Biomedical subjects

J F Feldman

Publications and source records attributed to J F Feldman.

At least 19 recordsLinked to original sources

PubMed2001

Genetic interactions between clock mutations in Neurospora crassa: can they help us to understand complexity?

Recent work on circadian clocks in Neurospora has primarily focused on the frequency (frq) and white-collar (wc) loci. However, a number of other genes are known that affect either the period or temperature compensation of the rhythm. These include the period (no relationship to the period gene of Drosophila) genes and a number of genes that affect cellular metabolism. How these other loci fit into the circadian system is not known, and metabolic effects on the clock are typically not considered in single-oscillator models. Recent evidence has pointed to multiple oscillators in Neurospora, at least one of which is predicted to incorporate metabolic processes. Here, the Neurospora clock-affecting mutations will be reviewed and their genetic interactions discussed in the context of a more complex clock model involving two coupled oscillators: a FRQ/WC-based oscillator and a 'frq-less' oscillator that may involve metabolic components.

Circadian Rhythm↗

PubMed2001

Behavioural problems in children who weigh 1000 g or less at birth in four countries.

BACKGROUND: The increased survival chances of extremely low-birthweight (ELBW) infants (weighing <1000 g at birth) has led to concern about their behavioural outcome in childhood. In reports from several countries with different assessments at various ages, investigators have noted a higher frequency of behavioural problems in such infants, but cross-cultural comparisons are lacking. Our aim was to compare behavioural problems in ELBW children of similar ages from four countries. METHODS: We prospectively studied 408 ELBW children aged 8-10 years, whose parents completed the child behaviour checklist. The children came from the Netherlands, Germany, Canada, and USA. The checklist provides a total problem score consisting of eight narrow-band scales. Of these, two (aggressive and delinquent behaviour) give a broad-band externalising score, three (anxious, somatic, and withdrawn behaviour) give a broad-band internalising score, and three (social, thought, and attention problems) indicate difficulties fitting neither broad-band dimension. For each cohort we analysed scores in ELBW children and those in normal- birthweight controls (two cohorts) or national normative controls (two cohorts). Across countries, we assessed deviations of the ELBW children from normative or control groups. FINDINGS: ELBW children had higher total problem scores than normative or control children, but this increase was only significant in European countries. Narrow-band scores were raised only for the social, thought, and attention difficulty scales, which were 0.5-1.2 SD higher in ELBW children than in others. Except for the increase in internalising scores recorded for one cohort, ELBW children did not differ from normative or control children on internalising or externalising scales. INTERPRETATION: Despite cultural differences, types of behavioural problems seen in ELBW children were very similar in the four countries. This finding suggests that biological mechanisms contribute to behavioural problems of ELBW children.

Canada↗

PubMed2001

Visual short-term memory in the first year of life: capacity and recency effects.

A span task was developed to assess the amount of information infants could hold in short-term memory. In this task, infants were presented with up to 4 items in succession and then tested for recognition by successively pairing each item with a novel one. A large sample of full-terms and low-birth-weight preterms (< 1,750 g) was tested longitudinally, at 5, 7, and 12 months of age. Results were similar for both groups: (a) Longer spans were more difficult, especially at the 2 younger ages; (b) memory capacity increased over the 1st year of life--whereas less than 25% of the sample could hold as many as 3-4 items in mind at once at the younger ages, nearly half could do so by 12 months of age; (c) there was a marked recency effect (greater memory for the final item) for spans of 3 and 4 at all ages; and (d) there were modest cross-age correlations, indicating that individual differences in memory capacity showed some stability from age to age.

Child, Preschool↗

PubMed2001

Epistatic and synergistic interactions between circadian clock mutations in Neurospora crassa.

We identified a series of epistatic and synergistic interactions among the circadian clock mutations of Neurospora crassa that indicate possible physical interactions among the various clock components encoded by these genes. The period-6 (prd-6) mutation, a short-period temperature-sensitive clock mutation, is epistatic to both the prd-2 and prd-3 mutations. The prd-2 and prd-3 long-period mutations show a synergistic interaction in that the period length of the double mutant strain is considerably longer than predicted. In addition, the prd-2 prd-3 double mutant strain also exhibits overcompensation to changes in ambient temperature, suggesting a role in the temperature compensation machinery of the clock. The prd-2, prd-3, and prd-6 mutations also show significant interactions with the frq(7) long-period mutation. These results suggest that the gene products of prd-2, prd-3, and prd-6 play an important role in both the timing and temperature compensation mechanisms of the circadian clock and may interact with the FRQ protein.

Alleles↗

PubMed2001

Attention and recognition memory in the 1st year of life: a longitudinal study of preterm and full-term infants.

Several aspects of visual attention and their implications for recognition memory were examined in a longitudinal sample of full-term and preterm (birth weight < 1,750 g) infants seen at 5, 7, and 12 months of age. At all 3 ages, full-terms had shorter look durations, faster shift rates, less off-task behavior, and higher novelty scores than preterms. Both groups followed similar developmental trajectories, with older infants having shorter looks and more shifts. Infants were consistent in attentional style across problems of the same type, across problems that used different types of stimuli (faces and patterns), and across the familiarization and test phases of this paired-comparison design; there was also modest cross-age stability. Shorter looks and higher shift rates during familiarization were related to better recognition memory, with shift rate adding to prediction independently of either peak or mean look. These findings underscore the importance of attention to infant information processing.

Attention↗

PubMed1999

Relation of cranial ultrasound abnormalities in low-birthweight infants to motor or cognitive performance at ages 2, 6, and 9 years.

This study sought to determine whether neonatal cranial ultrasound abnormalities are related to motor and cognitive outcomes in low-birthweight (LBW, <2000 g) children without major motor or cognitive disability. The relation of neonatal cranial ultrasound abnormalities to motor performance and general cognitive ability at ages 2, 6, and 9 years was examined in a prospectively followed regional cohort of LBW children, excluding those with major disability, and controlling for other risk factors. Compared with children without ultrasound abnormalities, children with abnormalities indicative of ischemic white-matter injury had poorer motor performance at all three ages and, at age 2, lower general cognitive ability. The latter finding was not seen when motor performance was also controlled for. It was concluded that in LBW children without major motor or cognitive disability, ischemic white-matter injury indicated by neonatal cranial ultrasound abnormalities adversely affected motor performance at ages 2, 6, and 9 years, but not general cognitive ability.

Age Factors↗

PubMed1998

Continuity in tactual-visual cross-modal transfer: infancy to 11 years.

The present study demonstrated that individual differences in cross-modal transfer showed continuity over a 10-year span. Tactual-visual tasks, requiring visual recognition of shapes that had previously been felt but not seen, were given to full-term and preterm children at 2 ages, 1 and 11 years. Cross-modal performance showed a left-hand advantage at 11 years and, for both groups, cross-age correlations were significant when tactual exploration at 11 years was done with the left hand (r = .34-.36). The continuity showed some specificity in that the infant measure did not relate to other types of cross-modal performance at 11 years and was not dependent on aspects of spatial ability involving form perception. This continuity accounted for most of the previously reported relation of infant cross-modal ability to 11-year IQ.

Child↗

PubMed1997

Analysis of frequency (frq) clock gene homologs: evidence for a helix-turn-helix transcription factor.

The frq gene plays a key role in the organization of the Neurospora crassa circadian clock. Our previous analysis of a C-terminal fragment of the putative FRQ protein suggested it is a nuclear transcription factor but did not identify a known DNA-binding domain. If the hypothesis is correct that FRQ is a transcription factor, sequences consistent with this function should be conserved in distantly related species. To investigate, we have cloned frq homologs from other filamentous fungi including Chromocrea spinulosa, and Leptosphaeria australiensis. Alignment of the Leptosphaeria and Chromocrea proteins with the published (complete) sequences for Neurospora crassa and Sordaria fimicola shows that they are respectively about 47%, and 43%, identical to both Neurospora and Sordaria. The alignment identifies several short regions of high conservation punctuated by regions showing near total divergence. Sequences consistent with FRQ being a transcription factor are generally conserved. Most importantly, we show that a highly conserved segment of the protein has strongly predicted helix-turn-helix (HTH) structure as supported by three independent methods. Further, this segment shows the defining sequence characteristics of known HTH DNA-binding domains. Amino acids at positions altered in frq mutant alleles are conserved in all species examined. Transformation of the Neurospora frq9 (conditionally arrhythmic) mutant with the Chromocrea homolog rescued the pigmentation and conidiation defects of the mutant but not the circadian defect; the Leptosphaeria homolog failed to rescue any defect. Together, these data provide the first testable hypotheses concerning several specific aspects of FRQ structure and function.

Amino Acid Sequence↗

PubMed1997

Psychiatric outcomes in low-birth-weight children at age 6 years: relation to neonatal cranial ultrasound abnormalities.

BACKGROUND: This study examined the relation of neonatal cranial ultrasound abnormalities to psychiatric disorder at age 6 years in a regional birth cohort of low-birth-weight children. METHODS: Neonatal cranial ultrasound abnormalities were classified as (1) isolated germinal matrix and/or intraventricular hemorrhage (suggestive of injury to glial precursors) or (2) parenchymal lesions and/or ventricular enlargement (suggestive of white matter injury) with or without germinal matrix-intraventricular hemorrhage. Psychiatric disorders by DSM-III-R at age 6 years were assessed by means of a structured parent interview. Children with severe mental retardation were excluded. Analyses were conducted first in the entire sample and then in children with normal intelligence. RESULTS: Twenty-two percent of the cohort had at least 1 psychiatric disorder, the most common being attention deficit hyperactivity disorder (15.6%). In the entire sample, parenchymal lesions and/or ventricular enlargement increased risk relative to no abnormality, independently of other biological and social predictors, for any disorder (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.8-10.3; P < .001), attention deficit hyperactivity disorder (OR, 3.4; CI, 1.3-8.7; P = .02), and tic disorders (OR, 8.7; CI, 1.3-57.7; P = .02). In children of normal intelligence, parenchymal lesions/ventricular enlargement independently increased risk for any disorder (OR, 4.8; CI, 1.6-12.0; P < .01), attention deficit hyperactivity disorder (OR, 4.5; CI, 1.3-16.0; P = .02), and separation anxiety (OR, 5.3; CI, 1.1-24.8; P = .03). These effects were not ameliorated by female sex or social advantage. Isolated germinal matrix/intraventricular hemorrhage was not related to psychiatric disorder at age 6 years. CONCLUSION: Neonatal cranial ultrasound abnormalities suggestive of white matter injury significantly increased risk for some psychiatric disorders at age 6 years in low-birth-weight children.

Age Factors↗

PubMed1997

Isolation and characterization of a temperature-sensitive circadian clock mutant of Neurospora crassa.

A new circadian clock mutant has been isolated in Neurospora crassa. This new mutation, called period-6 (prd-6), has two features novel to known clock mutations. First, the mutation is temperature sensitive. At restrictive temperatures (above 21 degrees) the mutation shortens circadian period length from a wild-type value of 21.5 hr to 18 hr. At permissive temperatures (below 21 degrees) the mutant has a 20.5-hr period length close to that of the wild-type strain. Second, the prd-6 mutation is epistatic to the previously isolated clock mutation period-2 (prd-2). This epistasis is unusual in that the prd-2 prd-6 double mutant strain has an 18-hr period length at both the restrictive and permissive temperatures. That is, the temperature-sensitive aspect of the phenotype of the prd-6 strain is lost in the prd-2 prd-6 double mutant strain. This suggests that the gene products of the prd-2 and prd-6 loci may interact physically and that the presence of a normal prd-2+ protein is required for low temperature to "rescue" the prd-6 mutant phenotype. These results, combined with our recent finding that prd-2 and some alleles of the frq gene show genetic synergy, suggest that it may be possible to establish a more comprehensive model of the Neurospora circadian clock.

Biological Clocks↗

PubMed1997

Memory and speed: their role in the relation of infant information processing to later IQ.

This study examined the extent to which memory and processing speed accounted for relations we had found earlier between infant information processing and childhood IQ. The measures of speed and memory were obtained when the children were 11 years of age using paper-and-pencil tasks and an extensive battery of computer-administered tasks. The relations of 7 months visual recognition memory and 1 year cross-modal transfer to 11 year IQ were both substantially reduced with statistical control of factors derived from these measures. These results suggest that speed and memory underlie some of the infant-childhood continuities in cognition. Path and structural equation modeling indicated that the significant pathways from 7 month visual recognition memory to 11 year IQ were both direct and indirect, the indirect paths going through memory and speed.

Age Factors↗

PubMed1996

Evolution of the frequency (frq) clock locus in Ascomycete fungi.

The frequency (frq) locus of Neurospora crassa plays a key role in the organization of circadian rhythms. Similar timing systems have been found in nearly all eukaryotes as well as some prokaryotes; thus, frq may be an excellent gene with which to conduct evolutionary studies. To investigate, we used the cloned frq locus from ascomycete fungi representing two classical taxonomic classes and three orders to examine two open questions in ascomycete evolution. Class Pyrenomycetidae is represented by several species of Neurospora, Sordaria fimicola, and Chromocrea spinulosa; class Loculoascomycetidae is represented by the marine fungus Leptosphaeria australiensis. Generation of detailed restriction maps of homologs from the Neurospora species allows analysis of evolutionary relationships among these closely related species. A maximum-parsimony tree based on these restriction data suggests that Neurospora tetrasperma groups more closely with Neurospora sitophila than with Neurospora crassa using the homothallic species Neurospora galapagosensis as an outgroup. A maximum-parsimony tree derived using amino acid sequences from Neurospora crassa, Sordaria fimicola, Chromocrea spinulosa, and Leptosphaeria australiensis surprisingly suggests that Leptosphaeria austral should be classified within Pyrenomycetes rather than in a separate class. This suggestion is based on the observations that Leptosphaeria groups with Chromocrea on an evolutionary tree, is more closely related to Neurospora and Sordaria than is Chromocrea, and shares a conserved intron with Chromocrea. Together, these data show that frq is a useful gene with which to conduct evolutionary studies.

Amino Acid Sequence↗

PubMed1996

Neonatal cranial ultrasound abnormalities in low birth weight infants: relation to cognitive outcomes at six years of age.

OBJECTIVE: To assess the independent relation of neonatal cranial ultrasound (US) abnormalities in low birth weight (LBW) infants to cognitive outcomes at 6 years of age. DESIGN: Prospective cohort study. SAMPLE AND METHODS: Six-year follow-up data were obtained on a regional birth cohort of LBW infants (< 2 kg) systematically screened as neonates with serial US. US abnormalities were dichotomized into isolated germinal matrix/intraventricular hemorrhage (GM/IVH) and parenchymal lesions/ventricular enlargement (PL/VE). Global cognitive outcomes (mental retardation, borderline intelligence, and normal intelligence) and selected specific cognitive abilities were assessed at 6 years of age with standardized instruments. Multivariate techniques were used to assess the effects of US independent of maternal social disadvantage at birth and other perinatal and neonatal risk factors. RESULTS: The sample as a whole had a significantly elevated rate of mental retardation (MR; 5%), almost all moderate to profound in severity. PL/VE was independently related to MR (odds ratio [OR], 65.8; confidence interval [CI], 19.1 to 22.4) and borderline intelligence (OR, 3.7; CI, 1.3 to 10.8); isolated GM/IVH was more modestly related to MR (OR, 4.6; CI, 1.2 to 18.6) but not related to borderline intelligence. Approximately half of the cases of MR were attributable to PL/VE independent of other factors. Of non-US factors, the number of days receiving mechanical ventilation increased the risk for MR. Maternal social disadvantage increased the risk for borderline intelligence but not MR. Among children of normal intelligence, those with PL/VE, but not isolated GM/IVH, performed more poorly than those without US abnormalities on tests of visual perceptual organization but not on tests of language, memory, or quantitative skills. CONCLUSION: Prevention of white matter injury would substantially improve cognitive outcomes for LBW infants.

Aging↗

PubMed1996

Memory and processing speed in preterm children at eleven years: a comparison with full-terms.

This study examined the effects of prematurity on 11-year-olds' performance on 2 specific aspects of cognition--memory and processing speed, using a new computer-administered battery, the Cognitive Abilities Test (CAT: Detterman). Preterms performed more poorly than their full-term controls on all memory tasks; this relative deficit was associated with the presence and severity of neonatal Respiratory Distress Syndrome (RDS). Preterms were also slower on selected aspects of processing speed but not on motor speed. Memory and processing speed, taken together, accounted for much of the 10-point difference in WISC-R IQ between groups.

Birth Weight↗

PubMed1994

Psychiatric morbidity in school-age children with congenital human immunodeficiency virus infection: a pilot study.

This study examined the relationship between human immunodeficiency virus (HIV) infection and psychiatric morbidity within the context of prenatal drug exposure. Twenty-six HIV-infected, 14 seroreverted, and 20 control (non-HIV-exposed) children were studied; the sample consisted of nonreferred children living in foster placement who had been exposed to maternal drug addiction. Each child received a psychiatric diagnostic evaluation which included completion by the caretaker of a structured diagnostic interview and a behavior checklist on the child as well as a child self-report on a pictorial interview. Age, ethnicity, and IQ were controlled in the analyses because of group differences. There were high rates of behavioral and psychiatric morbidity, especially with respect to disruptive behavior disorders, in this sample of school-age children with HIV infection, but similarly high rates were found in the seroreverted and non-HIV-exposed children. There was some suggestion that the HIV-infected children were experiencing higher levels of subjective distress than either the nonexposed or seroreverted children. The possible relevance of drug exposure to the behavioral outcomes observed here is discussed, as well as the importance of using age-appropriate materials to elicit subjective distress in HIV-infected school-age children. Clinical implications and directions for further research are discussed.

Anxiety↗

PubMed1992

Infant information processing in relation to six-year cognitive outcomes.

As part of a longitudinal follow-up of full-terms and preterms, infant measures of information processing obtained at 7 months and 1 year were related to various 6-year outcomes: general intelligence, language proficiency, early reading and quantitative skills, and several facets of perceptual organization (N = 91). 7-month Visual recognition memory (VRM) was associated with 6-year performance in all domains, and 3 1-year measures--VRM, cross-modal transfer (CMT), and object permanence--were related to IQ and/or one or more specific outcomes (r's = .20 to .47). Many of the infant-childhood relations remain significant even with IQ partialed. Additionally, 7-month VRM and 1-year CMT scores were lower for infants who, at 6 years, were considered at risk for learning disabilities. Overall, measures from the first year of life predicted both specific cognitive abilities and IQ at 6 years; to some extent, the specific abilities were predicted independently of IQ.

Achievement↗

PubMed1989

The development of gender-related behavior in females following prenatal exposure to diethylstilbestrol (DES).

Animal research has shown that diethylstilbestrol (DES) present during the sensitive developmental periods of the hypothalamus and adjacent areas of the brain affects the development of sex-dimorphic brain structures and subsequent behavior. To test for corresponding behavioral effects in humans, 30 women with a history of prenatal DES exposure were contrasted with 30 unexposed women who had been referred to the same clinic for a colposcopic examination because of an abnormal Pap smear. Gender-role behavior of childhood, adolescence, and adulthood was assessed by means of a semistructured interview, the Gender Role Assessment Schedule-Adult, and the Bem Sex Role Inventory. The mothers of these women were interviewed about their daughters with the "mother form" of the same interview schedule. The results suggest that DES women show less orientation toward parenting than the controls. There were no consistent group differences in other domains of gender-role behavior.

Adolescent↗

PubMed1988

On the role of protein synthesis in the circadian clock of Neurospora crassa.

Inhibitors of protein synthesis reset the biological clocks of many organisms. This has been interpreted to mean either that the synthesis per se of proteins is a step in the oscillatory feedback loop or merely that certain unstable protein(s) are required at certain times of the cycle to complete the feedback loop. We report here that Neurospora strains bearing the clock mutation frq-7 are relatively insensitive to the resetting action of the protein-synthesis-inhibitor cycloheximide. Protein synthesis itself in this mutant is inhibited by the drug to the same extent as in wild type. Since the clock of frq-7 continues to run relatively unimpeded even in the virtual absence of protein synthesis, it is unlikely that synthesis per se can be a part of the feedback cycle. Rather, we suggest that for normal operation of the Neurospora clock, certain protein(s) with a high turnover rate are required daily and, thus, must be resynthesized each day (at least) during discrete times in the cycle. The frq-7 mutation simultaneously alters several distinct clock characteristics--period length, temperature compensation, and resetting by cycloheximide. A model is presented to unify these observations.

Circadian Rhythm↗