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Mammalian mitochondria may contain up to 1,500 different proteins, and many of them have neither been confidently identified nor characterized. In this study, we demonstrated that C11orf83, which was lacking experimental characterization, is a mitochondrial inner membrane protein facing the intermembrane space. This protein is specifically associated with the bc1 complex of the electron transport chain and involved in the early stages of its assembly by stabilizing the bc1 core complex. C11orf83 displays some overlapping functions with Cbp4p, a yeast bc1 complex assembly factor. Therefore, we suggest that C11orf83, now called UQCC3, is the functional human equivalent of Cbp4p. In addition, C11orf83 depletion in HeLa cells caused abnormal crista morphology, higher sensitivity to apoptosis, a decreased ATP level due to impaired respiration and subtle, but significant, changes in cardiolipin composition. We showed that C11orf83 binds to cardiolipin by its α-helices 2 and 3 and is involved in the stabilization of bc1 complex-containing supercomplexes, especially the III2/IV supercomplex. We also demonstrated that the OMA1 metalloprotease cleaves C11orf83 in response to mitochondrial depolarization, suggesting a role in the selection of cells with damaged mitochondria for their subsequent elimination by apoptosis, as previously described for OPA1.

1α-acetoxy-5α, 7β-dihydroxycassa-11,13(15)-diene-16,12-lactone, a new cassane-type diterpene was isolated from Caesalpinia crista. The structure of this compound was elucidated by analysis of NMR spectra, and the relative configuration was established by NOE experiment. The new compound was evaluated for antitumour activity against T47D, DU145 and showed significant inhibitory activities.

In this study we describe an isolated petrosal from the middle Eocene of northwestern Argentina assigned to Dasypodinae (Mammalia, Xenarthra, Cingulata). The specimen was recovered from the Geste Formation, Antofagasta de la Sierra, Catamarca, Argentina. The material is an incomplete right petrosal preserving the pars cochlearis and the anterior third of the pars canalicularis. It is described in detail and compared with extant and fossil cingulates. Additionally, we performed a cladistic analysis in order to define its phylogenetic position. The most remarkable traits of this petrosal include an anteromedially-posterolaterally elongated Promontorium, open cavum supracochleare, wide and smooth crista interfenestralis, roof of the post-promontorial tympanic sinus triangular, reduced, and well separated from the stapedius fossa, and poorly developed epitympanic wing and crista petrosa. The phylogenetic analysis reveals affinities with Dasypus and Stegotherium that are supported by the weakly develo...

Objective: The Volchok (Vlk) mouse originated as a part of a large-scale ENU program on a C3HeB/FeJ background. The mice present a dominant pattern of inheritance refl ected mainly by circling activity, which led us to search for the causative mutation underlying the vestibular phenotype. Study design: Linkage analysis and subsequent sequencing were used to narrow down the genomic region and uncover the mutation, respectively. Behavioral analysis and examination of the inner ear phenotype was performed using the modifi ed SHIRPA protocol, auditory brainstem response (ABR), immunofl uorescence, light microscopy, scanning electron microscopy (SEM), paint-fi ll and neurofi lament staining techniques. Results: A nonsense mutation was discovered in the Chd7 gene responsible for CHARGE syndrome in humans, which leads to a decrease in Chd7 expression in the nuclei of the vestibular and cochlear cells and structural abnormalities in the inner ear. A mild hearing loss was found in the mutant mice. The malformations detected include a truncated lateral semicircular canal and smaller lateral crista, a decrease in size or absence of the round window in the cochlea and lack of innervations to the posterior crista. Conclusion: Vlk joins a series of previously characterized mice bearing a Chd7 mutation, linking abnormalities found both in ENU-induced mutants and a knock-out mouse model. Combining the information from multiple Chd7 alleles provides a more comprehensive understanding of the mechanisms underlying this human disease.

Conclusion: With half-sized cupula, the semicircular canal nerve potentials decreased under slow stimulus, thus potentially leading to reduced caloric response. This also suggests that shrunken cupula may cause dizziness because of its hypermobility. Objectives: To examine the physiological effect of half-sized cupula on the semicircular canal nerve potential. Methods: The isolated cupula of the bullfrog was sectioned in half with fine scissors and was replaced on the crista. Mechanical endolymphatic flow and slow and fast stimuli were delivered and the evoked action potentials were recorded. Results: The cupula was successfully sectioned in half and was replaced on the crista. With the half-sized cupula, the action potentials became smaller under slow stimulus than under fast stimulus.

Effect of temperature changes on the vestibular receptor was studied using isolated posterior semicircular canals (PSC) of bull frogs. Cupula was removed from the crista. PSC was placed in the inner compartment of the double chamber. Warm or cool water was filled in the outer compartment to change the temperature of the inner compartment. Changes of the spontaneous discharge were recorded from the ampullary nerve. When cooled, the discharge temporarily increased, followed by a gradual decrease. When warmed, it temporarily decreased and then increased, forming response curves of a mirror image. After addition of streptomycin, the temperature dependent response disappeared. These results suggest that the semicircular canal receptor is activated by direct temperature effects.

The degeneration and regeneration of afferent and efferent nerves to the crista ampullaris in the frog were studied after transsection of the ampullar nerves. In some experiments one or both rostral ampullar nerves were simply divided and left in place. In other experiments the ampullar nerves to the horizontal and to the anterior vertical crista were divided and the branch to the former was brought into contact with the distal stump of the anterior vertical ampullar nerve. Sensory cells in the labyrinth survived total denervation for 1-2 weeks without regular signs of ultrastructural damage. The afferent synaptic structures in these cells were often preserved in the denervated stage. The afferent nerve fibres degenerated earlier than the efferent ones. Both type of fibres reinnervated the vestibular epithelium after division of the ampullar nerve. The fibres from a horizontal ampullar nerve could reinnervate a denervated anterior vertical crista, resulting in misdirected reflexes. About 40 days after division both function and morphological organization had been restored to normal.

The embryonic development of the crista ampullaris of the CBA/CBA mouse was followed both in organ culture of explanted inner ears of the 16th gestational day and in vivo from the 16th gestational day until the 21st day, an age corresponding to birth. Cytodifferentiation of the sensory epithelium of the crista ampullaris occurs during this period. At partus, there is a rather mature crista with well developed hair cells and 1-2 layers of supporting cells. Innervation and differentiation into type I and type II hair cells have started prior to partus but occur mainly post partum. The in vitro development followed that of the in vivo but with a slight delay, especially concerning the later stages of the in vitro development. At the time corresponding to partus, differentiation of hair cells is almost identical in the two groups but innervation is delayed in the in vitro group of inner ears. Because of the very high reproducibility/stability in vitro and morphologic maturation of both hair cells and gross structure of the crista ampullaris, organ culture of the 16th gestational day inner ear explant is a suitable model in the study of the late embryonic development under normal and pathological conditions.

The fine structures of the epithelial cells in the planum semilunatum were investigated using scanning and transmission electron microscopy. The chicks and guinea pigs were used for this study. In both guinea pig and chick, the body of the planum semilunatum cell was cylindrical. Its length decreased towards the utricular and canal side, resulting in cuboid-shaped cells. In the guinea pig, the flat surfaced hexagonal cells with few microvilli were arranged like flagstones over the whole area of the planum semilunatum, while in the chick the cells with many prominent microvilli were found on both sides of the crista. The cytoplasm contained well developed endoplasmic reticula and abundant granules. Interdigitations between the neighbouring cells were well developed. Basement membrane was slightly folded but no basal infolding was observed. The morphological characteristics of the planum semilunatum cell highly suggest that these cells have some secreting function.

The sensory epithelium of the crista ampullaris can be divided both structurally and as regards sensitivity to noxious agents into a central and a peripheral zone. The question is, whether this differentiation is also reflected in the distribution of the two types of sensory cells. The present electron microscopic study, based on morphornetric investigations of longitudinal and transverse sections through the crista. shows that in the guinea pig. the relative distribution of the two cell types is uniform throughout the sensory epithelium. There are about 60 % type I and about 40% type II cells in both the central and peripheral areas of the crista.

The distribution, origin and fine structure of nerve terminals immunoreactive to calcitonin gene-related peptide (CGRP) were investigated in the vestibular end-organs of the rat by means of immunocytochemistry. Dense plexus of CGRP-like immunoreactive (CGRPI) fibres were observed just beneath the sensory epithelial layers of the ampullary crista of the semicircular canal, and utricular and saccular maculae of the otolith organ. Some CGRPI fibres left the plexus to enter the sensory epithelial layer. Parasagittal transection of the brain just medial to the cochlear nucleus revealed the presence of a few CGPRI fibres in the vestibular end-organs ipsilaterally, indicating that these fibres originate in the central nervous system. A combination of retrograde tracing and immunocytochemistry was then used to identify the origins of CGRPI fibres found in the vestibular end-organs. After injection of fast blue dye (FB) into the vestibular cistern, CGRPI neurons in the area dorsolateral to the genu of the facial nerve were labelled by FB bilaterally. The present ultrastructural study has revealed that most of the CGRPI fibres in the vestibular end-organs form direct contacts with afferent nerve terminals which surround type I vestibular sensory cells.

We studied the spatial relations of the semicircular canals (SCCs) and their cristae, by computer-aided three-dimensional reconstruction, a graphic method we developed. The angles between pairs of SCCs, between pairs of SCC cristae, and between a SCC and its crista were measured using histology sections of a normal temporal bone from a 14-year-old female. Angles between pairs of SCCs and pairs of cristae deviated 11.3 to 18.2 degrees and 4.8 to 18.0 degrees, respectively, from right angles and the long axis of each crista deviated 25.0 to 30.4 degrees from the line perpendicular to the plane of the corresponding SCC; thus none of these structures lies at a right angle to another. We believe these new anatomical findings will help in the clinical evaluation of SCC function.

Intracellular recordings were made in the VIIIth nerve of the bullfrog (Rana catesbiana) to measure the membrane characteristics and obtain records of spontaneous and evoked spike activity of primary semicircular canal afferents. Physiological stimulation of the canals was achieved by rotating the preparation on a servomotor driven turntable with the animals' head centered in the rotational axis. The responses of each neuron to sinusoidal rotations at frequencies of 0.05Hz, 0.5Hz and for impulsive accelerations of 400 deg/sec2 were obtained. Membrane characteristics measured included the cell resting and action potential amplitude, and spike-activation threshold for applied currents. Physiologically characterized neurons were injected with horseradish peroxidase by applying pneumatic pressure and/or iontophoretic currents to the micropipettes containing 5% HRP in 1 M KCI. Following survival times of 12--48 h, the VIIIth nerve and attached vestibular end organ was removed for histochemical processing using a diaminobenzidine procedure to visualize the HRP reaction product. Light microscopy was used to discern the anatomical features of the neurons and to trace their peripheral dendritic trajectories from the ganglion to their termination(s) in the crista. Our studies have revealed that the bullfrog's primary vestibular afferents are characterized by a broad range of soma and axon diameters which correspond to an equally broad range of spontaneous and evoked activity characteristics. The largest neurons had more irregular spontaneous firing rates and consistently exhibited the greatest gain and smallest phase shifts with respect to head acceleration. These neurons consistently terminated at or near the central region of the crista. On the other hand, the smallest neurons were characterized by having the most regular spontaneous discharge patterns, the lowest gains, and greatest phase shifts with respect to head acceleration. Our findings are thus consistent with the view that the anatomical features of the primary vestibular neurons are important in determining the neuron's physiological characteristics. In terms of response dynamics our observations indicate that the receptors in the frog's crista ampullaris are heterogeneous and differentially sensitive to a wide range of stimulus frequencies.

The effect of vestibular efferent system stimulation on the vestibular action potential (VAP) recorded after brief mechanical ampullopetal stimulation of the lateral canal crista was studied in the cat. When an inhibitory action was recorded it had an effect on the VAP component N2 potential and was also characterized by a positive post potential. When stimulation seemed to have no effect, computer averaging showed a weak facilitating action affecting the N1 potential. The hypothesis of a double efferent system is discussed.

The morphological changes after kanamycin intoxication of the inner ear, including both the cochlea and the vestibule, were quantitatively analysed by the surface preparation technique after succinic dehydrogenase staining. 75 guinea pigs were used. The outer hair cells in the basal coil and the inner hair cells in the upper coils of the cochlea were the most severely damaged, but many unusual modes of damage were also revealed. For example, the initial hair cell damage in the cochlea appeared in the upper hair cells. The clearly observed vestibular damage contradicts the general belief that kanamycin is not so toxic to the vestibular hair cells. The utricular macula and the lateral crista were most severely damaged. The delayed ototoxicity of kanamycin was observed for the first time in the vestibular hair cells.

The effect of Gentamicin (GM) on the vestibular organ was studied using bullfrogs. The ototoxicity was compared among 3 different ways of administration, i.e., intraperitoneal (IP), intramuscular (IM) and intralabyrinthine (IL) injections. Morphological change of the posterior canal crista was observed by SEM. The posterior canal ampullary nerve action potentials (AP) were recorded, and were compared with SEM findings of the sensory epithelia. Morphological and physiological changes were severe in the order of IL greater than IM greater than IP. Morphological and physiological changes developed as the postinjection time elapsed. Morphological damage started at the narrow portion of the crista and developed towards the center and finally towards the periphery. Physiological change was already observed before the morphological damage. Physiological change tended to correlate with the morphological damage.

The 16th gestational day inner ear of the CBA/CBA mouse was used in an organ culture system as a model for ototoxicity studies. The specimens in culture were exposed to 1, 10, 100 and 1 000 micrograms/ml of gentamicin base during 1-5 days in culture. Minor changes were found after only one day of exposure. Pathological changes of vestibular hair cells characteristic for aminoglycoside antibiotics occurred after exposure to 1 and 10 micrograms/ml. Concentrations of 100 and 1 000 micrograms/ml caused a general toxicity with destruction of the whole morphology of the crista ampullaris. Hair cells were, however, more affected than were supporting cells. Initially, variation of hair cell damage occurred within each crista and between different cristae but this became less apparent after 5 days in culture. The 16th gestational day organ culture system can serve as a useful model system with many controlled experimental parameters in the testing of ototoxic drugs.

Definite pathologic changes were noted within the horizontal crista ampullaris after cryosurgery. The amount of damage was dependent upon the temperature of the crista during cooling. For example, when the horizontal crista was cooled to-70°C (intralabyrinthine temperature + 18°C) exudate was observed in the endolymphatic space. Electron microscopically, however, definite cellular damage (myelin figures) was detected primarily in the specialized cells (dark and light). Ruptures of the membranous wall of the crista was observed at cryosurgical dosage of-90°C (intralabyrinthine temperature + 13°C). Gross histological damage was noted when the horizontal crista was cooled to-120 and-190°C (intralabyrinthine temperature +5 and-6°C respectively). The functional (rotatory tests), ultrastructural and histologic results correlate extremely well. These results indicate that the critical cryosurgical threshold dosage necessary to alter the morphology and function of the semicircular canal system is approximately-70...

The pathological patterns of the sensory epithelium of the crista ampullaris of a guinea pig were studied after streptomycin and kanamycin administration. The silver reaction method and succinic dehydrogenase staining were applied for the entire surfaces of all specimens. Differences in sensitivity to antibiotics were confirmed in the sensory cells of the central and the peripheral regions of the crista (Lindeman, 1969 a).

1. Measurements of each of the inner ear sensory areas are reported and compared for various vertebrates. These indicate:a. 5:5 and 6:4 ratios are most common in comparing the total pars superior sensory area of the inner ear with the total pars inferior area;b. 7:3 to 2:8 ratios exist, in comparing the canal type with the macular type areas, which appear to be related to the equilibratory demands made upon the organism;c. that, in comparing cochlear type with saccular type areas, the tailless amphibians exhibit a surprisingly high value for the former;d. that in some forms the crista horizontalis is larger than the average of the two vertical cristae, possibly associated with the mode of locomotion;e. that the macula sacculi, throughout vertebrates, is of considerable size, as is the macula lagenae (where present);f. that there is a great actual and relative variation in the size of the papilla basilaris (organ of Corti), particularly among reptiles;g. that it is the size of the papilla amphibiorum which...

Vestibular end organ pathology was studied electron microscopically in the squirrel monkey and cat, after systemic and local administration of viomycin sulfate. The ampullar crista was more vulnerable than the utricular macula in both species when viomycin sulfate was injected systemically. On the other hand, less differences in pathology were noticed when the drug was used topically. Vacuolization, vesicle formation, degenerated mitochondria, nuclear chromatin aggregation, etc. were more commonly observed in Type I hair cells which were consistently more damaged than Type II hair cells. The free cellular surface was usually not involved after systemic injection. The nerve chalice was swollen and the cytoplasmic contents were decreased. This indicates that primary involvement of this area after viomycin sulfate injection also occurs, as irregular cytoplasmic boundary was found where the hair cells were least involved.This investigation was supported in part by the National Institutes of Health Grants 5-K0...

The microphonics of the cochlea and of the crista are important for three reasons. (1) They demonstrate that by the stimulation with sound the various parts of the labyrinth vibrate. (2) By the parallelism between the voltage of the microphonics and the excitability of the organ of Corti and the crista. (3) They can give a better insight into the problem of transformation of the mechanical energy into electric energy by the inner ear. With regard to (3), there is a discussion of the hair hypothesis of de Vries. Kuiper demonstrated that this hypothesis is not right, as the facts cannot be explained by the pulling at the hairs. But two important facts remain and require explanation: the double frequency of the lateral line organ in the fish and the superposition effect. This phenomenon in the pigeon is discussed. It occurs when a low and a high frequency component are presented together to the ear.

The phaserelations between the microphonic crista effect of the three semicircular canals of the pigeon are found to “reflect” the second law of Ewald. Evidence is obtained that the crista effect has the same phase at both sides of the crista. The cochlea effect, recorded from the round window has its maximum negative value at the moment the stapes has its maximum inward velocity for frequencies between 200 and 1000/sec. For lower frequencies the phase of the microphonic effect is ahead of the phase of the stapes.The results are discussed in relation with the model of the processes in the labyrinth organs recently developed from measurements on lateral line organs of fishes. It is shown that the second law of Ewald is a result of the histological structure of the cristae. The phaserelations between the microphonic effects of the cristae, the cochlear microphonics and the mechanical stimulus prove to be in accord with the model. The microphonics are in phase with the displacement of the cupulae (or tectori...