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Biomedical subjects

C S Watson

Publications and source records attributed to C S Watson.

At least 73 records · Page 4Linked to original sources

Temporal discrimination for single components of nonspeech auditory patterns.

This paper extends previous research on listeners' abilities to discriminate the details of brief tonal components occurring within sequential auditory patterns (Watson et al., 1975, 1976). Specifically, the ability to discriminate increments in the duration delta t of tonal components was examined. Stimuli consisted of sequences of ten sinusoidal tones: a 40-ms test tone to which delta t was added, plus nine context tones with individual durations fixed at 40 ms or varying between 20 and 140 ms. The level of stimulus uncertainty was varied from high (any of 20 test tones occurring in any of nine factorial contexts), through medium (any of 20 test tones occurring in ten contexts), to minimal levels (one test tone occurring in a single context). The ability to discriminate delta t depended strongly on the level of stimulus uncertainty, and on the listener's experience with the tonal context. Asymptotic thresholds under minimal uncertainty approached 4-6 ms, or 15% of the duration of the test tones; under high uncertainty, they approached 40 ms, or 10% of the total duration of the tonal sequence. Initial thresholds exhibited by inexperienced listeners are two-to-four times greater than the asymptotic thresholds achieved after considerable training (20,000-30,000 trials). Isochronous sequences, with context tones of uniform, 40-ms duration, yield lower thresholds than those with components of varying duration. The frequency and temporal position of the test tones had only minor effects on temporal discrimination. It is proposed that a major determinant of the ability to discriminate the duration of components of sequential patterns is the listener's knowledge about "what to listen for and where." Reduced stimulus uncertainty and extensive practice increase the precision of this knowledge, and result in high-resolution discrimination performance. Increased uncertainty, limited practice, or both, would allow only discrimination of gross changes in the temporal or spectral structure of the sequential patterns.

Acoustic Stimulation↗

Genetic regulation of androgen-induced accumulation of mouse renal beta-glucuronidase messenger ribonucleic acid.

Mouse kidney beta-glucuronidase is induced by androgens in a receptor-dependent fashion. Genetic regulatory mutations have been described which govern this response. In mice carrying the Gus-ra allele (A/J), the induction of enzyme activity is 3-5 times greater than in animals with the Gus-rb allele (C57BL/6J). To study this hormonal and genetic control at the molecular level, we measured changes in beta-glucuronidase mRNA concentrations in these two mouse strains using cloned cDNA. The specificity of the regulation was assessed by following changes in the concentration of kidney androgen-regulated protein (KAP) mRNA, which is also under androgen control in mouse kidney. Female mice were treated with Silastic implants that released 120 micrograms testosterone/day over a 20-day time course. Induction of specific mRNA was analyzed by either Northern blot hybridization or a more quantitative assay in which renal poly(A) RNA was covalently bound to aminophenylthioether paper discs. The induction of beta-glucuronidase mRNA was about 10-fold higher in the strain carrying the Gus-ra regulatory allele, indicating that the Gus-r locus controls the beta-glucuronidase structural gene (Gus-s) at the level of mRNA accumulation. Regulation by Gus-r was specific for beta-glucuronidase mRNA as kidney androgen-regulated protein mRNA accumulation did not differ between these two strains of mice after androgen treatment.

Animals↗

Central factors in the discrimination and identification of complex sounds.

The paper by Jesteadt and Norton [J. Acoust. Soc. Am. 78, 365-374 (1985)] described certain similarities between psychophysical and physiological measures of frequency selectivity. Although the hearing of naturally occurring sounds is dependent upon these peripherally based relationships, recent research has shown that other, more central, processes are also strongly involved in the perception of complex acoustic events. The present paper describes research on the discrimination of complex sounds other than those of speech or music. In contrast to the more peripherally determined limits on the listener's sensitivity for single tones and other simple stimuli, the processing of complex sounds requires the interaction of peripheral and central mechanisms. These issues are discussed in relation to recent studies of the responses of the cochlea to speech stimuli. It is suggested that the peripheral processor may be relatively transparent to the essential spectral-temporal properties of speech, whereas more central processing severely limits the rates and amount of information that can be extracted from complex sounds.

Attention↗

Learning to detect auditory pattern components.

Listeners' abilities to learn to hear all the details of an initially unfamiliar sequence of ten 45-ms tones were studied by tracking detection thresholds for each tonal component over a prolonged period of training. After repeated listening to this sequence, the presence or absence of individual tones could be recognized, even though they were attenuated by 40-50 dB relative to the remainder of the pattern. Threshold-tracking histories suggest that listeners tend to employ two different learning strategies, one of which is considerably more efficient. Special training by reducing stimulus uncertainty and extending the duration of the target component was effective in increasing the rate of threshold improvement. Strategies acquired with the first pattern studied generalized to new sequences of tones. The possible implications of these results for the perceptual learning of speech or other auditory codes are discussed.

Auditory Perception↗

Hormonal regulation and expression of vitellogenin multigene family.

Yolk proteins are the most abundant egg proteins in oviparous animals. They are deposited during oocyte maturation for use after fertilization and are synthesized in the liver or fat body as a common precursor termed vitellogenin. Hybridization with cloned DNA complementary to vitellogenin messenger RNA has revealed a surprisingly high degree of evolutionary conservation of sequence of vitellogenin genes among insects, amphibians and birds. The synthesis of vitellogenin in vertebrates is directly under the control of oestrogen at the level of gene transcription. In the frog, Xenopus, vitellogenin genes occur as a multigene family, four of which are actively expressed and are grouped as A and B genes. This multiplicity offers a useful system for investigating the possible selective hormonal regulation of expression of individual members of multigene families. When X. laevis vitellogenin genes were activated by oestrogen in the liver of whole animals or in cultures of parenchymal cells, the two groups of expressed genes were not induced in an identical manner in cells from male and female animals. The activation of A and B groups of genes was non-coordinate in male hepatocytes and coordinate in female cells. Prior exposure of male hepatocytes to oestradiol in vivo or in culture caused the pattern of expression to shift to that in female cells. Since the X. laevis oocyte itself does not synthesize vitellogenin in response to oestrogen, an attempt was made to activate its dormant vitellogenin genes by transferring oestrogen-binding proteins from the liver. Preliminary results show that the microinjection into the oocyte of a preparation containing liver receptor-hormone complex led to the synthesis of vitellogenin by the oocyte. Extension of these experiments will not only enable a more precise analysis of the activation of the vitellogenin multigene family to be made but will also provide direct functional evidence for the role played by steroid hormone receptors in regulating gene expression.

Animals↗

Heterogeneity of estrogen binding sites in mammary tumors.

This paper provides a brief summary of our recent work on the heterogeneity of estradiol binding sites in mammary tumors of the mouse and human. Mammary tumors from both species contain the classical estrogen receptor and a second site(s) which we call type II. These type II sites are found in the cytoplasmic and nuclear compartments of both tumors, and can interfere with the measurement of estrogen receptors. The function of type II sites is not known; however, an assessment of these sites in conjunction with an accurate measurement of the estrogen receptor may provide a clearer picture of the true hormone dependence of breast tumors.

Animals↗

Factors in the discrimination of tonal patterns. III. Frequency discrimination with components of well-learned patterns.

Estimates of the effectiveness of selective auditory attention were obtained by adjusting the level of a target tone, which was presented as one 40-msec component in a ten-tone sequential pattern. When the levels of target and nontarget tones were the same, frequency-discrimination thresholds (delta f/f) following prolonged training varied from 0.01-0.02 for minimal-uncertainty testing conditions to 0.1-0.2 under high trial-to-trial stimulus uncertainty. The functions relating frequency discrimination to target-tone level are widely separated for the two conditions; comparing them, we conclude that the effects of selective auditory attention can be equated to a 50-dB variation in signal level. Patterns that had been well-learned during the minimal-stimulus (remembered standard) procedure. The results of these latter experiments are consistent with a "top-down" processing interpretation in which well-learned patterns are first identified to locate the portions requiring further resolution.

Acoustics↗

Estrogenic effects of nafoxidine on ovarian-dependent and independent mammary tumor lines in the mouse.

Nafoxidine (1-[2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]ethyl]-pyrrolidine hydrochloride); a triphenylethylene derivative] and estradiol cause translocation of the estrogen receptor to the nucleus, elevate the levels of cytoplasmic progesterone receptors, and do not effect levels of nuclear progesterone receptor in hormone-dependent and -independent MXT-3590 mammary tumor lines. Cytoplasmic and nuclear receptor levels were measured by the dextran-coated charcoal assay and a modified protamine sulfate nuclear exchange assay, respectively. Both estradiol (2.5 microgram) and nafoxidine (40 microgram) stimulate partial growth in the independent line. These data are the first evidence of the estrogenic effects of a so-called antiestrogen (nafoxidine) on the quantity of progesterone receptors in a hormone-independent experimental mammary tumor. The growth effects of antiestrogens demonstrated here in ovariectomized mice should alert clinicians to be watchful of these effects when using such drugs in the treatment of human breast cancer. These results also confirm recent suggestions that growth and progesterone receptor synthesis are controlled separately by estrogenic compounds. (Endocrinology 108: 668, 1981)

Animals↗

Characterization of progesterone receptors, estrogen receptors, and estrogen (type II)-binding sites in the hormone-independent variant of the MXT-3590 mouse mammary tumor.

A hormone-independent mouse mammary tumor line was derived by transplantation of a hormone-dependent line (MXT-3590) into ovariectomized-adrenalectomized animals and subsequent transplantation of surviving tumors. Although the tumor line is hormone independent, it contains a full complement of estrogen and progesterone receptors which are similar to those found in hormone-dependent tumors. This similarity includes the criteria of nuclear translocation of the estrogen receptor and subsequent stimulation of progesterone receptor synthesis. In addition to the estrogen receptor, a secondary estrogen-binding site (type II) is also present; this binding site was previously described in the hormone-dependent companion tumor line. Thus, while this variant tumor line contains the biosynthetic pathways that control estrogen and progesterone receptor synthesis, its growth does not depend on these steroids. Therefore, it may provide a good model for the study of this class of hormone-independent tumors.

Animals↗

Age differences in resolving power and decision strategies in a weight discrimination task.

Current theories of aging suggest that at least part of the decline in performance on psychophysical tasks, commonly observed in older subjects, may be the result of their becoming more cautious about sensory decisions. This conclusion has been supported by experiments in which the criterion index, beta, from signal detection theory is shown to be higher (indicating a strict criterion) for older subjects. A weight-discrimination experiments is reported which failed to replicate the earlier results; older subjects' criteria were the same or more lax than those of younger controls on that task. The possibility that extreme caution on the part of older people may be specific to certain classes of task is discussed.

Adult↗