Biomedical subjects

Timothy J Bradley

Publications and source records attributed to Timothy J Bradley.

At least 19 recordsLinked to original sources

PubMed2006

Fecundity in Drosophila following desiccation is dependent on nutrition and selection regime.

Life-history trade-offs of populations of Drosophila melanogaster selected for enhanced desiccation resistance (D populations) include increased pupal mortality, retarded development, increased longevity, and decreased fecundity. We tested the effects of acute desiccation on fecundity and the effects of various nutritional regimes on fecundity following a bout of desiccation in the D populations and their control populations (C populations). Female flies were desiccated for 8 h (C populations) or 24 h (D populations) and then recovered on one of four treatments: distilled water, a saline solution, a saline and sucrose solution, or food. Each treatment was tested in the presence and absence of a yeast supplement. Fecundity was then measured on an oviposition medium over a 12-h period. Fecundity was also measured in flies that did not undergo a desiccation stress. Yeast increased fecundity under all conditions examined in the C populations but not in the D populations. There was an overall effect of recovery treatment on fecundity but no effect of desiccation stress.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Discontinuous ventilation in insects: protecting tissues from O2.

The "oxidative damage model" of proposes that the respiratory system of insects operates in manner that reduces and then regulates the partial pressure of oxygen around the tissues at a very low level. This is achieved through the actions of the discontinuous gas exchange cycle. Resting insects often exhibit a ventilatory cycle in which the spiracular valves severely limit gas exchange. The "oxidative damage model" argues that this pattern serves to minimize oxidative damage to the tissues. This interpretation is discussed in the context of a large literature describing oxidative damage in insects and other animals as normal a feature of organismal aging. Evidence is presented from a number of animal phyla demonstrating respiratory strategies designed to maintain similarly low partial pressures of oxygen at the tissue level.

Animals↗

PubMed2006

Evidence from mosquitoes suggests that cyclic gas exchange and discontinuous gas exchange are two manifestations of a single respiratory pattern.

In this paper we demonstrate that the apparent pattern of gas exchange in insects, as observed using flow-through respirometry, is strongly affected by the rate of flow of air through the system. This is true not only because of the time constant of the respiratory chamber in which the insect resides, but also due to the effect of flow rate on the residence time of air as it passes through the detection chamber in the gas analyzer. It is demonstrated that insects respiring with a discontinuous gas exchange pattern can appear to be using a cyclic respiratory pattern. The effects of flow rate on the respiratory pattern discerned are illustrated using the mosquito Culiseta inornata. It is demonstrated that these mosquitoes respire discontinuously. They are among the smallest insects to date in which the discontinuous gas exchange cycle has been observed.

Animals↗

PubMed2005

Aortopulmonary window with anomalous origin of the right coronary artery from the pulmonary artery: two cases highlighting the importance of complete pre-operative echocardiographic evaluation of the coronary arteries in all conotruncal anomalies.

This report describes two infants with an aortopulmonary window in association with anomalous origin of the right coronary artery from the pulmonary artery. In both cases the diagnosis was made pre-operatively by transthoracic echocardiography, with the initial clue being extensive collateral flow within the myocardium. In each case there was surgical confirmation of the echocardiographic findings. These two cases demonstrate that coronary artery evaluation should be an integral part of every new echocardiographic evaluation, particularly in the setting of conotruncal anomalies.

Aortopulmonary Septal Defect↗

PubMed2005

Echocardiographic Doppler assessment of the biophysical properties of the aorta in pediatric patients with the Marfan syndrome.

In the Marfan syndrome (MS), aortic root involvement is usually clinically monitored according to the aortic sinus of Valsalva dilation. Using an echocardiographic Doppler method in this cross-sectional study, abnormal biophysical properties of the ascending aorta were found in pediatric patients with MS compared with healthy controls but not consistently in association with the aortic sinus of Valsalva dilation.

Adolescent↗

PubMed2005

Insects breathe discontinuously to avoid oxygen toxicity.

The respiratory organs of terrestrial insects consist of tracheal tubes with external spiracular valves that control gas exchange. Despite their relatively high metabolic rate, many insects have highly discontinuous patterns of gas exchange, including long periods when the spiracles are fully closed. Two explanations have previously been put forward to explain this behaviour: first, that this pattern serves to reduce respiratory water loss, and second, that the pattern may have initially evolved in underground insects as a way of dealing with hypoxic or hypercapnic conditions. Here we propose a third possible explanation based on the idea that oxygen is necessary for oxidative metabolism but also acts as a toxic chemical that can cause oxidative damage of tissues even at relatively low concentrations. At physiologically normal partial pressures of CO2, the rate of CO2 diffusion out of the insect respiratory system is slower than the rate of O2 entry; this leads to a build-up of intratracheal CO2. The spiracles must therefore be opened at intervals to rid the insect of accumulated CO2, a process that exposes the tissues to dangerously high levels of O2. We suggest that the cyclical pattern of open and closed spiracles observed in resting insects is a necessary consequence of the need to rid the respiratory system of accumulated CO2, followed by the need to reduce oxygen toxicity.

Animals↗

PubMed2005

Physiology of desiccation resistance in Anopheles gambiae and Anopheles arabiensis.

Desiccation resistance and water balance were studied in the adult female mosquitoes Anopheles arabiensis and Anopheles gambiae sensu stricto. When the two species were reared from egg to adult under identical conditions, An. arabiensis had significantly higher desiccation resistance than did An. gambiae. Data are presented that indicate that this difference in desiccation resistance is associated with a higher body water content prior to desiccation in An. arabiensis. No differences in rate of water loss during desiccation or water content at death were observed. Measurements of metabolic rate and respiratory pattern also showed no statistically significant differences between the species. This study provides the first physiologic measurements of desiccation resistance in adults of these species and offers insights into the physiologic differences associated with differential resistance to desiccation stress.

Animals↗

PubMed2004

Long on QT and low on calcium.

Acquired lengthening of the QT interval due to hypocalcaemia is a rare cause of arrhythmia in childhood. Early recognition, rapid institution of appropriate cardiac monitoring, and replacement therapy are essential. An endocrinal work-up may be necessary to exclude primary disorders of calcium metabolism. We report four cases documenting the varied clinical spectrum in which hypocalcaemic-induced prolongation of the QT interval and arrhythmia can occur in childhood.

Adolescent↗

PubMed2004

Osmotic regulation in adult Drosophila melanogaster during dehydration and rehydration.

We have examined the osmoregulatory capacities of laboratory populations of the insect Drosophila melanogaster by measuring hemolymph osmotic concentration during desiccation and upon recovery from a bout of desiccation. Recovery treatments entailed allowing the flies access to distilled water, a saline solution or a saline+sucrose solution after a desiccation bout shown to reduce hemolymph volume by approximately 60%. Prior to desiccation, the hemolymph osmotic concentration was 353+/-11 mOsm. We found that Drosophila display strict osmotic regulation under prolonged conditions of dehydration. Osmotic regulation continued during recovery from desiccation, regardless of the fluid provided. This result is evidence that this insect does not require an external source of osmolytes or energy to regulate its hemolymph osmotic concentration or to restore hemolymph volume, which is reduced during desiccation. We also examined populations that have been selected for over 250 generations for enhanced desiccation resistance to identify physiological characters that have evolved in response to the selection regime. The selected lines displayed a reduced pre-desiccation hemolymph osmotic concentration (315+/-7 mOsm) and a marginally improved capacity for osmoregulation.

Adaptation, Physiological↗

PubMed2004

The evolution of recovery from desiccation stress in laboratory-selected populations of Drosophila melanogaster.

We examined the capacity for physiological recovery from the effects of desiccation in five replicate populations of Drosophila melanogaster that have been selected for enhanced desiccation resistance (D populations) and in five replicate control populations (C populations). The capacity to recover was signified by the ability to restore three somatic components, namely whole-body water, dry mass and sodium content, all of which are reduced during desiccation. Throughout a period of recovery following a bout of desiccation, the flies were offered one of three fluids: distilled water, saline solution, or saline+sucrose solution. Our findings indicate that, when allowed to recover on saline+sucrose solution, D populations have the capacity to restore water at a greater rate than C populations and are able to fully restore dry mass and sodium content to the levels observed in non-desiccated, hydrated D flies. When provided with this same solution during recovery, C flies are unable to restore dry mass and are faced with an elevated sodium load. Desiccation resistance of the flies subsequent to recovery was also examined. We provide evidence that the greatest desiccation resistance in the D populations is associated with the restoration of all three somatic components, suggesting that not only water content, but also dry mass and sodium, may contribute to the enhanced desiccation resistance that has evolved in these populations.

Adaptation, Physiological↗

PubMed2003

Clipped tube fenestration after extracardiac Fontan allows for simple transcatheter coil occlusion.

BACKGROUND: Expensive devices are increasingly used to close a patent fenestration after a modified Fontan operation. We report our 5-year institutional experience of clipped tube fenestration after extracardiac Fontan operation, which allows for simple transcatheter coil occlusion. METHODS: We retrospectively reviewed 30 children, median age of 4.0 years (range, 2.4 to 8.8 years) who underwent extracardiac Fontan operation between May 1996 and May 2001, and were fenestrated using a 4- to 8-mm diameter clipped tube graft. RESULTS: Ten children had a patent fenestration occluded by transcatheter placement of 15 detachable coils (5- to 8-mm diameter). Aortic oxygen saturations increased on average by 5.5% (2% to 14%) and mean pressures in the Fontan circuit by 2.5 mm Hg (0 to 3 mm Hg). Four had immediate complete occlusion angiographically and 6 had trivial residual shunt, but complete occlusion by echocardiography at follow-up. There have been no immediate complications, late coil embolizations, thromboembolic events, or documented hemolysis within a follow-up after coil implantation of 1.7 years (0.4 to 4.5 years). Spontaneous fenestration closure was documented in 8 patients at cardiac catheterization and 9 patients by echocardiography with consistent improvement in resting transcutaneous oxygen saturation. Two children with a patent fenestration have been considered inappropriate for closure, and there was one early surgical death. There have been no complications related to the tube fenestration modification within a follow-up postoperation of 2.6 years (0.1 to 5.5 years). CONCLUSIONS: Clipped tube fenestration after extracardiac Fontan operation is a useful surgical modification that allows for simple transcatheter coil occlusion.

Cardiac Catheterization↗

PubMed2003

Evolved patterns and rates of water loss and ion regulation in laboratory-selected populations of Drosophila melanogaster.

We have investigated water loss from, and ion regulation within, the hemolymph and tissues of five replicate populations of Drosophila melanogaster that have undergone laboratory selection for enhanced desiccation resistance (i.e. the D populations). We compared the patterns and rates of water loss and the ion content of the D populations prior to and during desiccation with those of five replicate control (C) populations. The net rate of water loss in the C flies was approximately 3-fold greater than that of the D flies during the initial hours of desiccation. After 8 h, both C and D flies had considerable reductions in water loss rate. During 24 h of desiccation, the tissue water content of the D flies was conserved, while the C flies were faced with significant loss of tissue water during the initial 8 h of desiccation. We propose that the increased hemolymph volume of the D flies plays a role in buffering water loss from the tissues. One consequence of this large hemolymph pool is that the hydrated D flies contained approximately seven times more sodium within the hemolymph than did the hydrated C flies. Despite a continual loss of hemolymph volume in the D flies during lengthy periods of desiccation, the sodium content of the hemolymph was significantly reduced only during a single event. We provide evidence that the regulation of extracellular sodium, as well as chloride, occurred via excretory processes during desiccation. In addition, whole-body potassium was not significantly decreased in the D flies during desiccation but was reduced (i.e. excreted) in the C flies; hence, we suggest that the potassium content paralleled tissue water level.

Adaptation, Physiological↗

PubMed2003

Metabolic rate in female Culex tarsalis (Diptera: Culicidae): age, size, activity, and feeding effects.

We used flow-through respirometry on female mosquitoes to observe individual ventilatory pattern and to measure metabolic rate at rest, during activity and after a blood-meal. At rest, young adult females of the species Culex tarsalis ventilated cyclically with an average VCO2 of 6.5 nl/min and frequency of 45 mHz. Both resting metabolic rate and body mass of females increased between emergence and 4 d, but only body mass continued to increase until 12 d. Mating status had no effect on the body mass or resting metabolic rate of the females. Both lipid and carbohydrate stores strongly increased during the first week of adult life, in particular between emergence and 4 d, in which lipid mass increased 8.3-fold and carbohydrate mass increased 3.6-fold. Hourly metabolic rate after a blood or sugar meal was measured over a 6-d period in two groups of 14 females. Sugar-fed mosquitoes remained calm during the day and had nocturnal increases in metabolic rate associated with flight activity. Blood feeding elicited a specific dynamic action lasting approximately 55 h, at the peak of which metabolic rate of the blood-fed females was twice that of the sugar-fed group. Eggs were laid on the third night. The increase in metabolic rate presumably reflected the cost of blood digestion and egg production. The females were not active during digestion, so that although their metabolic rate was increased, the overall energy expenditure of the blood-fed group was not very different from that of the sugar-fed group.

Aging↗

PubMed2002

Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster.

A transgenic system ("FLP-out") based on yeast FLP recombinase allowed induced overexpression of MnSOD enzyme in adult Drosophila melanogaster. With FLP-out a brief heat pulse (HP) of young, adult flies triggered the rearrangement and subsequent expression of a MnSOD transgene throughout the adult life span. Control (no HP) and overexpressing (HP) flies had identical genetic backgrounds. The amount of MnSOD enzyme overexpression achieved varied among six independent transgenic lines, with increases up to 75%. Life span was increased in proportion to the increase in enzyme. Mean life span was increased by an average of 16%, with some lines showing 30-33% increases. Maximum life span was increased by an average of 15%, with one line showing as much as 37% increase. Simultaneous overexpression of catalase with MnSOD had no added benefit, consistent with previous observations that catalase is present in excess in the adult fly with regard to life span. Cu/ZnSOD overexpression also increases mean and maximum life span. For both MnSOD and Cu/ZnSOD lines, increased life span was not associated with decreased metabolic activity, as measured by O2 consumption.

Analysis of Variance↗

PubMedDate not supplied

The characterization of ion regulation in Amazonian mosquito larvae: evidence of phenotypic plasticity, population-based disparity, and novel mechanisms of ion uptake.

This study is the first step in characterizing ion uptake mechanisms of mosquito larvae from the Amazon region of Brazil. Hemolymph NaCl levels and rates of unidirectional Na(+) and Cl(-) uptake were measured in larvae of Aedes aegypti and Culex quinquefasciatus in a series of environmental manipulations that are known to challenge ion regulation in other aquatic animals. Despite being reared for numerous generations in dilute media (20 micromol L(-1) NaCl), both species were able to maintain high hemolymph NaCl concentrations, a departure from previous studies. Exposure to distilled water or high-NaCl media did not affect hemolymph ion levels, but pH 3 caused significant decreases in hemolymph Na(+) and Cl(-) levels in both species. Exposure to water from Rio Negro (pH 5.5), an organically rich but ion-poor body of water, did not disturb hemolymph Na(+) and Cl(-) levels or the uptake of these ions. Acute exposure to control media or Rio Negro water titrated to pH 3.5 caused inhibition of Na(+) uptake and stimulation of Cl(-) uptake in C. quinquefasciatus, but A. aegypti larvae experienced only a significant reduction of Na(+) uptake in Rio Negro/pH 3.5 treatment. The stimulation of Cl(-) uptake at low pH has been documented only in aquatic insects and differs from all other invertebrate and vertebrate species. A similar pattern of Na(+) uptake inhibition and Cl(-) uptake stimulation was observed in A. aegypti larvae exposed to bafilomycin A(1), a blocker of V-type H(+) ATPase. Culex quinquefasciatus larvae were unaffected by this drug. Both Na(+) and Cl(-) uptake were reduced when C. quinquefasciatus larvae were exposed to acetazolamide, indicating that H(+) and HCO(3)(-), derived from hydration of CO(2), are involved with Na(+) and Cl(-) uptake. Kinetic analysis of Na(+) and Cl(-) uptake in C. quinquefasciatus, A. aegypti, and Anopheles nuneztovari larvae indicate that these Amazonian species share similar high-capacity and high-affinity mechanisms. Comparison of the Amazonian C. quinquefasciatus with a Californian population provided evidence of both phenotypic plasticity and population disparity in Na(+) and Cl(-) uptake, respectively. When the California population of C. quinquefasciatus was reared in a medium similar to that of the Amazonian group (60 micromol L(-1) NaCl) instead of 4,000 micromol L(-1) NaCl, larvae increased both Na(+) uptake capacity (J(max)) and affinity (i.e., reduced K(m)), yet Cl(-) uptake did not change from its nonsaturating, low-capacity pattern. In the reverse experiment, Amazonian C. quinquefasciatus demonstrated plasticity in both Na(+) and Cl(-) uptake by significantly reducing rates when held in 4,000 micromol L(-1) NaCl for 3 d.

Adaptation, Physiological↗

PubMedDate not supplied

Ion regulatory patterns of mosquito larvae collected from breeding sites in the Amazon rain forest.

We examined the ion composition of mosquito breeding sites located in the Amazon rain forest and the ion regulatory patterns of larvae from these habitats. We found larvae of Toxorhynchites haemorroidalis, Limatus durhamii, Culex (Carrollia) bonnei, and Culex (Culex) sp. residing in fallen palm bracts, leaves, and tree holes that were filled with water. These breeding sites had micromolar levels of Na(+) (1.6-99 micromol L(-1)), but K(+) and Cl(-) concentrations were higher and varied over a large range (231-17,615 micromol L(-1) K(+); 355-2,700 micromol L(-1) Cl(-)). Despite the variability in environmental ion levels and ratios, all four species maintain high hemolymph NaCl levels (80-120 mmol L(-1) Na(+); 60-80 mmol L(-1) Cl(-)). However, the species differed in the means by which they maintain hemolymph ion balance, as indicated by the range of unidirectional Na(+) and Cl(-) uptake rates. Toxorhynchites haemorroidalis had extremely low rates of Na(+) uptake and undetectable Cl(-) uptake, whereas L. durhamii had high rates of uptake for both ions. This variability in rates of uptake may reflect species differences in rates of diffusive ion loss (i.e., permeability). We observed the same curious pattern of Na(+) inhibition and Cl(-) stimulation by low-pH exposure in all four species of mosquitoes, as has been documented in other mosquitoes and aquatic insects. Kinetic analyses of Na(+) and Cl(-) uptake in C. bonnei larvae revealed an unusual pattern of Na(+) uptake that increases linearly (nonsaturable) to extremely high rates, while Cl(-) uptake is a low-affinity, low-capacity system. This pattern contrasts with L. durhamii and Culex (Culex) sp. larvae, which had large increases in both Na(+) and Cl(-) uptake when external NaCl levels were increased. Our results suggest that although these rain forest mosquito larvae are residing in habitats with similar low Na(+), high Cl(-) composition and maintain similar hemolymph NaCl levels, the underlying mechanisms of ion regulation differ among the species.

Adaptation, Physiological↗

PubMedDate not supplied

Changes in the rate of CO2 release following feeding in the insect Rhodnius prolixus.

We describe for the first time changes in the rate of CO2 release (as a surrogate of metabolic rate) in the terminal larval stage of the insect Rhodnius prolixus following a blood meal and during the molt leading to the adult stage. These data are presented on a whole-animal basis as well as per gram wet and dry weight. We have also used techniques that allow us to describe the rate of release per gram of actual body tissue (i.e., removing the weight of the remaining bloodmeal in the gut and the metabolically inactive portion of the cuticle). While the metabolic rate of the whole animal rises approximately 10-fold in 15 d following feeding, the rate per gram of dry body mass rises only twofold. We use these data to provide insights into the relative contributions of tissue growth and increases in metabolic intensity to the massive increases in metabolic rate observed in these insects following feeding. Our analyses indicate that the majority of nutrient uptake occurs in the first 4 d following feeding. It is well known in this species that day 4 following feeding is the end of a critical period for the insect in determining whether it will proceed to the next molt. Our results indicate that the insects may be able to make this decision based on nutrients already transported into the body. We examined the "down regulation" of metabolism observed in the latter stages of the molt cycle in this insect. We express these changes on both a per animal and per gram basis and demonstrate that this down regulation extends even into the adult stage before feeding. Using a comparison of the allometric relationships of metabolic rate to mass in insects and ticks, we demonstrate that unfed R. prolixus show a marked decrease in metabolic rate compared to other insects, while fed Rhodnius are similar in metabolic rate to other insects. Rhodnius has a markedly higher metabolic rate (as do all insects) than that found in ticks.

Animals↗

PubMedDate not supplied

Analyses of physiological evolutionary response.

Selection studies are useful if they can provide us with insights into the patterns and processes of evolution in populations under controlled conditions. In this context it is particularly valuable to be able to analyze the limitations of and constraints on evolutionary responses to allow predictions concerning evolutionary change. The concept of a selection pathway is presented as a means of visualizing this predictive process and the constraints that help define the population's response to selection. As pointed out by Gould and Lewontin, history and chance are confounding forces that can mask or distort the adaptive response. Students of the evolutionary responses of organisms are very interested in the effects of these confounding forces, since they play a critical role not only in the laboratory but also in natural selection in the field. In this article, we describe some methods that are a bit different from those used in most studies for examining data from laboratory selection studies. These analytical methods are intended to provide insights into the physiological mechanisms by which evolutionary responses to the environment proceed. Interestingly, selection studies often exhibit disparate responses in replicate populations. We offer methods for analyzing these disparate responses in replicate populations to better understand this very important source of variability in the evolutionary response. We review the techniques of Travisano et al. and show that these approaches can be used to investigate the relative roles of adaptation, history, and chance in the evolutionary responses of populations of Drosophila melanogaster to selection for enhanced desiccation resistance. We anticipate that a wider application of these techniques will provide valuable insights into the organismal, genetic, and molecular nature of the constraints, as well as the factors that serve to enhance or, conversely, to mask the effects of chance. Such studies should help to provide a more detailed understanding of the processes producing evolutionary change in populations.

Adaptation, Physiological↗