Summer fades, deer change: Photoperiodic control of cellular seasonal acclimatization of skeletal muscle.

We found major seasonal changes of polyunsaturated fatty acids (PUFAs) in muscular phospholipids (PL) in a large non-hibernating mammal, the red deer (Cervus elaphus). Dietary supply of essential linoleic acid (LA) and α-linolenic acid (ALA) had no, or only weak influence, respectively. We further found correlations of PL PUFA concentrations with the activity of key metabolic enzymes, independent of higher winter expression. Activity of the sarcoplasmic reticulum (SR) Ca++-ATPase increased with SR PL concentrations of n-6 PUFA, and of cytochrome c oxidase and citrate synthase, indicators of ATP-production, with concentrations of eicosapentaenoic acid in mitochondrial PL. All detected cyclic molecular changes were controlled by photoperiod and are likely of general relevance for mammals living in seasonal environments, including humans. During winter, these changes at the molecular level presumably compensate for Arrhenius effects in the colder peripheral body parts and thus enable a thrifty life at lower body temperature.

Insular giant leporid matured later than predicted by scaling.

The island syndrome describes morphological, behavioral, and life history traits that evolve in parallel in endemic insular organisms. A basic axiom of the island syndrome is that insular endemics slow down their pace of life. Although this is already confirmed for insular dwarfs, a slow life history in giants may not be adaptive, but merely a consequence of increasing body size. We tested this question in the fossil insular giant leporid Nuralagus rex. Using bone histology, we constructed both a continental extant taxon model derived from experimentally fluorochrome-labeled Lepus europaeus to calibrate life history events, and a growth model for the insular taxon. N. rex grew extremely slowly and delayed maturity well beyond predictions from continental phylogenetically corrected scaling models. Our results support the life history axiom of the island syndrome as generality for insular mammals, regardless of whether they have evolved into dwarfs or giants.

The Influence of Photoperiod, Intake of Polyunsaturated Fatty Acids, and Food Availability on Seasonal Acclimatization in Red Deer (Cervus elaphus).

Hypometabolism and hypothermia are common reactions of birds and mammals to cope with harsh winter conditions. In small mammals, the occurrence of hibernation and daily torpor is entrained by photoperiod, and the magnitude of hypometabolism and decrease of body temperature (Tb) is influenced by the dietary supply of essential polyunsaturated fatty acids. We investigated whether similar effects exist in a non-hibernating large mammal, the red deer (Cervus elaphus). We fed adult females with pellets enriched with either linoleic acid (LA) or α-linolenic acid (ALA) during alternating periods of ad libitum and restricted feeding in a cross-over experimental design. Further, we scrutinized the role of photoperiod for physiological and behavioral seasonal changes by manipulating the amount of circulating melatonin. The deer were equipped with data loggers recording heart rate, core and peripheral Tb, and locomotor activity. Further, we regularly weighed the animals and measured their daily intake of food pellets. All physiological and behavioral parameters measured varied seasonally, with amplitudes exacerbated by restricted feeding, but with only few and inconsistent effects of supplementation with LA or ALA. Administering melatonin around the summer solstice caused a change into the winter phenotype weeks ahead of time in all traits measured. We conclude that red deer reduce energy expenditure for thermoregulation upon short daylength, a reaction amplified by food restriction.

Effects of severe anthropogenic disturbance on the heart rate and body temperature in free-living greylag geese (Anser anser).

Anthropogenic disturbances are a major concern for the welfare and conservation of wildlife. We recorded heart rate and body temperature of 20 free-living greylag geese in response to a major regularly re-occurring anthropogenic disturbance-New Year's Eve fireworks. Heart rate and body temperature were significantly higher in the first and second hour of the new year, compared with the same hour on the 31st of December, the average during December and the average during January. Heart rate and body temperature was not significantly affected by sex or age. From 0200 to 0300 onwards, 1st of January heart rates did not significantly differ from the other periods; however, body temperatures were significantly increased until 0300-0400. From 0400 to 0500, heart rate was not affected by any of the investigated factors, whereas body temperature was significantly increased on the 1st of January compared with the 31st of December and the December average but not compared with the January average. To conclude, our results show that New Year's Eve fireworks cause a substantial physiological response, indicative of a stress response in greylag geese, which is costly in terms of energy expenditure.

Effect of season and diet on heart rate and blood pressure in female red deer (Cervus elaphus) anaesthetised with medetomidine-tiletamine-zolazepam.

Temperate zone ungulates like red deer (Cervus elaphus) show pronounced seasonal acclimatisation. Hypometabolism during winter is associated with cardiovascular changes, including a reduction in heart rate (fH) and temporal peripheral vasoconstriction. How anaesthesia with vasoactive substances such as medetomidine affect the seasonally acclimatised cardiovascular system is not yet known. We anaesthetised eleven healthy female red deer with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (3 mg/kg) twice in winter (ad libitum and restricted feed) and in summer (ad libitum and restricted feed), with a two-week washout-period in-between, to test for the effect of season, food availability and supplementation with omega-3 or omega-6 polyunsaturated fatty acid (PUFA) on fH and arterial blood pressure (ABP) during anaesthesia. Six animals received pellets enriched with omega-6 fatty acids (FA), and five animals with omega-3 FA. Anaesthesia significantly decreased fH in summer but not in winter and ABP was lower in winter (p < 0.05). The combination of omega-6 FA enriched pellets and food restriction resulted in a lower fH and higher ABP during anaesthesia with more pronounced changes in winter (p < 0.001). Our results demonstrate that season, food availability and type of PUFA supplementation in red deer affect the cardiovascular system during anaesthesia.

Labelling experiments in red deer provide a general model for early bone growth dynamics in ruminants.

Growth rates importantly determine developmental time and are, therefore, a key variable of a species' life history. A widely used method to reconstruct growth rates and to estimate age at death in extant and particularly in fossil vertebrates is the analysis of bone tissue apposition rates. Lines of arrested growth (LAGs) are of special interest here, as they indicate a halt in bone growth. However, although of great importance, the time intervals between, and particularly the reason of growth arrests remains unknown. Therefore, experiments are increasingly called for to calibrate growth rates with tissue types and life history events, and to provide reliable measurements of the time involved in the formation of LAGs. Based on in vivo bone labelling, we calibrated periods of bone tissue apposition, growth arrest, drift and resorption over the period from birth to post-weaning in a large mammal, the red deer. We found that bone growth rates tightly matched the daily weight gain curve, i.e. decreased with age, with two discrete periods of growth rate disruption that coincided with the life history events birth and weaning, that were visually recognisable in bone tissue as either partial LAGs or annuli. Our study identified for the first time in a large mammal a general pattern for juvenile bone growth rates, including periods of growth arrest. The tight correlation between daily weight gain and bone tissue apposition suggests that the red deer bone growth model is valid for ruminants in general where the daily weight gain curve is comparable.

Determinants of heart rate in Svalbard reindeer reveal mechanisms of seasonal energy management.

Seasonal energetic challenges may constrain an animal's ability to respond to changing individual and environmental conditions. Here, we investigated variation in heart rate, a well-established proxy for metabolic rate, in Svalbard reindeer (Rangifer tarandus platyrhynchus), a species with strong seasonal changes in foraging and metabolic activity. In 19 adult females, we recorded heart rate, subcutaneous temperature and activity using biologgers. Mean heart rate more than doubled from winter to summer. Typical drivers of energy expenditure, such as reproduction and activity, explained a relatively limited amount of variation (2-6% in winter and 16-24% in summer) compared to seasonality, which explained 75% of annual variation in heart rate. The relationship between heart rate and subcutaneous temperature depended on individual state via body mass, age and reproductive status, and the results suggested that peripheral heterothermy is an important pathway of energy management in both winter and summer. While the seasonal plasticity in energetics makes Svalbard reindeer well-adapted to their highly seasonal environment, intraseasonal constraints on modulation of their heart rate may limit their ability to respond to severe environmental change. This study emphasizes the importance of encompassing individual state and seasonal context when studying energetics in free-living animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Maternal effects on reproduction in the precocial European hare (Lepus europaeus).

In female mammals, reproduction, and in particular lactation, is the energetically most exigent life-history phase. Reproduction is strongly controlled by body reserves and food availability, so females with better body condition or food supply are believed to have higher reproductive output. Additionally, the growth and mortality of young mammals depends on their postnatal development. Therefore, the degree of precociality affects energetic demands for both mothers and young. To study the reproductive performance of the precocial European hare (Lepus europaeus), we analysed relationships between six predictor variables describing maternal and environmental effects and nine response variables relating to reproduction from 217 captive females. We compared the data with those of precocial and altricial mammal species from an extensive literature search. For hares, we found: (1) Heavier females had heavier litters at birth. (2) In summer and spring, total litter mass was larger than in winter. (3) At the end of lactation, the litters of multiparous females were heavier than those of primiparous females. (4) Both older females and females giving birth for the first time had relatively high leveret mortality during lactation. Comparing our results with the literature for other mammals revealed that the body condition (i.e., body mass) of females before birth is predictive of reproductive parameters in both precocial and altricial species. In the precocial hare, female body condition is no longer predictive of reproductive parameters at the end of lactation, whereas in altricial species, female body condition remains predictive of reproduction (litter mass at the end of lactation, offspring mortality) until the end of lactation. We conclude that these effects are caused by precocial offspring feeding on solid food soon after birth and, thus, being less dependent on the mother's body condition during lactation than altricial offspring. In line with this, precociality might have evolved as a way of buffering offspring against maternal effects.

[Modern diagnosis and therapy of benign thyroid diseases]. / Moderne Abklärung und Therapie benigner Schilddrüsenerkrankungen.

Modern diagnosis and therapy of benign thyroid diseases Abstract. Benign thyroid diseases continue to be widespread endocrine disorders. Early recognition of their symptoms and exact diagnosis are the prerequisite of targeted therapy and minimal impairment of the patient's well-being. Drug treatment, radioiodine therapy, thermal ablation procedures and surgery have been shown to be successful treatment options. As guidelines for diagnosis and treatment of patients continue to evolve, an interdisciplinary approach ensures optimal diagnosis and management on every step in the care for these patients. We present three clinical scenarios for benign thyroid disease: the symptomatic goitre, the painful thyroid and the thyroid with hyperthyroidism.

Pembrolizumab in a Patient With a Metastatic CASTLE Tumor of the Parotid.

Carcinoma showing thymus-like elements (CASTLE) is a rare tumor, most commonly found in the thyroid gland. Here we report a case of CASTLE tumor localized to the parotid gland, recognized in retrospect after a late manifestation of symptomatic pleural carcinomatosis. The original tumor in the parotid gland was treated by surgery followed by radiotherapy. Ten years later, a metastatic disease with recurrent pleural effusions occurred. Pleural carcinomatosis was strongly positive for CD5, CD117, and p63 as was the original tumor of the parotid, which allowed the diagnosis of a CASTLE tumor. Additionally, the pleural tumor expressed high levels of programmed death ligand 1 (PD-L1), and the patient underwent treatment with the monoclonal PD-L1 inhibitor pembrolizumab achieving a partial remission. To the best of our knowledge, this is the first patient with a metastatic CASTLE tumor treated with a PD-L1 inhibitor.

Marmots.

Walter Arnold introduces the biology of marmots.

Calibration of life history traits with epiphyseal closure, dental eruption and bone histology in captive and wild red deer.

The study of skeletochronology and bone tissue as a record of information on ontogenetic stages and events is widely used for improving the knowledge about life histories (LHs) of extinct and extant vertebrates. Compared with dinosaurs and extant reptiles, mammalian bone histology has received little attention. Here, we calibrate for the first time bone and dental age with histological bone characteristics and LH stages in ontogenetic series of red deer. We rely on known LHs of different aged individuals of captive Cervus elaphus hippelaphus from Austria to correlate epiphyseal closure, dental eruption pattern, bone growth marks and bone tissue patterns in femora and tibiae, and of wild Cervus elaphus hispanicus from Spain. Our data show that females (of both subspecies) attain skeletal maturity earlier than males. At this moment, epiphyseal closure (in femora and tibiae) and dental eruption are complete and long bones start to deposit an external fundamental system. The results also show that the attainment of reproductive maturity in red deer occurs slightly before skeletal maturity.

Muscle nonshivering thermogenesis in a feral mammal.

Muscle nonshivering thermogenesis (NST) was recently suggested to play an important role in thermoregulation of species lacking brown adipose tissue (BAT). The mechanism, which is independent of muscle contractions, produces heat based on the activity of an ATPase pump in the sarcoplasmic reticulum (SERCA1a) and is controlled by the protein sarcolipin. To evaluate whether muscle NST could indeed play an important role in thermoregulation in species lacking BAT, we investigated the thermogenic capacities of newborn wild boar piglets. During cold exposure over the first 5 days of life, total heat production was improved while shivering intensity decreased, indicating an increasing contribution of NST. Sampling skeletal muscle tissue for analyses of SERCA activity as well as gene expression of SERCA1a and sarcolipin, we found an age-related increase in all three variables as well as in body temperature. Hence, the improved thermogenesis during the development of wild boars is not due to shivering but explained by the observed increase in SERCA activity. Our results suggest that muscle NST may be the primary mechanism of heat production during cold stress in large mammals lacking BAT, strengthening the hypothesis that muscle NST has likely played an important role in the evolution of endothermy.

Energy expenditure and body temperature variations in llamas living in the High Andes of Peru.

Some large herbivores exhibit seasonal adjustments in their energy metabolism. Therefore, our aim was to determine if the llama (one of the most extensively kept livestock breeds) exhibits seasonal adjustment of their energy expenditure, body temperature and locomotion, under its natural high altitude Andean habitat. For this purpose, energy expenditure, body temperature and locomotion were measured in seven non-pregnant llama dams for ten months on the Andean High Plateau (4400 m above sea level). Daily energy expenditure was measured as field metabolic rate using the doubly labelled water method at four different measurement times. Additionally, a telemetry system was used to continuously record activity, body temperature (3 min intervals) as well as the position (hourly) of each animal. The results show that llamas adjusted their body temperature and daily energy expenditure according to environmental conditions. Furthermore, llamas under high altitude Andean climatic conditions exhibited a pronounced daily rhythm in body temperature and activity, with low values at sunrise and increasing values towards sunset. Llamas also had remarkably low energy expenditure compared to other herbivores. Thus, despite the domestication process, llamas have not lost the ability to adjust their body temperature and daily energy expenditure under adverse environmental conditions, similar to some wild herbivores.

Dietary Lipids Affect the Onset of Hibernation in the Garden Dormouse (Eliomys quercinus): Implications for Cardiac Function.

Dietary lipids strongly influence patterns of hibernation in heterotherms. Increased dietary uptake of n-6 polyunsaturated fatty acids (PUFAs), particularly of linoleic acid (LA, C18:2 n-6), enables animals to reach lower body temperatures (Tb), lengthens torpor bout duration, and results in lower energy expenditure during hibernation. Conversely, dietary n-3 PUFA impacts negatively on hibernation performance. PUFA in surrounding phospholipids (PLs) presumably modulate the temperature-dependent activity of the sarcoplasmic reticulum (SR) Ca2+ ATPase 2 (SERCA2) and thus determine the threshold Tb still allowing proper heart function during torpor. We tested the effect of diets enriched with 10% of either corn oil ("CO," high n-6 PUFA, e.g., LA) or menhaden oil ["MO," long-chain n-3 PUFA, e.g., docosahexaenoic acid (DHA)] on hibernation performance and SERCA2 activity levels during torpor in garden dormice, an insectivorous, fat-storing hibernator. Prior to hibernation, individuals fed the MO diet showed an almost nine-times higher DHA levels and 30% lower LA proportions in white adipose tissue (WAT), reflecting the fatty acid composition of SR membranes, compared to CO-diet fed animals. When fed the MO diet, dormice significantly delayed their mean onset of hibernation by almost 4 days (range: 0-12 days), compared with CO-diet fed animals. Hibernation onset correlated positively with WAT-DHA levels and negatively with WAT-LA proportions prior to hibernation. Subsequently, hibernating patterns were similar between the two dietary groups, despite a significant difference in WAT-LA but not in WAT-DHA levels in mid-hibernation. SR-PL fatty acid composition and SERCA2 activity were identical in torpid individuals from the two dietary groups in mid-hibernation. In line with our previous findings on Syrian hamsters, a granivorous, food-storing hibernator, SERCA2 activity correlated positively with LA and negatively with DHA levels of SR-PL in torpid dormice, although SERCA2 activity was about three-times higher in garden dormice than in Syrian hamsters at similar PL-DHA proportions. Similarly, minimal Tb during torpor decreased as SERCA2 activity increased. We conclude that: (1) fatty acid composition of SR membranes modulates cardiac SERCA2 activity, hence determining the minimum Tb tolerated by hibernators, and (2) high DHA levels prevent hibernators from entering into torpor, but the critical levels differ substantially between species.

Circadian rhythmicity persists through the Polar night and midnight sun in Svalbard reindeer.

Studies of locomotor activity in Svalbard reindeer reported the temporary absence of diel rhythms under Arctic photic conditions. However, using Lomb-Scargle periodogram analyses with high statistical power we found diel or circadian rhythmicity throughout the entire year in measures of behaviour, temperature in the rumen and heart rate in free-living Svalbard reindeer. Significant diel rhythmicity was only lacking during some of the 15-day intervals analysed in the less frequently measured heart rate. During Polar Night these rhythms were free-running and attenuated. During continual daylight in summer, rhythms where entrained to 24 hours corresponding with the daily variation in the intensity of solar radiation, but attenuated when continuous daylight coincided with the period of growing forage. Diel rhythmicity was reduced during this short period of peak foraging activity, which coincided with peak heart rate and temperature in the rumen, most likely to facilitate fattening when food is abundant. For the rest of the year, heart rate and temperature showed the most pronounced and long-lasting suppression ever found in ungulates. The profound seasonal changes in foraging, metabolic activity, and power of diel and circadian rhythmicity of Svalbard reindeer can be viewed as adaptations to the extreme living conditions in the High Arctic.

Free-living greylag geese adjust their heart rates and body core temperatures to season and reproductive context.

Animals adaptively regulate their metabolic rate and hence energy expenditure over the annual cycle to cope with energetic challenges. We studied energy management in greylag geese. In all geese, profound seasonal changes of heart rate (fH) and body temperature (Tb) showed peaks in summer and troughs during winter, and also daily modulation of fH and Tb. Daily mean fH was on average 22% lower at the winter trough than at the summer peak, whereas daily mean Tb at the winter trough was only about 1 °C below the summer peak. Daily means of Tb together with those of air temperature and day length were the most important predictors of daily mean fH, which was further modulated by precipitation, reproductive state, and, to a minor degree, social rank. Peaks of fH and Tb occurred earlier in incubating females compared to males. Leading goslings increased daily mean fH. Our results suggest that in greylag geese, pronounced changes of fH over the year are caused by photoperiod-induced changes of endogenous heat production. Similar to large non-hibernating mammals, tolerance of lower Tb during winter seems the major factor permitting this. On top of these major seasonal changes, fH and Tb are elevated in incubating females.

Novel treatment strategies for chronic kidney disease: insights from the animal kingdom.

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

Muscle Non-shivering Thermogenesis and Its Role in the Evolution of Endothermy.

The development of sustained, long-term endothermy was one of the major transitions in the evolution of vertebrates. Thermogenesis in endotherms does not only occur via shivering or activity, but also via non-shivering thermogenesis (NST). Mammalian NST is mediated by the uncoupling protein 1 in the brown adipose tissue (BAT) and possibly involves an additional mechanism of NST in skeletal muscle. This alternative mechanism is based on Ca2+-slippage by a sarcoplasmatic reticulum Ca2+-ATPase (SERCA) and is controlled by the protein sarcolipin. The existence of muscle based NST has been discussed for a long time and is likely present in all mammals. However, its importance for thermoregulation was demonstrated only recently in mice. Interestingly, birds, which have evolved from a different reptilian lineage than mammals and lack UCP1-mediated NST, also exhibit muscle based NST under the involvement of SERCA, though likely without the participation of sarcolipin. In this review we summarize the current knowledge on muscle NST and discuss the efficiency of muscle NST and BAT in the context of the hypothesis that muscle NST could have been the earliest mechanism of heat generation during cold exposure in vertebrates that ultimately enabled the evolution of endothermy. We suggest that the evolution of BAT in addition to muscle NST was related to heterothermy being predominant among early endothermic mammals. Furthermore, we argue that, in contrast to small mammals, muscle NST is sufficient to maintain high body temperature in birds, which have enhanced capacities to fuel muscle NST by high rates of fatty acid import.

Seasonal reproductive tactics: annual timing and the capital-to-income breeder continuum.

Tactics of resource use for reproduction are an important feature of life-history strategies. A distinction is made between 'capital' breeders, which finance reproduction using stored energy, and 'income' breeders, which pay for reproduction using concurrent energy intake. In reality, vertebrates use a continuum of capital-to-income tactics, and, for many species, the allocation of capital towards reproduction is a plastic trait. Here, we review how trophic interactions and the timing of life-history events are influenced by tactics of resource use in birds and mammals. We first examine how plasticity in the allocation of capital towards reproduction is linked to phenological flexibility via interactions between endocrine/neuroendocrine control systems and the sensory circuits that detect changes in endogenous state, and environmental cues. We then describe the ecological drivers of reproductive timing in species that vary in the degree to which they finance reproduction using capital. Capital can be used either as a mechanism to facilitate temporal synchrony between energy supply and demand or as a means of lessening the need for synchrony. Within many species, an individual's ability to cope with environmental change may be more tightly linked to plasticity in resource allocation than to absolute position on the capital-to-income breeder continuum.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.