Cell-cycle-regulated phosphorylation of the transcription factor Oct-1.
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Amino Acid Sequence↗
Biomedical subjects
S B Roberts
Publications and source records attributed to S B Roberts.
Use of p-aminobenzoic acid to monitor compliance with prescribed dietary regimens during metabolic balance studies in man.
A new method is described for simultaneously monitoring compliance with prescribed-diet and urine-collection regimens during metabolic balance studies. It involves incorporation of the potassium salt of p-aminobenzoic acid (PABA) into provided foods and measurement of its extent of recovery in urine. A validation study was conducted in 10 healthy adults. During three consecutive 24-h periods, subjects consumed four foods per day that had each been supplemented with 72.0 mg PABA and also made complete urine collections. An additional 24-h urine collection was made by each subject for determination of baseline PABA excretion. The PABA was easily incorporated into the test foods and was not detected by taste. The recovery of the PABA in urine, determined by colorimetric assay, was 98.7 +/- 3.7% (means +/- SD) of intake. Thus, in metabolic studies for greater than or equal to 3 d, PABA can be used to provide a sensitive index of dietary compliance.
4-Aminobenzoic Acid↗
Energy expenditure and subsequent nutrient intakes in overfed young men.
We investigated the mechanisms of body weight regulation in young men of normal body weight leading unrestricted lives. Changes in total and resting energy expenditure, body composition, and subsequent voluntary nutrient intakes in response to overeating by 4,230 +/- 115 (SE) kJ/day (1,011 +/- 27 kcal/day) for 21 days were measured in seven subjects consuming a typical diet. On average, 85-90% of the excess energy intake was deposited (with 87% of this amount in fat and 13% in protein on average). There was no detectable difference between individuals in susceptibility to energy deposition. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (mean +/- SE, 628 +/- 197 kJ/day, P less than 0.01), but at least some of this amount was obligatory expenditure associated with nutrient assimilation. No significant increase in energy expenditure for physical activity or thermoregulation resulted from overfeeding. Thus energy expenditure did not substantially adapt to increased energy intake. However, significant decreases in voluntary energy intake (1,991 +/- 824 kJ/day, P less than 0.05) and fat intake (48 +/- 11 g/day, P less than 0.01) followed overeating, indicating that adaptive changes in nutrient intakes can contribute significantly to body weight regulation after overeating.
Adult↗
Nucleotide sequences of Caenorhabditis elegans core histone genes. Genes for different histone classes share common flanking sequence elements.
We have determined the nucleotide sequence of core histone genes and flanking regions from two of approximately 11 different genomic histone clusters of the nematode Caenorhabditis elegans. Four histone genes from one cluster (H3, H4, H2B, H2A) and two histone genes from another (H4 and H2A) were analyzed. The predicted amino acid sequences of the two H4 and H2A proteins from the two clusters are identical, whereas the nucleotide sequences of the genes have diverged 9% (H2A) and 12% (H4). Flanking sequences, which are mostly not similar, were compared to identify putative regulatory elements. A conserved sequence of 34 base-pairs is present 19 to 42 nucleotides 3' of the termination codon of all the genes. Within the conserved sequence is a 16-base dyad sequence homologous to the one typically found at the 3' end of histone genes from higher eukaryotes. The C. elegans core histone genes are organized as divergently transcribed pairs of H3-H4 and H2A-H2B and contain 5' conserved sequence elements in the shared spacer regions. One of the sequence elements, 5' CTCCNCCTNCCCACCNCANA 3', is located immediately upstream from the canonical TATA homology of each gene. Another sequence element, 5' CTGCGGGGACACATNT 3', is present in the spacer of each heterotypic pair. These two 5' conserved sequences are not present in the promoter region of histone genes from other organisms, where 5' conserved sequences are usually different for each histone class. They are also not found in non-histone genes of C. elegans. These putative regulatory sequences of C. elegans core histone genes are similar to the regulatory elements of both higher and lower eukaryotes. The coding regions of the genes and the 3' regulatory sequences are similar to those of higher eukaryotes, whereas the presence of common 5' sequence elements upstream from genes of different histone classes is similar to histone promoter elements in yeast.
Animals↗
Use of the doubly labeled water method for measurement of energy expenditure, total body water, water intake, and metabolizable energy intake in humans and small animals.
The basis of the doubly labeled water method is measurement of the differential rates of disappearance of two isotopes of water (H2 18O and either 2H2O or 3H2O, administered at the start of the study) from body water. Published studies indicate that, in its current forms, this technique can be used to provide accurate and reasonably precise information on carbon dioxide production, total body water, and water intake in free-living humans and many small animals. Total energy expenditure can be calculated from carbon dioxide production with little loss of precision. Metabolizable energy intake can also be predicted, as the sum of total energy expenditure plus an estimate for the change in body energy stores during the measurement, but this prediction is unlikely to be accurate and precise unless the subject is in approximate energy balance.
Animals↗
Energy expenditure and intake in infants born to lean and overweight mothers.
We investigated the contributions of low energy expenditure and high energy intake to excessive weight gain in infants born to overweight mothers. The subjects were infants of 6 lean and 12 overweight mothers, recruited soon after birth. Total energy expenditure and metabolizable energy intake were measured with a new doubly labeled water method over a period of seven days when the infants were 3 months of age, and the postprandial metabolic rate was measured by indirect calorimetry when the infants were 0.1 and 3 months of age. The results were related to weight gain in the first year of life. No significant difference was observed between infants who became overweight by the age of one year (50 percent of infants born to overweight mothers) and those who did not, with respect to weight, length, skinfold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at three months of age was 20.7 percent lower in the infants who became overweight than in the other infants (means +/- SE, 256 +/- 27 and 323 +/- 12 kJ per kilogram of body weight per day; P less than 0.05). This difference could account for the mean difference in weight gain. These data suggest that reduced energy expenditure, particularly on physical activity, was an important factor in the rapid weight gain during the first year of life in infants born to overweight mothers.
Body Weight↗
Energy costs of fat and protein deposition in the human infant.
The energy costs of depositing fat and protein in the low-birth-weight infant were determined by multiple-regression analysis from published information on metabolizable-energy intake and fat and protein deposition in groups of subjects fed different dietary regimes. The total energy requirement for deposition was 1.17 kJ/kJ deposited for fat (ie, 1 kJ deposited and 0.17 kJ expended for deposition, and 2.38 kJ/kJ for protein. These values are similar to published determinations for animal species with simple stomachs. The metabolizable-energy requirement for weight gain during infancy was calculated (range, 12.2-25.1 kJ/g, or 2.9-6.0 kcal/g; means, 18.7 kJ/g, or 4.5 kcal/g) from the energy costs of fat and protein deposition and published information on changes in body composition during the first year of life.
Animals↗
Purification of the human histone H4 gene-specific transcription factors H4TF-1 and H4TF-2.
Transcription of the cell-cycle-regulated human histone genes increases approximately fivefold during S phase. One step toward the elucidation of the biochemical mechanisms that govern cell-cycle-regulated expression of these genes is to purify and characterize the transcription factors that regulate these promoters. Here, we describe the purification of two previously identified factors, H4TF-1 and H4TF-2, which bind the human histone H4 promoter. Purification was achieved through a combination of ion-exchange and oligonucleotide affinity chromatography. On the basis of analysis of purified fractions by SDS-polyacrylamide gels and UV cross-linking, we believe that H4TF-1 is two polypeptides of 105 and 110 kD. This factor binds to a GC-rich DNA sequence required for maximal expression of the H4 gene but does not bind to any Sp1 consensus elements tested. H4TF-2 is a 65-kD protein that binds specifically to sequences within that highly conserved H4 subtype-specific consensus promoter element. Both highly purified factors activated transcription in vitro only from H4 promoters that contained their binding sequences, demonstrating that H4TF-1 and H4TF-2 are H4-specific transcription factors that potentiate expression of this gene.
Base Sequence↗
Effect of weaning on accuracy of doubly labeled water method in infants.
Variations in background 2H and 18O abundances in body water influence the accuracy and precision of the 2H218O method for determination of energy expenditure. To investigate the effect of weaning during infancy on background 2H and 18O abundances, urine samples from 44 breast- or formula-fed infants aged 5-16 wk were analyzed. 2H and 18O abundances were significantly higher (P less than 0.001) in breast- than in formula-fed infants. The relationship between 2H and 18O abundances was linear and independent of diet [slope, 4.16 +/- 0.43 (SE)]. By use of this information, the effect of weaning on the accuracy of the 2H218O method was evaluated, taking into account the effect of 2H-18O abundances in the isotope loading dose. In infants weaned completely from breast milk to formula during the measurement, energy expenditure can be overestimated by 18.0%, even if 2H-18O abundances in the isotope dose equal the ratio of naturally occurring background changes. However, this error can be reduced to less than 3.0% by manipulating the study duration and isotope dose. During gradual weaning, the overestimation of energy expenditure is only 0.3-2.0%.
Aging↗
Theoretical and practical considerations in the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man.
In the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man, single exponential disappearance curves for 2H2O and H2(18)O in body water are used; the precision with which the slopes and intercepts of the curves are estimated determines the precision of the estimate of carbon dioxide production rate. In studies with infants, and in computer simulations, the effect of different experimental regimes on the overall precision of the carbon dioxide production estimate was investigated. When the number of data points used was progressively reduced by shortening the total observation period from 7 d (about 3 biological half-lives for the isotopes) to 1 d there was a deleterious effect on precision and in the infants there was an upward bias in the values for carbon dioxide production. When the number of data points was reduced by removing points from the middle of the exponential curves with the maintenance of the 7-d experimental period, precision was also reduced but by less than in the former procedure and there were no consistent trends in the average values for carbon dioxide production.
Carbon Dioxide↗
How much energy does the breast fed infant consume and expend?
Energy intake in breast fed infants is uncertain. The doubly labelled water method was used to measure, simultaneously and non-invasively, energy expenditure, energy intake, milk volume intake, energy deposition, and the energy content of breast milk in 12 "free living" breast fed babies at 5 and 11 weeks of age. The validity of this new approach was assessed in a parallel study in 12 formula fed infants. The babies who were exclusively breast fed expended 1.28 and 1.68 MJ/day at five and 11 weeks and had intakes of 1.81 and 2.22 MJ/day; these intakes were associated with normal growth but were well below those recommended previously. At five and 11 weeks the calculated energy content of breast milk was 0.24 and 0.25 MJ/100 ml, which is substantially lower than that commonly reported in milk obtained unphysiologically by expression of the breast. These data cast doubt on the widely used published standards for infant feeding.
Breast Feeding↗
Molecular characterization of the histone gene family of Caenorhabditis elegans.
The core histone genes (H2A, H2B, H3 and H4) of Caenorhabditis elegans are arranged in approximately 11 dispersed clusters and are not tandemly arrayed in the genome. Three well-characterized genomic clones, which contain histone genes, have one copy of each core histone gene per cluster. One of the clones (lambda Ceh-1) carries one histone cluster surrounded by several thousand base-pairs of non-histone DNA, and another clone (lambda Ceh-3) contains a histone cluster duplication surrounded by non-histone DNA. A third clone (lambda Ceh-2) carries a cluster of core histone genes flanked on one side (12,000 base-pairs away) by a single H2B gene and on the other by non-histone DNA. A fourth cluster (clone BE9) has one copy each of H3 and H4 and two copies each of H2A and H2B. This cluster is also flanked by non-histone DNA. Analysis of cosmid clones which overlap three of the clusters shows that no other histone clusters are closer than 8000 to 60,000 base-pairs, although unidentified non-histone transcription units are present on the flanking regions. Gene order within the histone clusters varies, and histone mRNAs are transcribed from both DNA strands. No H1 sequences are found on these core histone clones. Restriction fragment length polymorphisms between two related nematode strains (Bristol and Bergerac) were used as phenotypic markers in genetic crosses to map one histone cluster to linkage group V and another to linkage group IV. Hybridization of gene-specific probes from sea urchin to C. elegans RNA identifies C. elegans core histone messenger RNAs of sizes similar to sea urchin early stage histone mRNAs (H2A, H2B, H3 and H4). The organization of histone genes in C. elegans resembles the clustering found in most vertebrate organisms and does not resemble the tandem patterns of the early stage histone gene family of sea urchins or the major histone locus of Drosophila.
Animals↗
The nutritional role of breast-milk IgA and lactoferrin.
The nutritional enigma concerning the extent to which breast-milk immune proteins are digested has been investigated by measuring the intakes and faecal outputs of IgA and lactoferrin over 7 days in 10 exclusively breast-fed (BF) and 9 formula-fed (FF) fullterm infants at 6 and 12 weeks post-partum. BF outputs (mg/day) greatly exceeded FF values (p less than 0.001): at 6 weeks secretory-IgA BF = 160 +/- 28, FF = 14 +/- 2, lactoferrin BF = 14 +/- 2, FF = 0.9 +/- 0.1; at 12 weeks secretory-IgA BF = 94 +/- 17, FF = 25 +/- 5, lactoferrin BF = 7 +/- 1, FF = 1 +/- 0.3. Secretory-IgA represented 42% and 27% of BF faecal protein at 6 and 12 weeks compared with 6% for FF infants at both ages. BF secretory-IgA outputs were highly correlated with intakes (r = 0.83, p less than 0.001). IgA and lactoferrin outputs and the presence of faecal secretory-IgA fragments in BF and FF infants were influenced by defaecation rate, suggesting that partial degradation occurred in the large intestine. By 6 weeks post-partum only 1% lactoferrin and 17% secretory-IgA intakes appeared in the faeces and 95% breast-milk protein could be regarded as nutritionally available. The elevated BF outputs of IgA and lactoferrin relative to endogenous excretion suggest, however, that breast-milk may still make a considerable contribution to intestinal defence mechanisms after the neonatal period despite the small proportion of daily intake which escapes digestion. The protective action of IgA and lactoferrin may also depend on their site of degradation and the nature of fragments.
Feces↗
RNA polymerase II transcription factors H4TF-1 and H4TF-2 require metal to bind specific DNA sequences.
Specific DNA-binding and in vitro transcription activities of H4TF-1 and H4TF-2 are inactivated by chelating agents. Binding activity is restored by addition of Zn2+, and H4TF-2 is also reactivated by Fe2+. In contrast, preformed factor-DNA complexes are resistant to chelators. Therefore, metal ions are a required component of the H4TF-1 and H4TF-2 DNA-binding domains.
Cations, Divalent↗
Measurement of milk intake by deuterium dilution.
In 14 studies, each lasting seven days, on eight bottle fed infants milk intake was measured by deuterium dilution and by weighing the formula consumed and oral losses. Mean (SD) milk intake was 829 (108) g/day when measured by isotope dilution and 837 (98) g/day when measured by direct weighing, giving a mean difference between methods of 1.0 (5.0)%. Thus the stable isotope procedure is a potentially useful method for investigating lactation and nutritional problems.
Animals↗
Measurement of carbon dioxide production rate in sick ventilated premature infants.
A new method is described for measuring the rate of carbon dioxide production, and hence for estimating energy expenditure, in preterm infants receiving assisted ventilation. In a validation study, the mean error in carbon dioxide measurement was 1.9%. Measurements were made, over a 45-min period, on 11 sick, ventilated subjects and carbon dioxide production rate was 5.2 +/- 0.7 (SD) ml/min X kg body weight. We suggest that continuous monitoring of carbon dioxide output will contribute to the clinical assessment of the effects of different ventilator settings on pulmonary gas exchange and that estimated values for energy expenditure will be of value in nutritional studies on sick ventilated infants.
Carbon Dioxide↗
Long-term variation in oxygen consumption rate in preterm infants.
An investigation was made of long-term variation in oxygen consumption rate (VO2) in preterm infants. Four subjects (gestational age 27-34 weeks, postnatal age 17-38 days, weight at study 1.1-2.6 kg) were studied for 5 days each using open-circuit, indirect calorimetry. The mean VO2 for each subject (11.0-11.5 litres/kg/day) was within the reported range. However, the between-subject coefficient of variation during the study (2.1%) was smaller than the mean between-measurement coefficient of variation for daily VO2 (3.8%, range 1.7-6.3%). In addition, the between-measurement coefficient of variation was increased further for measurement intervals of less than 24 h (reaching a mean of 8.3% for 1-hour periods), and a relationship between measurement duration and the precision of estimating VO2 over 3 or 5 days is described. Thus, even 24-hour measurements of VO2 in these preterm infants were less representative of the individual's VO2 over 3 days than the group mean estimate. This finding is of relevance to future studies in this area, particularly those in which short-term measurements of energy expenditure are combined with a nutrient balance study to determine the composition of weight gain, because even small errors in the estimate of total energy expenditure can lead to unacceptably large errors in calculated energy deposition.
Calorimetry, Indirect↗
Energetic efficiency and nutrient accretion in preterm infants fed extremes of dietary intake.
The role of diet-induced thermogenesis (DIT) in the regulation of energy utilization in preterm infants was investigated by measuring energy expenditure and nutrient deposition in groups of subjects fed either banked drip breast milk (BBM) or a preterm formula (PF). Nutrient deposition was determined by combining a 3-d nutrient balance study and measurement of energy expenditure. Infants fed PF consumed 57 per cent more metabolizable energy (ME) than those fed BBM. There were significant differences between groups in energy expenditure, energy deposition and protein deposition; 76 per cent of the additional ME intake consumed by the PF-fed group was deposited while the remaining 24 per cent was expended. Infants fed PF gained weight 39 per cent faster than those fed BBM (19, compared to 14 g/kg/d), and deposited 128 per cent more fat and 86 per cent more protein. These findings indicate that nutrient deposition, rather than DIT, was the primary use of the extra ME received by the infants fed PF. However, the effect of the high energy intake on weight gain in these subjects was reduced, compared to its effect on nutrient deposition, by increases in the concentrations of fat and protein in new tissue.
Body Weight↗