nils-herrmann/clean_scirepeval huggingface dataset:
Gene expression analysis and microdialysis suggest hypothalamic triiodothyronine (T3) gates daily torpor in Djungarian hamsters (Phodopus sungorus)
Venue: Journal of Comparative Physiology B

Thyroid hormones play an important role in regulating seasonal adaptations of mammals. Several studies suggested that reduced availability of 3,3′,5-triiodothyronine (T3) in the hypothalamus is required for the physiological adaptation to winter in Djungarian hamsters. We have previously shown that T3 is involved in the regulation of daily torpor, but it remains unclear, whether T3 affects torpor by central or peripheral mechanisms. To determine the effect of T3 concentrations within the hypothalamus in regulating daily torpor, we tested the hypothesis that low hypothalamic T3 metabolism would favour torpor and high T3 concentrations would not. In experiment 1 gene expression in torpid hamsters was assessed for transporters carrying thyroid hormones between cerebrospinal fluid and hypothalamic cells and for deiodinases enzymes, activating or inactivating T3 within hypothalamic cells. Gene expression analysis suggests reduced T3 in hypothalamic cells during torpor. In experiment 2, hypothalamic T3 concentrations were altered via microdialysis and torpor behaviour was continuously monitored by implanted body temperature transmitters. Increased T3 concentrations in the hypothalamus reduced expression of torpor as well as torpor bout duration and depth. Subsequent analysis of gene expression in the ependymal layer of the third ventricle showed clear up-regulation of T3 inactivating deiodinase 3 but no changes in several other genes related to photoperiodic adaptations in hamsters. Finally, serum analysis revealed that increased total T3 serum concentrations were not necessary to inhibit torpor expression. Taken together, our results are consistent with the hypothesis that T3 availability within the hypothalamus significantly contributes to the regulation of daily torpor via a central pathway.
The magnetic map sense and its use in fine-tuning the migration programme of birds
Venue: Journal of Comparative Physiology A

The Earth’s magnetic field is one of several natural cues, which migratory birds can use to derive directional (“compass”) information for orientation on their biannual migratory journeys. Moreover, magnetic field effects on prominent aspects of the migratory programme of birds, such as migratory restlessness behaviour, fuel deposition and directional orientation, implicate that geomagnetic information can also be used to derive positional (“map”) information. While the magnetic “compass” in migratory birds is likely to be based on radical pair-forming molecules embedded in their visual system, the sensory correlates underlying a magnetic “map” sense currently remain elusive. Behavioural, physiological and neurobiological findings indicate that the sensor is most likely innervated by the ophthalmic branch of the trigeminal nerve and based on magnetic iron particles. Information from this unknown sensor is neither necessary nor sufficient for a functional magnetic compass, but instead could contribute important components of a multifactorial “map” for global positioning. Positional information could allow migratory birds to make vitally important dynamic adaptations of their migratory programme at any relevant point during their journeys.
Lipid emulsion enhances cardiac performance after ischemia–reperfusion in isolated hearts from summer-active arctic ground squirrels
Venue: Journal of Comparative Physiology B

Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.
Magnetic activation in the brain of the migratory northern wheatear (Oenanthe oenanthe)
Venue: Journal of Comparative Physiology A

Behavioural and neurobiological evidence suggests the involvement of the visual and trigeminal sensory systems in avian magnetoreception. The constantly growing array of new genetic approaches becoming available to scientists would bear great potential to contribute to a generally accepted understanding of the mechanisms underlying this ability, but would require to breed migratory birds in captivity. Here we show that the transcontinental night-migratory Northern Wheatear (Oenanthe oenanthe), which is currently the only migratory songbird successfully being bred in reasonable numbers in captivity, shows magnetic-field-induced neuronal activation in the trigeminal brainstem areas receiving their input through the ophthalmic branch of the trigeminal nerve. In addition, preliminary data indicate night vision-triggered activation in the anterior visual forebrain. This brain area could represent the same brain region, which has previously been named “Cluster N” and shown to be involved in processing magnetic compass information in European Robins. Thus, based on brain activation data, both visually and trigeminally mediated magnetic senses known from other birds seem to exist in Northern Wheatears. This makes this species a potentially excellent model species for future genetic research on magnetoreception in migratory birds.
Influence of leptin and GABAB-receptor agonist and antagonist on neurons of the hypothalamic infundibular nucleus in the chicken
Venue: Journal of Comparative Physiology A

In birds and mammals, the neuroendocrine regulation of energy balance is conserved in many aspects. Despite significant similarities between the two groups, differences in the regulatory mechanisms were detected. The present study was performed to carry out investigations of the influence of human leptin and GABAB-receptor agonist and antagonist on the firing rate of neurons of the Nucleus infundibuli hypothalami in brain slices from juvenile chickens. For the first time, we demonstrated a clear, dose-related change in the firing rate of hypothalamic neurons in juvenile chickens after the acute application of recombinant human leptin (1, 10, and 100 nM). All investigated neurons increased their subsequent firing rate. Application of GABAB-receptor agonist baclofen (1 µM) blocked, while antagonist CGP 35348 (10 µM) increased the spontaneous neuronal activity. Simultaneous application of baclofen and leptin reduced the effect observed from single leptin application. This was not found after simultaneously application of leptin and CGP. Altogether, our results indicate that in bird brain slices, and exemplarily in those of the chicken, hypothalamic neurons show mammalian-like responsiveness after acute leptin and GABA application. GABAB-mechanisms involved in GABA release play a likely important role in the leptin-mediated effects on NI neurons via functional leptin receptors.
Identification of HIF-1 signaling pathway in Pelteobagrus vachelli using RNA-Seq: effects of acute hypoxia and reoxygenation on oxygen sensors, respiratory metabolism, and hematology indices
Venue: Journal of Comparative Physiology B

Oxygen is a vital element in aquatic environments. The concentration of oxygen to which aquatic organisms are exposed is influenced by salinity, water temperature, weather, and surface water runoff. Hypoxia has a serious effect on fish populations, and can lead to the loss of habitat and die-offs. Therefore, in the present study we used next-generation sequencing technology to characterize the transcriptomes of Pelteobagrus vachelli and identified 70 candidate genes in the HIF-1 signaling pathway that are important for the hypoxic response in all metazoan species. For the first time, the present study reported the effects of acute hypoxia and reoxygenation on oxygen sensors, respiratory metabolism, and hematology indices in P. vachelli. The predicted physiological adjustments show that P. vachelli’s blood oxygen-carrying capacity was increased through increased RBC, HB, and SI after hypoxia exposure. Glycolysis-related enzyme activities (PFK, HK, and PK) and LDH in the brain and liver also increased, indicating a rise in anaerobic metabolism. The observed reduction in oxidative enzyme level (CS) in the liver during hypoxia suggests a concomitant depression in aerobic metabolism. There were significant increases in oxygen sensor mRNA expression and HIF-1α protein expression during hypoxia and reoxygenation exposure, suggesting that the HIF-1 signaling pathway was activated in the liver and brain of P. vachelli in response to acute hypoxia and reoxygenation. Our findings suggest that oxygen sensors (e.g., HIF-1α) of P. vachelli are potentially useful biomarkers of environmental hypoxic exposure. These data contribute to a better understanding of the molecular mechanisms of the hypoxia signaling pathway in fish under hypoxia and reoxygenation.
Embracing heterothermic diversity: non-stationary waveform analysis of temperature variation in endotherms
Venue: Journal of Comparative Physiology B

Recent research is revealing incredible diversity in the thermoregulatory patterns of wild and captive endotherms. As a result of these findings, classic thermoregulatory categories of ‘homeothermy’, ‘daily heterothermy’, and ‘hibernation’ are becoming harder to delineate, impeding our understanding of the physiological and evolutionary significance of variation within and around these categories. However, we lack a generalized analytical approach for evaluating and comparing the complex and diversified nature of the full breadth of heterothermy expressed by individuals, populations, and species. Here we propose a new approach that decomposes body temperature time series into three inherent properties—waveform, amplitude, and period—using a non-stationary technique that accommodates the temporal variability of body temperature patterns. This approach quantifies circadian and seasonal variation in thermoregulatory patterns, and uses the distribution of observed thermoregulatory patterns as a basis for intra- and inter-specific comparisons. We analyse body temperature time series from multiple species, including classical hibernators, tropical heterotherms, and homeotherms, to highlight the approach’s general usefulness and the major axes of thermoregulatory variation that it reveals.
Benign neonatal deep hypothermia in rodents and its relations to hibernation
Venue: Journal of Comparative Physiology B

The neonates of many rodent species survive deep hypothermia (Tb = 0–8 °C). In key respects, this hypothermia is more akin to hibernation than was thought during much of the twentieth century, indicating that studies of neonatal hypothermia may usefully supplement studies of hibernation in understanding evolved tissue adaptations to near-freezing Tb. To clarify evolutionary diversity in neonatal survival of deep hypothermia, neonates of six species or strains were subjected to a standardized procedure: exposure for 2.5 h to test Tbs followed by autoresuscitation. Mus and Peromyscus differed dramatically, the lowest Tb survived by all ages studied (3–10 days) being 7–8 °C in Mus and 0–1 °C in Peromyscus. There was, however, no evidence of intrageneric plasticity because feral and laboratory Mus were identical, and Peromyscus species with cold- and warm-climate distribution ranges were identical. When neonates survive deep hypothermia, a key question is whether the experience is benign, meaning neonates tolerate hypothermia. To test the benign nature of deep hypothermia, neonates of Peromyscus leucopus were exposed four times (3 h each) to Tb = 1–2 °C when 3–10 days old; controls were same-sex siblings not hypothermia exposed. When 74 such sibling pairs were exposed after weaning to predation by screech owls, the hypothermia-treated and control siblings did not differ in which was caught first. Based on study of deaths in 253 sibling pairs prior to weaning while under parental care, parents cared for hypothermia-treated siblings as attentively as controls. The results indicate that the experience of multiple neonatal deep-hypothermic episodes is benign in P. leucopus.
Actogram analysis of free-flying migratory birds: new perspectives based on acceleration logging
Venue: Journal of Comparative Physiology A

The use of accelerometers has become an important part of biologging techniques for large-sized birds with accelerometer data providing information about flight mode, wing-beat pattern, behaviour and energy expenditure. Such data show that birds using much energy-saving soaring/gliding flight like frigatebirds and swifts can stay airborne without landing for several months. Successful accelerometer studies have recently been conducted also for free-flying small songbirds during their entire annual cycle. Here we review the principles and possibilities for accelerometer studies in bird migration. We use the first annual actograms (for red-backed shrike Lanius collurio) to explore new analyses and insights that become possible with accelerometer data. Actogram data allow precise estimates of numbers of flights, flight durations as well as departure/landing times during the annual cycle. Annual and diurnal rhythms of migratory flights, as well as prolonged nocturnal flights across desert barriers are illustrated. The shifting balance between flight, rest and different intensities of activity throughout the year as revealed by actogram data can be used to analyse exertion levels during different phases of the life cycle. Accelerometer recording of the annual activity patterns of individual birds will open up a new dimension in bird migration research.
Mapping brain structure and function: cellular resolution, global perspective
Venue: Journal of Comparative Physiology A

A comprehensive understanding of the brain requires analysis, although from a global perspective, with cellular, and even subcellular, resolution. An important step towards this goal involves the establishment of three-dimensional high-resolution brain maps, incorporating brain-wide information about the cells and their connections, as well as the chemical architecture. The progress made in such anatomical brain mapping in recent years has been paralleled by the development of physiological techniques that enable investigators to generate global neural activity maps, also with cellular resolution, while simultaneously recording the organism’s behavioral activity. Combination of the high-resolution anatomical and physiological maps, followed by theoretical systems analysis of the deduced network, will offer unprecedented opportunities for a better understanding of how the brain, as a whole, processes sensory information and generates behavior.
How do energy stores and changes in these affect departure decisions by migratory birds? A critical view on stopover ecology studies and some future perspectives
Venue: Journal of Comparative Physiology A

In birds, accumulating energy is far slower than spending energy during flight. During migration, birds spend, therefore, most of the time at stopover refueling energy used during the previous flight. This elucidates why current energy stores and actual rate of accumulating energy are likely crucial factors influencing bird’s decision when to resume migration in addition to other intrinsic (sex, age) and extrinsic (predation, weather) factors modulating the decision within the innate migration program. After first summarizing how energy stores and stopover durations are generally determined, we critically review that high-energy stores and low rates of accumulating energy were significantly related to high departure probabilities in several bird groups. There are, however, also many studies showing no effect at all. Recent radio-tracking studies highlighted that migrants leave a site either to resume migration or to search for a better stopover location, so-called “landscape movements”. Erroneously treating such movements as departures increases the likelihood of type II errors which might mistakenly suggest no effect of either trait on departure. Furthermore, we propose that energy loss during the previous migratory flight in relation to bird’s current energy stores and migration strategy significantly affects its urge to refuel and hence its departure decision.
Temperature effects on the activity, shape, and storage of platelets from 13-lined ground squirrels
Venue: Journal of Comparative Physiology B

The objective of this study is to determine how a hibernating mammal avoids the formation of blood clots under periods of low blood flow. A microfluidic vascular injury model was performed to differentiate the effects of temperature and shear rate on platelet adhesion to collagen. Human and ground squirrel whole blood was incubated at 15 or 37 °C and then passed through a microfluidic chamber over a 250-µm strip of type I fibrillar collagen at that temperature and the shear rates of 50 or 300 s−1 to simulate torpid and aroused conditions, respectively. At 15 °C, both human and ground squirrel platelets showed a 90–95% decrease in accumulation on collagen independent of shear rate. At 37 °C, human platelet accumulation reduced by 50% at 50 s−1 compared to 300 s−1, while ground squirrel platelet accumulation dropped by 80%. When compared to platelets from non-hibernating animals, platelets from animals collected after arousal from torpor showed a 60% decrease in binding at 37 °C and 300 s−1, but a 2.5-fold increase in binding at 15 °C and 50 s−1. vWF binding in platelets from hibernating ground squirrels was decreased by 50% relative to non-hibernating platelets. The source of the plasma that platelets were stored in did not affect the results indicating that the decreased vWF binding was a property of the platelets. Upon chilling, ground squirrel platelets increase microtubule assembly leading to the formation of long rods. This shape change is concurrent with sequestration of platelets in the liver and not the spleen. In conclusion, it appears that ground squirrel platelets are sequestered in the liver during torpor and have reduced binding capacity for plasma vWF and lower accumulation on collagen at low shear rates and after storage at cold temperatures, while still being activated by external agonists. These adaptations would protect the animals from spontaneous thrombus formation during torpor but allow them to restore normal platelet function upon arousal.
Comparative tissue transcriptomics highlights dynamic differences among tissues but conserved metabolic transcript prioritization in preparation for arousal from torpor
Venue: Journal of Comparative Physiology B

During the hibernation season, 13-lined ground squirrels spend days to weeks in torpor with body temperatures near freezing then spontaneously rewarm. The molecular drivers of the drastic physiological changes that orchestrate and permit torpor are not well understood. Although transcription effectively ceases at the low body temperatures of torpor, previous work has demonstrated that some transcripts are protected from bulk degradation in brown adipose tissue (BAT), consistent with the importance of their protein products for metabolic heat generation during arousal from torpor. We examined the transcriptome of skeletal muscle, heart, and liver to determine the patterns of differentially expressed genes in these tissues, and whether, like BAT, a subset of these were relatively increased during torpor. EDGE-tags were quantified from five distinct physiological states representing the seasonal and torpor-arousal cycles of 13-lined ground squirrels. Supervised clustering on relative transcript abundances with Random Forest separated the two states bracketing prolonged torpor, entrance into and aroused from torpor, in all three tissues. Independent analyses identified 3347, 6784, and 2433 differentially expressed transcripts among all sampling points in heart, skeletal muscle, and liver, respectively. There were few differentially expressed genes in common across all three tissues; these were enriched in mitochondrial and apoptotic pathway components. Divisive clustering of these data revealed unique cohorts of transcripts that increased across the torpor bout in each tissue with patterns reflecting various combinations of cycling within and between seasons as well as between torpor and arousal. Transcripts that increased across the torpor bout were likewise tissue specific. These data shed new light on the biochemical pathways that alter in concert with hibernation phenotype and provide a rich resource for further hypothesis-based studies.
Seasonal loss and resumption of circadian rhythms in hibernating arctic ground squirrels
Venue: Journal of Comparative Physiology B

Circadian clocks are near universal among organisms and play a key role in coordinating physiological and metabolic functions to anticipate or coincide with predictable daily changes in the physical and social environment. However, whether circadian rhythms persist and are functionally important during hibernation in all mammals is currently unclear. We examined whether circadian rhythms of body temperature (Tb) persist during multi-day, steady-state torpor and investigated the association between timing of animal emergence, exposure to light, and resumption of activity and Tb rhythms in free-living and captive male arctic ground squirrels. High-resolution (0.02 °C) temperature loggers revealed that circadian rhythms of Tb were not present during deep torpor in free-living arctic ground squirrels. Significant circadian rhythms of Tb resumed, however, following the resumption of euthermia, but prior to emergence, though rhythms became much more robust coincident with aboveground emergence. Additionally, squirrels maintained in captivity under conditions of constant darkness spontaneously developed significant circadian rhythms of Tb and activity soon after ending torpor. Exposing animals to a 5-s pulse of light within a week when they ended torpor increased the strength of rhythms. Our results are consistent with the hypothesis that circadian clock function is inhibited during hibernation in arctic ground squirrels, and we postulate that exposure to external stimuli, such as light in free-living animals, and meals or acute disturbance for captive squirrels, may enhance Tb rhythmicity by synchronizing loosely coupled circadian oscillators within the suprachiasmatic nucleus.