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Biomedical subjects

J F Feldman

Publications and source records attributed to J F Feldman.

At least 37 records · Page 2Linked to original sources

Perinatal factors in the development of gender-related play behavior: sex hormones versus pregnancy complications.

This report addresses the question of biological factors that may contribute to the development of gender-typical and gender-atypical play behavior. In lower mammals, sex differences in juvenile behavior are to a considerable extent determined by organizational effects of prenatal or perinatal androgenic hormones. Birke and Sadler (1983) showed that not only perinatal androgens but also progestogens such as medroxyprogesterone acetate (MPA) affect (in this case: demasculinize) the play behavior of both sexes in the rat. Here, we report on a study of sex-dimorphic play behavior of children born from pregnancies that were treated with various sex hormones. The Child Game Participation Questionnaire (Bates and Bentler 1973) was administered to 13 boys and 15 girls prenatally exposed to MPA, 22 boys and 15 girls exposed to a variety of synthetic progestogens or estrogens singly or in combination, and to pair-matched control subjects, all between 8 and 14 years old. Pregnancy complications were assessed by two scores, 1) "Pregnancy Complications Summary Score (excluding bleeding)," 2) "Vaginal Bleeding During Pregnancy." The results of paired t-tests showed a number of hypomasculinization effects for the hormone-exposed groups. Controlling for the effects of pregnancy complications and age at study by exploratory hierarchical multiple regression analysis indicated that these variables did not account for the hormone-exposure effects. Our results provide further evidence that prenatal hormones influence the sex-dimorphic play behavior of human children in the same direction as that of other mammals.

Child↗

Individual differences in infants' information processing: reliability, stability, and prediction.

A group of 46 full-term and 54 high-risk preterm (less than 1,500 grams birthweight) infants were tested at 6, 7, and/or 8 months of age (corrected age for preterms) on a battery of problems assessing visual recognition memory and tactual-visual cross-modal transfer. At all 3 ages, scores obtained on aggregates of 6-11 problems in the battery significantly predicted 3-year Stanford-Binet IQ: correlations ranged from r = .37 to r = .63, and clustered between r = .50 and r = .60. When aggregates from 2 or 3 ages were used as predictors, multiple correlations were as high as R = .60 and R = .70. Cutoffs for predicting children at risk for mental retardation (IQ less than 70) or cognitive delay (IQ less than 85) showed reasonable sensitivity and specificity, although low scores were poor at detecting IQs less than 70. The internal consistency of composites, indexed by alpha coefficients, was unexpectedly low, primarily because the problems shared little variance. However, stability coefficients between assessments as much as 1 and 2 months apart were moderate in magnitude, ranging from r = .30 to r = .50. Considering the high degree of predictive validity, the stability figures appear to be better estimates of reliability for these measures than are indices of internal consistency. The relations reported here were similar for both full-terms and preterms.

Age Factors↗

Information processing in seven-month-old infants as a function of risk status.

7-month-old full-terms and high-risk preterms (less than 1,500 grams at birth) were compared on problems of visual recognition memory and tactual-to-visual cross-modal transfer. On the visual problems, preterm infants showed significantly less differential attentiveness to novelty than full-terms. They also required longer exposure times during visual familiarization, primarily because of longer pauses between fixations. Preterms and full-terms exhibited different patterns of looking, as indicated by the duration of fixation and the frequency in shifts of gaze. On the cross-modal problems, preterms and full-terms both exhibited similar and significant preferences for familiar rather than novel stimuli, a direction of preference which suggests that these problems were relatively difficult for both groups. For the preterms, novelty and exposure-time scores were found to be related to several medical risk factors. Novelty preferences were compromised in preterms who had suffered RDS postnatally, particularly those who had required prolonged mechanical ventilation. In general, high-risk preterms exhibited deficits in visual recognition memory and in the ability to recruit, sustain, and shift attention.

Attention↗

A recessive circadian clock mutation at the frq locus of Neurospora crassa.

A circadian clock mutant of Neurospora crassa, the most distinctive characteristic of which is the complete loss of temperature compensation of its period length, maps to the frq locus where seven other clock mutants have previously been mapped. This mutant, designated frq-9, is recessive to the wild-type allele and to each of the other frq mutants; thus, it differs from the other mutants, which show incomplete dominance to wild type and to each other. Complementation analysis suggests either that the frq locus is a single gene or that frq-9 is a deletion that overlaps adjacent genes. Preliminary efforts at fine structure mapping have indicated that recombination between certain pairs of frq mutations is less than 0.005%, a distance consistent with the locus being a single gene. The recessive nature of frq-9, coupled with complete loss of temperature compensation, suggests that this mutant may represent the null phenotype of the locus and that the frq gene is involved in the temperature compensation mechanism of the clock.--Genetic mapping studies have placed the frq locus on linkage group VIIR, midway between oli (oligomycin resistance) and for (formate auxotrophy), about 2 map units from each, and clearly indicate that frq and oli are separate genes.

Alleles↗

Loss of temperature compensation of circadian period length in the frq-9 mutant of Neurospora crassa.

A new circadian clock mutant of Neurospora crassa has been isolated, whose most distinctive characteristic is the complete loss of temperature compensation of its period length. The Q10 of the period length was found to be equal to about 2 in the temperature range from 18 degrees to 30 degrees C. The period length was also found to be dependent on the composition of the medium, including the nature and concentration of both the carbon source and the nitrogen source. Although the rate of the clock and the growth rate were directly related when affected by varying the temperature, they were inversely related when altered by changing the composition of the medium. Therefore, the mutation has not simply coupled clock rate to growth rate in this strain. The mutation maps to the frq locus, where seven other clock mutations previously studied also map. Therefore, this mutant has been called frq-9. Since several of the other frq mutants show partial loss in temperature compensation, it is suggested that the frq gene or its product is closely related to the temperature compensation mechanism of the circadian clock of Neurospora.

Circadian Rhythm↗

Sexual orientation after prenatal exposure to exogenous estrogen.

Thirty women aged 17 to 30 years with documented prenatal exposure to the nonsteroidal synthetic estrogen diethylstilbestrol (DES) were compared to thirty women of similar demographic characteristics from the same medical clinic who had a history of abnormal Pap smear findings. A subsample of the DES women were also compared to their DES-unexposed sisters. Sexual orientation in its multiple components was assessed by systematic semistructured interviews. In comparison to both control groups, the DES women showed increased bisexuality and homosexuality. However, about 75% of the DES women were exclusively or nearly exclusively heterosexual. Nonhormonal and hormonal interpretations of these findings are discussed.

Adolescent↗

Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens.

Thirteen boys and 15 girls with a history of prenatal exposure to medroxyprogesterone acetate only and 22 boys and 15 girls with exposure to a variety of progestogens and estrogens singly or in combination were studied at age 8-14 years in comparison to closely pair-matched, unexposed controls. This report concerns the findings on sex-dimorphic behavior as assessed by separate interviews with the child and his/her mother. Hormone-exposed boys and controls differed little, while in girls prenatal sex hormone treatment seemed to be associated with some degree of increased stereotypic femininity.

Adolescent↗

Effects of prenatal hormone exposure versus pregnancy complications on sex-dimorphic behavior.

The existing literature on human subjects indicates demasculinization as an effect of prenatal exposure to various exogenous sex hormones, except for 19-nor progestogens. For the samples described in Ehrhardt et al. (1984), the current study examines whether the demasculinization can be explained by pregnancy complications. Corresponding covariates were constructed. In order to permit parametric analysis, the primary rating scales used previously were factor-analyzed and aggregated to form cluster scales where feasible. The factor analysis also demonstrated the existence of a general factor of sex-dimorphic behavior. Subsequent case-control comparisons by t test and by analysis of covariance for the general-factor and cluster scales showed that pregnancy complications do not explain the modest demasculinization effects of prenatal hormone exposure observed in females. A few paradoxical results emerged in males, likely to be due to chance.

Estrogens↗

Psychosexual milestones in women prenatally exposed to diethylstilbestrol.

Thirty women aged 17 to 30 years with a record-confirmed history of prenatal exposure to diethylstilbestrol (DES) were compared to 30 women of similar age and demographic background with a history of abnormal Pap smear findings. Heterosocial and heterosexual histories were assessed by systematic semistructured interviews. The groups differed neither in the age at menarche nor in the age at attainment of various psychosexual milestones.

Adolescent↗

Cycloheximide and heat shock induce new polypeptide synthesis in Neurospora crassa.

Treatment of Neurospora crassa with 0.1 microgram of cycloheximide per ml, a concentration which inhibited protein synthesis by about 70%, resulted in the greatly enhanced synthesis of at least three polypeptide bands with estimated molecular weights of 88,000, 30,000, and 28,000. A temperature shift from 25 to 37 degrees C resulted in the appearance of a single new polypeptide band of 70,000 daltons, the same size as the major heat shock-induced proteins observed in species of Drosophila and Dictyostelium. Synthesis of the cycloheximide-stimulated polypeptide bands was on cytoplasmic ribosomes rather than on mitochondrial ribosomes, as incorporation of isotope into the polypeptide bands was inhibited by 1.0 microgram of cycloheximide per ml but not by 1 mg of chloramphenicol per ml. In a mutant with cycloheximide-resistant ribosomes, 0.1 microgram of cycloheximide per ml failed to alter the pattern of protein synthesis from that of the controls. It is suggested that the new synthesis of the polypeptide bands reflects specific mechanisms of adaptation to different kinds of environmental stress, including inhibition of protein synthesis and temperature increases.

Chloramphenicol↗

Assay and Characteristics of Circadian Rhythmicity in Liquid Cultures of Neurospora crassa.

Previous work on circadian rhythms of Neurospora crassa has been done almost exclusively with cultures expressing rhythmic conidiation and growing on solid agar medium. Such conditions severely restrict the kinds of biochemical experiments that can be carried out. We have now developed systems which allow indirect assay of circadian rhythmicity in liquid culture. Neurospora was grown in glucose and acetate liquid media under conditions which result in a range of growth rates and morphologies. Liquid media were inoculated with conidia and the cultures were grown in constant light for 33 or 48 hours, by which time floating mycelial pads had formed. Experimental pieces of mycelium then were cut and placed in fresh new liquid medium. As controls, other pieces of mycelium were cut and put directly on solid agar medium in race tubes. All cultures were transferred to constant darkness at this time. This light-to-dark transition set the phase of the circadian clock of both the liquid and solid cultures. At various times after the light-to-dark transition, the mycelial pieces in the liquid were transferred in the dark to solid medium in race tubes, where they grew normally and conidiated rhythmically. Comparison of the phase of the rhythm in these race tubes to the controls demonstrated that, under appropriate conditions, the circadian clock of the liquid cultures functions normally for at least two cycles in constant conditions. Using these culture systems, a significantly greater variety of biochemical studies of circadian rhythmicity in Neurospora is now possible.

Journal Article↗

Temperature Compensation of Circadian Period Length in Clock Mutants of Neurospora crassa.

Temperature compensation of circadian period length in 12 clock mutants of Neurospora crassa has been examined at temperatures between 16 and 34 degrees C. In the wild-type strain, below 30 degrees C (the "breakpoint" temperature), the clock is well-compensated (Q(10) = 1), while above 30 degrees C, the clock is less well-compensated (Q(10) = 1.3). For mutants at the frq locus, mutations that shorten the circadian period length (frq-1, frq-2, frq-4, and frq-6) do not alter this temperature compensation response. In long period frq mutants (frq-3, frq-7, frq-8), however, the breakpoint temperature is lowered, and the longer the period length of the mutants the lower the breakpoint temperature. Long period mutants at other loci exhibit other types of alterations in temperature compensation-e.g. chr is well-compensated even above 30 degrees C, while prd-3 has a Q(10) significantly less than 1 below 30 degrees C. Prd-4, a short period mutant, has several breakpoint temperatures. Among four double mutants examined, the only unusual interaction between the individual mutations occurred with chr prd, which had an unusually low Q(10) value of 0.86 below 27 degrees C. There was no correlation between circadian period length and growth rate. These strains should be useful tools to test models for the temperature compensation mechanism.

Journal Article↗

Cycloheximide-induced phase shifting of circadian clock of Neurospora.

Cycloheximide (CHX), an inhibitor of cytosolic (80S) protein synthesis in eucaryotes, causes phase shifts of the circadian clock of Neurospora crassa when administered as 4-h pulses to cultures in liquid medium. Differential effects of the pulses at different phases of the circadian cycle were observed and plotted as a phase-response curve (PRC). Nearly all phase shifts observed were phase advances, with maximum sensitivity in the middle of the subjective day. Inhibition of protein synthesis by CHX was the same at both phases of the cycle. The PRC was the same at 20 and 25 degrees C. Dose-response curves for the effects of CHX on phase shifting and inhibition of protein synthesis were determined and showed a striking parallel in the responses of these two phenomena to CHX. These results support the view that synthesis of one or more proteins at specific phases of the circadian cycle is necessary for the normal operation of the circadian clock of Neurospora.

Biological Transport↗

The frq locus in Neurospora crassa: a key element in circadian clock organization.

Four new circadian clock mutants of Neurospora crassa have been isolated that alter the period length of the circadian conidiation rhythm. Three of these are at the frq locus on linkage group VIIR, where four other clock mutants are located. In contrast to wild type, which has a period length of 21.6 hr, frq-6 has a period length of 19 hr, while frq-7 and frq-8 have period lengths of 29 hr and represent the largest effects of any single gene mutants on circadian periodicity. Thus, seven mutants have now been isolated that map to the frq locus, with period lengths ranging from 16.5 to 29 hr, and each mutant alters clock periodicity by an integral multiple of 2.5 hr. In addition, all frq mutants show incomplete dominance in heterokaryons. The large percentage of clock mutants that map to this locus, coupled with their unique properties, suggests that the frq locus plays an important role in clock organization.--The fourth mutant, designated chrono (chr), has a period length of 23.5 hr, shows incomplete dominance and is unlinked to either of the previously identified clock loci, frq or prd (formerly called frq-5). Double mutants between various combinations of clock mutants show additive effects and indicate no significant gene interaction among mutants at these three loci.

Biological Clocks↗

Spatial Distribution of Circadian Clock Phase in Aging Cultures of Neurospora crassa.

Neurospora crassa has been utilized extensively in the study of circadian clocks. Previously, the clock in this organism has been monitored by observing the morphological and biochemical changes occurring at the growing front of cultures grown on solid medium. A method has been developed for assaying the clock in regions of the culture behind the growing front, where no apparent morphological changes occur during the circadian cycle. Using this assay with Petri dish cultures that were 2 to 7 days old, the presence of a functional circadian clock not only at the growing front but in all other regions of the culture as well was demonstrated. Furthermore, the entire culture is not in the same phase, but shows a gradient of phases which is a function of the length of time the clock in a given part of the culture has been free-running. This gradient may be the result of a somewhat longer period of the oscillator behind the growing front compared to that at the growing front. The phase differences within a single culture of interconnected mycelium demonstrate the absence of total internal synchronization between adjacent regions of the hyphae under these conditions.

Journal Article↗

Genetic and physiological characteristics of a slow-growing circadian clock mutant of Neurospora crassa.

A circadian clock mutant of Neurospora crassa with a period length of about 25.8 hours (4 hr longer than wild type) has been isolated after mutagenesis of the band strain. This mutant, called frq-5, segregates as a single nuclear gene, maps near the centromere on linkage group III, and is unlinked to four previously described clock mutants clustered on linkage group VII R (Feldman and Hoyle 1973, 1976). frq-5 differs from the other clock mutants in at least two other respects: (1) it is recessive in heterokaryons, and (2) it grows at about 60% the rate of the parent band strain on both minimal and complete media. Double mutants between frq-5 and each of the other clock mutants show additivity of period length--two long period mutants produce a double mutant whose period length is longer than either of the two single mutants, while a long and a short period double mutant has an intermediate period length. Although slow growth and long periodicity of frq-5 have segregated together among more than 300 progeny, slow growth per se is not responsible for the long period, since all the double mutants have the slow growth characteristic of frq-5, but have period lengths both shorter and longer than wild type.

Circadian Rhythm↗