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Biomedical subjects

T J Morgan

Publications and source records attributed to T J Morgan.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative trait loci for thermotolerance phenotypes in Drosophila melanogaster.

For insects, temperature is a major environmental variable that can influence an individual's behavioral activities and fitness. Drosophila melanogaster is a cosmopolitan species that has had great success in adapting to and colonizing diverse thermal niches. This adaptation and colonization has resulted in complex patterns of genetic variation in thermotolerance phenotypes in nature. Although extensive work has been conducted documenting patterns of genetic variation, substantially less is known about the genomic regions or genes that underlie this ecologically and evolutionarily important genetic variation. To begin to understand and identify the genes controlling thermotolerance phenotypes, we have used a mapping population of recombinant inbred (RI) lines to map quantitative trait loci (QTL) that affect variation in both heat- and cold-stress resistance. The mapping population was derived from a cross between two lines of D. melanogaster (Oregon-R and 2b) that were not selected for thermotolerance phenotypes, but exhibit significant genetic divergence for both phenotypes. Using a design in which each RI line was backcrossed to both parental lines, we mapped seven QTL affecting thermotolerance on the second and third chromosomes. Three of the QTL influence cold-stress resistance and four affect heat-stress resistance. Most of the QTL were trait or sex specific, suggesting that overlapping but generally unique genetic architectures underlie resistance to low- and high-temperature extremes. Each QTL explained between 5 and 14% of the genetic variance among lines, and degrees of dominance ranged from completely additive to partial dominance. Potential thermotolerance candidate loci contained within our QTL regions are identified and discussed.

Adaptation, Physiological↗
PubMed2006

The evolution of aging and age-related physical decline in mice selectively bred for high voluntary exercise.

We tested whether selective breeding for early-age high voluntary exercise behavior over 16 generations caused the evolution of lifelong exercise behavior, life expectancy, and age-specific mortality in house mice (Mus domesticus). Sixteenth-generation mice from four replicate selection lines and four replicate random-bred control lines were individually housed from weaning through death and divided between two activity treatments (either with or without running wheels). Thus, there were four treatment groups: selection versus control crossed with active versus sedentary. The effects of selective breeding on life expectancy and age-specific mortality differed between females and males. In females, sedentary selection mice had early and high initial adult mortality and thus the lowest increases in mortality with age. Active selection females had the lowest early adult mortality, had limited mortality during midlife, and exhibited rapid increases in mortality rates at the very end of life; thus, they had deferred senescence. Median life expectancy was greater for both groups of selection females than for the two complementary groups of control females. Like females, sedentary selection males had the highest early adult mortality, and slow but steadily increasing mortality over the entire lifetime. Unlike the active selection females, active control males had the lowest mortality across the lifespan (until the end of life). Interestingly, the males with the lowest median life expectancy were those in the active selection treatment group. In both sexes, running (km/week) decreased over the lifetime to very low and virtually equivalent levels at the end of life in control and selection mice. Overall, these results demonstrate an evolutionary cost of selective breeding for males, regardless of exercise level, but a benefit for females when they have an outlet for the up-selected behavior. We conclude that correlated evolution of senescence occurs in mice selectively bred for high voluntary wheel running; exercise per se is beneficial for control mice of both sexes, but the impact on the effect of selection depends on sex; and the behavioral effect of exercise selection at an early age declines throughout the life span, which demonstrates decreasing genetic correlations over age for the genes involved in increased exercise.

Aging↗
PubMed2005

Examination of soil contaminated by coal-liquids by size exclusion chromatography in 1-methyl-2-pyrrolidinone solution to evaluate interference from humic and fulvic acids and extracts from peat.

Soil from a redundant coke oven site has been examined by extraction of soluble materials using 1-methyl-2-pyrrolidinone (NMP) followed by size exclusion chromatography (SEC) of the extracted material. The extracted material was found to closely resemble a high temperature coal tar pitch. Standard humic and fulvic acids were also examined since these materials are very soluble in NMP and would be extracted with pitch if present in the soil. Humic substances derived from peat samples and NMP-extracts of peats were also examined. The results show that the humic and fulvic substances were not extracted directly by NMP from peats. They were extracted using caustic soda solution and were different from the peat extracts in NMP. These results indicate that humic and fulvic acids were soluble in NMP in the protonated polyelectrolyte form but not in the original native polyelectrolyte form. The extraction of soil using NMP followed by SEC appears to be a promising method for identifying contamination by coal-based industries.

Benzopyrans↗
PubMed2005

Molecular and quantitative genetic divergence among populations of house mice with known evolutionary histories.

Evolutionary biologists have long been interested in the processes influencing population differentiation, but separating the effects of neutral and adaptive evolution has been an obstacle for studies of population subdivision. A recently developed method allows tests of whether disruptive (ie, spatially variable) or stabilizing (ie, spatially uniform) selection is influencing phenotypic differentiation among subpopulations. This method, referred to as the F(ST) vs Q(ST) comparison, separates the total additive genetic variance into within- and among-population components and evaluates this level of differentiation against a neutral hypothesis. Thus, levels of neutral molecular (F(ST)) and quantitative genetic (Q(ST)) divergence are compared to evaluate the effects of selection and genetic drift on phenotypic differentiation. Although the utility of such comparisons appears great, its accuracy has not yet been evaluated in populations with known evolutionary histories. In this study, F(ST) vs Q(ST) comparisons were evaluated using laboratory populations of house mice with known evolutionary histories. In this model system, the F(ST) vs Q(ST) comparisons between the selection groups should reveal quantitative trait differentiation consistent with disruptive selection, while the F(ST) vs Q(ST) comparisons among lines within the selection groups should suggest quantitative trait differentiation in agreement with drift. We find that F(ST) vs Q(ST) comparisons generally produce the correct evolutionary inference at each level in the population hierarchy. Additionally, we demonstrate that when strong selection is applied between populations Q(ST) increases relative to Q(ST) among populations diverging by drift. Finally, we show that the statistical properties of Q(ST), a variance component ratio, need further investigation.

Animals↗
PubMed2004

Thin-layer chromatography of pitch and a petroleum vacuum residue. Relation between mobility and molecular size shown by size-exclusion chromatography.

A coal tar pitch and a petroleum vacuum residue have been separated by TLC using pyridine, acetonitrile, toluene and pentane to develop the chromatograms. The bands of material detected were recovered in 1-methyl-2-pyrrolidinone (NMP) solvent and examined by size-exclusion chromatography (SEC) in NMP eluent. The relation between elution time in SEC and mobility on the TLC plate indicated that molecular size increased steadily with increasing immobility on the plate. This relation was reinforced by UV fluorescence spectroscopy in that the fluorescence moved to longer wavelengths with increasing immobility. The molecular size of the material excluded from the porosity of the SEC column remains undefined; some excluded material was found in all of the fractions from both samples. The valley of zero intensity separating the retained material from the excluded material may suggest a change of structure from near-planar in the retained region to three-dimensional in the excluded region.

Chromatography, Gel↗
PubMed2004

Estimation of the molecular mass range of the tar from pyrolysis of casein by gas chromatography-mass spectrometry, probe mass spectrometry and size exclusion chromatography with 1-methyl-2-pyrrolidinone as eluent.

Casein has been pyrolysed to obtain a biochar (28.3% yield), with mostly meso- and macro-pore structure, and a liquid tar product of high yield (37.5%) with the balance as gas (20.9%) and water (13.3%). The elemental composition of the casein tar was: C 66.7%, H 8.3%, N 12.1% and O 12.9% (by difference). The tar sample has been characterised by mass spectrometry, gas chromatography (GC)/MS and heated-probe MS, to give molecular mass distributions for comparison with molecular mass ranges indicated by analytical-scale size-exclusion chromatography (SEC). The tar appeared to be completely soluble in 1-methyl-2-pyrrolidinone (NMP), the solvent used for SEC. It appeared to consist mostly of lower molecular mass fractions with elution times at 18-26 min. GC/MS analysis showed the presence of both aliphatic and aromatic nitrogen-containing components. Neither GC/MS nor heated-probe MS were able to detect more than about half the tar components.

Animals↗
PubMed2003

Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart.

We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice (Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change (n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer (n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level.

Age Factors↗
PubMed2003

Designing 'balanced' crystalloids.

OBJECTIVE: To present a rationale for the design of balanced resuscitation and renal replacement crystalloids based on Stewart's physical chemical approach to acid-base. DATA SOURCES: Articles and published abstracts on acid-base physiology, crystalloid infusions and renal replacement therapy. SUMMARY OF REVIEW: Although it is uncertain that crystalloid-induced metabolic acidosis causes significant harm, Stewart's approach assists in designing balanced fluids without this side effect. In his analysis, the three independent variables determining acid-base balance are PCO2, the total concentration of non-volatile weak acid (A(TOT)) and the strong ion difference (SID). Raising and lowering A(TOT) while holding SID constant cause a metabolic acidosis and alkalosis respectively. Lowering and raising plasma SID while clamping A(TOT) cause a metabolic acidosis and alkalosis respectively. The SID of a crystalloid is its [HCO3-], or that part of an organic bicarbonate surrogate which is metabolised on infusion. Rapid infusion alters plasma SID towards crystalloid SID, but also lowers A(TOT) by haemodilution. We have shown that the SID of a balanced infusion crystalloid is 24 mEq/L. This generates a fall in plasma SID precisely counteracting the A(TOT) dilutional alkalosis. In contrast, a balanced renal replacement crystalloid must generate a higher plasma SID appropriate for the existing A(TOT), since there is no dilution. If A(TOT) is low, as in hypoalbuminaemia, the balanced dialysis SID falls correspondingly. A further SID reduction is needed to counteract Donnan effects within the filter. CONCLUSIONS: A crystalloid SID of 24 mEq/L is 'balanced' for rapid intravenous administration. The 'balanced' SID of renal replacement fluids is likely to be significantly higher, although less than the normal plasma SID of 42 mEq/L.

Journal Article↗
PubMed2003

Interpreting CSF lactic acidosis: effect of erythrocytes and air exposure.

OBJECTIVE: Elevated cerebrospinal fluid (CSF) lactate concentrations in neurotrauma and sub-arachnoid haemorrhage are associated with a poor prognosis. However, in blood-stained CSF, elevated lactate levels may arise from red cell metabolism, even without ischaemia, potentially reducing specificity. This study was undertaken to quantify the erythrocyte contribution to CSF lactate measurements, with and without, exposure to room air. METHODS: Blood was added to CSF to achieve three different red cell concentrations. The CSF was then exposed at 37 degrees C to either room air or 5% CO2 and 95% oxygen. Vancomycin and gentamycin were added to inhibit bacterial growth. Lactate concentrations and red cell concentrations were measured prior to the addition of blood and 10 minutes, 6 hours and 24 hours later. CSF without the addition of blood was used as a control. RESULTS: In the control specimens there were no increases in CSF lactate concentrations over time, either in air or CO2, whereas all specimens with blood added demonstrated significant increases in lactate at 6 and 24 hours (P < 0.01). The lactate increases in both air and CO2 were correlated directly with red cell counts (R2 = 0.62 to 0.87). At all red cell concentrations, the mean lactate increase was greater in air. CONCLUSIONS: Red cells in CSF cause significant increases in lactate concentrations, more so when exposed to air. This should be considered when interpreting lactate in blood stained CSF. Blood-stained CSF specimens for lactate assay should be collected directly from an external ventricular drain rather than a reservoir bag.

Journal Article↗
PubMed2002

Pyrolysis-gas chromatography/mass spectrometry of fractions separated from a low-temperature coal tar: an attempt to develop a general method for characterising structures and compositions of heavy hydrocarbon liquids.

A low-temperature coal tar has been fractionated by column chromatography into acetonitrile, pyridine and 1-methyl-2-pyrrolidinone- (NMP) solubles. The tar and its fractions have been examined by pyrolysis-gas chromatography/mass spectrometry (GC/MS). Fractionation by planar chromatography was also carried out for purposes of comparison. Molecular masses of the fractions were estimated by size-exclusion chromatography (SEC), and bulk structural characterisation was carried out by (13)C-NMR and UV-fluorescence spectrometry. SEC showed that the fractions shifted to progressively shorter elution times (higher apparent masses) with diminishing solubility, i.e. from acetonitrile to NMP solubles. UV-fluorescence spectra showed parallel shifts to longer wavelengths and lower fluorescence quantum yields, indicating increasing sizes of aromatic ring systems and increasingly complex molecules. GC/MS analysis of the tar showed alkanes from C10 to C32 and extensive series of alkylated aromatics, phenols, indenes, naphthalenes, phenanthrenes and fluoranthenes. Pyrolysis-GC/MS results for the acetonitrile solubles closely resembled the data for the tar sample, with extensive series of alkylated benzenes, phenols and naphthalenes as well as alkanes from C16 to C28. The pyridine-soluble fraction showed no significant aromatic pyrolysis products and only relatively weak signals for alkanes between C16 and C27. The NMP-soluble fraction showed even less overall signal, with no significant aromatic components and weak signals for alkanes between C21 and C25, even though (13)C-NMR analyses showed that approximately half of the carbon detected was aromatic. The aliphatics are assumed to provide bridging structures between polycyclic aromatic (PCA) ring systems.

Journal Article↗
PubMed2002

Survival following mechanical ventilation of recipients of bone marrow transplants and peripheral blood stem cell transplants.

Survival of bone marrow transplant recipients requiring mechanical ventilation is poor but improving. This study reports a retrospective audit of all haematopoietic stem cell transplant (HSCT) recipients requiring mechanical ventilation at an Australian institution over a period spanning 11 years from 1988 to 1998. Recipients of autologous transplants are significantly less likely to require mechanical ventilation than recipients of allogeneic transplants. Of 50 patients requiring mechanical ventilation, 28% survived to discharge from the intensive care unit, 20% to 30 days post-ventilation, 18% to discharge from hospital and 12% to six months post-ventilation. Risk factors for mortality in the HSCT recipient requiring mechanical ventilation include renal, hepatic and cardiovascular insufficiency and greater severity of illness. Mechanical ventilation of HSCT recipients should not be regarded as futile therapy.

Adolescent↗
PubMed2002

Monitoring tissue gas tensions in critical illness.

OBJECTIVE: To review the technology and the role of monitoring tissue oxygenation in critical illness. DATA SOURCES: Articles and published peer review abstracts on monitoring tissue oxygenation. SUMMARY OF REVIEW: Miniaturised optodes and electrode systems are the commonly used technology for measurement of tissue gas tensions. Reductions in tissue perfusion frequently leads to a decrease in tissue PO2 and an increase in tissue PCO2 which has been confirmed in a number of animal and human trials in hypovolaemic shock. Monitoring tissue oxygenation has also enabled the delineation of cytopathic hypoxia, which is one of the important pathophysiological mechanisms of sepsis. Although these devices have improved our understanding of pathophysiological mechanisms of critical illness, at a clinical level titrating oxygen therapy to tissue oxygen tensions has only been shown to be useful in patients with impaired wound healing. A number of questions remain unanswered in relation to the monitoring of tissue oxygenation in critical illness. These include establishing normal values of PO2 and PCO2 in humans at the various tissue beds, establishing dysoxic thresholds for the various tissues, identifying optimal sites for monitoring and improving measurement accuracy. Furthermore, the nature of microcirculatory blood flow and tissue gas exchange in critical illness is complex and incompletely understood, limiting our ability to interpret changes from the baseline. Knowing critical tissue PO2 thresholds will provide the clinician with practical resuscitation endpoints in hypoxia and shock, and may even modify the practice of 'permissive hypoxia' in severe respiratory failure. These questions need answers in the years to come. CONCLUSIONS: Monitoring of tissue oxygenation is largely a research tool. For its application in the critically ill patient there needs to be a greater understanding of normal values of PO2 and PCO2 at the various tissue beds, dysoxic thresholds for the various tissues and optimal sites for monitoring.

Journal Article↗