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C S Watson

Publications and source records attributed to C S Watson.

At least 19 recordsLinked to original sources

The "proportion-of-the-total-duration rule" for the discrimination of auditory patterns.

A principle of auditory perception that governs the detectability of changes in components in unfamiliar sequences of tones is demonstrated in four experiments. The proportion-of-the-total-duration (PTD) rule can be stated as follows: Each individual component of an unfamiliar sequence of tones is resolved with an accuracy that is a function of its proportion of the total duration of the sequence or "pattern." An adaptive-tracking frequency-discrimination task was used in all experiments. Experiment 1 demonstrated that the PTD rule holds over a wide range of total pattern durations, numbers of components, and component durations. Experiment 2 demonstrated that the PTD rule governs discrimination performance despite variation in the relative durations of context and target tones. Experiment 3, using a variable temporal position for the target, confirmed that the PTD effect does not require that a listener be able to anticipate the temporal location of the target tone. Experiment 4, using two target tones, showed that the PTD rules applies to the proportional duration of individual components within patterns and not to the total proportional duration of nonadjacent components within the pattern. These findings are incompatible with performance limitations based on a fixed-duration short-term memory capacity and with versions of informational limitations in which the amount of information in a pattern varies either with the number of components or with the total pattern duration. The PTD rule appears to reflect the way listeners distribute their attention when presented with unfamiliar complex sounds that have no structural properties (other than proportional duration) that significantly increase the salience of individual components.

Acoustic Stimulation

Size and steroid-binding characterization of membrane-associated glucocorticoid receptor in S-49 lymphoma cells.

The precise mechanism for glucocorticoid-mediated lymphocytolysis is not understood, although it is presumed to be receptor mediated. We have recently presented evidence that this response is mediated by a specialized form of the glucocorticoid receptor (GR) that resides in the plasma membrane (mGR). Confirmation of the previous receptor identification studies in a population of S-49 cells enriched for mGR is now made using another antibody specific for the rodent GR, BUGR-2. The membrane resident receptor could be labeled competitively with the affinity ligand dexamethasone 21-mesylate, and Scatchard analysis of whole cell binding revealed that receptor number, but not the affinity for hormone, varied between the mGR-enriched and -deficient cell populations. Steroid specificity displacement analyses showed an order of affinities as follows: triamcinolone acetonide greater than progesterone greater than dexamethasone greater than testosterone = estrogen. Studies of mGR by one- and two-dimensional gel electrophoresis, immunoblot, autoradiography, and density gradients revealed a species with an equivalent size to cytosolic receptor as well as multiple higher molecular weight species, confirming earlier studies. To offer a possible explanation for the nucleic acid origins of the mGR, RNA from the mGR-enriched cells was probed with rat GR cDNA; mGR-enriched cells contained higher levels of GR mRNA. Possible molecular etiologies of larger receptor species in membrane are discussed.

Affinity Labels

Studies on the arrangement of glucocorticoid receptors in the plasma membrane of S-49 lymphoma cells.

The presence of glucocorticoid receptors is required for glucocorticoid-mediated lymphocytolysis to take place. However, the explicit mechanism of involvement of this receptor continues to be debated. We have recently presented evidence that this response is mediated by a specialized form of the glucocorticoid receptor that resides in the plasma membrane (mGR). Using sequential cell separation techniques ("immunopanning," fluorescent cell sorting, and soft agar cloning), a resultant population of membrane receptor-enriched cells have remained stable and provided material for further analysis. The mGR patching and capping phenomenon originally observed with fluoresceinated monoclonal antibody techniques was verified here with electron micrographic analysis using colloidal gold-conjugated antibody. Using 3H-labeled monoclonal antibody, a radioimmunoassay for membrane receptors was developed. Trypsin treatment removed the membrane receptor antigenic site from the surface of cells. Peptide mapping of receptor purified from plasma membranes reveals several trypsin and alpha-chymotrypsin cleavage sites. Larger fragments resulted from cleavage of the membrane receptor of cells enriched for mGR versus those found in cells depleted of the membrane form, although most of the resulting fragments are shared by the two forms. Confirmation of previous studies correlating membrane receptor with the mechanism of glucocorticoid sensitivity is now extended to include elimination of the lymphocytolysis effect in membrane receptor-stripped (trypsinized) S-49 cells.

Animals

Human estrogen receptor introduced into the Xenopus oocyte represses expression from an artificial frog estrogen response element.

Although the estrogen responsiveness and estrogen receptors of Xenopus hepatocytes have been well described, oocytes of this species have not previously been shown to contain estrogen receptors (ER). Recombinant human ER (HER) was expressed in oocytes in a dose dependent fashion as measured by [35S]methionine incorporation into newly synthesized proteins. Chloramphenicol acetyl transferase (CAT) reporter plasmids, driven by a herpes simplex thymidine kinase promotor with or without a 17 base pair estrogen response element (ERE) from the vitellogenin A2 gene, were also injected into oocytes. When injected without the accompanying HER sequences, the construct containing the ERE expressed 10-fold more CAT activity, and this response was saturable as demonstrated by injecting increasing amounts of reporter plasmid. These results suggest either the activity of small amounts of a Xenopus ER (measured here by LH-20 assay), or the presence of some endogenous oocyte protein other than the ER that can interact with this ERE. When HER was co-expressed with ERECAT, CAT expression was suppressed over a wide range of HER concentrations. This unexpected repression may be due to displacement of an estrogen receptor or other endogenous oocyte regulatory protein on the ERE. HER's positive regulatory activity may require transcription factors that are lacking or insufficient in the oocyte. Alternatively the simple 17 base pair ERE may not provide DNA binding sites for such transcription factors.

Animals

Auditory perceptual learning and the cochlear implant.

Recent studies of the perception of complex nonspeech sounds have shown that individual parts of spectral-temporal waveforms become more salient through experience or selective training. One consequence of this is that the same sound can be perceived quite differently, depending on prior experience and also on the listener's expectations. The time course of learning to identify initially unfamiliar speech sounds by normal-hearing listeners has been shown to extend over many months, possibly even years, before reaching a stable high level of performance. If implant users or users of other types of speech aids (acoustic hearing aids, vibrotactile aids) are required to learn to interpret sounds as unfamiliar as the nonspeech sounds used in research are to normal listeners, similar lengthy experience should be required for them to achieve maximum performance. Why this has not been the case in some clinical studies is a puzzle. A possible explanation is that speech perception strongly depends on abilities other than sensory acuity or resolving power. Studies of individual differences in auditory temporal and spectral acuity have not shown strong correlations between individual differences in those abilities and individual differences in speech perception. It is argued that one way to interpret this observation is that differences in the ability to hear speech (as by two hearing-impaired listeners with the same audiogram) may be the result of central differences in the ability to infer an original stimulus from its fragments; this ability may be independent of the sensory modality in which the information is presented.

Adult

Limits of auditory patterns discrimination for patterns with various durations and numbers of components.

In three experiments, listeners' abilities to detect changes in randomly generated tonal sequences were determined for sequences or "patterns" ranging in total duration from 62.5 ms to 2 s. Experiment 1 utilized an adaptive-tracking procedure, with n, the number of pattern components, as the dependent variable, and included a variety of spectral and temporal discrimination tasks with isochronous patterns. When the to-be-detected change was the only variation on a given dimension (e.g., the presence or location of a brief pause), patterns were discriminable when the absolute duration of the changed element, or pause, exceeded a critical value. However, when each pattern component varied on the dimension of the to-be-detected change (e.g., frequency), discriminability was strongly related to the number of tones in the pattern, and only weakly to the durations of either the target components or the total pattern. This dependence of discrimination performance on n was also demonstrated with anisochronous patterns in experiment 2. Experiment 3 revealed the same dependence of performance on the number of components per pattern as did experiments 1 and 2, but with delta f/f as the dependent variable, rather than n. The number of pattern components and the proportional duration of the target components, relative to total pattern duration, were confounded in these experiments. Additional research is therefore required to determine whether number or proportional target-tone duration is the primary determinant of pattern discriminability.

Adult

Expression and translocation of cloned human estrogen receptor in the Xenopus oocyte does not induce expression of the endogenous oocyte vitellogenin genes.

Estrogen-receptor complex activates the genes coding for the egg yolk protein precursor vitellogenin in hepatocytes of oviparous vertebrates, while oocyte vitellogenin genes are unresponsive to the hormone. Localization of [3H]steroid hormones (estradiol, progesterone, testosterone, and dexamethasone) was assayed in 10% trichloroacetic acid-precipitated dissected Xenopus oocytes (germinal vesicle vs. the rest of the oocyte). Whether hormones were introduced by incubation in the medium surrounding the oocytes or by injection of an equivalent amount into the oocyte cytoplasm, all hormones partitioned into the nucleus at equivalent levels (approximately 5%), reflecting that portion of the oocyte volume occupied by its nucleus. Therefore, intracellular receptors for these hormones were not detectable. Subsequently, we introduced a species-heterologous estrogen receptor into the Xenopus oocyte via a recombinant plasmid containing the coding sequence for the human estrogen receptor (HER) housed in a vector that ensures highly efficient transcription and translation of inserted sequences. HER synthesis was directed from injected plasmid (2 ng/oocyte germinal vesicle) as shown by [35S]methionine incorporation into newly synthesized proteins; however, vitellogenin was not synthesized under these conditions. When HER plasmid-injected oocytes were incubated in [3H]estradiol, they translocated to the nucleus 38% of the radiolabeled estradiol taken up by the cells, compared to 5% nuclear localization for vector-injected controls. Therefore, although the oocyte can readily transcribe and translate HER sequences as well as appropriately partition the completed protein in the nuclear compartment, the endogenous, potentially estrogen-responsive vitellogenin genes of the oocyte are not expressed.

Animals

The Indiana Speech Training Aid (ISTRA). I: Comparisons between human and computer-based evaluation of speech quality.

Experimental comparisons are reported between computer-based and human judgments of speech quality for the same sets of utterances. Speech stimuli were recorded from two normal talkers, who intentionally varied the quality of their speech, and from a hearing-impaired child who was receiving speech therapy on the Indiana Speech Training Aid (ISTRA). The tape recordings were submitted for evaluation to a naive jury, an expert jury, and the ISTRA System, a microcomputer equipped with a speaker-dependent speech recognition board that generated scores representing how well utterance matched a stored template. Correlational analyses of these data indicated that humans were slightly better at judging speech quality than was the computer, but that the computer was much more reliable. These results demonstrate that computer-based speech evaluation may be a reasonable substitute for human judgments for certain types of speech drill.

Computer Systems

Nucleotide sequence of kidney androgen-regulated protein mRNA and its cell-specific expression in Tfm/Y mice.

Kidney androgen-regulated protein (KAP) mRNA is an abundant renal mRNA that was originally identified by comparisons of the products of in vitro translation of poly(A) RNA from animals before and after androgen stimulation. KAP mRNA is 607 nucleotides long, excluding its poly(A) segment, and encodes a protein of 13,265 mol wt. A hydrophobic N-terminal domain forms a putative signal peptide of 18 amino acids, the cleavage of which results in a 103-amino acid mature protein with a molecular size of 11,297. The protein is highly negatively charged and contains regions of clustered Pro, Glu/Asp, Ser, and Thr residues that are associated with proteins with short half-lives. KAP mRNA is unusual in that it is expressed in two distinct regions of the kidney under different hormonal treatments. It is expressed throughout the cortex in the epithelial lining of the proximal tubules in response to androgen stimulation. After castration, only tubules in the outer stripe of the medulla express KAP mRNA. The androgen receptor-deficient Tfm/Y mutant strain exhibits KAP mRNA induction only in this juxtamedullary region after testosterone treatment. Expression of KAP mRNA in these cells is responsible for the relatively high basal levels of KAP mRNA in female and castrated male animals, and induction in these cells occurs by an androgen receptor (AR)-independent mechanism.

Animals

Auditory temporal acuity in relation to category boundaries; speech and nonspeech stimuli.

Experiments were conducted to determine the underlying resolving power of the auditory system for temporal changes at the onset of speech and nonspeech stimuli. Stimulus sets included a bilabial VOT continuum and an analogous nonspeech continuum similar to the "noise-buzz" stimuli used by Miller et al. [J. Acoust. Soc. Am. 60, 410-417 (1976)]. The main difference between these and earlier experiments was that efforts were made to minimize both the trial-to-trial stimulus uncertainty and the cognitive load inherent in some of the testing procedures. Under conditions of minimal psychophysical uncertainty, not only does discrimination performance improve overall, but the local maximum, usually interpreted as evidence of categorical perception, is eliminated. Instead, discrimination performance for voice onset time (VOT) or noise lead time (NLT) is very accurate for short onset times and generally decreases with increasing onset time. This result suggests that "categorization" of familiar sounds is not the result of a psychoacoustic threshold (as Miller et al. have suggested) but rather of processing at a more central level of the auditory system.

Acoustic Stimulation

Modeling sensorineural hearing loss. I. Model and retrospective evaluation.

The present article describes an approach to the evaluation of psychoacoustic data from the hearing impaired. The results obtained from the hearing impaired in several studies of frequency resolution, temporal resolution, and speech recognition are compared to the results expected for noise-masked normal listeners. It is presumed in this approach that the hypothetical noise-masked normal listeners have masked thresholds that agree perfectly with the quiet thresholds of the hearing-impaired subjects. Using this approach, most of the results obtained from impaired ears on spectral-resolution and speech-recognition tasks could be accurately predicted, an exception being results from spectral-resolution paradigms using fixed-level signals. Some of the data from hearing-impaired listeners on temporal-resolution tasks, on the other hand, could not be adequately described with this approach. The latter data, however, were much more limited. Additional data are needed to better evaluate the adequacy of this approach in describing the performance of the hearing impaired on temporal-resolution tasks.

Adult

Some remarks on Pastore (1988).

Pastore [J. Acoust. Soc. Am. 84, 2262-2266 (1988)] has written a lengthy response to Kewley-Port, Watson, and Foyle [J. Acoust. Soc. Am. 83, 1133-1145 (1988)]. In this reply to Pastore's letter, several of his arguments are addressed, and new data are reported which support the conclusion of the original article. That conclusion is, basically, that the temporal acuity of the auditory system does not appear to be the origin of categorical perception of speech or nonspeech sounds differing in temporal onsets.

Attention

Unique patterns of androgen regulation of the expression of two genes in murine kidney.

The kidneys of androgen stimulated mice exhibit a hypertrophic response but no hyperplasia or concomitant DNA replication. Androgens increase the expression of several genes in mouse kidney. The response of the beta-glucuronidase gene to testosterone in this tissue is characterized by a 1-2 day lag and relatively slow induction kinetics. The gene coding for kidney androgen-regulated protein (KAP) exhibits quite a different response to the hormone when compared on the basis of initial response to a given dose, dose required to produce maximal response, and apparent sensitivity to low levels of androgen-receptor complexes in renal nuclei. The analysis of the accumulation of the mRNAs produced by these two genes suggests that gene-specific differential sensitivity to androgen receptor complexes governs the development of the cellular male phenotype in this tissue.

Androgens

Individual differences in auditory capabilities. I.

Twenty-eight audiometrically normal adult listeners were given a variety of auditory tests, ranging from quiet and masked thresholds through the discrimination of simple and moderately complex temporal patterns. Test-retest reliability was good. Individual differences persisted on a variety of psychoacoustic tasks following a period of training using adaptive threshold-tracking methods, and with trial-by-trial feedback. Large individual differences in performance on temporal-sequence-discrimination tasks suggest that this form of temporal processing may be of clinical significance. In addition, high correlations were obtained within given classes of tests (as, between all tests of frequency discrimination) and between certain classes of tests (as, between tests of frequency discrimination and those of sequence discrimination). Patterns of individual differences were found which support the conclusion that individual differences in auditory performance are, in part, a function of patterns of independent abilities.

Adolescent