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Objective: Disulfiram has been repurposed as a potential candidate to suppress various cancers. However, its anti‐tumor effects and molecular mechanisms of oral squamous cell carcinoma remain unclear. In this study, we aimed to assess the anti‐cancer activity and underlying mechanisms of disulfiram in the context of oral squamous cell carcinoma. Materials and Methods: We tested the cytotoxicity of disulfiram in oral squamous cell carcinoma using a 3D culture model and a PDX model. Cell proliferation, cell death, and related signaling pathways were evaluated. Mitochondrial DNA copy number, mitochondrial respiration, mitochondrial mass, and mitochondrial complexes were analyzed. Results: Disulfiram can induce excessive autophagy in oral squamous cell carcinoma cells as a result of OXPHOS deficiency. Disulfiram‐induced OPA1 degradation can impair the functional cristae structure, which results in a dramatic reduction in mitochondrial respiration capability as well as ATP production. Subsequently, energy deprivation leads to excessive autophagy through AMPK activation. In addition, exogenous ATP blocked the activation of AMPK and rescued disulfiram‐induced cell death. Conclusion: DSF targets mitochondrial inner membrane protein OPA1 to disturb the energy supply, triggering excessive autophagy, and cell death in OSCC. Our study suggests OPA1‐dependent ATP generation is pharmacologically targetable in OSCC treatment. [ABSTRACT FROM AUTHOR]

• Nestin is associated with pluripotency and is expressed in the inner ear. • A lineage-tracing model tracked nestin-expressing cells in early postnatal mice. • Nestin-expressing cells are mitotically active in cochlear and vestibular tissues. • Nestin-expressing cells did not facilitate hair cell regeneration after ablation. • Further research into the mitotic activity of nestin-expressing cells is warranted. Nestin expression is associated with pluripotency. Growing evidence suggests nestin is involved in hair cell development. The objective of this study was to investigate the morphology and role of nestin-expressing cells residing in the early postnatal murine inner ear. A lineage-tracing nestin reporter mouse line was used to further characterize these cells. Their cochleae and vestibular organs were immunostained and whole-mounted for cell counting. We found Nestin-expressing cells present in low numbers throughout the inner ear. Three morphotypes were observed: bipolar, unipolar, and globular. Mitotic activity was noted in nestin-expressing cells in the cochlea, utricle, saccule, and crista. Nestin-expressing cell characteristics were then observed after hair cell ablation in two mouse models. First, a reporter model demonstrated nestin expression in a significantly higher proportion of hair cells after hair cell ablation than in control cochleae. However, in a lineage tracing nestin reporter mouse, none of the new hair cells which repopulated the organ of Corti after hair cell ablation expressed nestin, nor did the nestin-expressing cells change in morphotype. In conclusion, Nestin-expressing cells were identified in the cochlea and vestibular organs. After hair cell ablation, nestin-expressing cells did not react to the insult. However, a small number of nestin-expressing cells in all inner ear tissues exhibited mitotic activity, supporting progenitor cell potential, though perhaps not involved in hair cell regeneration. [ABSTRACT FROM AUTHOR]

Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings. To investigate the role of Na+ currents (INa) in firing mechanisms, we investigated biophysical properties of INa in calyx-bearing afferents. Whole cell patch-clamp recordings were made from calyx terminals in thin slices of gerbil crista at different postnatal ages: immature [postnatal day (P)5-P8, young (P13-P15), and mature (P30-P45)]. A large transient Na+ current (INaT) was completely blocked by 300 nM tetrodotoxin (TTX) in mature calyces. In addition, INaT was accompanied by much smaller persistent Na+ currents (INaP) and distinctive resurgent Na+ currents (INaR), which were also blocked by TTX. ATX-II, a toxin that slows Na+ channel inactivation, enhanced INaP in immature and mature calyces. 4,9-Anhydro-TTX (4,9-ah-TTX), which selectively blocks Nav1.6 channels, abolished the enhanced INa in mature, but not immature, calyces. Therefore, Nav1.6 channels mediate a component of INaT and INaP in mature calyces, but are minimally expressed at early postnatal days. INaR was expressed in less than one-third of calyces at P6-P8, but expression increased with development, and in mature cristae INaR was frequently found in peripheral calyces. INaR served to increase the availability of Na+ channels following brief membrane depolarizations. In current clamp, the rate and regularity of action potential firing decreased in mature peripheral calyces following 4,9-ah-TTX application. Therefore, Nav1.6 channels are upregulated during development, contribute to INaT, INaP, and INaR, and may regulate excitability by enabling higher mean discharge rates in a subpopulation of mature calyx afferents. NEW & NOTEWORTHY Action potential firing patterns differ between groups of afferent neurons innervating vestibular epithelia. We investigated the biophysical properties of Na+ currents in specialized vestibular calyx afferent terminals during postnatal development. Mature calyces express Na+ currents with transient, persistent, and resurgent components. Nav1.6 channels contribute to resurgent Na+ currents and may enhance firing in peripheral calyx afferents. Understanding Na+ channels that contribute to vestibular nerve responses has implications for developing new treatments for vestibular dysfunction. [ABSTRACT FROM AUTHOR]

The mammalian vestibular epithelia exhibit a remarkably stereotyped organization featuring cellular characteristics under planar cell polarity (PCP) control. PCP mechanisms are responsible for the organization of hair cell morphologic polarization vectors, and are thought to be responsible for the postsynaptic expression of the calcium-binding protein calretinin that defines the utricular striola and cristae central zone. However, recent analyses revealed that subtle differences in the topographic expression of oncomodulin, another calcium-binding protein, reflects heterogeneous factors driving the subtle variations in expression. Calbindin represents a third calcium-binding protein that has been previously described to be expressed in both hair cells and afferent calyces in proximity to the utricular striola and crista central zone. The objective of the present investigation was to determine calbindin's topographic pattern of expression to further elucidate the extent to which PCP mechanisms might exert control over the organization of vestibular neuroepithelia. The findings revealed that calbindin exhibited an expression pattern strikingly similar to oncomodulin. However, within calyces of the central zone calbindin was colocalized with calretinin. These results indicate that organizational features of vestibular epithelia are governed by a suite of factors that include PCP mechanisms as well others yet to be defined. [ABSTRACT FROM AUTHOR]

The LIM homeodomain transcription factor Lmx1a shows a dynamic expression in the developing mouse ear that stabilizes in the non-sensory epithelium. Previous work showed that Lmx1a functional null mutants have an additional sensory hair cell patch in the posterior wall of a cochlear duct and have a mix of vestibular and cochlear hair cells in the basal cochlear sensory epithelium. In E13.5 mutants, Sox2-expressing posterior canal crista is continuous with an ectopic "crista sensory epithelium" located in the outer spiral sulcus of the basal cochlear duct. The medial margin of cochlear crista is in contact with the adjacent Sox2-expressing basal cochlear sensory epithelium. By E17.5, this contact has been interrupted by the formation of an intervening non-sensory epithelium, and Atoh1 is expressed in the hair cells of both the cochlear crista and the basal cochlear sensory epithelium. Where cochlear crista was formerly associated with the basal cochlear sensory epithelium, the basal cochlear sensory epithelium lacks an outer hair cell band, and gaps are present in its associated Bmp4 expression. Further apically, where cochlear crista was never present, the cochlear sensory epithelium forms a poorly ordered but complete organ of Corti. We propose that the core prosensory posterior crista is enlarged in the mutant when the absence of Lmx1a expression allows JAG1-NOTCH signaling to propagate into the adjacent epithelium and down the posterior wall of the cochlear duct. We suggest that the cochlear crista propagates in the mutant outer spiral sulcus because it expresses Lmo4 in the absence of Lmx1a. [ABSTRACT FROM AUTHOR]

This article aims to provoke a reflection on the dialogue, with a view to concrete action, between two areas vital to the activity and life of the Church: Christian Education and Hermeneutics. The Church, which is very present in the ecclesial communities through the programs of biblical teaching developed by them, is best known in the context of the Theological Academy as a discipline, but still a pressing need to bring the Church closer to the biblical text, which, as a rule, its interpretation. In order to do so, it is necessary first to define, although succinctly, both areas, in order to understand their contributions and relevance to the Church, and then to draw the possible relationship between Christian Education through the work of the educator Christian, with Hermeneutics, and this in a concrete way. It is recognized that, in a sense, teaching the Scriptures, as well as the Christian truths stemming from these same Scriptures, is a hermeneutical doing. It requires a great deal of hermeneutical work. It is necessary to ask how this relation can be effected, and it is to this question that the present text aims to respond. [ABSTRACT FROM AUTHOR]

In the vestibular periphery neurotransmission between hair cells and primary afferent nerves occurs via specialized ribbon synapses. Type I vestibular hair cells (HCIs) make synaptic contacts with calyx terminals, which enclose most of the HCI basolateral surface. To probe synaptic transmission, whole cell patchclamp recordings were made from calyx afferent terminals isolated together with their mature HCIs from gerbil crista. Neurotransmitter release was measured as excitatory postsynaptic currents (EPSCs) in voltage clamp. Spontaneous EPSCs were classified as simple or complex. Simple events exhibited a rapid rise time and a fast mono-exponential decay (time constant ＜ 1 ms). The remaining events, constituting ~40% of EPSCs, showed more complex characteristics. Extracellular Sr²⁺ greatly increased EPSC frequency, and EPSCs were blocked by the AMPA receptor blocker NBQX. The role of presynaptic Ca²⁺ channels was assessed by application of the L-type Ca²⁺ channel blocker nifedipine (20 µM), which reduced EPSC frequency. In contrast, the L-type Ca²⁺ channel opener BAY K 8644 increased EPSC frequency. Cyclothiazide increased the decay time constant of averaged simple EPSCs by approximately twofold. The low-affinity AMPA receptor antagonist γ-D-glutamylglycine (2 mM) reduced the proportion of simple EPSCs relative to complex events, indicating glutamate accumulation in the restricted cleft between HCI and calyx. In crista slices EPSC frequency was greater in central compared with peripheral calyces, which may be due to greater numbers of presynaptic ribbons in central hair cells. Our data support a role for L-type Ca²⁺ channels in spontaneous release and demonstrate regional variations in AMPA-mediated quantal transmission at the calyx synapse. NEW & NOTEWORTHY In vestibular calyx terminals of mature cristae we find that the majority of excitatory postsynaptic currents (EPSCs) are rapid monophasic events mediated by AMPA receptors. Spontaneous EPSCs are reduced by an L-type Ca²⁺ channel blocker and notably enhanced in extracellular Sr²⁺. EPSC frequency is greater in central areas of the crista compared with peripheral areas and may be associated with more numerous presynaptic ribbons in central hair cells. [ABSTRACT FROM AUTHOR]

During development of vestibular hair cells, K + conductances are acquired in a specific pattern. Functionally mature vestibular hair cells express different complements of K + channels which uniquely shape the hair cell receptor potential and filtering properties. In amniote species, type I hair cells (HCI) have a large input conductance due to a ubiquitous low–voltage-activated K + current that activates with slow sigmoidal kinetics at voltages negative to the membrane resting potential. In contrast type II hair cells (HCII) from mammalian and non-mammalian species have voltage-dependent outward K + currents that activate rapidly at or above the resting membrane potential and show significant inactivation. A-type, delayed rectifier and calcium-activated K + channels contribute to the outward K + conductance and are present in varying proportions in HCII. In many species, K + currents in HCII in peripheral locations of vestibular epithelia inactivate more than HCII in more central locations. Two types of inward rectifier currents have been described in both HCI and HCII. A rapidly activating K + -selective inward rectifier current (I K1 , mediated by Kir2.1 channels) predominates in HCII in peripheral zones, whereas a slower mixed cation inward rectifier current (I h ), shows greater expression in HCII in central zones of vestibular epithelia. The implications for sensory coding of vestibular signals by different types of hair cells are discussed. This article is part of a Special Issue entitled . [ABSTRACT FROM AUTHOR]

Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K+ currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K+ currents (IK) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 mM) rapidly reduced peak outward IK by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 mM) reduced outward IK by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of IK observed in mature cells. Intracellular application of gentamicin and neomycin also reduced IK in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce IK and the neomycin-induced reduction in IK was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-D-lysine to sequester PIP2 did not reduce IK. Application of the K+ channel blocker 4-aminopyridine (4-AP) strongly reduced IK, and extracellular AG in the presence of 4-AP gave no further inhibition of IK. In summary, AG significantly reduce the 4-AP-sensitive IK in early postnatal and mature HCI. K+ current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP2 sequestration or KCNQ channels. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Afferent innervation patterns in the vestibular periphery are complex, and vestibular afferents show a large variation in their regularity of firing. Calyx fibers terminate on type I vestibular hair cells and have firing characteristics distinct from the bouton fibers that innervate type II hair cells. Whole-cell patch clamp was used to investigate ionic currents that could influence firing patterns in calyx terminals. Underlying K(Ca) conductances have been described in vestibular ganglion cells, but their presence in afferent terminals has not been investigated previously. Apamin, a selective blocker of SK-type calcium-activated K(+) channels, was tested on calyx afferent terminals isolated from gerbil semicircular canals during postnatal days 1-50. Lowering extracellular calcium or application of apamin (20-500 nM) reduced slowly activating outward currents in voltage clamp. Apamin also reduced the action potential afterhyperpolarization (AHP) in whole-cell current clamp, but only after the first two postnatal weeks. K(+) channel expression increased during the first postnatal month, and SK channels were found to contribute to the AHP, which may in turn influence discharge regularity in calyx vestibular afferents. [ABSTRACT FROM AUTHOR]

The experiment was carried out to evaluate which is the best the diet energy level diet for male broiler breeders of cutting Cobb 500 and the influence of the presence of the crest on parameters such as body weight, semen volume, sperm cell concentration and fertility. Were used 32 roosters for 22 to 44 weeks of age, they were randomly assigned to cages equipped with feeders and drinkers type gutter. The experimental design was entirely casualized in a factorial scheme 2×2 two comb conditions (with and without crest) and two levels of metabolizable energy (2600 and 2800kcal kg-1). There was four treatments with eight replications, with one bird per experimental unit. At week 24th began collecting data for statistical analysis, when merging the week weighing the birds to the collection of semen, which was collected through the American method and count of sperm cells, The dilution of semen-based formaldehyde buffered saline and then reading in a Neubauer chamber. We assessed male fertility through artificial insemination of six females per treatment, twice weekly with 0.05mL of semen per female. Eggs were collected four times a day, identified, disinfected and incubated in the same conditions. After 21 of incubation, eggs not hatched were broken and macroscopically examined to calculate the fertility. The energy levels studied revealed no significant difference in body weight and volume of semen of roosters during the experimental period. Since cutting the crest reduced body weight and fertility of 9.5% and 24% respectively in relation to birds crested whole. In the weeks 29th, 35th, 37th and 43th there was a higher concentration of sperm cells in birds fed the diet with 2600kcal kg-1. It is concluded that the level of 2600kcal kg-1 is sufficient to meet the reproductive parameters of roosters and the presence of the crest is needed to maintaining high fertility in 42 and 43 weeks of age birds. [ABSTRACT FROM AUTHOR]

A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5 on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears. [ABSTRACT FROM AUTHOR]

High-resolution X-ray microtomography (micro-CT) was used to show the spatial configuration of the membranous labyrinth of the fixed guinea pig and human inner ear. Whole temporal bones were en bloc stained in 2% osmium tetroxide for 2 days or more to allow the osmium to attach to the membranes of the inner ear, and then scanned with a Skyscan 1172 micro-CT with highest resolution of 8 microns. The scans were segmented and reconstructed. The findings for guinea pigs and humans are similar. The saccular macula is closely attached to the curved medial wall of the temporal bone, but in both human and guinea pig the utricular macula is attached to the temporal bone only at the anterior region of the macula, and, as others have reported previously, much of the caudal area of the utricular macula is tenuously supported by a thin membrane, just above the dorsal margin of the stapes. This tenuous support may have important consequences for the sensing of forces by the utricular macula. Combining information from a dissected human horizontal canal with CT images allows an estimate of the orientation of the horizontal canal crista in human subjects, data which are necessary for treatment of benign paroyxsmal positional vertigo of the horizontal canal. The very high resolution achieved by micro-CT shows that reconstruction from inadequately sampled CT data produces images that are not anatomically correct, so that canal deformations and aplasias may appear to be present. [ABSTRACT FROM AUTHOR]

The objective of this trial was evaluated the effect of different crude protein (CP) levels of diet for males with or without coumbing. Body weight, semen volume, number of spermatic cells and fertility were evaluated. A total of 32 males Cobb 500 were used being 50% coumbed and 50% decoumbed males. The roosters were exposed the same management conditions in starting and rearing phases. They were housed in individual metallic cages with feeders and drinkers. The experimental design was entirely casualized in a factorial 2x2, two comb conditions (with or without) and two levels of crude protein (12 and 16%). Semen was collected using the American methods and number of spermatic cells was determined by counting in Neubauer chamber. At 42, 43 and 44 weeks of age, six females were artificially inseminated by treatment, twice a week, with dosage of 0.05ml of fresh semen. The eggs were collected four times a day, identified, disinfected and incubated in similar conditions. After 21 day of incubation they were broken and examined macroscopically to analyze the fertility. The level of 12% of crude protein was enough to assist the reproductive demands and the permanence of males. Combed males had body weight higher than without combed males. [ABSTRACT FROM AUTHOR]

Mitochondria display considerable structural diversity particularly in terms of the folding of the energy-transducing inner membrane. The hypothesis is forwarded that the topology of the mitochondrial inner membrane is not random but rather is a regulated cell parameter. Its effects on internal diffusion of metabolites and soluble proteins can influence such mitochondrial processes as ATP production and protein release during apoptosis. Progress toward understanding the factors that control mitochondrial inner-membrane curvature and dynamics (fusion and fission) is summarized, with a focus on remodeling events associated with apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

Abstract: The vitamin A-derived morphogen retinoic acid (RA) plays important roles during the development of chordate animals. The Aldh1a-family of RA-synthesizing enzymes consists of three members, Aldh1a1–3 (Raldh1–3), that are dynamically expressed throughout development. We have searched the known teleost genomes for the presence of Raldh family members and have found that teleost fish possess orthologs of Aldh1a2 and Aldh1a3 only. Here we describe the expression of aldh1a3 in the zebrafish, Danio rerio. Whole mount in situ hybridization shows that aldh1a3 is expressed during eye development in the retina flanking the optic stalks and later is expressed ventrally, opposite the expression domain of aldh1a2. During inner ear morphogenesis, aldh1a3 is expressed in developing sensory epithelia of the cristae and utricular macula and is specifically up-regulated in epithelial projections throughout the formation of the walls of the semicircular canals and endolymphatic duct. In contrast to the mouse inner ear, which expresses all three Raldhs, we find that only aldh1a3 is expressed in the zebrafish otocyst, while aldh1a2 is present in the periotic mesenchyme. During larval stages, additional expression domains of aldh1a3 appear in the anterior pituitary and the swim bladder. Our analyses provide a starting point for genetic studies to examine the role of RA in these organs and emphasize the suitability of the zebrafish inner ear in dissecting the contribution of RA signaling to the development of the vestibular system. [Copyright &y& Elsevier]

Abstract: The “wave turbopause” is defined as the mesospheric altitude level where the temperature fluctuation field indicates a substantial increase in wave amplitudes in the vertical direction. The turbopause altitude is analyzed on the basis of four years of SABER data (2002–2005, Version 1.06). Substantial seasonal and latitudinal variations are found, with some interannual variability also present. Seasonal changes are annual at high latitudes, semi-annual at low latitudes, and a mixture of both at middle latitudes. Southern hemisphere data are similar as in the North if shifted by half a year. Latitudinal variations show a minimum in the tropics and two relative maxima at middle latitudes. The “wave turbopause” is found near to zero-wind lines or low-wind zones (zonal wind). It is compared to rocket and other measurements, and interesting similarities are obtained. The wave turbopause can also be found in the HAMMONIA GCM. A preliminary analysis shows results similar to those of the SABER measurements. [Copyright &y& Elsevier]

Abstract: Anosmin-1, encoded by the KAL-1 gene, is the protein defective in the X-linked form of Kallmann syndrome. This human developmental disorder is characterized by defects in cell migration and axon target selection. Anosmin-1 is an extracellular matrix protein that plays a role, in vitro, in processes such as cell adhesion, neurite outgrowth, axon guidance, and axon branching. The zebrafish possesses two orthologues of the KAL-1 gene: kal1a and kal1b, which encode anosmin-1a and anosmin-1b, respectively. Previous in situ hybridization studies have shown that kal1a and kal1b mRNAs are expressed in undetermined cells of the inner ear but not in neuromast cells. Using specific antibodies against anosmin-1a and anosmin-1b, we report here that both proteins are expressed in sensory hair cells of the inner ear cristae ampullaris and the lateral line neuromasts. Accumulation of these proteins was observed mainly at the level of the hair bundle and also at the cell membrane. In neuromast hair cells, immunogold scanning electronmicroscopy demonstrated that anosmin-1a and anosmin-1b were present at the surface of the stereociliary bundle. In addition, anosmin-1a, but not anosmin-1b, was detected on the track of the ampullary nerve. This is the first report of anosmin-1 expression in sensory hair cells of the inner ear and lateral line, and along the ampullary nerve track. [Copyright &y& Elsevier]

Abstract: Carbon monoxide, temperature, and potential vorticity data (November, 1994) from the cryogenic infrared spectrometers and telescopes for the atmosphere (CRISTA) experiment are used to analyze the relationship between the mesospheric surf zone in the winter hemisphere and simultaneously observed thermal inversions just above. The observed upward propagating planetary waves rapidly decay when they approach the critical wind line in the upper mesosphere and a distinct surf zone is formed between 60–75km. Above 85km, the planetary wave activity increases again revealing an out-of-phase behavior with the waves below. This is likely due to momentum forcing associated with breaking gravity waves that have been filtered by the stratospheric and lower mesospheric planetary waves. The abrupt vertical phase shift of the planetary waves thus induces a strong vertical geopotential curvature that is sufficiently large, through hydrostatic equilibrium, to invert the thermal structure around 80km. The CRISTA observations and their interpretation are consistent with simulations of the thermosphere–ionosphere–mesosphere-electrodynamics general circulation model (TIME-GCM) that was run for the same time period. Both the observation and the model results rather point to a more indirect, though essential, role of the gravity waves in the formation of the mesospheric inversion layers in early winter 1994. [Copyright &y& Elsevier]

Abstract: In November 1994 and August 1997 the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) instrument performed a global measurement (–) of infrared limb radiance from 4 to in the altitude range 6–180km. Using a non-local thermodynamic equilibrium (non-LTE) model that couples the collisional, radiative and photochemical processes, the kinetic temperature was recovered from emission for CRISTA-1 and -2 missions by direct assimilation of the integrated limb radiances between 72 and 120km. Falling sphere and airglow validation measurements at NASA/GSFC Wallops Flight Facility (WFF) and the Mesosphere–Thermosphere Emissions for Ozone Remote Sensing (METEORS) experiment at White Sands Missile Range were coordinated with CRISTA during the field campaign. The derived temperatures show good agreement with these rocket soundings, partial climatology obtained from Rayleigh scattering observations by Wind Imaging Interferometer (WINDII) on the Upper Atmosphere Research Satellite (UARS) and NRLMSISE-00 model. [Copyright &y& Elsevier]

Abstract: Most information on the properties of mammalian vestibular primary afferents has been obtained in deeply anesthetized animals, in vivo. Generally, non-human primates and larger rodents have been the species of choice. Investigations using smaller rodents, such as the laboratory mouse, have been limited despite the increasing availability of naturally occurring or engineered mutants that result in balance disorders. Furthermore, in vitro preparations of the intact peripheral vestibular apparatus are only available for non-mammalian vertebrates. To take advantage of the genetic/molecular advances available in mice and the utility of in vitro preparations that permit manipulations of the extracellular milieu, we developed an isolated mouse inner ear preparation with the attached eighth cranial nerve for electrophysiological recording. Intra-axonal recordings of background activity in vestibular primary afferents were obtained in a modified Ringer''s solution (0.25mMCa2+; 3.25mMMg2+) at 22°C. We also recorded afferent activity in the presence of neuroactive drugs known to affect various stages of the transduction cascade. These results, together with responses to sinusoidal mechanical deformation of the membranous ducts, showed that transduction mechanisms remain viable. Where possible, we also obtained results in vivo for comparison. In future, the in vitro mouse preparation will allow investigation of the effects of genetic manipulations and pharmacological agents on the intact peripheral vestibular apparatus. [Copyright &y& Elsevier]

During the second mission of the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) from August 8 to 16, 1997, over 45,000 altitude profiles of infrared spectra were collected. A variety of atmospheric trace gases have been retrieved. Due to its unprecedented spatial and temporal resolution CRISTA data is especially suited to study variability on small scales. Variability of selected trace gases is presented in terms of standard deviations from the zonal means in 5° latitude bands: altitude range is about 15–50 km for the mixing ratios of O3, N2O, CH4, CFC 11, and HNO3. Results are compared to CIRA 1996, Part III, and agreements or disagreements are discussed. Variability is found to be not constant, but quite variable itself. It is generally higher in winter than in summer. Beyond that there are considerable variations of standard deviations with latitude and with altitude. They show interesting peculiarities that will be discussed. The results indicate that most part of the data variability are atmospheric fluctuations rather than measurement errors. [Copyright &y& Elsevier]

Trace gas assimilation is an attractive method for the generation of synoptic trace gas fields from asynoptic satellite observations. Moreover, it allows for quantitative transport studies based on observational data. In this paper, we present a case study based on CFC-11 measurements of the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) experiment in November 1994. It is shown that assimilation of CFC-11 into a transport model significantly influences calculated transport quantities compared to results obtained from simulations without trace gas assimilation. [Copyright &y& Elsevier]

The CRISTA experiment provided global measurements of atmospheric trace gases in the stratosphere and upper troposphere during its second mission in August 1997. A new data product has recently been developed, yielding water vapor mixing ratios around the tropopause. The high data density of CRISTA makes an efficient assimilation of the water vapor field (by means of the NCAR ROSE CTM) possible. From these data turbulent trace gas fluxes v′χ′ are derived. The global distribution of the H2O fluxes is found to be highly structured at a given pressure level. Zonal means of fluxes indicate transport barriers at the equator and near the tropopause. This is compared to effective diffusivities of P. Haynes and E. Shuckburgh [J. Geophys. Res. 105 (2000) 22795] and general agreement is obtained. There is one important discrepancy, though: the effective diffusivities show a transequatorial “bridge” at about 350 K potential temperature (about 12 km), a “bridge” which is also seen in the CRISTA water vapor data, but at a considerably higher altitude. This finding is confirmed by ozone data from CRISTA and from UARS. [Copyright &y& Elsevier]

Simple radiance ratios have been used for the detection of clouds around the tropopause and in the winter polar stratosphere from the infra-red spectra of two remote sensing instruments, the cryogenic infrared spectrometers and telescopes for the atmosphere (CRISTA) flown on two space shuttle missions in 1994 and 1997 and the Michelson interferometer for passive atmospheric sounding (MIPAS) launched on ENVISAT in March 2002. This very successful approach was first applied to different wavelength regions of the CRISTA measurements and was then used as a pre-flight validation test for a cloud detection algorithm of the operational retrieval processor for MIPAS. Preliminary results are now available from the MIPAS instrument and are presented here. First, cloud top heights have been derived down to 12 km by the detection method and show quite reasonable results. In addition, modelled spectra and measurements show that the extension of the method to lower altitudes – potentially down to 6 km – should be possible. Second, the high spectral resolution of the MIPAS measurements allows in addition the detection of scattering effects in the spectra, which gives the future opportunity to retrieve information about the size of the scattering particles. In particular, an index has been developed which allows large particle clouds to be identified. Finally, investigations of CRISTA spectra have already shown that the differentiation of polar stratospheric cloud (PSC) types is possible based on their characteristic spectral features. Application of the differentiation method to the tropics shows no indication for clouds containing PSC-like nitric-acid-hydrate particles. [Copyright &y& Elsevier]

The vertebrate inner ear is a marvel of structural and functional complexity, which is all the more remarkable because it develops from such a simple structure, the otic placode. Analysis of inner ear development has long been a fascination of experimental embryologists, who sought to understand cellular mechanisms of otic placode induction. More recently, however, molecular and genetic approaches have made the inner ear a useful model system for studying a much broader range of basic developmental mechanisms, including cell fate specification and differentiation, axial patterning, epithelial morphogenesis, cytoskeletal dynamics, stem cell biology, neurobiology, physiology, etc. Of course, there has also been tremendous progress in understanding the functions and processes peculiar to the inner ear. The goal of this review is to recount how historical approaches have shaped our understanding of the signaling interactions controlling early otic development; to discuss how new findings have led to fundamental new insights; and to point out new problems that need to be resolved in future research. [Copyright &y& Elsevier]

The inner membrane system of mitochondria is known to consist of two contiguous but distinct membranes: the inner boundary membrane, which apposes the outer membrane, and the cristal membrane, which forms tubules or lamellae in the interior. Using immunolabeling and transmission electron microscopy of bovine heart tissue, we have calculated that around 94% of both Complex III of the respiratory chain and the ATP synthase are located in the cristal membrane, and only around 6% of either is in the inner boundary membrane. When accounting for the topographical ratio of cristal membrane versus inner boundary membrane, we find that both complexes exist at a 2.2–2.6-fold higher concentration in the cristal membrane. The residual protein in the inner boundary membrane may be newly assembled complexes destined for cristal membranes. Our results argue for restricted diffusion of complexes through the cristal junctions and indicate that the mitochondrial cristae comprise a regulated submitochondrial compartment specialized for ATP production. [Copyright &y& Elsevier]

Calpains, a family of calcium-activated proteases that breakdown proteins, kinases, phosphatases and transcription factors, can promote cell death. Since leupeptin, a calpain inhibitor, protected against hair cell loss from acoustic overstimulation, we hypothesized that it might protect cochlear and vestibular hair cells against gentamicin (GM) ototoxicity. To test this hypothesis, mouse organotypic cultures from the cochlea, maculae of the utricle and the crista of the semicircular canal (P1–P3) were treated with different doses of GM (0.1–3 mM) alone or in the presence of leupeptin (0.1–3 mM). The percentage of outer hair cells (OHCs) and inner hair cells (IHCs) decreased with increasing doses of GM between 0.1 and 3 mM. The addition of 1 mM of leupeptin significantly reduced GM-induced damage to IHCs and OHCs; this protective effect was dose-dependent. GM also significantly reduced hair cell density in the crista and utricle in a dose-dependent manner between 0.1 and 3 mM. The addition of 1 mM of leupeptin significantly reduced hair cell loss in the crista and utricle for GM concentrations between 0.1 and 3 mM. These results suggest that one of the early steps in GM ototoxicity may involve calcium-activated proteases that lead to the demise of cochlear and vestibular hair cells. [ABSTRACT FROM AUTHOR]