The proton collecting function of the inner surface of cytochrome c oxidase from Rhodobacter sphaeroides

The experiments presented in this study address the problem of how the cytoplasmic surface (proton-input side) of cytochrome c oxidase interacts with protons in the bulk. For this purpose, the cytoplasmic surface of the enzyme was labeled with a fluorescein (Flu) molecule covalently bound to Cys223 of subunit III. Using the Flu as a proton-sensitive marker on the surface and phiOH as a soluble excited-state proton emitter, the dynamics of the acid-base equilibration between the surface and the bulk was measured in the time-resolved domain. The results were analyzed by using a rigorous kinetic analysis that is based on numeric integration of coupled nonliner differential rate equations in which the rate constants are used as adjustable parameters. The analysis of 11 independent measurements, carried out under various initial conditions, indicated that the protonation of the Flu proceeds through multiple pathways involving diffusion-controlled reactions and proton exchange among surface groups. The surface of the protein carries an efficient system made of carboxylate and histidine moieties that are sufficiently close to each other as to form a proton-collecting antenna. It is the passage of protons among these sites that endows cytochrome c oxidase with the capacity to pick up protons from the buffered cytoplasmic matrix within a time frame compatible with the physiological turnover of the enzyme.     

Brain cytochrome oxidase activity after kindled seizures: a quantitative histochemical mapping study

A Japanese male patient with myelodysplastic syndrome (MDS) was shown to have associated Tn syndrome; the first report of Tn syndrome with MDS. The Tn expression was demonstrated on erythrocytes, granulocytes, monocytes, platelets, and lymphocytes by flow cytometric analysis using a lectin and an antibody. Electrophoresis of erythrocyte membrane proteins revealed slower mobility of glycophorin B from the patient than that from normal individuals, suggesting a glycophorin B molecular abnormality.     

Otogelin: a glycoprotein specific to the acellular membranes of the inner ear

Efforts to identify the specific components of the mammalian inner ear have been hampered by the small number of neuroepithelial cells and the variety of supporting cells. To circumvent these difficulties, we used a PCR-based subtractive method on cDNA from 2-day-old mouse cochlea. A cDNA encoding a predicted 2910-amino acid protein related to mucin has been isolated. Several lines of evidence indicate, however, that this protein does not undergo the O-glycosylation characteristic to mucins. As confirmed by immunocytochemistry and biochemical experiments, this protein is specific to the inner ear. Immunohistofluorescence labeling showed that this protein is a component of all the acellular membranes of the inner ear: i.e., the tectorial membrane of the cochlea, the otoconial and accessory membranes of the utricule and saccule, the cupula of the semicircular canals, and a previously undescribed acellular material covering the otoconia of the saccule. The protein has been named otogelin with reference to its localization. A variety of nonsensory cells located underneath these membranes could be identified as synthesizing otogelin. Finally, this study revealed a maturation process of the tectorial membrane, as evidenced by the progressive organization of otogelin labeling into thick and spaced radial fiber-like structures.     

Functional characteristics of the inner voice and the inner ear: Single or double agency?

Double agency theories of short-term memory posit the functional independence of a phonological store (inner ear) and articulatory process (inner voice). A series of 5 experiments challenges this view. Articulatory suppression during retention of 9-item lists gives rise to a changing-state effect similar to that shown for irrelevant speech. Also, vocalized suppression is more disruptive than silently mouthed suppression, but this difference arises from vocalization itself rather than from any auditory feedback to which it gives rise. Class similarity between the to-be-remembered items and the articulatory material is not a critical determinant, but the effect occurs only with tests of serial order. For mouthed suppression, the irrelevant speech effect is only attenuated with changing-state suppression. Also, the presence of changing-state irrelevant speech abolishes the changing-state effect of articulatory suppression. Functional equivalence of codes from auditory, visual, and articulatory sources is claimed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mammalian mitochondrial DNA evolution: a comparison of the cytochrome b and cytochrome c oxidase II genes

The evolution of two mitochondrial genes, cytochrome b and cytochrome c oxidase subunit II, was examined in several eutherian mammal orders, with special emphasis on the orders Artiodactyla and Rodentia. When analyzed using both maximum parsimony, with either equal or unequal character weighting, and neighbor joining, neither gene performed with a high degree of consistency in terms of the phylogenetic hypotheses supported. The phylogenetic inconsistencies observed for both these genes may be the result of several factors including differences in the rate of nucleotide substitution among particular lineages (especially between orders), base composition bias, transition/transversion bias, differences in codon usage, and different constraints and levels of homoplasy associated with first, second, and third codon positions. We discuss the implications of these findings for the molecular systematics of mammals, especially as they relate to recent hypotheses concerning the polyphyly of the order Rodentia, relationships among the Artiodactyla, and various interordinal relationships.     

Effect of ibudilast on microcirculation thrombosis in rat inner ear

Arterial wall thickening may be quantitatively assessed by measuring the intima-media thickness (IMT) with high resolution ultrasound. Previous studies have shown a good inter/intraobserver variability of IMT measurements in the common carotid. In this study we evaluated the inter/intraobserver variability of IMT measurements in 10 randomly selected asymptomatic subjects (age 55.4 +/- 6). Two carotids and two femorals were studied in each subject. IMT for each patient was the average of five IMT measurements at the artery bifurcation. Three observers repeated the scanning and the measurements twice with no knowledge of the previous readings. The between observer coefficient of variation (CV) was 8.45%; the intraobserver CV (mean of carotids and femorals) varied from 4.4 to 5.1% for the three observers who measured IMT three times. The mean absolute difference between the first and the third measurement was 0.0738 mm. In conclusion IMT measurement variability is mostly due to differences between observers. The intraobserver variability is very small. IMT measurements at the carotid and femoral bifurcations have a low variability and are a good expression of atherosclerosis as they consider early lesions at the bifurcation level which may not be observed in the common carotid.     

Thermodynamic volume cycles for electron transfer in the cytochrome c oxidase and for the binding of cytochrome c to cytochrome c oxidase

Determining the way in which deleterious mutations interact in their effects on fitness is crucial to numerous areas in population genetics and evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last (synergistic epistasis), then the evolution of sex and recombination may be favored to facilitate the elimination of deleterious mutations. However, there is a severe shortage of relevant data. Three relatively simple experimental methods to test for epistasis between deleterious mutations in haploid species have recently been proposed. These methods involve crossing individuals and examining the mean and/or skew in log fitness of the offspring and parents. The main aim of this paper is to formalize these methods, and determine the most effective way in which tests for epistasis could be carried out. We show that only one of these methods is likely to give useful results: crossing individuals that have very different numbers of deleterious mutations, and comparing the mean log fitness of the parents with that of their offspring. We also reconsider experimental data collected on Chlamydomonas moewussi using two of the three methods. Finally, we suggest how the test could be applied to diploid species.     

Molecular cloning of a zinc finger gene eZNF from a human inner ear cDNA library, and in situ expression pattern of its mouse homologue in mouse inner ear

A mathematical model of posttetanic processes launched by rhythmic stimulation of the excitatory and inhibitory inputs to the dendritic spine of a pyramidal neuron in hippocampal field CA3 was used to study conditions for modifying the efficiency of the inhibitory input. The level of dephosphorylation of GABAa and GABAb receptors, which determines the GABA sensitivity of these receptors, was shown to depend on the Ca(2+)-dependent ratio of active protein kinases and protein phosphatases; the level of dephosphorylation decreased monotonically as the intracellular Ca2+ increased. Posttetanic increases and decreases in the Ca2+ concentration, as compared with the level achieved during the previous stimulation, led to increases or decreases respectively in the number of dephosphorylated GABA receptors and to induction of long-term potentiation and depression, respectively, in the efficiency of inhibitory transmission. The extent of the modification effect depended on the ratio of the quantities of inhibitory and excitatory mediators in the synaptic cleft. At very low or very high GABA concentrations, modification of inhibitory transmission was insignificant.     

Childhood personality influences on social-cognitive development: a longitudinal study

The relation of childhood personality to the development of friendship understanding and moral judgment in adolescence was considered in a longitudinal study. Personality at age 7, assessed with the California Child Q-Set, was characterized in terms of ego-resiliency and ego-control. IQ and social class were also measured. Friendship understanding was assessed when the participants were ages 7, 9, 12, 15, and 19, and moral judgment was elicited when the participants were 12, 15, and 19. Ego-resiliency was found to predict social-cognitive development in adolescence, even after the effects of IQ and childhood measures of social-cognitive development were controlled for. Analyses indicate that the effects of ego-resiliency on social-cognitive development are largely unmediated by the ability to focus attention or by social participation.     

Guanylate cyclase activity in the inner ear and auditory nerve of the rat

Novel molecular mediation in the sound transductional process is implicitly suggested. We investigated the presence of the cGMP-synthesis enzyme, guanylate cyclase, in Corti's organ and auditory nerve of the rat. The soluble guanylate cyclase activity found was sensitive to changes of sound intensity in the different acoustic media used, suggesting a potential role for the system that involves this enzyme. The guanylate cyclase activity appeared to be inversely related (in the inner ear) with the sound intensity to which the animals were exposed; different behavior was observed for the auditory nerve. The enzymatic activity found in Corti's organ, a direct bio-receptor of sound, represents the first reported enzymatic activity of this type in this tissue, which apparently could be influenced by the intensity of a physical stimulus such as sound. Finally, an adequate ionic environment appears to play a potential role in the expression of the changes observed, indicating that it may function according to the requirements of the biological sensor.     

The role of micro-noise trauma in the etiology of aging-related changes in the inner ear

Eleven chinchillas between 1 and 2.4 years of age had the malleus/incus complex removed from one middle ear and then lived in the Washington University animal facilities for 4 years post-surgery. Each animal had one ear (termed ambient-noise) in which the conductive apparatus was intact; the other ear (termed noise-protected) had a 50-60 dB conductive hearing loss. The background sound level in the animal facility was 59 dBA with periodic brief sounds up to 102 dBA. After the 4-year experimental period, both ears were fixed, embedded in plastic and dissected for microscopic examination as flat preparations. The quantitative and qualitative findings in the noise-protected ears were compared to those in the ambient-noise ears. Both groups of ears sustained losses of sensory and supporting cells throughout the organ of Corti. A variable amount of age pigment was found to have accumulated in the outer hair cells and all supporting cells. In the noise-protected ears, inner hair cell loss ranged from 1.0 to 3.1% and averaged 1.7 +/- 0.8%; outer hair cell loss ranged from 1.8 to 6.4% and averaged 3.6 +/- 1.2%. In the ambient-noise ears, inner hair cell loss ranged from 0.7 to 2.8% and averaged 1.6 +/- 0.7%; outer hair cell loss ranged from 1.3 to 5.4% and averaged 3.6 +/- 1.2%. Within-animal comparison of cell losses in the noise-protected and ambient-noise ears revealed no significant difference between the two groups. It is concluded that long-term exposure to micro-noise does not accelerate the spontaneous loss of sensory cells which occurs with aging. Although not quantified, there was no obvious difference in the amount or cellular distribution of age pigment in the two groups. Thus, it appears that the formation of age pigment in the ear is the result of the cells' basic metabolic processes rather than the wear and tear from sensory transduction.     

Identification and localization of type IV collagen chains in the inner ear cochlea

The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied by in situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.     

Petrous bone tumors: primary non-Hodgkin lymphoma of the inner ear canal and cerebellopontile angle

BACKGROUND: We report about a primary Non-Hodgkin Lymphoma (NHL) of the internal auditory canal. The only previously known manifestations of a NHL in the temporal bone have been infiltrations or hemorrhagic complications due to a late manifestation or advanced systemic disease. Involvement of both temporal bones is typical. CLINICAL CASE: The 60-year-old female patient complained of an acute one-sided deafness, accompanied by a high-pitched tinnitus, rotating vertigo, and paralysis of the left half of the face. RESULTS: We found a deafness in the left ear, spontaneous nystaxis, which was interpreted as a deficiency in excitement of the vestibular organ, and a complete peripheral facial paralysis. Diagnostic imaging studies revealed a large, intrameatal solid mass in the temporal bone, measuring 1.2 x 0.8 cm. Histologic examination after translabyrinthine tumor removal demonstrated a centroblastic Non-Hodgkin Lymphoma. The following extensive interdisciplinary staging examination showed no other tumor manifestations; the CSF analysis was negative. CONCLUSIONS: The uniqueness of this case lies in the detection of a primary nongeneralized centroblastic lymphoma of the internal auditory canal. In contrast to infiltrations of systemic NHL in the same location, in which the advanced disease is responsible for the bad prognosis, this isolated lymphoma of the internal auditory canal seems analogous to extranodal MALT Lymphomas with a better prognosis. The primary extranodal NHL of the temporal bone, not reported in previous studies, is discussed with regard to clinical symptoms, differential diagnoses, and therapeutic strategies.     

Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women

The association between current and past dietary intake and bone mineral density (BMD) was investigated in 994 healthy premenopausal women aged 45-49 y. BMD was measured with dual-energy X-ray absorptiometry (DXA). Dietary intake was assessed with a food-frequency questionnaire (FFQ). Energy-adjusted nutrient intakes were grouped into quartiles and mean BMD at the lumbar spine (LS), femoral neck (FN), femoral trochanter (FT), and femoral Wards (FW) were calculated. With higher intakes of zinc, magnesium, potassium, and fiber, LS BMD was significantly higher (P < 0.05-0.006), and a significant difference in LS BMD was also found between the lowest and highest quartiles for these nutrients and vitamin C intake (P < 0.05-0.01). These results remained significant after adjustment for important confounding factors. LS BMD and FT BMD were lower in women reporting a low intake of milk and fruit in early adulthood than in women with a medium or high intake (P < 0.01). High, long-term intake of these nutrients may be important to bone health, possibly because of their beneficial effect on acid-base balance.     

Studies on a stabilisation of ubisemiquinone by Escherichia coli quinol oxidase, cytochrome bo

The Escherichia coli quinol oxidase, cytochrome bo, is closely related to the cytochrome c oxidase, cytochrome aa3 in all aspects of its structure and function except for the replacement of the cytochrome-c-binding site and its attendant CuA prosthetic group with a quinone-binding site. The putative oxidation of quinol by ferrihaem (cytochrome b) at this site in sequential one-electron steps requires the stabilisation of semiquinone. We have observed, by electron paramagnetic resonance, the properties of a ubisemiquinone radical in appropriately poised samples of purified enzyme reconstituted with excess ubiquinone. The ubisemiquinone is highly stabilised with respect to free ubisemiquinone; significant free radical can be observed even at pH 7.0, while at pH 9.0 the stability constant is 5-10. The pH dependence of the stability constant indicates that the anionic form of the semiquinone predominates above pH 7.5. The two-electron couple has an Em7 of approximately 70 mV. Below pH 9, the pH dependence of the two-electron couple is -60mV/pH, indicative of a 2H+/2e- reaction. The line width of the EPR spectrum is approximately 0.9 mT, which is consistent with a ubisemiquinone anion. In comparison with other respiratory chain Q.- species that have been described, the relaxation rate in the presence of reduced haems appears comparable to magnetically isolated Q.- radicals. Partially resolved splittings of approximately 0.4 mT can be observed in the spectrum of Q.-bo (QH.bo).     

Spatial distributions of retinoic acid receptor gene transcripts in the prenatal mouse inner ear

Thirty-one patients with a presentation compatible with an acquired demyelinating polyradiculoneuropathy were prospectively evaluated for proximal conduction block using root stimulation (RS) of cervical and/or lumbar roots. These same techniques were applied to 78 controls (40 pathological). Proximal conduction block was noted in 20/31 cases and none of the controls. Only 7 of 31 cases met published demyelinating criteria. Intravenous immune globulin therapy was completed by 21/31 patients and 20/21 responded. RS is superior to published electrophysiologic criteria for identifying demyelinating polyneuropathies and predicting who will respond to treatment. RS should be performed in all patients suspected of having an acquired demyelinating polyneuropathy when traditional nerve conduction studies criteria are nondiagnostic. RS reliably predicts those likely to respond to immunosuppressive therapy.