A review of terms for regulated vs. forced,neurochemical-induced changes in body temperature

Deviations of the body temperature of homeothermic animals may be regulated or forced. A regulated change in core temperature is caused by a natural or synthetic compound that displaces the set-point temperature. A forced shift occurs when an excessive environmental or endogenous heat load, or heat sink, exceeds the body's capacity to thermoregulate but does not affect set-point. A fever is the paradigm of a regulated increase in body temperature, but the term fever has acquired a strict pathological definition over the past two decades. Consequently, other forms of nonpathological, regulated elevations in body temperature have generally been classified as hyperthermia; and decreases in core temperature--either forced or regulated--have generally been classified as hypothermia. Since the terms hyperthermia and hypothermia fail to distinguish a regulated vs. a forced temperature change, a confusion of terms has been created in the literature. It would appear that “resisted or unregulated hyperthermia” and “hypothermia,” respectively, are appropriate terms for describing a forced increase and decrease in core temperature. A nonpathological but regulated elevation in temperature may be defined as unresisted or regulated hyperthermia, whereas a regulated decrease in temperature may be termed unresisted or regulated hypothermia. This simple scheme appears to be the most practical means for distinguishing between forced and regulated changes in core temperature.     

Effect of temperature control upon a mouse model of partial hepatic ischaemia/reperfusion injury

In vivo models of hepatic ischaemia/reperfusion injury (IRI) are widely used to study both the mechanisms of hepatic ischaemic injury and to seek means of hepatic protection. Achieving high-quality reproducible data are essential if the results of multiple studies are to be compared and reconciled. This paper presents our findings concerning the effect of intraoperative thermoregulation upon signal to noise ratios of hepatic IRI experiments in mice. Four experiments were conducted, using three different strategies for core temperature maintenance. Animals underwent hepatic IRI and euthanized 24 h postoperatively for measurement of plasma alanine aminotransferase (ALT). Duration of ischaemia was used to adjust the severity of injury. Experiment 1 utilized a constant output heating system and resulted in rising postoperative ALTs following increasing durations of hepatic ischaemia. Experiment 2, using the same constant output heating system confirmed a difference between ischaemic and sham-operated animals. Experiment 3 used a thermostatically controlled heating system and resulted in highly variable results with a small, but statistically significant correlation between ALT levels and rectal temperature readings. Experiment 4 used a homeothermic warming system and demonstrated highly reproducible data from increasing durations of ischaemia. High-quality data from hepatic ischaemia/reperfusion models are dependent upon careful control of intraoperative temperature. The use of homeothermic warming systems is recommended and conversely, the use of thermostatically controlled warming mats is to be avoided in these models.     

Effect of ambient temperature on the circadian activity rhythm in common marmosets, Callithrix j. jacchus (primates)

Whereas the (zeitgeber) effect of ambient temperature T_a and temperature cycles TaC's on circadian rhythmicity has been well documented for heterofhermic mammals, inconsistent results have been obtained for strictly homeothermic species. Hence, it might be inferred that the susceptibility of the mammalian circadian timing system (CTS) to Ta and TaC's depends on the range of the animals' core and/or brain temperature rhythm. This hypothesis was tested in the common marmoset (Callithrix j. jacchus, n=12), a small diurnal primate with an amplitude in body temperature rhythm that is larger than for other homeothermic primates studied so far. Within the range 20-30°C, no systematic effects of constant Ta on most parameters of the marmosets' light-dark (LD)-entrained and free-running circadian activity rhythm (CAR) were found. Significant differences could be established in the average amount of activity per circadian cycle. It was highest at Ta 25°C (LD) and 20°C (light-light, LL) and most probably reflected a temperature-induced masking effect. A 24h trapezoidal TaC of 20:30°C entrained the free-running CAR in two of six marmosets and produced relative coordination in all others. Accordingly, in all animals tested, it had an effect on the CTS. In marmosets free running in LL at a Ta of 20°C or 30°C, 3h warm and cold pulses of 30°C and 20°C, respectively, produced neither systematic phase responses nor period responses of the CAR. So, there is no evidence of a phase-response mechanism underlying circadian entrainment. The results show that large-amplitude TaC's function as a weak zeitgeber for the marmosets' CTS. Since this zeitgeber effect is significantly larger than that found in owl monkeys, the results are consistent with the starting hypothesis that the zeitgeber effect of a given T,C on the mammalian CTS may be related to the amplitude of the species' core and/or brain temperature cycle.     

Selenoprotein expression and function—Selenoprotein W

Selenoprotein W (SeW) is a small selenoprotein (85 to 88 amino acids) first identified in sheep suffering from selenium deficiency. The levels are highest in muscle, heart (except rodents) spleen and brain. The deduced amino acid sequence has been obtained for mice, rats, monkeys, humans, sheep, pigs, fish and chickens. The sequences of SeW are identical in rats and mice as well as monkeys and humans. In all eight species of animals cysteine is present at residue number 9 and selenocysteine at residue number 13. Residue number 37 is cysteine in six species of animal with fish and chickens as the exceptions. Of those examined, the rodent SeW is the only one containing four cysteines whereas the others contain only two cysteines. Glutathionylaltion has been shown for SeW from rats and monkeys but has not been confirmed for this selenoprotein from the other six animals. The biological function of SeW has not been definitely identified. Evidence has been obtained that it can serve as an antioxidant, responds to stress, involved in cell immunity, specific target for methylmercury, and has thioredoxin-like function.     

High Cadmium Accumulation Among Humans and Primates: Comparison Across Various Mammalian Species—A Study from Japan

The majority of existing literature reports that cadmium (Cd) is toxic to humans and most living organisms. This paper reports the results of our study that measured Cd levels in the livers and kidneys of humans and other 50 mammalian species under normal conditions in Japan. The study tests the differences in the Cd concentrations across different mammalian species and sexes. Our results revealed that (1) there is a strong correlation between the Cd levels in the livers and kidneys across all examined species, (2) humans exhibit the highest Cd accumulation level in both organs, (3) primates also show a high Cd concentration at a level close to humans, (4) mice and rats show low Cd levels in both organs, indicating that humans accumulate about a few thousand times more Cd than mice and rats, and (5) the Cd concentration of female mammals is more than double of males for both organs. Our results indicate that these cross-sex as well as cross-species discrepancies cannot be explained by the difference in daily Cd intake. While further research is necessary to determine any potential role of Cd accumulation, we speculate that Cd plays some physiological function in the renal cortex of humans and primates.     

Anatomy of rodent and human livers: What are the differences?

The size of the liver of terrestrial mammals obeys the allometric scaling law over a weight range of >3 1 10⁶. Since scaling reflects adaptive changes in size or scale among otherwise similar animals, we can expect to observe more similarities than differences between rodent and human livers. Obvious differences, such as the presence (rodents) or absence (humans) of lobation and the presence (mice, humans) or absence (rats) of a gallbladder, suggest qualitative differences between the livers of these species. After review, however, we conclude that these dissimilarities represent relatively small quantitative differences. The microarchitecture of the liver is very similar among mammalian species and best represented by the lobular concept, with the biggest difference present in the degree of connective tissue development in the portal tracts. Although larger mammals have larger lobules, increasing size of the liver is mainly accomplished by increasing the number of lobules. The increasing role of the hepatic artery in lobular perfusion of larger species is, perhaps, the most important and least known difference between small and large livers, because it profoundly affects not only interventions like liver transplantations, but also calculations of liver function.     

Ontogeny and phylogeny of endothermy and torpor in mammals and birds

Endothermic thermoregulation in small, altricial mammals and birds develops at about one third to half of adult size. The small size and consequently high heat loss in these young should result in more pronounced energetic challenges than in adults. Thus, employing torpor (a controlled reduction of metabolic rate and body temperature) during development would allow them to save energy. Although torpor during development in endotherms is likely to occur in many species, it has been documented in only a few. In small, altricial birds (4 orders) and marsupials (1 order), which are poikilothermic at hatching/birth, the development of competent endothermic thermoregulation during cold exposure appears to be concurrent with the capability to display torpor (i.e. poikilothermy is followed by heterothermy), supporting the view that torpor is phylogenetically old and likely plesiomorphic. In contrast, in small, altricial placental mammals (2 orders), poikilothermy at birth is followed first by a homeothermic phase after endothermic thermoregulation is established; the ability to employ torpor develops later (i.e. poikilothermy-homeothermy-heterothermy). This suggests that in placentals torpor is a derived trait that evolved secondarily after a homeothermic phase in certain taxa perhaps as a response to energetic challenges. As mammals and birds arose from different reptilian lineages, endothermy likely evolved separately in the two classes, and given that the developmental sequence of torpor differs between marsupials and placentals, torpor seems to have evolved at least thrice.     

The possible functional role of neuronal gangliosides in temperature adaptation of vertebrates

Comparative studies on brain gangliosides of more than 60 vertebrate species show correlations between concentration and the level of evolutionary organization: poikilothermic lower vertebrates (fish, amphibs, reptiles) contain about 110 to 700 μg ganglioside bound NeuAc/g. fresh wt., homeothermic birds and mammals, on the other side, 500 to 1000 μg. The composition of brain gangliosides in poikilotherms is much more complex and variable (more multisialogangliosides) as compared with homeotherms (domination of less polar fractions). There are distinct correlations between brain ganglioside composition and state of thermal adaptation: Fishes being adapted to habitates with extreme temperatures (antarctic icefish — tropic fish) are characterized by quite opposite ganglioside patterns (domination of high versus less polar fractions). During seasonal acclimatization and experimental acclimation of fish to cold or during hibernation and early postnatal development of mammals poly-sialylations of brain gangliosides occur. With regard to this the individual brain structures react differently.

The results are taken for evidence that variations in the composion of synaptic membrane-bound gangliosides may induce long-term alterations in viscosity and permeability of the neuronal membrane by which the neuronal transmission might be kept on a constant level during the process of temperature adaptation.     

Expanding our scientific horizons: utilization of unique model organisms in biological research

During the past century, research studies using animal models have contributed to numerous scientific discoveries and have been vital for the understanding of numerous biological processes, including disease. Over the past decades, the scientific community has defined a small number of model organisms that includes a few mammals, fish (mainly zebrafish), birds (mainly chicken), frogs, flies, and nematodes. Rodents are by far the most commonly employed laboratory animals in biomedical research. Mice share many biological similarities to humans and can be genetically manipulated to express mutations linked to human diseases. Mice and rats reproduce relatively quickly and have a short life span, which allows scientists to study progressive disorders, including aging. A large range of inbred mice strains enables accurate and reproducible experiments by decreasing the variability often associated with animal models and biological systems in general. Finally, mice are cost‐effective, small, and relatively easy to handle, transport, and house. All of these advantages combine to make mice the major species for recapitulating and studying human diseases. However, focusing exclusively on one or very few animal models may lead researchers to lose sight of other species with vastly different biology that might inform and affect our understanding of disease pathogenesis.     

Quantifying the instability of core temperature in rodents

Radiotelemetry provides researchers with the ability to sample the core temperature of rodents and other species rapidly. Compared to large mammals, the time-course of core temperature of rodents is variable and their data are often averaged into bins of one or more hours for publication. When viewing averaged data, a stable core temperature over a wide range of ambient temperatures is observed; however, if the time-course of core temperature of individual animals is examined closely with a sampling period of 1–10 min, a continuous waxing and waning of temperature is observed. It is proposed that calculating the change in temperature from one time point to the next (i.e., temperature differential) is an informative measure of the performance of the thermoregulatory system. A quantitative measure of the stability of the thermoregulatory system can be determined by calculating the absolute value of the temperature differential. It is shown that the absolute temperature differential (ATD) is dependent on ambient temperature, genetic strain, type of cage bedding, and body size. The ATD is simple to calculate from telemetry data and may be an important parameter for the study of rodent thermal physiology.     

Advances in molecular biology of hibernation in mammals

Mammalian hibernation is characterized by profound reductions in metabolism, oxygen consumption and heart rate. As a result, the animal enters a state of suspended animation where core body temperatures can plummet as low as -2.9 degrees C. Not only can hibernating mammals survive these physiological extremes, but they also return to a normothermic state of activity without reperfusion injury or other ill effects. This review examines recent findings on the genes, proteins and small molecules that control the induction and maintenance of hibernation in mammals. The molecular events involved with remodeling metabolism, inducing hypothermia and maintaining organ function are discussed and considered with respect to analogous processes in non-hibernating mammals such as mice and humans. The advent of sequenced genomes from three distantly related hibernators, a bat, hedgehog and ground squirrel, provides additional opportunities for molecular biologists to explore the mechanistic aspects of this biological adaptation in greater detail.     

Heterothermy in large mammals: inevitable or implemented?

Advances in biologging techniques over the past 20 years have allowed for the remote and continuous measurement of body temperatures in free‐living mammals. While there is an abundance of literature on heterothermy in small mammals, fewer studies have investigated the daily variability of body core temperature in larger mammals. Here we review measures of heterothermy and the factors that influence heterothermy in large mammals in their natural habitats, focussing on large mammalian herbivores. The mean 24 h body core temperatures for 17 species of large mammalian herbivores (>10 kg) decreased by ～1.3°C for each 10‐fold increase in body mass, a relationship that remained significant following phylogenetic correction. The degree of heterothermy, as measured by the 24 h amplitude of body core temperature rhythm, was independent of body mass and appeared to be driven primarily by energy and water limitations. When faced with the competing demands of osmoregulation, energy acquisition and water or energy use for thermoregulation, large mammalian herbivores appear to relax the precision of thermoregulation thereby conserving body water and energy. Such relaxation may entail a cost in that an animal moves closer to its thermal limits for performance. Maintaining homeostasis requires trade‐offs between regulated systems, and homeothermy apparently is not accorded the highest priority; large mammals are able to maintain optimal homeothermy only if they are well nourished, hydrated, and not compromised energetically. We propose that the amplitude of the 24 h rhythm of body core temperature provides a useful index of any compromise experienced by a free‐living large mammal and may predict the performance and fitness of an animal.     

Some physiological and developmental considerations of the temperature-gradient hypothesis of bone marrow distribution

In adult humans, active bone marrow is confined to the proximal portion of the skeleton. Huggins and Blocksom (J. Exp. Med., 64: 253, '36) concluded that a high temperature is needed for hematopoiesis in rats. However, precise thermal regulation of human marrow was not found (Petrakis, J. Appl. Physiol., 4: 549, '52). Because these experiments made on the rat tail are the basis for a commonly accepted hypothesis attempting to explain marrow distribution in man, it was considered of importance to re-examine the caudal vertebra model upon which the temperature-gradient hypothesis is based. The sacral and coccygeal vertebrae were examined in rats, mice and humans with respect to marrow cellularity and temperature. In rats and mice and man it was observed that the transition between hematopoietically-active and inactive (fatty) vertebral marrow cavities is abrupt, occurring at the level of the first and second caudal and coccygeal vertebrae. All vertebrae distal to this point have fatty marrow. Of significance was the finding that the vertebral and coccygeal temperatures, as measured with a thermister needle, remain unaltered over this area of changing cellular activity. These anatomical and thermal observations of the caudal vertebrae of rats, mice, and humans indicate that the use of the tail as an experimental model does not support the hypothesis that temperature is a primary factor in the physiological maintenance of hematopoiesis in bone marrow. The possible relationship of hematopoietic activity to developmental and other factors peculiar to the caudal vertebra model is under study.     

Lateral cerebral ventricle and preoptic-anterior hypothalamic area infusion and perfusion of beta-endorphin and ACTH to unrestrained rats: core and surface temperature responses

Both beta-endorphin and ACTH have been found in high concentrations within the hypothalami of mammals and each neuropeptide has been proposed to play a physiological role in regulating body temperature. In an attempt to determine how these peptides may alter thermoregulation, small, microgram concentrations of beta-endorphin and ACTH were injected either into lateral cerebral ventricle (ICV) or directly into the preoptic-anterior hypothalamic area (POAH) or perfused into the POAH of unrestrained rats. Core (rectal) and surface (tail) temperatures were recorded before and after ICV and POAH injection of 1 microgram of beta-endorphin or ACTH or perfusion (10 ng/microL) of either neuropeptide. POAH perfusion of naloxone HCl following the neuropeptide perfusion was tested to determine the specificity of the temperature responses. Regardless of the route of central administration, beta-endorphin, in the concentrations used, consistently evoked a hyperthermic core temperature response, that could be antagonized by naloxone. Increased core temperatures may, in part, have been due to peripheral vasoconstriction, as suggested by the decreases seen in tail temperature. The same concentrations of ACTH failed to show any prominent core temperature changes. Results suggest that beta-endorphin is a more potent modulator than ACTH in altering core temperatures of unrestrained rats. Whether beta-endorphin and ACTH act physiologically in an antagonistic manner to maintain a constant body temperature remains to be proven.     

Studying the effects of multiple invasive mammals on Cory��s shearwater nest survival

The most common invasive mammals??mice, rats, and cats??have been introduced to islands around the world, where they continue to negatively affect native biodiversity. The eradication of those invasive mammals has had positive effects on many species of seabirds. However, the removal of one invasive mammal species may result in abundance changes of other species due to trophic and competitive interactions among species. Understanding the overall impact of several invasive species is a key challenge when evaluating the possible effects of eradication programmes. Here we assess the influence of the three most common invasive mammals on nest survival of Cory??s shearwater (Calonectris diomedea). We monitored six breeding colonies over 3?years and measured the activity of mice, rats and cats to examine the influence of invasive mammals on nest survival. We found that nest survival showed a similar temporal trend in all years, with lowest weekly survival probabilities shortly after chicks hatched. Cats were identified as major predators of chicks, but no measure of colony-specific cat activity was able to adequately explain variation in shearwater nest survival. Nest survival was on average 0.38 (95?% confidence interval 0.20?C0.53) and varied among colonies as well as over time. We found a small positive influence of rats on nest survival, which may indicate that the presence of small rodents as alternative prey may reduce cat predation of chicks. Our findings suggest that the eradication of rodents alone may exacerbate the adverse effects of cats on shearwater nest survival.     

Sites and regulation of carnitine biosynthesis in mammals

Although the pathway of carnitine biosynthesis in mammals is known, the location of active synthesis of carnitine and regulation of the pathway have not been clearly defined. Studies in several laboratories have shown that the enzymes that collectively convert epsilon-N-trimethyllysine (epsilon-N-TML) to gamma-butyrobetaine are found in all tissues studied in rats and humans, but distribution of the final enzyme of the pathway, gamma-butyrobetaine, 2-oxoglutarate dioxygenase (gamma-butyrobetaine hydroxylase) is variable from one species to another. Evidence from studies in rats and humans indicates that uptake and metabolism of epsilon-N-TML by the kidney is necessary for carnitine biosynthesis from circulating epsilon-N-TML. Limited data now available suggest that some of the intracellularly derived epsilon-N-TML is metabolized to gamma-butyrobetaine and carnitine in the tissue of origin, and some is released into the circulation. epsilon-N-TML in mammals is apparently derived from lysine residues in proteins, which are methylated and later released by protein hydrolysis. This source probably provides sufficient substrate for carnitine biosynthesis. Carnitine biosynthesis from epsilon-N-TML is not regulated by end-product feedback mechanisms. Hepatic gamma-butyrobetaine hydroxylase activity in rats and humans is developmentally regulated, and is increased by dietary L-thyroxine in adult rats. No other mechanisms for regulation of carnitine biosynthesis have been identified.     

Humans running in place on water at simulated reduced gravity

Background

On Earth only a few legged species, such as water strider insects, some aquatic birds and lizards, can run on water. For most other species, including humans, this is precluded by body size and proportions, lack of appropriate appendages, and limited muscle power. However, if gravity is reduced to less than Earth’s gravity, running on water should require less muscle power. Here we use a hydrodynamic model to predict the gravity levels at which humans should be able to run on water. We test these predictions in the laboratory using a reduced gravity simulator.

Methodology/Principal Findings

We adapted a model equation, previously used by Glasheen and McMahon to explain the dynamics of Basilisk lizard, to predict the body mass, stride frequency and gravity necessary for a person to run on water. Progressive body-weight unloading of a person running in place on a wading pool confirmed the theoretical predictions that a person could run on water, at lunar (or lower) gravity levels using relatively small rigid fins. Three-dimensional motion capture of reflective markers on major joint centers showed that humans, similarly to the Basilisk Lizard and to the Western Grebe, keep the head-trunk segment at a nearly constant height, despite the high stride frequency and the intensive locomotor effort. Trunk stabilization at a nearly constant height differentiates running on water from other, more usual human gaits.

Conclusions/Significance

The results showed that a hydrodynamic model of lizards running on water can also be applied to humans, despite the enormous difference in body size and morphology.     

Effect of temperature on postillumination isoprene emission in oak and poplar

Isoprene emission from broadleaf trees is highly temperature dependent, accounts for much of the hydrocarbon emission from plants, and has a profound effect on atmospheric chemistry. We studied the temperature response of postillumination isoprene emission in oak (Quercus robur) and poplar (Populus deltoides) leaves in order to understand the regulation of isoprene emission. Upon darkening a leaf, isoprene emission fell nearly to zero but then increased for several minutes before falling back to nearly zero. Time of appearance of this burst of isoprene was highly temperature dependent, occurring sooner at higher temperatures. We hypothesize that this burst represents an intermediate pool of metabolites, probably early metabolites in the methylerythritol 4-phosphate pathway, accumulated upstream of dimethylallyl diphosphate (DMADP). The amount of this early metabolite(s) averaged 2.9 times the amount of plastidic DMADP. DMADP increased with temperature up to 35°C before starting to decrease; in contrast, the isoprene synthase rate constant increased up to 40°C, the highest temperature at which it could be assessed. During a rapid temperature switch from 30°C to 40°C, isoprene emission increased transiently. It was found that an increase in isoprene synthase activity is primarily responsible for this transient increase in emission levels, while DMADP level stayed constant during the switch. One hour after switching to 40°C, the amount of DMADP fell but the rate constant for isoprene synthase remained constant, indicating that the high temperature falloff in isoprene emission results from a reduction in the supply of DMADP rather than from changes in isoprene synthase activity.     

Comparing disturbance and generalism in birds and mammals: A hump-shaped pattern

Using indices as proxies, we observed that comparing a large number of common birds and mammals, the level of generalism peaks in species inhabiting habitats at intermediate disturbance levels. This pattern might be universal, at least in these homeothermic vertebrates. Birds show nonetheless some differences in pattern from mammals, where specialization at intermediate levels of disturbance is not present. Differences in ecological and evolutionary traits between birds and mammals might determine different adaptive responses to historical anthropogenic changes, explaining these taxa-specific hump-shaped patterns.