Exploring the importance of predicted camel NRAP exon 4 for environmental adaptation using a mouse model

BackgroundHypothermia is associated with many adverse clinical outcomes in pediatric patients, and thus, it is important to find an effective and safe method for preventing peri-operative hypothermia and its associated adverse outcomes in pediatric patients. This study aimed to investigate the effect of forced-air warming blankets with different temperatures on changes in the transforming growth factor-β (TGF-β), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels in children undergoing surgical treatment for developmental displacement of the hip (DDH).MethodsThe study included 123 children undergoing surgery for DDH under general anesthesia. The patients were randomly assigned to three groups, using a random number table: the 32, 38, and 43°C groups according to the temperature setting of the forced-air warming blankets. For each patient, body temperature was recorded immediately after anesthesia induction and intubation (T0), at initial incision (T1), at 1 h after incision (T2), at 2 h after incision (T3), at the end of surgery (T4), immediately upon return to the ward after surgery (T5), and then at 12 h (T6), 24 h (T7), 36 h (T8), and 48 h (T9) after the surgery. The serum levels of TGF-β, TNF-α, IL-1β, and IL-10 were measured at T0 and T4 for all groups.ResultsThe number of patients with fever in the 38°C group was significantly less than those in the 32 and 43°C groups (χ2 = 6.630, P = 0.036). At T0, the body temperatures in the 38 and 43°C groups were significantly higher than that in the 32°C group (F = 17.992, P < 0.001). At T2, the body temperature was significantly higher in the 43°C group than those in the 32 and 38°C groups (F = 12.776, P < 0.001). Moreover, at T4, the serum levels of TGF-β (F = 3286.548, P < 0.001) and IL-10 (F = 4628.983, P < 0.001) were significantly increased in the 38°C group, and the serum levels of TNF-α (F = 911.415, P < 0.001) and IL-1β (F = 322.191, P < 0.001) were significantly decreased in the 38°C group, compared with the levels in the 32 and 43°C groups.ConclusionForce-air warming blankets set at 38°C maintained stable body temperature with less adverse outcome and effectively inhibited the inflammatory response in pediatric patients undergoing surgery for DDH.Clinical trial registrationChiCTR1800014820; http://www.chictr.org.cn/showproj.aspx?proj=25240.

Sloths are a physiological conundrum tiptoeing a fine, physiological line. As herbivores, sloths get all of their nutrients and calories from a diet of low-nutritional leaves, leaving them with relatively few calories to burn for bodily processes after foraging. (Imagine how much energy you would have after eating nothing but unflavoured rice cakes.) Because sloths do not obtain many nutrients or calories from their diet and they use what little energy they have to gather and digest that poor-quality food, it would make sense that they cut corners on other physiological processes, such as body temperature regulation. Daisuke Muramatsu, with collaborators from Kyoto University, Nara University of Education, Nagoya University and Hokkaido Research Center, Japan, and Universidade Federal do Amazonas, Brazil, investigated the body temperature patterns of wild sloths in the Amazon rainforest of Brazil by monitoring the heart rate and skin temperature in free-ranging pale-throated sloths (Bradypus tridactylus) to find out how cheaply sloths regulate their body temperature on their low energy budget.The researchers attached heart rate monitors and temperature data loggers to 34 free-ranging sloths. They caught the animals near the Federal University of Amazonas in Brazil by climbing trees and gently taking the relatively undisturbed and unprotesting individuals back to the field lab. There, they used a custom-made harness to attach a modified sloth-friendly Fitbit to monitor each animal's heart rate, a temperature data logger for skin temperature measurements and a VHF transmitter to locate the individual animal to retrieve the precious data loggers. After attaching the harnesses, they released the sloths back to the trees where they had been captured and installed a temperature data logger on the trunk of the tree to measure the temperatures that each sloth experienced. Five days later, the scientists returned to the area and normally the animals had not moved too far.Analysing the information stored by the skin temperature data loggers, the team discovered that the sloths were always slightly warmer than the trunk temperatures, but those elevated skin temperatures did not appear to be very costly for the animals, as their heart rates did not increase with the temperature. Because the researchers don't know exactly where the sloths were hanging out during each temperature measurement, they assumed that perhaps the sloths were basking in sunny spots when their body temperatures were warmer. The sloths seem to be taking an easy option for maintaining their body temperature. Instead of increasing heart rate or using up expensive fuel to increase or maintain their body temperature, the animals were probably relying more on the sun and environment to do that work for them. This dependence on basking could help explain how sloths are able to maintain their body temperature cheaply instead of constantly burning expensive fuel when on such a tight energy budget.However, this study, posted online as a preprint at Social Science Research Network, has not yet been peer reviewed, so we should be cautious about some of the researchers’ conclusions. Referring to the sloths’ skin temperatures as body temperatures could lead to some incorrect conclusions about body temperature regulation, as the skin temperatures recorded by Muramatsu and colleagues are likely very different from core body temperatures. Skin temperatures tend to overestimate core temperature during warm environmental temperatures and underestimate it in cool conditions. Regardless, sloths are an exciting study species in which to study body temperature regulation, as they must strike a delicate balance between staying warm enough to keep their fermenting digestive microbiome happy, but doing so in a slow and measured way.

A comparative study of the temperature regulation and rate of metabolism of armadillos and armadillo-like mammals (hedgehogs and hedgehog tenrecs) is reported. Armadillos are characterized by low body temperatures, low basal rates of metabolism, and high minimal thermal conductances. Strictly temperate species of armadillos are confined in distribution to South America; they have higher body temperatures than tropical species, but these groups show no noticeable difference in basal rate or in minimal conductance. Armadillos that specialize on termites as food (e.g., Tolypeutes and Priodontes) have much lower basal rates and body temperatures than other species. Hedgehogs, hedgehog tentrecs, and marsupial bandicoots also have low body temperatures, low basal rates of metabolism, and high minimal conductances. The principal reason why armadillos have low rates of metabolism is to prevent overheating in burrows, although termite-eating species may have lower basal rates than other species due to variations in the spatial and temporal availability of prey. The high minimal conductances found in these mammals prevent overheating in burrows and reflect a protective armor of either horny plates (armadillos) or spines (hedgehogs and hedgehog tenrecs). The interaction of low basal rates and high minimal conductances results in temperature differentials between the body and environment that are independent of mass and only about 25% of the values expected in mammals. Studies of daily energy expenditure in Dasypus novemcinctus show a circadial rhythm of activity and indicate that this species responds to a sharp fall in environmental temperature by a reduction in activity and a modest reduction in body temperature. Large individuals may take as long as 3 or 4 days for normal body temperature to be reestablished after such a cold exposure. Armadillos have a limited capacity to invade cold, temperate environments because food is unavailable at environmental temperatures below 0°C and because of their high thermal conductances. Armadillos or other similar mammals enter cold, temperate environments either by storing enough fat to wait for foraging to be possible again (D. novemcinctus) or by entering torpor (Zaedyus, Eri-naceus, Setifer), a response that requires a small body size. Tolerance to starvation through an increased mass is limited by the necessity to seek refuge in a burrow. Young-of-the-year, lean individuals, and pregnant females are most susceptible to starvation at the geographic and climatic edge of their distribution.

Short-beaked echidnas, Tachyglossus aculeatus, are heterothermic, prototherian mammals whose distribution extends across Australia and parts of New Guinea. They are reputed to be poor physiological thermoregulators in the heat as they lack the evaporative cooling mechanisms associated with other mammals and can tolerate ambient temperatures in excess of 35 oC to 37 oC for only short periods in laboratory experiments. However, in the field in western Queensland, they routinely tolerate ambient temperatures in some of their daytime retreats that exceed 35 oC for several hours and peak at 42 oC. In other, and colder, situations, except when incubating, body temperatures of echidnas vary on a daily basis, increasing with activity and decreasing with inactivity. They appear to be fully coordinated even with body temperatures as low as 20 oC. This suggests that the classical model of mammalian thermoregulation, assuming as it does,the maintenance of high and stable body temperatures, is of little relevance to non-incubating echidnas.The primary aim of this project was to investigate physiological adjustments that allow echidnas to tolerate ambient temperatures in the field that would be lethally high in laboratories. The secondary aim of this project was to develop simple heat budget modelling that could be used to analyse physiological adjustments and responses in animals with significant thermal inertia, endothermy and heterothermy in complex, dynamically fluctuating (field) thermal environments. The third aim of the project was to investigate the relevance of traditional concepts about mammalian thermoregulation to echidnas within the context of their heterothermy.The first aim was addressed by experiments conducted under field conditions where metabolic rate, evaporative heat loss, thermal conductance and body temperature were determined in response to ambient temperature fluctuations similar to those experienced by echidnas in the wild. It was found that echidnas in these conditions utilised the low ambient temperatures of the early morning to lose body heat passively to their environment which then gave them scope to absorb heat as ambient temperatures increased during the day. In this way, resting echidnas tolerated ambient temperatures that peaked in the range 30 oC to 49 oC as long as their body temperatures remained below 33 oC: slightly higher than the modal body temperatures of foraging echidnas. Because body temperatures rose only slowly in these relatively large animals, echidnas were frequently unperturbed by experimental conditions until after ambient temperatures had reached their daytime peak.The second aim of the project was addressed by developing integrated parameter, a priori heat budget modelling to predict body temperature responses of animals in general to combined variations of metabolic heat production, thermal conductance and other physiological factors in dynamically fluctuating (field) thermal environments. This modelling was found to predict well the body temperature fluctuations in a wide range of ectotherms and endotherms of various sizes in various environments. When applied todata collected from echidnas under field experimental conditions, this modelling highlighted the importance of maintaining low thermal conductance and low metabolic heat production in the ability of echidnas to tolerate high ambient temperatures. It also showed that there was no evidence of aestivation or metabolic suppression in echidnas exposed to a high heat load while sheltering inside artificial retreats.The third aim of the project was addressed by experiments conducted under laboratory conditions where thermoregulatory responses of echidnas to constant ambient temperatures in the range 13 oC to 31 oC were determined. In these, similarities and differences between echidna and other mammalian thermoregulation were found. In common with many mammals, echidnas varied their thermal conductance from low levels in low ambient temperatures to higher levels in warmer conditions. Thermoneutrality was difficult to identify precisely but metabolic rate was minimal at ambient temperatures of between 25 oC and 28 oC and increased at higher temperatures. Below ambient temperatures of 25 oC, echidnas sometimes demonstrated shivering thermogenesis and sometimes torpor, both common responses in other mammals. However, unusually for an endotherm, echidnas also demonstrated varying metabolic rates intermediate to these two extremes. This resulted in variable or labile body temperatures with this variability increasing at lower ambient temperatures. Also unusual for an endotherm, echidnas continue to show apparently normal activity and behaviour with body temperatures as low as 20 oC without becoming torpid.These results suggest that echidnas have alternative thermoregulatory strategies to many mammals. Thermogenesis and evaporative cooling are usually associated with mammals as physiological mechanisms resulting in the maintenance of high and stable body temperatures. However echidnas are not only capable of tolerating fluctuations in body temperature, they use them to advantage. On the one hand, they use cyclic storage of heat to tolerate short term exposure to high ambient temperatures in some day time retreats without the need for cooling mechanisms which require energy. On the other hand, in cooler conditions, they frequently dispense with energetically expensive shivering thermogenesis, allowing their body temperature to fall as a result, apparently without compromise to their foraging activities. This energy economy likely gives to echidnas advantages unavailable to many mammals and may allow them to persist in relatively resource poor environments.

1. Selected body temperatures of female lizards, Sceloporus jarrovi, were measured on a photothermal gradient during late pregnancy and again when postpartum, and pregnant females were subjected to one of three fluctuating temperature regimes that simulated body temperatures of (1) pregnant females, (2) postpartum females or (3) allowed normal thermoregulation. 2. Overall, females selected lower body temperatures when pregnant (mean = 32·0°C) than when postpartum (mean = 33·5°C). 3. Females regulated body temperature more precisely when pregnant than when postpartum as judged by their smaller variances in body temperature throughout the day. 4. When pregnant, females selected a lower mean maximum body temperature (mean: pregnant = 32·8°C; postpartum = 34·5°C) than when postpartum, but selected mean minimum body temperatures did not differ. 5. None of the experimental temperature treatments was detrimental to pregnant females. Female body length increased during pregnancy but the rate of increase did not differ among treatments. Moreover, length‐adjusted body mass of postpartum females did not differ among treatments. 6. Pregnant females that experienced postpartum body temperatures produced neonates that were smaller in body mass and length than pregnant females that experienced pregnant body temperatures and females that were allowed to thermoregulate. 7. For neonates resulting from the postpartum body temperature treatment, the disparity in the body length, but not mass, was still observed at 9 days of age, although survival and growth of neonates was high and did not differ among treatments. 8. The results demonstrate that pregnant females could maintain higher postpartum body temperatures without compromising their physical condition, but select relatively low body temperatures, presumably to avoid decrements in offspring fitness.

Vocal regulation of body temperature in thermally dependent offspring can occur when cold-induced vocalizations elicit appropriate brooding and rewarming by a parent or surrogate. I tested the ability of young American white pelicans to regulate vocally body temperature in the laboratory by exposing them to moderate chilling (20-23°C), either continuously, or punctuated by brief (usually 2 min) periods of warmth in response to cold-induced calling. When continuously chilled, they began to call almost immediately (median latency 35 s), and body temperature began to drop. At 1 and 2 weeks of age, visible shivering also occurred, but was not sufficient to arrest the decline in body temperature. When chilling was then ameliorated by brief periods of warmth in response to cold-induced calling, body temperature shifted upwards, indicating a vocal thermoregulatory ability similar to, but somewhat faster, than that previously reported for late-stage embryos in this species. At 1 day of age, cold-induced calling occurred with a shorter latency and at a higher rate at lower body temperatures, as expected in a compensatory thermoregulatory system. After the onset of shivering thermogenesis at 1 and 2 weeks of age, the compensatory response decreased, but calling still occurred in response to chilling, as required by a simple on-off regulatory system. Begging for food was inhibited at body temperatures low enough to elicit shivering, suggesting that vocal maintenance of a relatively high body temperature may be of importance to normal begging and food acquisition prior to the full development of endothermy in this species. Effective functioning of the vocal thermoregulatory system requires that information about offspring body temperature be accurate. This requirement suggests a strong parallel between vocal thermoregulation and the concept of honest signalling in animal communication. Honest signalling of need by offspring has received recent theoretical support, but is controversial and has rarely been tested experimentally. I used the occurrence of shivering, which is the main source of endothermic heat in birds, as a standard against which to test empirically the honesty of cold-induced calls as signals of need for warmth. When 1 and 2-week old chilled, shivering chicks began to warm up during vocal regulation sessions, shivering eventually became periodic, starting each time a bird was chilled and ending during each subsequent period of rewarming. Calling at this time invariably (84 of 84 cases) began only after the onset of shivering, then ended while shivering was still in progress. To the extent that shivering is an honest, perhaps unfakable indicator of a biologically relevant need for warmth, the vocalizations associated with it appear to be honest signals indicating the presence of that need. Results are also consistent with a recent theoretical model of honest signalling of need by offspring, but it remains to be determined whether honest solicitation of warmth prevails when chicks are in naturally competitive situations at the nest.

This study quantifies the thermoregulatory ability and energetics of a mammal, the round-tailed ground squirrel Spermophilus tereticaudus, that can relax thermoregulatory limits without becoming inactive. We measured body temperature and metabolic rate in animals exposed for short periods (1 h) to air temperatures ranging from 10 to 45 degrees C and for long periods (8 h) to air temperatures ranging from 10 to 30 degrees C. Within 45 min of exposure to air temperatures ranging from 10 to 45 degrees C, the mean body temperatures of alert and responsive animals ranged from 32.1 degrees C (T(air)=10 degrees C) to 40.4 degrees C (T(air)=45 degrees C). This thermolability provided significant energetic savings below the thermoneutral zone, ranging from 0.63 W (18 %) at 10 degrees C to 0.43 W (43 %) at 30 degrees C. When exposed for 8 h to air temperatures between 10 and 30 degrees C, animals varied their body temperature significantly over time. At all air temperatures, the lowest body temperature (maintained for at least 1 h) was 31.2 degrees C. The highest body temperatures (maintained for at least 1 h) were 33.6 degrees C at 10 degrees C, 35.3 degrees C at 20 degrees C and 36.3 degrees C at 30 degrees C. The energetic savings realized by maintaining the minimum rather than the maximum body temperature was 0.80 W (25 %) at 10 degrees C, 0.71 W (33 %) at 20 degrees C and 0.40 W (47 %) at 30 degrees C. This study demonstrates in several ways the ability of this species to adjust energy expenditure through heterothermy.

Background: The importance of thyroid hormones (THs) for peripheral body temperature regulation has been long recognized, as medical conditions such as hyper- and hypothyroidism lead to alterations in body temperature and energy metabolism. In the past decade, the brain actions of THs and their respective nuclear receptors, thyroid hormone receptor α1 (TRα1) and thyroid hormone receptor beta (TRβ), coordinating body temperature regulation have moved into focus. However, the exact roles of the individual TR isoforms and their precise neuroanatomical substrates remain poorly understood. Methods: Here we used mice expressing a mutant TRα1 (TRα1+m) as well as TRβ knockouts to study body temperature regulation using radiotelemetry in conscious and freely moving animals at different ambient temperatures, including their response to oral 3,3',5-triiodothyronine (T3) treatment. Subsequently, we tested the effects of a dominant-negative TRα1 on body temperature after adeno-associated virus (AAV)-mediated expression in the hypothalamus, a region known to be involved in thermoregulation. Results: While TRβ seems to play a negligible role in body temperature regulation, TRα1+m mice had lower body temperature, which was surprisingly not entirely normalized at 30°C, where defects in facultative thermogenesis or tail heat loss are eliminated as confounding factors. Only oral T3 treatment fully normalized the body temperature profile of TRα1+m mice, suggesting that the mutant TRα1 confers an altered central temperature set point in these mice. When we tested this hypothesis more directly by expressing the dominant-negative TRα1 selectively in the hypothalamus via AAV transfection, we observed a similarly reduced body temperature at room temperature and 30°C. Conclusion: Our data suggest that TRα1 signaling in the hypothalamus is important for maintaining body temperature. However, further studies are needed to dissect the precise neuroanatomical substrates and the downstream pathways mediating this effect.

Reduction in metabolic rate and body temperature is a common strategy for small endotherms to save energy. The daily reduction in metabolic rate and heterothermy, or torpor, is particularly pronounced in regions with a large variation in daily ambient temperature. This applies most strongly in temperate bat species (Order Chiroptera), but it is less clear how tropical bats save energy if ambient temperatures remain high. However, many subtropical and tropical species use some daily heterothermy on cool days. We recorded the heart rate and the body temperature of free-ranging Pallas' mastiff bats ( Molossus molossus ) in Gamboa, Panama, and showed that these individuals have low field metabolic rates across a wide range of body temperatures that conform to high ambient temperature. Importantly, low metabolic rates in controlled respirometry trials were best predicted by heart rate, and not body temperature. Molossus molossus enter torpor-like states characterized by low metabolic rate and heart rates at body temperatures of 32°C, and thermoconform across a range of temperatures. Flexible metabolic strategies may be far more common in tropical endotherms than currently known.

Large-scale comparisons of mammalian basal metabolic rates often transform metabolism (using Q10 effects) to approximate a standard body temperature of 37°C. However, existing mammalian body temperature datasets do not take into account the high degree of within-species and within-individual variability in body temperatures. There is increasing recognition that rather than being fully homeothermic, most endotherms display some degree of flexibility in body temperature. Yet existing body temperature datasets use temperatures from different non-analog states (such as resting versus active or scotophase versus acrophase) or mean body temperature, which has increasingly been shown to have little biological relevance. Using a new dataset of standardised resting body temperatures in mammals, we show that the relationship between basal metabolism and body temperature is not as straightforward as has been presumed. We discuss the implications of correcting, or not, for body temperature in studies on metabolic scaling and discuss the role of thermoregulatory phenotypes in shaping mammalian basal metabolic rates.

Temperature regulation and appetitive behavior in chickens with hypothalamic lesions

Mammalian torpor saves enormous amounts of energy, but a widely assumed cost of torpor is immobility and therefore vulnerability to predators. Contrary to this assumption, some small marsupial mammals in the wild move while torpid at low body temperatures to basking sites, thereby minimizing energy expenditure during arousal. Hence, we quantified how mammalian locomotor performance is affected by body temperature. The three small marsupial species tested, known to use torpor and basking in the wild, could move while torpid at body temperatures as low as 14.8-17.9°C. Speed was a sigmoid function of body temperature, but body temperature effects on running speed were greater than those in an ectothermic lizard used for comparison. We provide the first quantitative data of movement at low body temperature in mammals, which have survival implications for wild heterothermic mammals, as directional movement at low body temperature permits both basking and predator avoidance.

Marine iguanas occasionally face severe food shortages because of algal dieback during El Ni&ntilde;o events. Research on their adaptations to these periods has highlighted their unique ability to shrink in body length, which reduces their energetic needs. Additional mechanisms, like sustaining lower body temperatures and metabolic rates, could potentially also lower energy consumption, but have never been examined. We measured 665 iguanas over an 11‐year period including three El Ni&ntilde;o events, and examined how heart rates (a proxy for metabolic rates) and body temperatures change with sea‐surface temperature oscillations (Oceanic Ni&ntilde;o Index, ONI). Heart rate (adjusting for body size, temperature, season, and study site) was negatively correlated with ONI and lower during El Ni&ntilde;o, whereas the adjusted body temperature did not correlate with ONI or differ between El Ni&ntilde;o and other periods. We therefore hypothesize that marine iguanas can depress their metabolic rates in response to the harsh conditions, an adaptation that is complementary to shrinking and may further enhance their survival through periods of limited food. Direct metabolic measurements are needed to test this hypothesis.

Marine iguanas occasionally face severe food shortages because of algal dieback during El Niño events. Research on their adaptations to these periods has highlighted their unique ability to shrink in body length, which reduces their energetic needs. Additional mechanisms, like sustaining lower body temperatures and metabolic rates, could potentially also lower energy consumption, but have never been examined. We measured 665 iguanas over an 11‐year period including three El Niño events, and examined how heart rates (a proxy for metabolic rates) and body temperatures change with sea‐surface temperature oscillations (Oceanic Niño Index, ONI). Heart rate (adjusting for body size, temperature, season, and study site) was negatively correlated with ONI and lower during El Niño, whereas the adjusted body temperature did not correlate with ONI or differ between El Niño and other periods. We therefore hypothesize that marine iguanas can depress their metabolic rates in response to the harsh conditions, an adaptation that is complementary to shrinking and may further enhance their survival through periods of limited food. Direct metabolic measurements are needed to test this hypothesis.

Effects of Niacin and Aspirin on Performance Parameters in Heifers Fed Endophyte-Infected Tall Fescue