PubMed Health⌕ Search

Biomedical subjects

C E Cooper

Publications and source records attributed to C E Cooper.

At least 19 recordsLinked to original sources
PubMed2006

Numbats and aardwolves--how low is low? A re-affirmation of the need for statistical rigour in evaluating regression predictions.

Many comparative physiological studies aim to determine if a particular species differs from a prediction based on a linear allometric regression for other species. However, the judgment as to whether the species in question conforms to this allometric relationship is often not based on any formal statistical analysis. An appropriate statistical method is to compare the new species' value with the 95% confidence limits for predicting an additional datum from the relationship for the other species. We examine the basal metabolic rate (BMR) of the termitivorous numbat (Myrmecobius fasciatus) and aardwolf (Proteles cristatus) to demonstrate the use of the 95% prediction limits to determine statistically if they have a lower-than-expected BMR compared to related species. The numbat's BMR was 83.6% of expected from mass, but fell inside the 95% prediction limits for a further datum; a BMR < 72.5% of predicted was required to fall below the one-tail 95% prediction limits. The aardwolf had a BMR that was only 74.2% of predicted from the allometric equation, but it also fell well within the 95% prediction limits; a BMR of only 41.8% of predicted was necessary to fall below the one-tail 95% prediction limits. We conclude that a formal statistical approach is essential, although it is difficult to demonstrate that a single species statistically differs from a regression relationship for other species.

Animals↗
PubMed2006

Environmental correlates of physiological variables in marsupials.

We analyzed body temperature (T(b)), basal metabolic rate (BMR), wet thermal conductance (C(wet)), and evaporative water loss (EWL) of marsupials by conventional and phylogenetically corrected regression. Allometric effects were substantial for BMR, C(wet), and EWL but not T(b). There was a strong phylogenetic signal for mass and all physiological traits. A significant phylogenetic signal remained for BMR, C(wet), and EWL even after accounting for the highly significant phylogenetic signal of mass. T(b), BMR, C(wet), and EWL allometric residuals were correlated with some diet, distribution, and climatic variables before and after correction for phylogeny. T(b) residuals were higher for marsupials from arid environments (high T(a) and more variable rainfall). The fossorial marsupial mole had a lower-than-expected T(b) residual. The allometric slope for BMR was 0.72-0.75. Residuals were consistently related to distribution aridity and rainfall variability, with species from arid and variable rainfall habitats having a low BMR, presumably to conserve energy in a low-productivity environment. The nectarivorous honey possum had a higher-than-expected BMR. For C(wet), the allometric slope was 0.55-0.62; residuals were related to diet, with folivores having low and insectivores high C(wet) residuals. The allometric slope for EWL was 0.68-0.73. EWL residuals were consistently correlated with rainfall variability, presumably facilitating maintenance of water balance during dry periods.

Animals↗
PubMed2005

Effect of torpor on the water economy of an arid-zone marsupial, the stripe-faced dunnart (Sminthopsis macroura).

Metabolic rate and evaporative water loss (EWL) were measured for a small, arid-zone marsupial, the stripe-faced dunnart (Sminthopsis macroura), when normothermic and torpid. Metabolic rate increased linearly with decreasing ambient temperature (T(a)) for normothermic dunnarts, and calculated metabolic water production (MWP) ranged from 0.85+/-0.05 (T(a)=30 degrees C) to 3.13+/-0.22 mg H2O g(-1) h(-1) (T(a)=11 degrees C). Torpor at T(a)=11 and 16 degrees C reduced MWP to 24-36% of normothermic values. EWL increased with decreasing T(a), and ranged from 1.81+/-0.37 (T(a)=30 degrees C) to 5.26+/-0.86 mg H2O g(-1) h(-1) (T(a)=11 degrees C). Torpor significantly reduced absolute EWL to 23.5-42.3% of normothermic values, resulting in absolute water savings of 50-55 mg H2O h(-1). The relative water economy (EWL/MWP) of the dunnarts was unfavourable, remaining >1 at all T(a) investigated, and did not improve with torpor. Thus torpor in stripe-faced dunnarts results in absolute, but not relative, water savings.

Adaptation, Physiological↗
PubMed2003

Ventilatory physiology of the numbat (Myrmecobius fasciatus).

This study examines the ventilatory physiology of the numbat (Myrmecobius fasciatus), a small to medium-sized (550 g) termitivorous marsupial. Ventilatory parameters at thermoneutrality reflect the slightly low (83% of predicted) basal metabolic rate of the numbat, with ventilation frequency (fR; 30.6+/-3.65 breaths min(-1)), tidal volume [VT; 6.0+/-0.66 ml at body temperature and pressure, saturated (BTPS)] and consequently minute volume (VI; 117.7+/-15.22 ml min(-1); BTPS) all being 80-87% of that expected for a marsupial of similar body mass. Oxygen extraction was 27.7+/-1.37% in the thermoneutral zone. As is typical of marsupials, numbats accommodated increased oxygen consumption rates at ambient temperatures (Ta) below the thermoneutral zone by increasing minute volume (up to 411.2+/-43.98 ml min(-1); BTPS at Ta=10 degrees C) rather than oxygen extraction. Minute volume at 10 degrees C increased more by changes in ventilation frequency (up to 45.5+/-4.85 breaths min(-1)) than tidal volume (9.4+/-1.03 ml, BTPS), as is also typical for a small-medium sized marsupial.

Animals↗
PubMed2003

Field metabolic rate and water turnover of the numbat (Myrmecobius fasciatus).

The numbat (Myrmecobius fasciatus) is a diurnal and exclusively termitivorous marsupial. This study examines interrelationships between diet, metabolic rate and water turnover for wild, free-living numbats. The numbats (488+/-20.8 g) remained in mass balance during the study. Their basal metabolic rate (BMR) was 3.6 l CO(2) day(-1), while their field metabolic rate (FMR) was 10.8+/-1.22 l CO(2) day(-1) (269+/-30.5 kJ day(-1)). The ratio FMR/BMR was 3+/-0.3 for numbats. We suggest that the most accurate way to predict the FMR of marsupials is from the regression log FMR=0.852 log BMR+0.767; ( r(2)=0.97). The FMR of the numbat was lower than, but not significantly different from, that of a generalised marsupial, both before (76%) and after (62-69%) correction for the significant effect of phylogeny on FMR. However the numbat's FMR is more comparable with that of other arid-habitat Australia marsupials (98-135%), for which the regression relating mass and FMR is significantly lower than for nonarid-habitat marsupials, independent of phylogeny. The field water turnover rate (FWTR) of free-living numbats (84.1 ml H(2)O day(-1)) was highly correlated with FMR, and was typical (89-98%) of that for an arid-habitat marsupial after phylogenetic correction. The higher than expected water economy index for the numbat (FWTR/FMR=0.3+/-0.03) suggests that either the numbats were drinking during the study, the water content of their diet was high, or the digestibility of their termite diet was low. Habitat and phylogenetic influences on BMR and FMR appear to have pre-adapted the numbat to a low-energy termitivorous niche.

Animals↗
PubMed2003

Biophysical properties of the pelt of a diurnal marsupial, the numbat (Myrmecobius fasciatus), and its role in thermoregulation.

Numbats are unusual marsupials in being exclusively diurnal and termitivorous. They have a sparse (1921 hairs cm(-2)) and shallow (1.19 mm) pelt compared with other marsupials. Coat reflectivity is low (19%) for numbats compared with nocturnal marsupials, but absorptivity is similar to that of diurnal North American ground squirrels (72%), indicating that the coat of the numbat may be adapted for acquisition of solar heat. Numbat coat thermal resistance decreases significantly with wind speed from 45.9 s m(-1) (at 0.5 m s(-1)) to 29.8 s m(-1) (at 3 m s(-1)). Erecting the fur significantly increases pelt depth (6.5 mm) and coat resistance (79.2-64.2 s m(-1)) at wind speeds between 0.5 m s(-1) and 3 m s(-1). Numbat coat resistance is much lower than that of other marsupials, and wind speed has a greater influence on coat resistance for numbats than for other mammals, reflecting the low pelt density and thickness. Solar heat gain by numbats through the pelt to the level of the skin (60-63%) is similar to the highest value measured for any mammal. However the numbat's high solar heat gain is not associated with the same degree of reduction in coat resistance as seen for other mammals, suggesting that its pelt has structural and spectral characteristics that enhance both solar heat acquisition and endogenous heat conservation. Maximum solar heat gain is estimated to be 0.5-3.6 times resting metabolic heat production for the numbat at ambient temperatures of 15-32.5 degrees C, so radiative heat gain is probably an important aspect of thermoregulation for wild numbats.

Acclimatization↗
PubMed2002

Metabolic physiology of the numbat (Myrmecobius fasciatus).

The numbat (Myrmecobius fasciatus) is unique amongst marsupials as it is exclusively diurnal, feeds only on termites and is semi-fossorial. This study examines the thermal and metabolic physiology of the numbat to determine if its physiology reflects its phylogeny, diet and semi-fossorial habit. Numbats (mean adult body mass 552 g) were able to regulate body temperature at ambient temperatures of 15-30 degrees C, with a body temperature at thermoneutrality (30 degrees C) of 34.1 degrees C. The thermoneutral body temperature was not significantly different from that predicted for an equivalent-sized marsupial. Basal metabolic rate, measured at 30 degrees C, was 0.389 +/- 0.025 ml O(2) g(-1) h(-1), and was slightly but not significantly lower at 82.5% of that predicted for a typical marsupial of equivalent body mass. Metabolic rate increased with decreasing ambient temperatures below 30 degrees C. Patterns of metabolic cycling observed for completely inactive numbats at ambient temperatures below 30 degrees C are likely to be related to sleep phase. Wet thermal conductance of 1.94 J g(-1) h(-1) degrees C(-1) (at 30 degrees C) was 131% of that predicted for a marsupial. Evaporative water loss of the numbat remained constant below the thermoneutral zone (<30 degrees C) at approximately 0.6 ml g(-1) h(-1), only 47.4% of that predicted for a marsupial. It increased to 1.01 +/- 0.16 ml g(-1) h(-1) at an ambient temperature of 32.5 degrees C. The thermal and metabolic physiology of the numbat is generally similar to that expected for other marsupials, and is also comparable to that of termitivorous placental mammals. Thus the reduction in body temperature and basal metabolic rate of placental termitivores is a "marsupial-like" low energy turnover physiology, and the numbat being a marsupial already has an appropriate physiology to survive exclusively on a low energy diet of termites.

Animals↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Structure-function investigation of the interaction of 1- and 2-substituted 3-hydroxypyridin-4-ones with 5-lipoxygenase and ribonucleotide reductase.

The structural and physiochemical properties of 3-hydroxypyridin-4-one chelators (HPOs) which influence inhibition of the iron-containing metalloenzymes ribonucleotide reductase (RR) and 5-lipoxygenase (5-LO) have been investigated. HPOs with substituents at the 1- and 2-positions of the pyridinone ring have been synthesized, and their inhibitory properties compared with those of desferrioxamine (DFO). Varying the alkyl substituents does not affect the affinity constant of these ligands for iron(III), but permits a systematic investigation of the effect of hydrophobicity and molecular shape on inhibitory properties. The inhibition of RR was monitored, indirectly by measuring tritiated thymidine incorporation into DNA and directly by the quantification of the EPR signal of the enzyme tyrosyl radical. 5-LO inhibition was examined spectrophotometrically, measuring the rate of linoleic hydroperoxide formation by soybean lipoxygenase. The results indicate that the substituent size introduced at the 2-position of the HPO ring is critical for determining inhibition of both enzymes. Large substituents on the 2-position, introduce a steric factor which interferes with accessibility to the iron centers. These studies have identified chelators such as 1,6-dimethyl-2-(N-4',N-propylsuccinamido)methyl-3-hydroxypyridin-4-one (CP358), which causes only a 10% inhibition of 5-LO after 24 h of incubation at 110 microm IBE (iron-binding equivalents) in comparison to simple dialkyl HPOs such as Deferiprone (CP20) which cause up to 70% inhibition. Using EPR spectroscopy, CP358 inhibits RR at a slower rate than CP20, while chelating intracellular iron(III) at a similar rate, a finding consistent with an indirect inhibition of the tyrosyl radical. However, hepatocellular iron is mobilized at a faster rate by CP358 (P < 0.001). These findings demonstrate that it is possible to design bidentate HPOs which access intracellular iron pools rapidly while inhibiting non-heme iron-containing enzymes relatively slowly, at rates comparable to DFO. It is anticipated that such compounds will possess a superior therapeutic safety margin to currently available bidentate HPOs.

Arachidonate 5-Lipoxygenase↗
PubMed2001

Nitric oxide synthases: structure, function and inhibition.

This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated.

Alternative Splicing↗
PubMed2000

The pH dependence of naturally occurring low-spin forms of methaemoglobin and metmyoglobin: an EPR study.

The paramagnetic species in human metHb and horse metmyoglobin (metMb) have been studied at low temperature using EPR spectroscopy. The high-spin (HS) haem signal in aquometMb has a greater rhombic distortion than the HS metHb signal. Nevertheless, the individual line width (g=6) is smaller in metMb than in metHb, consistent with non-identical signals from the alpha and beta Hb subunits. Three low-spin (LS) haem forms are present in metHb, while metMb has only two. The major LS form in both proteins is the alkaline species (with OH(-) at the sixth co-ordination position). The minor LS forms are assigned to different histidine hemichromes in equilibrium with the normal HS species at low temperature. LS forms disappear when the haem is bound by a ligand, such as fluoride, which ensures 100% occupancy of the HS state both at room temperature and at 25 K. The small differences in effective g-factors of the histidine hemichromes are interpreted in terms of different distances between the distal histidine and haem iron. The pH dependence of the inter-conversion of the different paramagnetic species is consistent with a model whereby protonation of a residue with a pK of 5.69 (metHb) or 6.12 (metMb), affects ligand binding and transformation from the HS to the LS form. Chemical and spectroscopic considerations suggest that the residue is unlikely to be the proximal or distal histidine. We therefore propose a model where protonation of this distant amino acid causes a conformational change at the iron site. Identical effects are seen in frozen human blood, suggesting that this effect may have physiological significance.

Animals↗
PubMed2000

Effects of nitric oxide and peroxynitrite on the cytochrome oxidase K(m) for oxygen: implications for mitochondrial pathology.

This review summarises current knowledge about the effect of oxygen on cytochrome oxidase activity in vitro and in vivo. Cytochrome oxidase normally operates above its K(m) for oxygen in vivo. However, decreases in the intracellular oxygen concentration (hypoxia) under physiological extremes, or during pathophysiology, can cause mitochondrial respiration to become oxygen limited. Inhibitors that raise the enzyme's K(m) will induce oxygen limitation under apparently normoxic conditions. It is known that the concentrations of nitric oxide and peroxynitrite are raised in a number of pathophysiological conditions. These compounds are capable of reversibly and irreversibly raising the cytochrome oxidase K(m) for oxygen. Therefore, measurements of cell and mitochondrial respiration in vitro that fail to systematically vary oxygen through the range of physiological concentrations are likely to underestimate the effects of nitric oxide and peroxynitrite in vivo.

Animals↗
PubMed2000

Cytochrome c oxidase rapidly metabolises nitric oxide to nitrite.

Previous studies have shown that the addition of nitric oxide to cytochrome c oxidase rapidly generates spectral changes compatible with the formation of nitrite at the binuclear haem:copper centre. Here we directly demonstrate nitrite release following nitric oxide addition to the enzyme. The nitrite complex is kinetically inactive and the off rate for nitrite was found to be slow (0.024 min(-1)). However, the presence of reductants enhances the off rate and enables cytochrome oxidase to catalyse the rapid oxidation of nitric oxide to nitrite free in solution. This may play a major role in the mitochondrial metabolism of nitric oxide.

Electron Transport Complex IV↗
PubMed2000

A new method for quantitation of spin concentration by EPR spectroscopy: application to methemoglobin and metmyoglobin.

A new method of EPR spectral analysis is developed to quantitate overlapping signals. The method requires double integration of a number of spectra containing the signals in different proportions and the subsequent solution of a system of linear equations. The result gives the double integral values of the individual lines, which can then be further used to find the concentrations of all the paramagnetic species present. There is no requirement to deconvolute the whole spectrum into its individual components. The method is employed to quantify different heme species in methemoglobin and metmyoglobin preparations. A significantly greater intensity of the high-spin signal in metmyoglobin, compared to methemoglobin at the same heme concentration, is shown to be due to larger amounts of low-spin forms in methemoglobin. Three low-spin types in methemoglobin and two in metmyoglobin are present in these samples. When their calculated concentrations are added to those of the high-spin forms, the results correspond to the total heme concentrations obtained by optical spectroscopy.

Animals↗
PubMed2000

NMR spectroscopy and imaging of the neonatal brain.

Magnetic resonance spectroscopy and imaging provide unique information about the brain to the biochemist and the clinician. In particular, the ability to image metabolites other than water and to get detailed information about dynamic cellular processes (such as blood flow, blood oxygenation and cell swelling) is leading to many new insights into brain function and dysfunction. This review describes the use of old and new NMR techniques which demonstrate that mitochondrial dysfunction plays an important role in the cell death that occurs following an hypoxic-ischaemic insult to the neonatal brain.

Adenosine Triphosphate↗
PubMed1999

The electron paramagnetic resonance characterisation of a copper-containing extracellular peroxidase from Thermomonospora fusca BD25.

The actinomycete Thermomonospora fusca BD25 contains a peroxidase with a high activity over a broad range of temperature and pH and a high stability against denaturing agents. Unusually this peroxidase (PO) is a non-haem enzyme. As prepared PO is characterised by two electron paramagnetic resonance (EPR) signals, detected at liquid helium temperature, a free radical signal (g=2.0045) and a broad signal at g=2.056. The peroxidase activity of the purified enzyme was assayed using H(2)O(2) and 2,4-dichlorophenol (DCP). The intensity of the free radical EPR signal correlated with the peroxidase activity in a variety of enzyme preparations. Furthermore, when DCP and H(2)O(2) were added to PO a significant increase of both the free radical signal and the broad signal at g=2.056 was observed. We associate the increase of the broad signal with the oxidation of the preparation since a similar increase can be achieved by the addition of ferricyanide. The high intensity of the broad signal in the ferricyanide treated PO allowed us to deconvolute the signal into several components using the difference in their relaxation characteristics: two distinct copper signals were detected, one of which was similar to a type 2 centre. Furthermore a symmetrical singlet was detected at g=2.059, consistent with the presence of an iron complex with a high degree of symmetry and weakly coordinated ligands.

Actinomycetales↗
PubMed1999

Nitric oxide and iron proteins.

Nitric oxide interactions with iron are the most important biological reactions in which NO participates. Reversible binding to ferrous haem iron is responsible for the observed activation of guanylate cyclase and inhibition of cytochrome oxidase. Unlike carbon monoxide or oxygen, NO can also bind reversibly to ferric iron. The latter reaction is responsible for the inhibition of catalase by NO. NO reacts with the oxygen adduct of ferrous haem proteins (e.g. oxyhaemoglobin) to generate nitrate and ferric haem; this reaction is responsible for the majority of NO metabolism in the vasculature. NO can also interact with iron-sulphur enzymes (e.g. aconitase, NADH dehydrogenase). This review describes the underlying kinetics, thermodynamics, mechanisms and biological role of the interactions of NO with iron species (protein and non-protein bound). The possible significance of iron reactions with reactive NO metabolites, in particular peroxynitrite and nitroxyl anion, is also discussed.

Animals↗