Peter Dallos - Academia.edu (original) (raw)

Papers by Peter Dallos

Archives of Otolaryngology-head & Neck Surgery, Apr 1, 1967

This 378-page volume represents a most ambitious undertaking. The book covers areas ranging from ... more This 378-page volume represents a most ambitious undertaking. The book covers areas ranging from auditory physiology, through psychoacoustics and audiometry, to music. Representative chapter titles are: "Anatomy and Physiology of the Ear," "Electrical Activity of the Auditory System," "Physical Characteristics of Speech," "The Alleviation of Deafness," and so forth. Altogether there are 15 chapters and five appendices. The title of the book should not frighten those potential readers whose background in physics and mathematics is inadequate. The book, with the exception of the last chapter where the author gives an introduction to Gabor's work, is definitely nonmathematical. The survey-style covering of subjects associated with hearing is quite broad and comprehensive, if not necessarily deep. The author starts with brief anatomical descriptions of the peripheral auditory system and the auditory neural pathways. A simplified description of neural and synaptic transmission is then followed by a fairly detailed analysis of the mechanical

Proceedings of the National Academy of Sciences of the United States of America, Feb 22, 2011

Journal of Neurophysiology, Jul 1, 1993

1. A theory of cochlear outer hair cell electromotility is developed and specifically applied to ... more 1. A theory of cochlear outer hair cell electromotility is developed and specifically applied to somatic shape changes elicited in a microchamber. The microchamber permits the arbitrary electrical and mechanical partitioning of the outer hair cell along its length. This means that the two partitioned segments are stimulated with different input voltages and undergo different shape changes. Consequently, by imposing more constraints than other methods, experiments in the microchamber are particularly suitable for testing different theories of outer hair cell motility. 2. The present model is based on simple hypotheses. They include a distributed motor associated with the cell membrane or cortex and the assumption that the displacement generated by the motor is related to the transmembrane voltage across the associated membrane element. It is expected that the force generated by the motor is counterbalanced by an elastic restoring force indigenous to the cell membrane and cortex, and a tensile force due to intracellular pressure. It is assumed that all changes take place while total cell volume is conserved. The above elements of the theory taken together permit the development of qualitative and quantitative predictions about the expected motile responses of both partitioned segments of the cell. Only a DC treatment is offered here. 3. Both a linear motor and an expanded treatment that incorporates a stochastic molecular motor model are considered. The latter is represented by a two-state Boltzmann process. We show that the linear motor treatment is an appropriate extrapolation of the stochastic motor theory for the case of small voltage driving signals. Comparison of experimental results with model responses permits the estimation of model parameters. Good match of data is obtained if it is assumed that the molecular motors undergo conformational length changes of 0.7-1.0 nm, that they have an effective displacement vector at approximately -20 degrees with the long axis of the cell, and that their linear density is approximately 80/microns. 4. An effort is made to parcel out motile response components that are a direct consequence of the motor action from those that are mediated by cytoplasmic pressure changes brought about by the concerted action of the motors. We show that pressure effects are of minor importance, and thus rule out models that rely on radial constriction/expansion-mediated internal pressure change as the primary cause of longitudinal motility. 5. As a consequence of the interaction between the Boltzmann process and the mechanical characteristics of the cell, the electromotile response is asymmetric.(ABSTRACT TRUNCATED AT 400 WORDS)

ENeuro, Nov 1, 2018

Spontaneous otoacoustic emissions (SOAEs) recorded from the ear canal in the absence of sound ref... more Spontaneous otoacoustic emissions (SOAEs) recorded from the ear canal in the absence of sound reflect cochlear amplification, an outer hair cell (OHC) process required for the extraordinary sensitivity and frequency selectivity of mammalian hearing. Although wild-type mice rarely emit, those with mutations that influence the tectorial membrane (TM) show an incidence of SOAEs similar to that in humans. In this report, we characterized mice with a missense mutation in Tecta, a gene required for the formation of the striated-sheet matrix within the core of the TM. Mice heterozygous for the Y1870C mutation (Tecta Y1870C/ϩ) are prolific emitters, despite a moderate hearing loss. Additionally, Kimura's membrane, into which the OHC stereocilia insert, separates from the main body of the TM, except at apical cochlear locations. Multimodal SOAEs are also observed in Tecta Y1870C/ϩ mice where energy is present at frequencies that are integer multiples of a lower-frequency SOAE (the primary). Second-harmonic SOAEs, at twice the frequency of a lower-frequency primary, are the most frequently observed. These secondary SOAEs are found in spatial regions where stimulus-evoked OAEs are small or in the noise floor. Introduction of high-level suppressors just above the primary SOAE frequency reduce or eliminate both primary and second-harmonic SOAEs. In contrast, second-harmonic SOAEs are not affected by suppressors, either above or below the second-harmonic SOAE frequency, even when they are much larger in amplitude. Hence, second-harmonic SOAEs do not appear to be spatially separated from their primaries, a finding that has implications for cochlear mechanics and the consequences of changes to TM structure.

Journal of Neurophysiology, Aug 1, 1993

1. The microchamber method was used to examine the motile responses of isolated guinea pig outer ... more 1. The microchamber method was used to examine the motile responses of isolated guinea pig outer hair cells to electrical stimulation. In the microchamber method, an isolated cell is drawn partway into a suction pipette and stimulated transcellularly. The relative position of the cell in the microchamber is referred to as the exclusion fraction. 2. The length changes of the included and excluded segments were compared for constant sinusoidal stimulus amplitude as functions of the exclusion fraction. Both included and excluded segments showed maximal responses when the cell was excluded approximately halfway. Both segments showed smaller or absent responses when the cell was almost fully excluded or almost fully included. 3. When the cell was near to, but not at, the maximum exclusion, the included segment response amplitude was zero, whereas the excluded segment response amplitude was nonzero. In contrast, when the cell was nearly fully included, the excluded segment response amplitude was zero, but the included segment response amplitude was still detectable. A simple model of outer hair cell motility based on these results suggests that the cell has finite-resistance terminations and that the motors are restricted to a region above the nucleus and below its ciliated apex (cuticular plate). 4. The function describing length change as a function of command voltage was measured for each segment as the exclusion fraction was varied. The functions were similar at midrange exclusions (i.e., when the segments were about equal length), showing nonlinearity and saturability. The functions were strikingly different when the segment lengths were different. The effects of exclusion on the voltage to length-change functions suggested that the nonlinearity and saturability are local properties of the motility mechanism. 5. The diameter changes of both segments were examined. The segment diameter changes were always antiphasic to the length changes. This finding implies that the motility mechanism has an active antiphasic diameter component. The diameter change amplitude was a monotonically increasing function of exclusion for the included segment, and a decreasing function for the excluded segment. 6. The voltage to length-change and voltage to diameter-change functions were measured for the same cell and exclusion fraction. The voltage to diameter-change function was smaller in amplitude than the voltage to length-change function. The functions were of opposite polarity to each other, but were otherwise similar in character. Thus it is likely that the same motor mechanism is responsible for both axial and diameter deformations.

Science, Jun 9, 1995

I N E W Rapid Immunodetection Method I specific antibody binding. Extensive washes dre also requi... more I N E W Rapid Immunodetection Method I specific antibody binding. Extensive washes dre also required to reduce the background for a better signal-tcmoise ratio.

Hearing Research, 1998

Our knowledge of cochlear geometry is based largely upon anatomical observations derived from fix... more Our knowledge of cochlear geometry is based largely upon anatomical observations derived from fixed, dehydrated, embedded and/or sputter-coated material. We have now developed a novel preparation, the hemicochlea, where for the first time living cochlear structures can be observed in situ and from a radial perspective. The experiments were performed on the Mongolian gerbil. Ion substitution experiments suggest that no significant swelling or shrinkage occurs when the preparation is bathed in normal culture medium, so long as calcium concentration is kept at endolymph-like (20 W WM) levels. The tectorial membrane-reticular lamina relationship appears to remain well preserved. Hensen's stripe maintains a close relationship with the inner hair cell stereociliary bundle, unless the mechanical coupling becomes disturbed. In addition, standard fixation and/or dehydration procedures are used to quantify changes due to shrinkage artifacts. Various morphometric gradients are examined in unfixed specimens from apical, middle, and basal turns.

Journal of the Acoustical Society of America, Nov 1, 1976

The Journal of Neuroscience, Mar 15, 1997

The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acet... more The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond with a somatic shape change to alterations in their membrane potential, and this electromotile response is believed to provide mechanical feedback to the basilar membrane. We examine the effects of ACh on electromotile responses in isolated OHCs and attempt to deduce the mechanism of ACh action. Axial electromotile amplitude and cell compliance increase in the presence of the ligand. This response occurs with a significantly greater latency than membrane current and potential changes attributable to ACh and is contemporaneous with Ca 2ϩ release from intracellular stores. It is likely that increased axial compliance largely accounts for the increase in motility. The mechanical responses are probably related to a recently demonstrated slow efferent effect. The implications of the present findings related to commonly assumed efferent behavior in vivo are considered.

Nucleation and Atmospheric Aerosols, 2018

Tecta Y1870C/+ mice with alterations in the structure and porosity of the tectorial membrane disp... more Tecta Y1870C/+ mice with alterations in the structure and porosity of the tectorial membrane display large numbers of spontaneous emissions

PLOS ONE, Jul 30, 2013

Especially in the last decade or so, there have been dramatic advances in fluorescence-based imag... more Especially in the last decade or so, there have been dramatic advances in fluorescence-based imaging methods designed to measure a multitude of functions in living cells. Despite this, many of the methods used to analyze the resulting images are limited. Perhaps the most common mode of analysis is the choice of regions of interest (ROIs), followed by quantification of the signal contained therein in comparison with another "control" ROI. While this method has several advantages, such as flexibility and capitalization on the power of human visual recognition capabilities, it has the drawbacks of potential subjectivity and lack of precisely defined criteria for ROI selection. This can lead to analyses which are less precise or accurate than the data might allow for, and generally a regrettable loss of information. Herein, we explore the possibility of abandoning the use of conventional ROIs, and instead propose treating individual pixels as ROIs, such that all information can be extracted systematically with the various statistical cutoffs we discuss. As a test case for this approach, we monitored intracellular pH in cells transfected with the chloride/bicarbonate transporter slc26a3 using the ratiometric dye SNARF-5F under various conditions. We performed a parallel analysis using two different levels of stringency in conventional ROI analysis as well as the pixels-as-ROIs (PAR) approach, and found that pH differences between control and transfected cells were accentuated by ~50-100% by using the PAR approach. We therefore consider this approach worthy of adoption, especially in cases in which higher accuracy and precision are required.

Springer eBooks, 1989

It is now well known that electrical stimulation of isolated mammalian outer hair cells results i... more It is now well known that electrical stimulation of isolated mammalian outer hair cells results in a motile response (Brownell, 1983;Ashmore,1987;Zenneret al.,1987). The fast response component is apparently capable of following a sinusoidal current stimulus in the audio frequency range (Ashmore, 1987; Zenner et al., 1987). Fast motility is a robust response that has been shown under conditions that are distinctly non-physiological. In all experiments reported thus far, all cell surfaces were bathed in a high-sodium medium. Of course, under in vivo conditions only the basolateral cell membrane is exposed to perilymph (high Na+) while the hair-bearing apical end is bathed in endolymph (high K+). We demonstrate here that isolated cells show two kinds of rectification in their motility with sinusoidal current stimuli, that there are quantitative differences in the responses as a function of cell length, and that these phenomena persist when the apical and basolateral cell surfaces are exposed to their proper biochemical environment.

The Journal of Physiology, Nov 1, 2005

Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency ... more Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency selectivity and outer hair cell (OHC) somatic electromotility. In addition, it has been reported by Liberman and colleagues that F2 generation heterozygotes exhibit a 6 dB reduction in sensitivity, as well as a decrease in protein and electromotility. Considering that the active process is non-linear, a halving of somatic electromotility would be expected to produce a much larger change in sensitivity. We therefore re-evaluated comparisons between heterozygotes and wildtype mice using both in vivo and in vitro electrophysiology, as well as molecular biology. Data reported here for F3–F5 generation mice indicate that compound action potential thresholds and tuning curves, as well as the cochlear microphonic, are similar in heterozygotes and wildtype controls. Measurements of non-linear capacitance in isolated OHCs demonstrate that charge density, as well as the voltage dependence and sensitivity of motor function, is indistinguishable in the two genotypes, as is somatic electromotility. In addition, both immunocytochemistry and western blot analysis in young adult mice suggest that prestin protein in heterozygotes is near normal. In contrast, prestin mRNA is always less than in wildtype mice at all ages tested. Results from F3–F5 generation mice suggest that one copy of the prestin gene is capable of compensating for the deleted copy and that heterozygous mice do not suffer peripheral hearing impairment.

Journal of the Acoustical Society of America, Jun 1, 1979

Audiology and Neuro-otology, 2002

Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. ... more Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by realtime polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 (p < 0.0001) and hsa_circRNA_104700 (p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis (p = 0.021) and tumor-node-metastasis stage (p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis (p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 (p < 0.0001) and 0.616 (p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

The Journal of Physiology, 2004

Gross‐potential recordings in mice lacking the Prestin gene indicate that compound action potenti... more Gross‐potential recordings in mice lacking the Prestin gene indicate that compound action potential (CAP) thresholds are shifted by ∼45 dB at 5 kHz and by ∼60 dB at 33 kHz. However, in order to conclude that outer hair cell (OHC) electromotility is associated with the cochlear amplifier, frequency selectivity must be evaluated and the integrity of the OHC's forward transducer ascertained. The present report demonstrates no frequency selectivity in CAP tuning curves recorded in homozygotes. In addition, CAP input–output functions indicate that responses in knockout mice approach those in controls at high levels where the amplifier has little influence. Although the cochlear microphonic in knockout mice remains ∼12 dB below that in wild‐type mice even at the highest levels, this deficit is thought to reflect hair cell losses in mice lacking prestin. A change in OHC forward transduction is not implied because knockout mice display non‐linear responses similar to those in controls. ...

Journal of Biological Chemistry, 2006

Prestin, a member of the solute carrier family 26, is expressed in the basolateral membrane of ou... more Prestin, a member of the solute carrier family 26, is expressed in the basolateral membrane of outer hair cells. This protein provides the molecular basis for outer hair cell somatic electromotility, which is crucial for the frequency selectivity and sensitivity of mammalian hearing. It has been long known that there are abundantly expressed~11 nm protein particles present in the basolateral membrane. These particles were hypothesized to be the motor proteins that drive electromotility. Because the calculated size of a prestin monomer is too small to form an~11 nm particle, the possibility of prestin's oligomerization was examined. We investigated possible quaternary structures of prestin by LDS-PAGE, PFO-PAGE, a membrane-based yeast two-hybrid system, and chemical cross linking experiments. Prestin, obtained from different host or native cells, is resistant to dissociation by lithium dodecyl sulfate and behaves as a stable oligomer on LDS-PAGE. In the membrane-based yeast two-hybrid system, homo-oligomeric interactions between prestin-bait/prestin-prey suggest that prestin molecules can associate with each other. Chemical cross linking experiments, PFO-PAGE/Western blot and affinity purification experiments all indicate that prestin exists as a higher-order oligomer, such as a tetramer, in prestin-expressing yeast, mammalian cell lines and native outer hair cells. Our data from experiments using hydrophobic and hydrophilic reducing reagents, suggest that the prestin dimer is connected by a disulfide bond embedded in prestin's hydrophobic core. This stable dimer may act as the building block for producing the higherorder oligomers that form the~11 nm particles in the outer hair cell's basolateral membrane.