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The field energetics and water fluxes of free-living wombats (Marsupialia: Vombatidae).

Wombats are large, fossorial, herbivorous marsupials exhibiting physical and behavioural characteristics indicative of extreme energy conservation. Previous energetics studies have been limited to their basal metabolism under laboratory conditions; little is known of the energetics of free-living wombats. We measured seasonal field metabolic rates (FMR) and water fluxes in the three species of free-living wombat using the doubly labelled water technique, to further investigate the extent of energy conservation in the Vombatidae. Measurements were taken during the wet and dry annual extremes of their characteristically harsh environments, which corresponded to seasonal extremes of food and water availability. Seasonal FMRs for all wombat species were lower than that recorded for other marsupials and well below that predicted for herbivorous mammals. Dry-season FMR of Lasiorhinus kreftii was 40% of that predicted for a mammal. Wombats maintained energy balance during the poor season by reducing FMR to about half that of the good season. Water flux rates during the dry season for the arid-adapted Lasiorhinus are amongst the lowest recorded for mammals, being only 25% of that predicted for a similarly sized herbivorous mammal. These low water flux rates enable wombats in semi-arid areas to maintain water balance without drinking. Estimated food and nitrogen intake rates were also low. We conclude that the energetically frugal lifestyle of the Vombatidae is amongst the most extreme for mammals.

Animals↗

Defensive burying in rodents: ethology, neurobiology and psychopharmacology.

Defensive burying refers to the typical rodent behavior of displacing bedding material with vigorous treading-like movements of their forepaws and shoveling movements of their heads directed towards a variety of noxious stimuli that pose a near and immediate threat, such as a wall-mounted electrified shock-prod. Since its introduction 25 years ago by Pinel and Treit [J. Comp. Physiol. Psychol. 92 (1978) 708], defensive (shock-prod) burying has been the focus of a considerable amount of research effort delineating the methodology/ethology, psychopharmacology and neurobiology of this robust and species-specific active avoidance or coping response. The present review gives a summary of this research with special reference to the behavioral (face and construct) and pharmacological (predictive) validity of the shock-prod burying test as an animal model for human anxiety. Emphasis is also placed on some recent modifications of the paradigm that may increase its utility and reliability as to individual differences in expressed emotional coping responses and sensitivity to pharmacological treatments. Overall, the behavioral and physiological responses displayed in the shock-prod paradigm are expressions of normal and functionally adaptive coping patterns and the extremes of either active (i.e., burying) or passive (i.e., freezing) forms of responding in this test cannot simply be regarded as inappropriate, maladaptive or pathological. For this reason, the shock-prod paradigm is not an animal model for anxiety disorder or for any other psychiatric disease, but instead possesses a high degree of face and construct validity for normal and functionally adaptive human fear and anxious apprehension. However, the apparent good pharmacological validation (predictive validity) of this test reinforces the view that normal and pathological anxiety involves, at least partly, common neurobiological substrates. Therefore, this paradigm is not only suitable for screening potential anxiolytic properties of new drugs, but seems to be especially valuable for unraveling the neural circuitry and neurochemical mechanisms underlying the generation of active and passive coping responses as different expressions of anxiety.

Adaptation, Psychological↗

Prediction of pesticide concentrations in the atmosphere using an atmospheric diffusion model (linear source plume model).

The foundational model to predict concentration of pesticides in the atmosphere outside of the sprayed area was developed using the results of measured concentration in the atmosphere, in reference to the atmospheric diffusion model utilized for the air pollution prediction model. The atmospheric diffusion model assumes that the applied area was a topographically flat farmland, that wind direction and wind speeds were constant, and the pesticide was constantly discharged from the emission line sources. Therefore the linear source plume model (LSPLM) was developed. The concentration in the atmosphere was predicted by assigning the property of the pesticides and various conditions of measurements of the model, and compared with the measured them, then the adaptability of the model was examined. As a result, the correlation between the measured value and the predicted value in paddy and forested areas was significant (P < 0.01) although deviations in the order of tens were observed, the measured value and the predicted value were generally in agreement.

Agriculture↗

Adaptation of energy metabolism of overweight women to low-energy intake, studied with whole-body calorimeters.

In 14 overweight women, 24-h energy expenditure (EE) was measured in a whole-body indirect calorimeter: before weight reduction (100% diet), after 1 wk on a 4.2-MJ diet, after 8 wk on 4.2-MJ diet, after weight reduction on 100% diet. Data of two subjects were excluded. Mean body weight declined from 93.3 +/- 7.4 (mean +/- SD) to 83.4 +/- 7.7 kg; 24-hEE decreased from 10.52 +/- 0.83 MJ on the 100% diet to 9.58 +/- 0.75 MJ on the 4.2-MJ diet. After 8 wk, 24-hEE had decreased by 15% of the initial 24-hEE to 8.92 +/- 0.65 MJ. After refeeding (1 wk), it increased to 9.45 +/- 0.75 MJ. Calculated energy requirement before weight reduction was 10.62 +/- 0.88 MJ/day; after weight reduction, 9.39 +/- 0.79 MJ/day. The decrease was more than that predicted from the change in body weight and body composition. An adaptation probably occurs, which may be metabolic.

Adaptation, Biological↗

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach.

In reviewing the tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defences, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses.

Adaptation, Physiological↗

Reduced dark-adaptation: an indication of lithium's neuronal action in humans.

Although lithium plays a major role in therapy and prophylaxis of affective psychoses, no direct indication of its neuronal action in humans exists. A lithium-induced strong reduction of foveal dark-adaptation was found in healthy volunteers, and a lithium-induced reduction was also measured in patients with affective psychoses. Dark-adaptation measurements apparently offer the opportunity for in vivo monitoring of lithium's CNS effects in humans and may predict lithium's clinical efficacy.

Adaptation, Ocular↗

Effects of prenatal alcohol exposure at school age. I. Physical and cognitive development.

Alcohol is a potent teratogen associated with dysmorphology, growth retardation, and neurological damage in children with the full fetal alcohol syndrome (FAS); alcohol is also associated with growth retardation and behavioral alterations in neonates prenatally exposed to various dosages. Questions remain about the long-term consequences of prenatal alcohol exposure. This study reports on the follow-up of a subsample of 68 children, the majority of whom were low income and black (mean age: 5 years, 10 months) who were first evaluated as neonates. Physical and cognitive outcomes of 25 children of women who drank throughout pregnancy [absolute alcohol (AA)/week: mean = 11.80 oz), even after receiving an educational intervention to stop drinking, were compared with outcomes of children in two contrast groups: a) women (n = 22) who stopped drinking (AA/week: mean = 11.46 oz) in the second trimester after an educational intervention but resumed postpartum; and b) women who did not drink during pregnancy and who drank little postnatally (n = 21). Children were compared for alcohol-related birth defects (ARBDs), growth (height, weight, and head circumference), and cognitive, academic, and adaptive measures. Neonatal and current physical measures were correlated to determine predictability of neonatal status. When the effects of age and gender were controlled, children in the continued-to-drink group showed significantly more ARBDs and had smaller head circumferences than those in the other two groups. When current drinking reported by caretakers was controlled, the children who were exposed throughout pregnancy also showed significant and consistent deficits in several areas of intellectual functioning including sequential processing (short-term memory and encoding) and overall mental processing. Alcohol-exposed children displayed significant deficits in preacademic skills when compared with children of nondrinkers, with both alcohol groups deficient in premath and reading skills. There were no differences in adaptive behavior at follow-up. These data suggest that alcohol exposure throughout pregnancy is correlated with persistent physical differences as well as identifiable deficits in sequential memory processes and specific academic skills. However, even when alcohol use is limited to the first part of pregnancy, significant deficits in academic skills and growth parameters are measurable.

Adult↗

Adaptive realtime compensatory feedback to open the light-pupil reflex loop.

Integrity of the visual pathway is often clinically determined from response of the pupil to light. The need for more quantitative measurement of pupillary response has led engineers to investigate the light-pupil reflex with systems analysis techniques. The results have made the light-pupil reflex a model of the application of the principles of control theory to physiologic mechanisms. This analysis required that the system be rendered open loop by focusing the stimulus at the center of the pupil. Patients may not be able to restrict their head and eye movement well enough to permit the feedback loop to be rendered open loop optically. Thus, clinical applications of the technique have been limited. A means of opening the feedback loop by using a realtime deterministic autoregressive moving average prediction algorithm integrated into a computer based television pupillometer has been developed. It employs a model reference adaptive scheme to identify the physiologic system, then predicts future values of pupil area to compensate for delays in the measuring apparatus. A computer driven liquid crystal display shutter controls retinal illuminance to render the light-pupil reflex open loop. This technique reduced the mean square error of retinal illuminance by about 75% compared to uncompensated pupil responses.

Algorithms↗

Dimensions and moment arms of the hind- and forelimb muscles of common chimpanzees (Pan troglodytes).

This paper supplies quantitative data on the hind- and forelimb musculature of common chimpanzees (Pan troglodytes) and calculates maximum joint moments of force as a contribution to a better understanding of the differences between chimpanzee and human locomotion. We dissected three chimpanzees, and recorded muscle mass, fascicle length, and physiological cross-sectional area (PCSA). We also obtained flexion/extension moment arms of the major muscles about the limb joints. We find that in the hindlimb, chimpanzees possess longer fascicles in most muscles but smaller PCSAs than are predicted for humans of equal body mass, suggesting that the adaptive emphasis in chimpanzees is on joint mobility at the expense of tension production. In common chimpanzee bipedalism, both hips and knees are significantly more flexed than in humans, necessitating muscles capable of exerting larger moments at the joints for the same ground force. However, we find that when subject to the same stresses, chimpanzee hindlimb muscles provide far smaller moments at the joints than humans, particularly the quadriceps and plantar flexors. In contrast, all forelimb muscle masses, fascicle lengths, and PCSAs are smaller in humans than in chimpanzees, reflecting the use of the forelimbs in chimpanzee, but not human, locomotion. When subject to the same stresses, chimpanzee forelimb muscles provide larger moments at the joints than humans, presumably because of the demands on the forelimbs during locomotion. These differences in muscle architecture and function help to explain why chimpanzees are restricted in their ability to walk, and particularly to run bipedally.

Animals↗

Cross-species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live-virus vaccines.

All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host-range barrier expanding their host range. However, in very rare cases cross-species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS-associated coronavirus (SARS-CoV). The opportunities for cross-species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live-vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross-species transfer of viruses in nature, with emphasis on the occurrence of host-range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses.

Animals↗

An estimate of the amount of genetic variation in the common mussel Mytilus edulis.

Allozyme variation in a population of the common mussel Mytilus edulis in Mumbles, South Wales, has been studied by starch gel electrophoresis. On the basis of data obtained for 34 loci, we estimate the proportion of loci polymorphic to be 30%. Using only the 29 loci for which individual genotypes can be accurately typed, the average heterozygosity is estimated to be 9.5 +/- 3.6%. The calculated expected average heterozygosity based on Hardy-Weinberg expectations is identical with the observed value. Allele frequency data at six polymorphic loci are given for several other British populations. There is no significant geographic heterogeneity. The results are discussed in relation to genetic adaptive strategies and are shown to be inconsistent with the predictions of the neutral hypothesis.

Alleles↗

Elimination of plant toxins by herbivorous woodrats: revisiting an explanation for dietary specialization in mammalian herbivores.

Constraints on rates of detoxification and elimination of plant toxins are thought to be responsible for limiting dietary specialization in mammalian herbivores. This hypothesis, known as the detoxification limitations hypothesis, suggests that most mammalian herbivores are generalists to avoid overdosing on toxins from a single plant species. The hypothesis also predicts that the few mammalian specialists that exist should have adaptations for rapid detoxification and elimination of plant secondary compounds. We took a pharmacological approach to test whether specialists eliminate toxins from the bloodstream faster than generalists. We compared elimination rate and total exposure of alpha-pinene in closely related dietary specialist and generalist woodrats, Neotoma stephensi and N. albigula, respectively. Animals were orally gavaged with alpha-pinene, a plant secondary compound present in the natural diets of both woodrat species. We collected venous blood at 3, 6, 10, 15, and 20 min post-ingestion of alpha-pinene. Blood was analyzed for alpha-pinene concentration using gas chromatography. We found that specialist and generalist woodrats did not differ in elimination rates of alpha-pinene. However, specialists had lower exposure levels of alpha-pinene than generalists due to lower initial delivery of alpha-pinene to the general circulation. The levels of alpha-pinene detected in the bloodstream of specialists were 4.7-5.3x lower over all time intervals than generalists. Thus, specialists encounter a functionally lower dose of toxin than generalists. We suggest that the lower exposure level of specialist woodrats may be due to mechanisms in the gut that decrease toxin absorption. Regardless of mechanism, lower exposure to plant toxins may allow specialists to forage on diets with high toxin concentrations thereby facilitating dietary specialization.

Absorption↗

The versatility of hydroxyapatite blocks in maxillofacial surgery.

There is considerable interest at present in the potential role of calcium hydroxyapatite as a biomaterial for bone augmentation in oral and maxillofacial surgery. Most of the published work has been on the particulate form, mainly in alveolar ridge procedures. However, hydroxyapatite is also available as solid or porous blocks. The blocks are more predictable in their use than are the particles, and are adaptable and versatile. This paper reviews the biological behaviour of the material and discusses the role of hydroxyapatite blocks in alveolar ridge augmentation and orthognathic surgery.

Alveolar Ridge Augmentation↗

QT dynamicity: a prognostic factor for sudden cardiac death in chronic heart failure.

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death in patients with chronic heart failure (CHF). METHODS: We prospectively included 175 CHF patients in sinus rhythm. QT dynamicity was evaluated by analyzing 24-h Holter recordings. The linear regression slope of QT interval measured to the apex and to the end of T wave plotted against RR intervals was calculated using a dedicated Holter algorithm. RESULTS: Mean follow-up was 29.9+/-17.9 months. There were 48 deaths, of which 21 were sudden. The actuarial 3-year mortality rates were 38.4% for overall mortality and 14.1% for sudden death. Of all the parameters, an increased QTe/RR slope (>0.28) was the strongest independent predictor of sudden death (relative risk 3.47, 95% confidence interval 1.43-8.40, p=0.006). CONCLUSION: Increased 24-h QTe dynamicity is independently predictive of sudden death among patients with heart failure. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.

Adult↗

A novel microstructural approach in tendon viscoelastic modelling at the fibrillar level.

Novel applications in rehabilitation, surgery and tissue engineering require the knowledge of the mechanical behaviour of the tissues at microstructural level. The aim of this work is to investigate the viscoelastic properties of the tendon from the interaction of its biological constituents in the fibrillar network. Traction, relaxation and creep in-vitro tests have been performed on porcine flexor digital tendons. A viscoelastic constitutive equation at finite deformation is presented. The fibrillar deformation modes are described through a network of adaptive links between collagen type I and decorin. The theoretical predictions fit accurately the experimental data. The results of the model demonstrate the mechanical importance of glycosaminoglycan chains of decorin for the differential recruitment and the activation of fibrillar collagen.

Biomechanical Phenomena↗

Sampling or intermittency in hand control system dynamics.

A hand control model is proposed. Investigation of the hand's intermittency synchronization shows it corresponds to an input-synchronized sampler rather than the clock-synchronized sampler more typical of engineering systems. A velocity control mechanism, similar to that in an eye tracking system is shown to be absent in the hand. A quantitative transfer function for predictable inputs serves further to define the hand's input adaptive characteristics. Stability margin adjustments of a linear reduced model enabled us to match the available quantitative data. The most exciting result of this study is the evidence for intermittency: a refractory period shown in the short pulse experiment, peaks in the frequency response experiments, and a saccadic sequence of steps in response to an open loop step input and to a closed loop ramp input.

Central Nervous System↗

Pulmonary bipartitioning and lobar transplantation: a new approach to donor organ shortage.

The scarcity of small donors has significantly limited lung transplantation for pediatric and small adult patients. Use of single lobes procured from size-unmatched donors has overcome this difficulty, but only in a few selected cases and, in addition, it represents a waste of lung tissue. In an animal model we have shown that it is possible to divide one lung with careful partitioning of the vascular and bronchial structures and thus obtain two viable lobar grafts suitable for bilateral implantation in a smaller animal. We have now applied this procedure clinically in seven patients operated on between May 1993 and November 1994. The indications were cystic fibrosis in three children, primary pulmonary hypertension in two adults, bronchiectasis in one, and idiopathic pulmonary fibrosis in one. There were three children aged 13 to 17 years (median 14) and four adults aged 40 to 53 years (median 45). There was a 46% to 50% discrepancy for weight between recipient and donor and a 12% to 17% discrepancy for height. The surgical technique consisted of careful partitioning of the left donor lung, bilateral anterior thoracotomy in the recipient, and, with the use of cardiopulmonary bypass, implantation of the lower lobe in the left hemithorax and the upper lobe in the right hemithorax. Vascular and bronchial connections were facilitated by leaving a long pedicle on the recipient side. The pulmonary artery anastomosis for the donor left upper lobe was done with the "fissure" side of the artery to ensure an anastomosis without tension. An end-to-end bronchial anastomosis overcame the problem of size discrepancy. Six patients are alive and well 10 to 27 months (median 19) after operation. One patient with cystic fibrosis died of systemic aspergillosis infection. All were discharged from the hospital within the first or second postoperative month. No technical problems were identified: repeated bronchoscopy has demonstrated satisfactory healing without early stricture formation. All patients remain well subjectively with good exercise tolerance and all patients achieve greater than 70% of predicted values of forced expiratory volume in 1 second. Perfect adaptation of the transplanted lobes to the recipient pleural space has been demonstrated by postoperative computed tomographic scan. In conclusion, bilateral lobar transplantation from a single donor lung is possible in small adults or children when there is a large size discrepancy with the donor. This may help resolve the problem of donor availability in the pediatric population.

Adolescent↗

Circadian timing in health and disease.

Metabolic status varies predictably on a daily and seasonal basis in order to adapt to the cyclical environment. The hypothalamic circadian pacemaker of the suprachiasmatic nuclei (SCN) co-ordinates these metabolic cycles. Circadian timing is based upon a transcriptional/post-translational negative feedback loop involving a series of core clock genes and their products. Local molecular clocks in peripheral tissues are synchronised by a variety of autonomic, paracrine and endocrine cues reflective of SCN time, thereby ensuring internal temporal co-ordination and optimal metabolic function. Disturbances of this co-ordination, as occur in long-term shift work, have a major impact on health.

Animals↗