This paper integrates the results of a series of studies on the supply of O2 and substrates for o... more This paper integrates the results of a series of studies on the supply of O2 and substrates for oxidative muscle metabolism and draws conclusions on the role of structural design in partitioning and limiting substrate supply. The studies compared dogs and goats exercising at different intensities and combined physiological, biochemical and morphometric investigations. In both species, the rate of fatty acid oxidation reached an upper limit at low exercise intensities, and only glucose consumption was increased at higher exercise intensities. The supply of both glucose and fatty acids from the capillaries reached maximal rates at low exercise intensities; this limitation is related to the design of the sarcolemma as calculations suggest that the endothelium introduces only a small resistance to substrate flux. From these findings, it appears that the capillaries are designed to satisfy O2 supply up to maximal O2 demand. The increase in substrate supply to the mitochondria at higher e...
ABSTRACTThis paper quantifies maximal flows of carbohydrates and lipids through the pathways supp... more ABSTRACTThis paper quantifies maximal flows of carbohydrates and lipids through the pathways supplying the mitochondria. Maximal flow rates are the main functional parameter used in testing the principle of symmorphosis, which states that structural capacities are quantitatively matched to functional demand. Only under rate-limiting conditions will all of the structural capacity be used. Dogs and goats were compared to obtain large differences in absolute rates. We exercised the animals for long enough to reach steady-state O2 and CO2 exchange rates at intensities eliciting 40 %, 60 %. and 85 % of the maximal rate of oxygen consumption (). We then calculated rates of fat and carbohydrate oxidation from the ratio of CO2 produced to O2 consumed (the respiratory exchange ratio). The dog’s was more than twice that of the goat (6517 versus 3026 μmol O2 kg−1 min−1). We found the same pattern of fuel selection as a function of exercise intensity in both species, and it appears to be genera...
This first paper in a series develops a model of structure–function relationships for the oxygen ... more This first paper in a series develops a model of structure–function relationships for the oxygen and substrate pathways of oxidative metabolism in working muscle. This will be used in the subsequent experimental papers in asking how biological structures are designed if they serve more than one function and whether one function can be served by more than one structural pathway. We have used the concept of symmorphosis to address this question; in its original form, it postulates that no more structure is built and maintained at each step in a pathway than is required to meet functional demands. The concept of symmorphosis was developed to deal with the problem of modelling the pathway for oxygen from the environment to mitochondria, essentially a single series of interconnected transfer steps. In the present context, the application of this concept is more complex. Both oxygen and substrates are transported directly from the blood to the mitochondria in what appear to be shared step...
ABSTRACTLarge animals have a much better fuel economy than small ones, both when they rest and wh... more ABSTRACTLarge animals have a much better fuel economy than small ones, both when they rest and when they run. At rest, each gram of tissue of the largest land animal, the African elephant, consumes metabolic energy at 1/20 the rate of a mouse; using existing allometric relationships, we calculate that it should be able to carry 1 g of its tissue (or a load) for 1 km at 1/40 the cost for a mouse. These relationships between energetics and size are so consistent that they have been characterized as biological laws. The elephant has massive legs and lumbers along awkwardly, suggesting that it might expend more energy to move about than other animals. We find, however, that its energetic cost of locomotion is predicted remarkably well by the allometric relationships and is the lowest recorded for any living land animal.
American Journal of Physiology-Endocrinology and Metabolism, 2000
We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal ... more We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 ± 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY signif...
As a charged particle passes through a non-gaseous medium, it polarizes the medium and induces wa... more As a charged particle passes through a non-gaseous medium, it polarizes the medium and induces wake fields behind it. Same thing happens in ionization cooling. The interaction with wake fields perturbs the stopping power of beam particles. The perturbation strongly depends on the densities of both the incident beam and the medium. To understand this collective effect, detailed studies have been carried out. Both analytic and simulation results are obtained and compared.
... and RM Edelstein, EJ Makuchowski, CM Meltzer,t EL Miller,t and JS Russ Carnegie-Mellon Univer... more ... and RM Edelstein, EJ Makuchowski, CM Meltzer,t EL Miller,t and JS Russ Carnegie-Mellon University, Pittsburgh, Pennsylvania 15213 and B. Gobbi, JL Rosen, and HA Scott Northwestern University, Evanston, Illinois 60201 and SL Shapiro§ and L. Strawczynski University of ...
SUMMARYTwo mutations at theniaDlocus (structural gene for nitrate reductase apo-protein) are geno... more SUMMARYTwo mutations at theniaDlocus (structural gene for nitrate reductase apo-protein) are genotypically suppressible. Both mutations result in loss of nitrate reductase enzyme activity and cross reacting material and are non complementing, nonleaky and highly revertible. They have the properties of nonsense mutations. This implies that some of the allele specific suppressors, which act on these and alleles at several other loci, are nonsense suppressors.
This paper integrates the results of a series of studies on the supply of O2 and substrates for o... more This paper integrates the results of a series of studies on the supply of O2 and substrates for oxidative muscle metabolism and draws conclusions on the role of structural design in partitioning and limiting substrate supply. The studies compared dogs and goats exercising at different intensities and combined physiological, biochemical and morphometric investigations. In both species, the rate of fatty acid oxidation reached an upper limit at low exercise intensities, and only glucose consumption was increased at higher exercise intensities. The supply of both glucose and fatty acids from the capillaries reached maximal rates at low exercise intensities; this limitation is related to the design of the sarcolemma as calculations suggest that the endothelium introduces only a small resistance to substrate flux. From these findings, it appears that the capillaries are designed to satisfy O2 supply up to maximal O2 demand. The increase in substrate supply to the mitochondria at higher e...
ABSTRACTThis paper quantifies maximal flows of carbohydrates and lipids through the pathways supp... more ABSTRACTThis paper quantifies maximal flows of carbohydrates and lipids through the pathways supplying the mitochondria. Maximal flow rates are the main functional parameter used in testing the principle of symmorphosis, which states that structural capacities are quantitatively matched to functional demand. Only under rate-limiting conditions will all of the structural capacity be used. Dogs and goats were compared to obtain large differences in absolute rates. We exercised the animals for long enough to reach steady-state O2 and CO2 exchange rates at intensities eliciting 40 %, 60 %. and 85 % of the maximal rate of oxygen consumption (). We then calculated rates of fat and carbohydrate oxidation from the ratio of CO2 produced to O2 consumed (the respiratory exchange ratio). The dog’s was more than twice that of the goat (6517 versus 3026 μmol O2 kg−1 min−1). We found the same pattern of fuel selection as a function of exercise intensity in both species, and it appears to be genera...
This first paper in a series develops a model of structure–function relationships for the oxygen ... more This first paper in a series develops a model of structure–function relationships for the oxygen and substrate pathways of oxidative metabolism in working muscle. This will be used in the subsequent experimental papers in asking how biological structures are designed if they serve more than one function and whether one function can be served by more than one structural pathway. We have used the concept of symmorphosis to address this question; in its original form, it postulates that no more structure is built and maintained at each step in a pathway than is required to meet functional demands. The concept of symmorphosis was developed to deal with the problem of modelling the pathway for oxygen from the environment to mitochondria, essentially a single series of interconnected transfer steps. In the present context, the application of this concept is more complex. Both oxygen and substrates are transported directly from the blood to the mitochondria in what appear to be shared step...
ABSTRACTLarge animals have a much better fuel economy than small ones, both when they rest and wh... more ABSTRACTLarge animals have a much better fuel economy than small ones, both when they rest and when they run. At rest, each gram of tissue of the largest land animal, the African elephant, consumes metabolic energy at 1/20 the rate of a mouse; using existing allometric relationships, we calculate that it should be able to carry 1 g of its tissue (or a load) for 1 km at 1/40 the cost for a mouse. These relationships between energetics and size are so consistent that they have been characterized as biological laws. The elephant has massive legs and lumbers along awkwardly, suggesting that it might expend more energy to move about than other animals. We find, however, that its energetic cost of locomotion is predicted remarkably well by the allometric relationships and is the lowest recorded for any living land animal.
American Journal of Physiology-Endocrinology and Metabolism, 2000
We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal ... more We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 ± 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY signif...
As a charged particle passes through a non-gaseous medium, it polarizes the medium and induces wa... more As a charged particle passes through a non-gaseous medium, it polarizes the medium and induces wake fields behind it. Same thing happens in ionization cooling. The interaction with wake fields perturbs the stopping power of beam particles. The perturbation strongly depends on the densities of both the incident beam and the medium. To understand this collective effect, detailed studies have been carried out. Both analytic and simulation results are obtained and compared.
... and RM Edelstein, EJ Makuchowski, CM Meltzer,t EL Miller,t and JS Russ Carnegie-Mellon Univer... more ... and RM Edelstein, EJ Makuchowski, CM Meltzer,t EL Miller,t and JS Russ Carnegie-Mellon University, Pittsburgh, Pennsylvania 15213 and B. Gobbi, JL Rosen, and HA Scott Northwestern University, Evanston, Illinois 60201 and SL Shapiro§ and L. Strawczynski University of ...
SUMMARYTwo mutations at theniaDlocus (structural gene for nitrate reductase apo-protein) are geno... more SUMMARYTwo mutations at theniaDlocus (structural gene for nitrate reductase apo-protein) are genotypically suppressible. Both mutations result in loss of nitrate reductase enzyme activity and cross reacting material and are non complementing, nonleaky and highly revertible. They have the properties of nonsense mutations. This implies that some of the allele specific suppressors, which act on these and alleles at several other loci, are nonsense suppressors.
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Papers by TJ Roberts