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Hibernation is characterized by significantly decreased metabolism, respiration, and heart rate. In this study, we assessed how immune responses were affected by hibernation, using the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) as a model organism. Ebola virus-like particles (eVLPs, which present Ebola antigens but are not infectious) were used to trigger an immune response. Twenty-four squirrels were housed in a hibernation chamber at 4°C, while eighteen were maintained at room temperature (21°C). In addition to eVLPs, a subset of squirrels were given either LPS (bacterial) or Poly (I: C) (synthetic dsRNA analog) adjuvants, which are biological molecules that help mount a more robust immune response and probe different immune pathways. Blood was drawn before immunization and 35 days later to measure the anti- Ebolavirus antibodies. Additionally, subdermal temperature loggers recorded the squirrel's body temperature every ten minutes throughout the study. Hibernating squirrels immunized with eVLP alone, eVLP + LPS, or eVLP + Poly (I: C) had a maximum temperature greater than sham- immunized squirrels during the first arousal post-immunization. Squirrels immunized with eVLP alone or eVLP + LPS produced a mean increase in temperature during both the first arousal post- immunization and subsequent arousals. During hibernation, only squirrels immunized with eVLP alone produced detectable antibody titers. The lack of antibody production in immunizations that contained adjuvants suggests that antibody production during hibernation is dependent on the type of immune response activated.

Demographic factors are fundamental in shaping infectious disease dynamics. Aspects of populations that create structure, like age and sex, can affect patterns of transmission, infection intensity and population outcomes. However, studies rarely link these processes from individual to population-scale effects. Moreover, the mechanisms underlying demographic differences in disease are frequently unclear. Here, we explore sex-biased infections for a multi-host fungal disease of bats, white-nose syndrome, and link disease-associated mortality between sexes, the distortion of sex ratios and the potential mechanisms underlying sex differences in infection. We collected data on host traits, infection intensity and survival of five bat species at 42 sites across seven years. We found females were more infected than males for all five species. Females also had lower apparent survival over winter and accounted for a smaller proportion of populations over time. Notably, female-biased infections were evident by early hibernation and likely driven by sex-based differences in autumn mating behaviour. Male bats were more active during autumn which likely reduced replication of the cool-growing fungus. Higher disease impacts in female bats may have cascading effects on bat populations beyond the hibernation season by limiting recruitment and increasing the risk of Allee effects.

ObjectivesComplex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos).Data descriptionThis dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.

In the temperate region, bats have evolved the strategy of hibernation to survive the harsh winter. During hibernation, bats enter the vulnerable state of torpor that requires specific environmental conditions to function optimally. Bats are known to use caves and anthropogenic structures as hibernation sites. However, the majority of the bat population cannot be accounted for when such structures are surveyed. There is evidence that bats use other natural structures as hibernation sites. To examine bat’s choices of hibernation sites and activity, acoustic monitoring of bats in south-west Sweden was performed during the winter of 2022-2023. Bat activity was measured in areas with potential hibernation sites in natural structures (rock outcrops), as well as inside and outside of known hibernation sites (anthropogenic structures). The level of activity and the ambient temperature were tested for a possible correlation. Additionally, data from 2006-2022 of surveys of bats in hibernation sites were examined for a possible relationship with outside ambient temperature. Bats were found to be active during the winter inside the known sites of hibernation. There was also activity recorded outside one of the known hibernation sites, but no bat activity was found in the areas of potential hibernation sites. No significant correlation was shown between bat activity and outside temperature, nor between number of bats inside a hibernation site and outside temperature. Further research is needed to develop the knowledge about bats’ hibernation behavior which in turn will aid more effective conservation of temperate bat species.

Organisms seldom exist in isolation. The transmission of an individual’s genes often depends on its social environment. From conception, an individual’s growth and survival are defined by the resources allocated by its mother. Similarly, in forming groups, the actions of conspecifics can mediate access to resources through competition or cooperation. Thus, phenotypic variation can be shaped by the dynamics of interactions with conspecifics, in addition to genetic effects. In this thesis, I explore questions related to the evolution of behavioural and life history strategies, using two species of long-lived horseshoe bat (Chiroptera: Rhinolophidae) as model systems. Chapter 2 examines whether bi-parental or maternal kinship influences spatial assortment in underground hibernacula among individual greater horseshoe bats (Rhinolophus ferrumequinum), driving population sociogenetic structure. Neither measure of kinship was an important predictor of assortment; rather, associations within roosts were age-structured. Chapter 3 investigates the potential benefits of group-living for hibernating lesser horseshoe bats (R. hipposideros), specifically the “social alarm-clock” hypothesis which proposes that torpid individuals may use the activity of nearby normothermic conspecifics as an inadvertent social cue indicating favourable conditions to arouse. Temperature cues proved most important for triggering arousals, but evidence for social transmission of arousals was found, particularly in Autumn. Chapter 4 applies quantitative genetic analysis to a long-term study of R. ferrumequinum to estimate the heritability and evolvability of morphological and life-history traits, and to investigate the role of maternal effects in shaping phenotypic variation. The results show high heritability but low evolvability for morphological traits and low heritability but high evolvability for life-history traits. Maternal effects were weak, implying limited maternal influe

BACKGROUND: Despite centuries of research, debate remains on the scaling of metabolic rate to mass especially for intraspecific cases. The high variation of body mass within brown bears presents a unique opportunity to study the intraspecific effects of body mass on physiological variables. The amplitude of metabolic rate reduction in hibernators is dependent on body mass of the species. Small hibernators have high metabolic rates when euthermic but experience a drastic decrease in body temperature during torpor, which is necessary to reach a very low metabolic rate. Conversely, large hibernators, such as the brown bear (Ursus arctos), show a moderate decrease in temperature during hibernation, thought to be related to the bear's large size. We studied body mass, abdominal body temperature, heart rate, and accelerometer-derived activity from 63 free-ranging brown bears (1-15 years old, 15-233 kg). We tested for relationships between body mass and body temperature, heart rate, and hibernation duration. RESULTS: The smallest individuals maintained lower body temperatures during hibernation, hibernated longer, and ended hibernation later than large bears. Unlike body temperature, winter heart rates were not associated with body mass. In summer, the opposite pattern was found, with smaller individuals having higher body temperature and daytime heart rates. Body mass was associated with body temperature in the winter hypometabolic state, even in a large hibernating mammal. Smaller bears, which are known to have higher thermal conductance, reached lower body temperatures during hibernation. During summer, smaller bears had higher body temperatures and daytime heart rates, a phenomenon not previously documented within a single mammalian species. CONCLUSION: We conclude that the smallest bears hibernated more deeply and longer than large bears, likely from a combined effect of basic thermodynamics, the higher need for energy savings, and a lower cost of warming up a smaller

The hazel dormouse is predominantly an arboreal species that moves down to the ground to hibernate in the autumn in temperate parts of its distributional ranges at locations not yet well understood. The main objective of this study is to test whether environmental characteristics surrounding hazel dormouse hibernacula can be identifed using high-resolution remote sensing and data collected in situ. To achieve this, remotely sensed variables, including canopy height and cover, topographic slope, sky view, solar radiation and cold air drainage, were modelled around 83 dormouse hibernacula in England (n=62) and the Netherlands (n=21), and environmental characteristics that may be favoured by pre-hibernating dormice were identifed. Data on leaf litter depth, temperature, canopy cover and distance to the nearest tree were collected in situ and analysed at hibernaculum locations in England. The fndings indicated that remotely sensed data were efective in identifying attributes surrounding the locations of dormouse hibernacula and when compared to in situ information, provided more conclusive results. This study suggests that remotely sensed topographic slope, canopy height and sky view have an infuence on hazel dormice choosing suitable locations to hibernate; whilst in situ data suggested that average daily mean temperature at the hibernaculum may also have an efect. Remote sensing proved capable of identifying localised environmental characteristics in the wider landscape that may be important for hibernating dormice. This study proposes that this method can provide a novel progression from habitat modelling to conservation management for the hazel dormouse, as well as other species using habitats where topography and vegetation structure infuence fne-resolution favourability.

The brown bear Ursus arctos undergoes exceptional physiological adaptions during annual hibernation that minimize energy consumption, including profound decrease in heart rate, cardiac output, and respiratory rate. These changes are completely reversible after the bears reenter into the active state in spring. In this case report, we show episodes of sinus arrest in a hibernating Scandinavian brown bear and in humans, recorded by implantable loop recorders and discuss the possible underlying mechanisms. Lessons learned from cardiac adaptations in hibernating bears might prove useful in the treatment of patients with sinus node dysfunction.

Brown bears hibernate throughout half of the year as a survival strategy to reduce energy consumption during prolonged periods with scarcity of food and water. Thyroid hormones are the major endocrine regulators of basal metabolic rate in humans. Therefore, we aimed to determine regulations in serum thyroid hormone levels in hibernation compared to the active state to investigate if these are involved in the adaptions for hibernation.We used electrochemiluminescence immunoassay to quantify total triiodothyronine (T3) and thyroxine (T4) levels in hibernation and active state in paired serum samples from six subadult Scandinavian brown bears. Additionally, we determined regulations in the liver mRNA levels of three major thyroid hormone-binding proteins; thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin, by analysis of previously published grizzly bear RNA sequencing data.We found that bears were hypothyroid when hibernating with T4 levels reduced to less than 44% (P = 0.008) and T3 levels reduced to less than 36% (P = 0.016) of those measured in the active state. In hibernation, mRNA levels of TBG and albumin increased to 449% (P = 0.031) and 121% (P = 0.031), respectively, of those measured in the active state. TTR mRNA levels did not change.Hibernating bears are hypothyroid and share physiologic features with hypothyroid humans, including decreased basal metabolic rate, bradycardia, hypothermia, and fatigue. We speculate that decreased thyroid hormone signaling is a key mediator of hibernation physiology in bears. Our findings shed light on the translational potential of bear hibernation physiology to humans for whom a similar hypometabolic state could be of interest in specific conditions.

The brown bear Ursus arctos undergoes exceptional physiological adaptions during annual hibernation that minimize energy consumption, including profound decrease in heart rate, cardiac output, and respiratory rate. These changes are completely reversible after the bears reenter into the active state in spring. In this case report, we show episodes of sinus arrest in a hibernating Scandinavian brown bear and in humans, recorded by implantable loop recorders and discuss the possible underlying mechanisms. Lessons learned from cardiac adaptations in hibernating bears might prove useful in the treatment of patients with sinus node dysfunction.

OBJECTIVES: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. METHODS: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. RESULTS: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. CONCLUSIONS: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future.

In this article, we present mass-spectrometry based plasma proteomics data from hibernating and active free-ranging Scandinavian brown bears (Ursus arctos). The brown bear hibernates for half the year. Despite obesity when entering the den and the prolonged period of inactivity, the bear shows no signs of the harmful effects associated with these conditions in humans. Thus, the hibernating bear is a potential translational model for addressing these complications in humans. We analyzed plasma samples from fourteen 2- to 3-year-old bears (6 males and 8 females) collected both during hibernation and the active state, and for some of the bears during two seasons, resulting in a total of 38 analyzed plasma samples. In triplicates, the plasma proteins were unfolded and reduced. To increase the chance of detecting low-molecular-weight proteins and peptides, we filtered the samples using a 50 K molecular weight cut-off filter with the aim to deplete larger abundant proteins, including albumin, and thereby increase the depth of the analysis. The proteins in the permeate were then tryptically digested, desalted, and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein identification and quantification was performed with the MaxQuant software searching against an Ursus arctos horribilis protein database. Here, we provide the raw data, a list with identified proteins in the plasma samples, and the databases applied for protein identification. Based on the provided data, differentially expressed proteins in hibernation compared to active state can be identified. These proteins may be involved in the bears' adaptions to hibernation physiology and hold potential as novel therapeutic targets., Funding agency:Lundbeckfonden R126-2012-12,408 R286-2018-367

Species that hibernate generally live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor-arousal cycles occur multiple times during hibernation, and it has been suggested that processes controlling the transition between torpor and arousal states cause ageing suppression. Metabolic rate is also a known correlate of longevity; we thus proposed the 'hibernation-ageing hypothesis' whereby ageing is suspended during hibernation. We tested this hypothesis in a well-studied population of yellow-bellied marmots (Marmota flaviventer), which spend 7-8 months per year hibernating. We used two approaches to estimate epigenetic age: the epigenetic clock and the epigenetic pacemaker. Variation in epigenetic age of 149 samples collected throughout the life of 73 females was modelled using generalized additive mixed models (GAMM), where season (cyclic cubic spline) and chronological age (cubic spline) were fixed effects. As expected, the GAMM using epigenetic ages calculated from the epigenetic pacemaker was better able to detect nonlinear patterns in epigenetic ageing over time. We observed a logarithmic curve of epigenetic age with time, where the epigenetic age increased at a higher rate until females reached sexual maturity (two years old). With respect to circannual patterns, the epigenetic age increased during the active season and essentially stalled during the hibernation period. Taken together, our results are consistent with the hibernation-ageing hypothesis and may explain the enhanced longevity in hibernators.

Disease results from interactions among the host, pathogen, and environment. Inoculation trials can quantify interactions among these players and explain aspects of disease ecology to inform management in variable and dynamic natural environments. White-nose Syndrome, a disease caused by the fungal pathogen, Pseudogymnoascus destructans (Pd), has caused severe population declines of several bat species in North America. We conducted the first experimental infection trial on the tri-colored bat, Perimyotis subflavus, to test the effect of temperature and humidity on disease severity. We also tested the effects of temperature and humidity on fungal growth and persistence on substrates. Unexpectedly, only 37% (35/95) of bats experimentally inoculated with Pd at the start of the experiment showed any infection response or disease symptoms after 83 days of captive hibernation. There was no evidence that temperature or humidity influenced infection response. Temperature had a strong effect on fungal growth on media plates, but the influence of humidity was more variable and uncertain. Designing laboratory studies to maximize research outcomes would be beneficial given the high costs of such efforts and potential for unexpected outcomes. Understanding the influence of microclimates on host-pathogen interactions remains an important consideration for managing wildlife diseases, particularly in variable environments.

Telomeres are specialized non-coding DNA sequences located at the end of chromosomes and that protect genetic information. Telomere loss over lifespan is generally viewed as a phenomenon associated with aging in animals. Recently, telomere elongation after hibernation has been described in several mammals. Whether this pattern is an adaptation to repair DNA damage caused during rewarming from torpor or if it coevolved as a mechanism to promote somatic maintenance in preparation for the upcoming reproductive effort remains unclear. In a longitudinal study measuring telomere length using buccal swabs, we tested if telomere elongation was related to reproductive success in wild adult female Columbian ground squirrels (Urocitellus columbianus) that were monitored from emergence from hibernation to the end of the reproductive season. We found three key results. First, female telomere length increased at the start of the breeding season, both in breeding and non-breeding individuals. Second, post-emergence telomere lengthening was unrelated to female future reproductive output. Third, telomere length decreased in breeding females during lactation, but remained stable in non-breeding females over a similar period. Within breeders, telomeres shortened more in females producing larger and heavier litters. We concluded that telomere lengthening after hibernation did not constrain immediate female reproductive capacities. It was more likely to be part of the body recovery process that takes place after hibernation. Telomere erosion that occurs after birth may constitute a physiological cost of female reproduction.

White-nose syndrome has killed millions of bats, yet both the origins and infection strategy of the causative fungus, Pseudogymnoascus destructans, remain elusive. We provide evidence for a novel hypothesis that P. destructans emerged from plant-associated fungi and retained invasion strategies affiliated with fungal pathogens of plants. We demonstrate that P. destructans invades bat skin in successive biotrophic and necrotrophic stages (hemibiotrophic infection), a mechanism previously only described in plant fungal pathogens. Further, the convergence of hyphae at hair follicles suggests nutrient tropism. Tropism, biotrophy, and necrotrophy are often associated with structures termed appressoria in plant fungal pathogens; the penetrating hyphae produced by P. destructans resemble appressoria. Finally, we conducted a phylogenomic analysis of a taxonomically diverse collection of fungi. Despite gaps in genetic sampling of prehistoric and contemporary fungal species, we estimate an 88% probability the ancestral state of the clade containing P. destructans was a plant-associated fungus.

Understanding hibernation in brown bears (Ursus arctos) can provide insight into some human diseases. During hibernation, brown bears experience periods of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic aspects of human diseases such as type 2 diabetes, muscle atrophy, as well as renal and heart failure. The reversibility of these states from hibernation to active season enables the identification of mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons in bears. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, full-length RNA-sequencing (Iso-Seq) was performed on adipose, skeletal muscle, and liver from three individual bears sampled during both active and hibernation seasons. The existing reference genome annotation was improved by combining it with the Iso-Seq data. Short-read RNA-sequencing data from six individuals were mapped to the new reference annotation to quantify differential isoform usage (DIU) between tissues and seasons. We identified differentially expressed isoforms in all three tissues, to varying degrees. Adipose had a high level of DIU with isoform switching, regardless of whether the genes were differentially expressed. Our analyses revealed that DIU, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.

The brown bear (Ursus arctos) is the second largest and most widespread extant terrestrial carnivore on Earth and has recently emerged as a medical model for human metabolic diseases. Here, we report a fully phased chromosome-level assembly of a male North American brown bear built by combining Pacific Biosciences (PacBio) HiFi data and publicly available Hi-C data. The final genome size is 2.47 Gigabases (Gb) with a scaffold and contig N50 length of 70.08 and 43.94 Megabases (Mb), respectively. Benchmarking Universal Single-Copy Ortholog (BUSCO) analysis revealed that 94.5% of single copy orthologs from Mammalia were present in the genome (the highest of any ursid genome to date). Repetitive elements accounted for 44.48% of the genome and a total of 20,480 protein coding genes were identified. Based on whole genome alignment to the polar bear, the brown bear is highly syntenic with the polar bear, and our phylogenetic analysis of 7,246 single-copy orthologs supports the currently proposed species tree for Ursidae. This highly contiguous genome assembly will support future research on both the evolutionary history of the bear family and the physiological mechanisms behind hibernation, the latter of which has broad medical implications.

A male mutation bias is observed across vertebrates, and, where data are available, this bias is accompanied by increased per-generation mutation rates with parental age. While continuing mitotic cell division in the male germline post puberty has been proposed as the major cellular mechanism underlying both patterns, little direct evidence for this role has been found. Understanding the evolution of the per-generation mutation rate among species requires that we identify the molecular mechanisms that change between species. Here, we study the per-generation mutation rate in an extended pedigree of the brown (grizzly) bear, Ursus arctos horribilis. Brown bears hibernate for one-third of the year, a period during which spermatogenesis slows or stops altogether. The reduction of spermatogenesis is predicted to lessen the male mutation bias and to lower the per-generation mutation rate in this species. However, using whole-genome sequencing, we find that both male bias and per-generation mutation rates are highly similar to that expected for a non-hibernating species. We also carry out a phylogenetic comparison of substitution rates along the lineage leading to brown bear and panda (a non-hibernating species) and find no slowing of the substitution rate in the hibernator. Our results contribute to accumulating evidence that suggests that male germline cell division is not the major determinant of mutation rates and mutation biases. The results also provide a quantitative basis for improved estimates of the timing of carnivore evolution.

Brown bears are obese when they enter the den, and after 6 mo of hibernation and physical inactivity, bears show none of the adverse consequences of a sedentary lifestyle in humans, such as cardiovascular disease, type 2 diabetes, and kidney failure. The metabolic mechanisms that drive hibernation physiology in bears are poorly defined, but systemic endocrine regulators are likely involved. To investigate the potential role of steroid hormones, we quantified the total levels of 12 steroid hormones, the precursor cholesterol, sex hormone-binding globulin (SHBG), and corticosterone-binding globulin (CBG) in paired serum samples from subadult free-ranging Scandinavian brown bears during the active and hibernation states. During hibernation, androstenedione and testosterone were significantly decreased in subadult female bears (n=13), whereas they increased in all males but one (n=6) and therefore did not reach a significant difference. Despite this difference, SHBG increased more than 20-fold during hibernation for all bears. Compared with SHBG concentrations in humans, bear levels were very low in the active state, but during hibernation, levels equaled high levels in humans. The increased SHBG levels likely maintain a state of relative quiescence of the reproductive hormones in hibernating bears. Interestingly, the combination of SHBG and testosterone levels results in similar free bioavailable testosterone levels of 70-80 pM in both subadult and adult sexually active male bears, suggesting a role for SHBG in controlling androgen action during hibernation in males. Dehydroepiandrosterone sulfate, dihydrotestosterone, and estradiol levels were below the detection limit in all but one animal. The metabolically active glucocorticoids were significantly higher in both sexes during hibernation, whereas the inactive metabolite cortisone was reduced and CBG was low approaching the detection limit. A potential caveat is that the glucocorticoid levels might be affected by the, Funding agency:Lundbeckfonden R126-2012-12408 R286-2018-367

Brown bears conserve muscle and bone mass during six months of inactive hibernation. The molecular mechanisms underlying hibernation physiology may have translational relevance for human therapeutics. We hypothesize that protective mechanisms involve increased tissue availability of the insulin-like growth factors (IGFs). In subadult Scandinavian Brown Bears, we observed that mean plasma IGF-1 and IGF-2 during hibernation was reduced to 36±10% and 56±15%, respectively, compared to the active state (N=12). Western ligand blotting identified IGFBP-3 as the major IGF binding protein in the active state, while IGFBP-2 was co-dominant during hibernation. Acid labile subunit (ALS) levels in hibernation were 41±16% those of the active state (N=6). Analysis of available grizzly bear RNA sequencing data revealed unaltered liver mRNA IGF-1, IGFBP-2, and IGFBP-3 levels, whereas ALS was significantly reduced during hibernation (N=6). Reduced ALS synthesis and circulating levels during hibernation should prompt a shift from ternary IGF/IGFBP/ALS to smaller binary IGF/IGFBP complexes, thereby increasing IGF tissue availability. Indeed, Size Exclusion Chromatography of bear plasma, demonstrate a shift to lower molecular weight IGF-containing complexes in the hibernating versus the active state. Further, we note that the major IGF-2 mRNA isoform expressed in liver in both Scandinavian brown bears and grizzly bears was an alternative splice variant in which Ser29 was replaced with a tetrapeptide possessing a positively charged Arg residue. Homology modelling of the bear IGF-2/IGFBP-2 complex showed the tetrapeptide in proximity to the heparin binding domain involved in bone-specific targeting of this complex. In conclusion, this study provides data which suggest that increased IGF tissue availability combined with tissue-specific targeting contribute to tissue preservation in hibernating bears., Funding agency:Lundbeckfonden R126-2012-1240 8 R286-2018-36 7

Trade-offs between specialist use of particular resources and opportunistic use of widespread materials may present different strategies for survival. Hazel dormice Muscardinus avellanarius are arboreal mammals that in Great Britain hibernate from late autumn to mid spring in nests that are specially built at ground level. Hibernation nests are rarely encountered, and little is known about the types of construction or materials used. Specifically, it is not known whether nest materials are selected opportunistically, based on their availability, or are specialised to suit local environmental conditions. We therefore conducted a study to characterise the main materials used to construct these nests, explore the distances travelled to col lect materials and investigate whether regional climate and/or local microclimate have an impact on the types of nests built. Thirty-three hibernation nests were located through radio-tracking, systematic searches and incidental finds. Struc turally, hibernation nests were built similarly to summer nests and were most commonly constructed with an outer layer of leaves and distinct core section made of woven material. We found no correlation between nest type and the temperature recorded at nest sites. Nests were built using a mean of two materials per nest, which were both in every case available within 3m of the nest. The most frequently used materials were bracken, hazel and beech leaves, and grasses. Dormice were flexible in their use of nest materials, using various materials harvested very locally. However, dormice travelled further to collect grasses, ferns, bracken and honeysuckle, and these materials made up most of the nests in which they were found. There were also positive correlations between material abundance and usage, and suitable materials for hibernation nest construction were therefore readily available within their home range.

Sex hormone-binding globulin (SHBG) regulates the bioavailability of sex steroid hormones in the blood. Levels of SHBG increase markedly in brown bears (Ursus arctos) during hibernation, suggesting that a key regulatory role of this protein is to quench sex steroid bioavailability in hibernation physiology. To enable characterization of ursine SHBG and a cross species comparison, we established an insect cell-based expression system for recombinant full-length ursine and human SHBG. Compared with human SHBG, we observed markedly lower secretion levels of ursine SHBG, resulting in a 10-fold difference in purified protein yield. Both human and ursine recombinant SHBG appeared as dimeric proteins in solution, with a single unfolding temperature of ~58 °C. The thermal stability of ursine and human SHBG increased 5.4 and 9.5 °C, respectively, in presence of dihydrotestosterone (DHT), suggesting a difference in affinity. The dissociation constants for [3 H]DHT were determined to 0.21±0.04 nM for human and 1.32±0.10 nM for ursine SHBG, confirming a lower affinity of ursine SHBG. A similarly reduced affinity, determined from competitive steroid binding, was observed for most steroids. Overall, we found that ursine SHBG had similar characteristics to human SHBG, specifically, being a homodimeric glycoprotein capable of binding steroids with high affinity. Therefore, ursine SHBG likely has similar biological functions to those known for human SHBG. The determined properties of ursine SHBG will contribute to elucidating its potential regulatory role in hibernation physiology., Funding agency:Lundbeckfonden R286-2018-367 R126-2012-12408

[Background] In temperate regions many small mammals including bats hibernate during winter. During hibernation these small mammals occasionally wake up (arouse) to restore electrolyte and water balance. However, field data on water stress and concentration of bodily fluids during hibernation is scarce. Urinary creatinine concentration has long been used to calibrate urinary hormone concentration due to its close correlation with urine concentration. Therefore, by investigating urinary creatinine concentration, we can estimate bodily fluid concentration. In this study, we investigated changes in urinary creatinine from greater horseshoe bats (Rhinolophus ferrumequinum) hibernating in abandoned mineshafts in two regions in South Korea. [Results] We collected 74 urine samples from hibernating greater horseshoe bats from 2018 to 2019. We found that urinary creatinine concentration was higher in February and March and then declined in April. There were also indications of a sex difference in the pattern of change in creatinine concentration over the three months. Bats in the warmer and less humid mineshaft had higher urinary creatinine concentrations than bats in the colder and more humid mineshaft. [Conclusions] These results indicate that hibernating bats face water stress as urinary concentration increases during winter and that water stress may vary depending on the microenvironment. Sex differences in behaviour during hibernation may influence arousal frequency and result in sex differences in changes in urinary creatinine concentration as hibernation progresses. Although further behavioural and endocrinal investigations are needed, our study suggests that urinary creatinine concentration can be used as a proxy to estimate the hydration status of bats and the effect of sex and environmental factors on arousal patterns during hibernation.

Body condition is an important life history challenge that directly impacts individual fitness and is particularly important for hibernating animals, whose maintenance of adequate body fat and mass is essential for survival. It is well documented that symbiotic microorganism’s play a vital role in animal physiology and behavior. Recent work demonstrates that gut microbes are associated with fat accumulation and obesity; Firmicutes is consistently associated with obesity while Bacteroidetes is associated with leanness both in humans and other animals. The focus of most microbiome studies has been on human health or involved lab reared animals used as a model system. However, these microbes likely are important for individual fitness in wild populations and provide potential mechanistic insights into the adaptability and survival of wildlife. Here we test whether symbiotic microorganisms within the phyla of Firmicutes and Bacteroidetes are associated with summer mass gain in an exceptionally well-studied wild population of yellow-bellied marmots (Marmota flaviventer) by quantifying microbial abundance over five years of fecal samples (2015 – 2019) collected during their summer active season. Results show that marmots with higher mass gain rates have a greater abundance of Firmicutes. In contrast, higher abundance of Bacteroidetes was associated with lower mass gain rates, but only for marmots living in harsher environments. Similar patterns were found at the family level where Ruminococcaceae, a member of Firmicutes, was associated with higher mass gain rates, and Muribaculaceae, a member of Bacteroidetes, was associated with lower mass gain rates, and similarly in harsher environments. Although correlative, these results highlight the importance of symbiotic gut microbiota to mass gain in the wild, a trait associated with survival and fitness in many taxonomic groups.

In nature, species are constantly challenged by biotic and abiotic factors. In order to thrive, individuals need mechanisms that regulate their responses according to the experienced conditions. I have studied aspects of regulatory responses to gain insights into how individuals are affected by environmental challenges. All chapters capitalized on long-term data collected at individual level. Chapter 1 introduce and summarize all chapters. Chapter 2 explores how the social environment affects maternal stress levels (glucocorticoid hormones) in a flexibly social mammal. I found that agonistic behavior challenges mothers, while affiliative social bonds can lower stress levels in a context-specific manner. Pups from highly stressed mothers are less likely to survive unless they come from small litters. Chapter 3 uses the estimated biological age (or epigenetic age) to investigate how hibernation, an adaptation to survive highly challenging periods, may affect individual aging patterns. I observed a much slower biological aging during hibernation, which suggests that biological processes involved in hibernation suppress aging. While chapters 2 and 3 evaluate the influence of the surrounding environment on individual fitness, chapter 4 focus on how inbreeding, an intrinsic individual trait, is associated with a higher aging speed. Indeed, inbred individuals appear to exhibit a higher age acceleration, but only at older chronological ages, which may be explained by a higher vulnerability of inbred individuals to the cumulative effects of environmental and physiological stressors. Thus, individual traits influence the chances of successful responses to challenges. And, while it is generally assumed that challenges affect negatively individual fitness, chapter 2 and 3 uncover strategies that maximize individual fitness under duress, which highlights the role of selective pressure on plastic phenotypes. Another contribution from this dissertation is the use of physiological

Torpor is a hypothermic, hypometabolic state engaged when the availability of nutrients is insufficient to maintain homeostasis. It is observed in a wide range of animals, including the laboratory mouse, and if mimicked in humans, a synthetic torpor state could have useful clinical applications. The mechanisms that control torpor are not known. This thesis explores the neuroanatomical basis of torpor induction. The core method used a genetic approach that allowed targeted expression of transgenes in neurons that are active during torpor. First, two protocols for torpor induction in mice were validated, alongside the use of surface thermography as a proxy for internal body temperature. A method to detect torpor was developed using a moving window of the mean and standard deviation of mouse surface temperature across the 24-hour cycle. I then used the transgenic mouse model to express a fluorescent protein in neurons that were active during torpor. This identified that the dorsomedial hypothalamus (DMH) and the preoptic area of the hypothalamus (POA) increase activity during torpor. Next, a chemogenetically modified receptor was expressed in neurons that were active during torpor. Reactivation of those neurons generated a synthetic torpor state in the absence of any natural stimulus for torpor. Targeted reactivation of only the POA neurons that were active during torpor recapitulated this synthetic torpor, demonstrating that the POA contains neurons that are sufficient for torpor induction. A similar approach in the DMH demonstrated that neurons in this nucleus promote, prolong, and deepen torpor bouts in calorie restricted mice, but are neither necessary nor sufficient for torpor induction. In summary, these findings represent the first demonstration of a synthetic torpor in the mouse. They indicate that the POA is sufficient for torpor induction, and that the DMH promotes torpor but is neither necessary nor sufficient.

The eastern fox squirrel, Sciurus niger, exhibits marked geographic variation in size and coat color, is a model organism for studies of behavior and ecology, and a potential model for investigating physiological solutions to human porphyrias. We assembled a genome using Illumina HiSeq, PacBio SMRT, and Oxford Nanopore MinION sequencing platforms. Together, the sequencing data resulted in a draft genome of 2.99 Gb, containing 32,830 scaffolds with an average size of 90.9 Kb and N50 of 183.8 Kb. Genome completeness was estimated to be 93.78%. A total of 24,443 protein-encoding genes were predicted from the assembly and 23,079 (94.42%) were annotated. Repeat elements comprised an estimated 38.49% of the genome, with the majority being LINEs (13.92%), SINEs (6.04%), and LTR elements. The topology of the species tree reconstructed using maximum-likelihood phylogenetic analysis was congruent with those of previous studies. This genome assembly can prove useful for comparative studies of genome structure and function in this rapidly diversifying lineage of mammals, for studies of population genomics and adaptation, and for biomedical research. Predicted amino acid sequence alignments for genes affecting heme biosynthesis, color vision, and hibernation showed point mutations and indels that may affect protein function and ecological adaptation.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation a

Aim For 80 years, popular opinion has held that most of Madagascar's terrestrial vertebrates arrived from Africa by transoceanic dispersal (i.e. rafting or swimming). We reviewed this proposition, focussing on three ad hoc hypotheses proposed to render this unlikely scenario more feasible: (a) Could hibernation have helped mammals to reach Madagascar? (b) Could the aquatic abilities of hippopotamuses have enabled them to swim the Mozambique Channel? (c) How valid is the Ali‐Huber model predicting that eastward Palaeogene surface currents allowed rafts to reach Madagascar in 3–4 weeks? Finally, we explored the alternative hypothesis of geodispersal via short‐lived land bridges between Africa and Madagascar. Location East Africa, Madagascar, Mozambique Channel. Taxa Fish, amphibians, reptiles, birds, mammals. Methods We established colonization timeframes using molecular divergence dates estimated for Malagasy vertebrate lineages. We reviewed the likelihood of the “torpid waif” and “swimming hippopotamus” hypotheses, and re‐investigated Ali and Huber's model of Eocene jet‐like currents by tracking particle trajectories in currents simulated using the Institut Pierre‐Simon Laplace Earth System Model. Finally, we summarized recent geological findings from the Mozambique Channel, and used them to compile palaeosedimentological maps using PLACA4D. Results Madagascar's vertebrate fauna has complex origins. Hibernation is probably an adaptation to Madagascar's hypervariable climate, rather than a facilitator of mammal dispersal. Hippopotamus physiology precludes the ability to cross an oceanic channel deeper than 4 m and hundreds of km wide. The Ali‐Huber model of Palaeogene currents considerably underestimated the time required to cross the Mozambique Channel under simulated palaeogeographic conditions. New geological data indicate the existence of three short‐lived land bridges between Africa and Madagascar at 66–60 Ma, 36–30 Ma and 12–05 Ma. Main conclusion The three Cen

Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. The data collected and analyzed from bears were also compared with those from healthy humans. In bears, the cholesterol ester, unesterified cholesterol, TG, and phospholipid contents of VLDL and LDL were higher in winter than in summer. The percentage lipid composition of LDL differed between bears and humans but did not change seasonally in bears. Bear LDL was larger, richer in TGs, showed prebeta electrophoretic mobility, and had 5-10 times lower binding to arterial PGs than human LDL. Finally, plasma CEC was higher in bears than in humans, especially the HDL fraction when mediated by ABCA1. These results suggest that in brown bears the absence of early atherogenesis is likely associated with a lower affinity of LDL for arterial PGs and an elevated CEC of bear plasma.

Dr. Eleine Mad är Madeleine Jacobsssons talesperson för dom vetenskapliga och paranormala upptäckter som uppstår i hennes världar. Hon beskriver innehåll, teknik och estetik utifrån ett kategoriseringssytem där konsten delas upp som olika typer av komponenter och därefter avkodas dessa allteftersom. För att förstå intuitionens inblandning i arbetsprocessen omförvandlas den till tre separata roller av en Sökare, Samlare och Myntare. Med rollerna försöker jag beskriva på vilka sätt som intuitionen är till gagn eller av förödelse för det konstnärliga arbetet. Sagan om M handlar om en grodlik karaktär, Delop, som lämnar sin hemplanet för att uppsöka andra världar. I sitt sökande hittar Delop ett folkslag vars syn och levnadssätt skiljer sig från hennes erfarenheter av “verkligheten” såsom hon lärt sig att överleva i den., Dr. Eleine Mad is Madeleine Jacobsson's spokesperson for the scientific and paranormal discoveries that arise in her worlds. She describes content, tecniques and aesthetics based on a categorization system where art is divided into different types of components and then decoded as they go. To understand the intuition's involvement in the work process, it is transformed into three separate roles by a Seeker, Collector and a Myntare(In swedish language the one who is a "myntare" -is verbally declaring a concept or term). With these roles I try to describe in what ways intuition is beneficial or devastating to the artistic work. The story of M is about a frog-like character, Delop, who leaves the home planet to seek out other worlds. In her search, Delop finds a world whose views and lifestyles differ from her experiences of "reality" as she learned to survive in it., Recorded sound and image material of the presentation is available for private use.

Hibernation allows individuals to conserve energy during seasonal low temperatures. As the physiological regulation of hibernation is inadequately understood, I examine hibernation using DNA methylation (DNAm). DNAm is the addition of a methyl group to cytosine at cytosine guanine dinucleotide (CpG) sites in the genome. DNAm in promoters can repress gene expression and be influenced by histone modifications. Using the big brown bat, Eptesicus fuscus, I examined how hibernation influences DNAm, independent of age, through comparing DNAm from bats that differed in hibernation history and comparing DNAm from the same individual between hibernating and active seasons. Both comparisons found evidence of differential enrichment of genes near significant CpG sites resulting from hibernation. The latter analysis found evidence consistent with a histone mark, associated with active transcription, is likely enriched in hibernating bats. These results suggest that DNAm and histone modifications associated with transcription factor binding regulate gene expression during hibernation.

Hibernation has been selected for increasing survival in harsh climatic environments. Seasonal variability in temperature may push the body temperatures of hibernating animals across boundaries of alternative states between euthermic temperature and torpor temperature, typical of either hibernation or summer dormancy. Nowadays, wearable electronics present a promising avenue to assess the occurrence of criticality in physiological systems, such as body temperature fluctuating between attractors of activity and hibernation. For this purpose, we deployed temperature loggers on two hibernating edible dormice for an entire year and under Mediterranean climate conditions. Highly stochastic body temperatures with sudden switches over time allowed us to assess the reliability of statistical leading indicators to anticipate tipping points when approaching a critical transition. Hibernation dynamics showed flickering, a phenomenon occurring when a system rapidly moves back and forth between two alternative attractors preceding the upcoming major regime shift. Flickering of body temperature increased when the system approached bifurcations, which were also anticipated by several metricand model-based statistical indicators. Nevertheless, some indicators did not show a pattern in their response, which suggests that their performance varies with the dynamics of the biological system studied. Gradual changes in air temperature drove transient between states of hibernation and activity, and also drove hysteresis. For hibernating animals, hysteresis may increase resilience when ending hibernation earlier than the optimal time, which may occur in regions where temperatures are sharply rising, especially during winter. Temporal changes in early indicators of critical transitions in hibernation dynamics may help to understand the effects of climate on evolutionary life histories and the plasticity of hibernating organisms to cope with shortened hibernation due to global warming.

Both animal hibernation and human renal osteodystrophy are characterized by high levels of serum parathyroid hormone. To test the hypothesis of hibernation in an extinct human species, we examined the hominin skeletal collection from Sima de los Huesos, Cave Mayor, Atapuerca, Spain, for evidence of hyperparathyroidism after a thorough review of the literature. We studied the morphology of the fossilized bones by using macrophotography, microscopy, histology and CT scanning. We found trabecular tunneling and osteitis fibrosa, subperiosteal resorption, ‘rotten fence post’ signs, brown tumours, subperiosteal new bone, chondrocalcinosis, rachitic osteoplaques and empty gaps between them, craniotabes, and beading of ribs mostly in the adolescent population of these hominins. Since many of the above lesions are pathognomonic, these extinct hominins suffered annually from renal rickets, secondary hyperparathyroidism, and renal osteodystrophy associated with Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD). We suggest these diseases were caused by poorly tolerated hibernation in dark cavernous hibernacula. This is particularly evidenced by the rachitic osteoplaques and the gaps between them in some of the adolescent individuals along with the evidence of healing mainly in the adults. The sublayers in the rachitic osteoplaques indicate bouts of arousal from hibernation. The strong projection of the external lip of the femoral trochlea, the rachitic osteoplaques with the empty gaps between them, the “rotten fence post" sign, and the evidence of annual healing also point to the presence of annually intermittent puberty in this extinct human species. The hypothesis of hibernation is consistent with the genetic evidence and the fact that the SH hominins lived during an extreme glaciation. Alternative hypotheses are examined. The present work will provide a new insight into the physiological mechanism of early human metabolism which could help in determining the life, Les périodes d’hibernation chez l’animal et l’ostéodystrophie rénale en pathologie humaine sont associées à des taux sériques élevés d’hormone parathyroïdienne. Après une revue approfondie de la littérature, nous avons examiné la collection de squelettes d’hominidés de Sima de los Huesos, Cave Mayor, Atapuerca, Espagne, pour y rechercher des traces d’hypersécrétion parathyroïdienne. L’étude a été réalisée en associant macrophotographie, analyses microscopiques, histologiques et imagerie par tomodensitométrie. Nous avons observé principalement dans la population adolescente de ces homininés des aspects de tunnelisation osseuse trabéculaire, d’ostéite fibreuse, de résorption sous-périostée métaphysaire, de tumeurs brunes, d’ossification sous-périosté, de chondrocalcinose, des ostéophytes disséminés, de craniotabès et de perles costales. Plusieurs de ces lésions sont pathognomoniques et montrent que ces hominines étaient atteints chaque année d’ostéomalacie, d’hyperparathyroïdie secondaire et d’ostéodystrophie rénale. Nous estimons que ces troubles sont consécutifs à une hibernation dans des grottes sombres. Ceci est particulièrement mis en évidence par la présence de plaques osseuses rachitiques disséminées chez certains des adolescents, et de lésions cicatrisées principalement chez les adultes. Les sous-couches dans les plaques osseuses rachitiques indiquent des épisodes de suractivité liée à l’hibernation. La forte saillie de la lèvre externe de la trochlée fémorale, les plaques osseuses rachitiques séparées par des zones normales, les zones de résorption sous-périostée et les preuves de guérison annuelle indiquent également la présence d’une puberté intermittente chaque année chez cette espèce humaine disparue. Notre hypothèse rattachant ces lésions osseuses aux conséquences de l’hibernation est cohérente avec les arguments génétiques et le fait que les hominidés de SH ont vécu pendant une glaciation extrême. Des hypothèses alternatives sont examinées. Le présent t, Ministerio de Ciencia e Innovación (MICINN)/FEDER, Junta de Castilla y León, Depto. de Geodinámica, Estratigrafía y Paleontología, Fac. de Ciencias Geológicas, TRUE, pub

One of the most profound adaptive strategies employed by animals in response to changes in environmental conditions is hibernation. Hibernation is an extended state of hypometabolism and dormancy induced to survive the low food availability and high physiological stress associated with winter. During the long periods of dormancy, hibernators experience changes in core biological processes, including drastic reductions in basal metabolic rate, core body temperature, oxygen consumption, heart rate and brain activity. Stress response pathways are also modulated to mitigate physiological challenges that would otherwise prove lethal to the animal. Modulation of these responses requires tightly controlled regulatory processes. While hibernation is a common response utilised by diverse lineages of animals, molecular investigations into this phenomenon have primarily focused on mammalian systems. In this thesis, I investigated the molecular mechanisms involved in the hibernation of the Australian central bearded dragon (Pogona vitticeps) using high-throughput sequencing technologies. The transcriptomic and proteomic changes in three tissues; brain, heart and skeletal muscle, during hibernation and at two time points post-arousal were examined. Hibernation was associated with the induction of common and tissue-specific stress response pathways in addition to the modulation of regulatory processes. I studied the role of microRNAs (miRNA) in mediating the changes in gene expression that are characteristic of the three tissues during hibernation and four days post-arousal. Cellular metabolism and neuroprotection of the brain emerged as key pathways under miRNA-mediated regulation. The DNA methylation dynamics in brain and skeletal muscle during hibernation and at two time points post-arousal were also examined. Alterations in DNA methylation were associated with changes in gene expression that lead to increased neuroprotection of the brain and a reduced potential for atrophy in

Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying intrinsic AGS cell resilience to metabolic stress. Through cell survival-based cDNA expression screens in neural progenitor cells, we identify a genetic variant of AGS Atp5g1 that confers cell resilience to metabolic stress. Atp5g1 encodes a subunit of the mitochondrial ATP synthase. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of endogenous AGS loci revealed causal roles of one AGS-specific amino acid substitution in mediating cytoprotection by AGS ATP5G1. AGS ATP5G1 promotes metabolic stress resilience by modulating mitochondrial morphological change and metabolic functions. Our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that critically contributes to intrinsic cytoprotection against metabolic stress.

Seasonal environmental conditions shape the behavior and life history of virtually all organisms. Climate change is modifying these seasonal environmental conditions, which threatens to disrupt population dynamics. It is conceivable that climatic changes may be beneficial in one season but result in detrimental conditions in another because life-history strategies vary between these time periods. We analyzed the temporal trends in seasonal survival of yellow-bellied marmots (Marmota flaviventer) and explored the environmental drivers using a 40-y dataset from the Colorado Rocky Mountains (USA). Trends in survival revealed divergent seasonal patterns, which were similar across age-classes. Marmot survival declined during winter but generally increased during summer. Interestingly, different environmental factors appeared to drive survival trends across age-classes. Winter survival was largely driven by conditions during the preceding summer and the effect of continued climate change was likely to be mainly negative, whereas the likely outcome of continued climate change on summer survival was generally positive. This study illustrates that seasonal demographic responses need disentangling to accurately forecast the impacts of climate change on animal population dynamics.

Hibernation represents an adaptation for coping with unfavorable environmental conditions. For brown bears Ursus arctos, hibernation is a critical period as pronounced temporal reductions in several physiological functions occur. Here, we review the three main aspects of brown bear denning: (1) den chronology, (2) den characteristics, and (3) hibernation physiology in order to identify (a) proximate and ultimate factors of hibernation as well as (b) research gaps and conservation priorities. Den chronology, which varies by sex and reproductive status, depends on environmental factors, such as snow, temperature, food availability, and den altitude. Significant variation in hibernation across latitudes occurs for both den entry and exit. The choice of a den and its surroundings may affect individual fitness, for example, loss of offspring and excessive energy consumption. Den selection is the result of broad‐ and fine‐scale habitat selection, mainly linked to den insulation, remoteness, and availability of food in the surroundings of the den location. Hibernation is a metabolic challenge for the brown bears, in which a series of physiological adaptations in tissues and organs enable survival under nutritional deprivation, maintain high levels of lipids, preserve muscle, and bone and prevent cardiovascular pathologies such as atherosclerosis. It is important to understand: (a) proximate and ultimate factors in denning behavior and the difference between actual drivers of hibernation (i.e., factors to which bears directly respond) and their correlates; (b) how changes in climatic factors might affect the ability of bears to face global climate change and the human‐mediated changes in food availability; (c) hyperphagia (period in which brown bears accumulate fat reserves), predenning and denning periods, including for those populations in which bears do not hibernate every year; and (d) how to approach the study of bear denning merging insights from different perspective

Hibernation represents the most refined adaptation of endothermic species to overcome unfavorable periods when food is scarce. Thus, hibernation should take place within specific time frames with respect to environmental factors. Flexibility in the timing of biological events is thus central to how well mammals can deal with varying climatic conditions. For brown bears (Ursus arctos), hibernation is not only a critical period that allows them to save vital energy reserves for times of food shortage, but also the period during which pregnant females give birth to cubs. Here, we analyzed the relationship between 74 den exit dates of females with cubs, recorded from 1995 to 2018 in the Cantabrian Mountains in northwestern Spain, with (1) average daily precipitation and (2) average maximum temperature during the 30 days before den exit, as well as with (3) the number of cubs. The bears exited from 1 April to 16 May, and the mean date was 28 April. Our results, which are consistent with the general latitudinal pattern of den emergence reported in other studies, suggested that in years with higher maximum temperatures, exit dates tended to be earlier, whereas the number of cubs and the average rainfall for the 30 days prior to den exit did not seem to determine the variation in den exit dates. Considering the relationship between spring temperatures and den exit dates of females with cubs, it is important to take into account the repercussions that current global warming may have on the reproduction of brown bears. Current trends of climate change might trigger earlier den exit dates than in the past, which may have negative consequences on the population dynamics of brown bear populations. For example, a mismatch between the chronology of hibernation and food availability might reduce cub survival and, consequently, the fitness of females.