598) and the canal affected by BPPV (p = 0.576) did not. The odds ratio of the abnormal BCV oVEMPs for the elderly group compared with the non-elderly group (aged < 65 years) was 2.676 (95% confidence interval, 1.254–5.079). The elderly group had no significant association with the abnormalities in ACS cVEMPs (p = 0.0955) or caloric testing (p = 0.488). Dysfunction of the utricle, where the dislodgement of the otoconia mainly occurs, is affected by aging in idiopathic BPPV

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients

Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required

Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment

The etiology of hearing impairment following cochlear damage can be caused by many factors, including congenital or acquired onset, ototoxic drugs, noise exposure, and aging. Regardless of the many different etiologies, a common pathologic change is auditory cell death. It may be difficult to explain hearing impairment only from the aspect of cell death including apoptosis, necrosis, or necroptosis because the level of hearing loss varies widely. Therefore, we focused on autophagy as an intracellular phenomenon functionally competing with cell death. Autophagy is a dynamic lysosomal degradation and recycling system in the eukaryotic cell, mandatory for controlling the balance between cell survival and cell death induced by cellular stress, and maintaining homeostasis of postmitotic cells, including hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear. Autophagy is considered a candidate for the auditory cell fate decision factor, whereas autophagy deficiency could be one of major causes of hearing impairment. In this paper, we review the molecular mechanisms and biologic functions of autophagy in the auditory system and discuss the latest research concerning autophagy-related genes and sensorineural hearing loss to gain insight into the role of autophagic mechanisms in inner-ear disorders

Role of Oxidative Stress and Antioxidants in Acquired Inner Ear Disorders

Oxygen metabolism in the mitochondria is essential for biological activity, and reactive oxygen species (ROS) are produced simultaneously in the cell. Once an imbalance between ROS production and degradation (oxidative stress) occurs, cells are damaged. Sensory organs, especially those for hearing, are constantly exposed during daily life. Therefore, almost all mammalian species are liable to hearing loss depending on their environment. In the auditory pathway, hair cells, spiral ganglion cells, and the stria vascularis, where mitochondria are abundant, are the main targets of ROS. Excessive generation of ROS in auditory sensory organs is widely known to cause sensorineural hearing loss, and mitochondria-targeted antioxidants are candidates for treatment. This review focuses on the relationship between acquired hearing loss and antioxidant use to provide an overview of novel antioxidants, namely medicines, supplemental nutrients, and natural foods, based on clinical, animal, and cultured-cell studies