Energetic Bottlenecks Research Articles

Electronic Polarization Leads to a Drier Dewetted State for Hydrophobic Gating in the Big Potassium Channel.

In the hydrophobic gating mechanism proposed for some ion channels, ion permeation is not blocked by the physical dimension of the channel pore but by its dewetted state which constitutes the energetic bottleneck. A major source of uncertainty in the mechanism is that the dewetted state was not observed in experiments and only probed in simulations using nonpolarizable force fields, which do not accurately represent the properties of confined water. Here we analyze hydration of the central cavity in the pore-gate domain of the Big Potassium channel using molecular dynamics and grand canonical Monte Carlo simulations with enhanced sampling techniques. Including polarization leads to a much drier dewetted state and a higher barrier for the transition to the wet state, suggesting more effective hydrophobic gating. The simulations also identify two backbone carbonyls at the bottom of the selectivity filter as good candidates for characterizing the dewetted state using infrared spectroscopies.

Genetic algorithm-based re-optimization of the Schrock catalyst for dinitrogen fixation

This study leverages a graph-based genetic algorithm (GB-GA) for the design of efficient nitrogen-fixing catalysts as alternatives to the Schrock catalyst, with the aim to improve the energetics of key reaction steps. Despite the abundance of nitrogen in the atmosphere, it remains largely inaccessible due to its inert nature. The Schrock catalyst, a molybdenum-based complex, offered a breakthrough but its practical application is limited due to low turnover numbers and energetic bottlenecks. The genetic algorithm in our study explores the chemical space for viable modifications of the Schrock catalyst, evaluating each modified catalyst’s fitness based on reaction energies of key catalytic steps and synthetic accessibility. Through a series of selection and optimization processes, we obtained fully converged catalytic cycles for 20 molecules at the B3LYP level of theory. From these results, we identified three promising molecules, each demonstrating unique advantages in different aspects of the catalytic cycle. This study offers valuable insights into the potential of generative models for catalyst design. Our results can help guide future work on catalyst discovery for the challenging nitrogen fixation process.

Molecular Simulations of Conformational Transitions within the Insulin Receptor Kinase Reveal Consensus Features in a Multistep Activation Pathway.

Modulating the transitions between active and inactive conformations of protein kinases is the primary means of regulating their catalytic activity, achieved by phosphorylation of the activation loop (A-loop). To elucidate the mechanism of this conformational activation, we applied the string method to determine the conformational transition path of insulin receptor kinase between the active and inactive conformations and the corresponding free-energy profiles with and without A-loop phosphorylation. The conformational change was found to proceed in three sequential steps: first, the flipping of the DFG motif of the active site; second, rotation of the A-loop; finally, the inward movement of the αC helix. The main energetic bottleneck corresponds to the conformational change in the A-loop, while changes in the DFG motif and αC helix occur before and after A-loop conformational change, respectively. In accordance with this, two intermediate states are identified, the first state just after the DFG flipping and the second state after the A-loop rotation. These intermediates exhibit structural features characteristic of the corresponding inactive and active conformations of other protein kinases. To understand the impact of A-loop phosphorylation on kinase conformation, the free energies of A-loop phosphorylation were determined at several states along the conformational transition path using the free-energy perturbation simulations. The calculated free energies reveal that while the unphosphorylated kinase interconverts between the inactive and active conformations, A-loop phosphorylation restricts access to the inactive conformation, thereby increasing the active conformation population. Overall, this study suggests a consensus mechanism of conformational activation between different protein kinases.

Saving energy via short and shallow torpor bouts

Maintaining a high and stable body temperature as observed in most endothermic mammals and birds is energetically costly and many heterothermic species reduce their metabolic demands during energetic bottlenecks through the use of torpor. With the increasing number of heterotherms revealed in a diversity of habitats, it becomes apparent that triggers and patterns of torpor use are more variable than previously thought. Here, we report the previously overlooked use of, shallow rest-time torpor (body temperature >30 °C) in African lesser bushbabies, Galago moholi. Body core temperature of three adult male bushbabies recorded over five months showed a clear bimodal distribution with an average active modal temperature of 39.2 °C and a resting modal body temperature of 36.7 °C. Shallow torpor was observed in two out of three males (n = 29 torpor bouts) between June and August (austral winter), with body temperatures dropping to an overall minimum of 30.7 °C and calculated energy savings of up to 10%. We suggest that shallow torpor may be an ecologically important, yet mostly overlooked energy-saving strategy employed by heterothermic mammals. Our data emphasise that torpor threshold temperatures need to be used with care if we aim to fully understand the level of physiological plasticity displayed by heterothermic species.

Behavioural flexibility in an Arctic seabird using two distinct marine habitats to survive the energetic constraints of winter

BackgroundHomeothermic marine animals in Polar Regions face an energetic bottleneck in winter. The challenges of short days and cold temperatures are exacerbated for flying seabirds with small body size and limited fat stores. We use biologging approaches to examine how habitat, weather, and moon illumination influence behaviour and energetics of a marine bird species, thick-billed murres (Uria lomvia).MethodsWe used temperature-depth-light recorders to examine strategies murres use to survive winter in the Northwest Atlantic, where contrasting currents create two distinct marine habitats: cold (−0.1 ± 1.2 °C), shallower water along the Labrador Shelf and warmer (3.1 ± 0.3 °C), deep water in the Labrador Basin.ResultsIn the cold shelf water, murres used a high-energy strategy, with more flying and less diving each day, resulting in high daily energy expenditure and also high apparent energy intake; this strategy was most evident in early winter when day lengths were shortest. By contrast, murres in warmer basin water employed a low-energy strategy, with less time flying and more time diving under low light conditions (nautical twilight and night). In warmer basin water, murres increased diving at night when the moon was more illuminated, likely taking advantage of diel vertically migrating prey. In warmer basin water, murres dove more at night and foraging efficiency increased under negative North Atlantic Oscillation (calmer ocean conditions).ConclusionsThe proximity of two distinct marine habitats in this region allows individuals from a single species to use dual (low-energy/high-energy) strategies to overcome winter energy bottlenecks.

Modelling and mapping how common guillemots balance their energy budgets over a full annual cycle

Abstract The ability of individual animals to balance their energy budgets throughout the annual cycle is important for their survival, reproduction and population dynamics. However, the annual cycles of many wild, mobile animals are difficult to observe and our understanding of how individuals balance their energy budgets throughout the year therefore remains poor. We developed a hierarchical Bayesian state‐space model to investigate how key components of animal energy budgets (namely individual energy gain and storage) varied in space and time. Our model used biologger‐derived estimates of time‐activity budgets, locations and energy expenditure to infer year‐round time series of energy income and reserves. The model accounted for seasonality in environmental drivers such as sea surface temperature and daylength, allowing us to identify times and locations of high energy gain. Our study system was a population of common guillemots Uria aalge breeding at a western North Sea colony. These seabirds manage their energy budgets by adjusting their behaviour and accumulating fat reserves. However, typically during severe weather conditions, birds can experience an energy deficit over a sustained period, leading to starvation and large‐scale mortality events. We show that guillemot energy gain varied in both time and space. Estimates of guillemot body mass varied throughout the annual cycle and birds periodically experienced losses in mass. Mass losses were likely to have either been adaptive, or due to energetic bottlenecks, the latter leading to increased susceptibility to mortality. Guillemots tended to be lighter towards the edge of their spatial distribution. We describe a framework that combines biologging data, time‐activity budget analysis and Bayesian state‐space modelling to identify times and locations of high energetic reward or potential energetic bottlenecks in a wild animal population. Our approach can be extended to address ecological and conservation‐driven questions that were previously unanswerable due to logistical complexities in collecting data on wild, mobile animals across full annual cycles. Read the free Plain Language Summary for this article on the Journal blog.

Living in a changing world: Physiological and behavioural flexibility of juvenile Garden Dormice

Heterothermy, or torpor, allows individuals to save energy by active reduction of metabolism and decreased body temperature. Social thermoregulation or huddling allows individuals to minimize energy needs while maintaining a relatively high body temperature. The Garden Dormouse (Eliomys quercinus), a highly endangered European rodent, uses both strategies of torpor and huddling, which are particularly beneficial for young individuals to cope with environmental fluctuations. Since juveniles are an important component of population renewal, determining the flexibility of energy-saving strategies and its consequences on somatic integrity of young individuals is key to protecting this species. We measured individual torpor patterns, body mass gain and structural growth, and assessed telomere dynamics in male and female juvenile Garden Dormice according to housing condition (singly or groups of four individuals) and food availability (fed ad-libitum or energy-limited) before and during hibernation. During development, juveniles used more frequent, longer and deeper torpor when housed singly than in groups. Torpor was encouraged by lower food availability. Juveniles showed similar body mass gain and growth, irrespective of experimental conditions. During hibernation, huddling dormice showed similar hibernating patterns and mass loss compared to single individuals regardless of food availability. Telomere lengthened across all individuals before hibernation, with larger elongation in males, which also experienced greater telomere loss than females during hibernation. We conclude that the use of torpor and huddling allows juvenile Garden Dormice to cope successfully with energetic bottlenecks, without major effects on somatic integrity. Future studies will need to confirm such findings under natural environmental conditions.

Bottom-up dust nucleation theory in oxygen-rich evolved stars

Context.Aluminium oxide (alumina; Al2O3) is a promising candidate as a primary dust condensate in the atmospheres of oxygen-rich evolved stars. Therefore, alumina ‘seed’ particles might trigger the onset of stellar dust formation and of stellar mass loss in the wind. However, the formation of alumina dust grains is not well understood.Aims.We aim to shed light on the initial steps of cosmic dust formation (i.e. nucleation) in oxygen-rich environments via a quantum-chemical bottom-up approach.Methods.Starting with an elemental gas-phase composition, we construct a detailed chemical-kinetic network that describes the formation and destruction of aluminium-bearing molecules and dust-forming (Al2O3)nclusters up to the size of dimers (n= 2) coagulating to tetramers (n= 4). Intermediary species include the prevalent gas-phase molecules AlO and AlOH as well as AlxOyclusters withx= 1–5,y= 1–6. The resulting extensive network is applied to two model stars, which represent a semi-regular variable and a Mira type, and to different circumstellar gas trajectories, including a non-pulsating outflow and a pulsating model. The growth of larger-sized (Al2O3)nclusters withn= 4–10 is described by the temperature-dependent Gibbs free energies of the most favourable structures (i.e. the global minima clusters) as derived from global optimisation techniques and calculated via density functional theory. We provide energies, bond characteristics, electrostatic properties, and vibrational spectra of the clusters as a function of size,n, and compare these to corundum, which corresponds to the crystalline bulk limit (n→∞).Results.The circumstellar aluminium gas-phase chemistry in oxygen-rich giants is primarily controlled by AlOH and AlO, which are tightly coupled by the reactions AlO+H2, AlO+H2O, and their reverse. Models of semi-regular variables show comparatively higher AlO abundances, as well as a later onset and a lower efficiency of alumina cluster formation when compared to Mira-like models. The Mira-like models exhibit an efficient cluster production that accounts for more than 90% of the available aluminium content, which is in agreement with the most recent ALMA observations. Chemical equilibrium calculations fail to predict both the alumina cluster formation and the abundance trends of AlO and AlOH in the asymptotic giant branch dust formation zone. Furthermore, we report the discovery of hitherto unreported global minimum candidates and low-energy isomers for cluster sizesn= 7, 9, and 10. A homogeneous nucleation scenario, where Al2O3monomers are successively added, is energetically viable. However, the formation of the Al2O3monomer itself represents an energetic bottleneck. Therefore, we provide a bottom-up interpolation of the cluster characteristics towards the bulk limit by excluding the monomer, approximately following ann−1∕3dependence.

Survivable hypothermia or torpor in a wild-living rat: rare insights broaden our understanding of endothermic physiology

Maintaining a high and stable body temperature as observed in endothermic mammals and birds is energetically costly. Thus, it is not surprising that we discover more and more heterothermic species that can reduce their energetic needs during energetic bottlenecks through the use of torpor. However, not all heterothermic animals use torpor on a regular basis. Torpor may also be important to an individual’s probability of survival, and hence fitness, when used infrequently. We here report the observation of a single, ~ 5.5 h long hypothermic bout with a decrease in body temperature by 12 °C in the native Australian bush rat (Rattus fuscipes). Our data suggest that bush rats are able to rewarm from a body temperature of 24 °C, albeit with a rewarming rate lower than that expected on the basis of their body mass. Heterothermy, i.e. the ability to withstand and overcome periods of reduced body temperature, is assumed to be an evolutionarily ancestral (plesiomorphic) trait. We thus argue that such rare hypothermic events in species that otherwise appear to be strictly homeothermic could be heterothermic rudiments, i.e. a less derived form of torpor with limited capacity for rewarming. Importantly, observations of rare and extreme thermoregulatory responses by wild animals are more likely to be discovered with long-term data sets and may not only provide valuable insight about the physiological capability of a population, but can also help us to understand the constraints and evolutionary pathways of different phenologies.

On the modulation and maintenance of hibernation in captive dwarf lemurs

In nature, photoperiod signals environmental seasonality and is a strong selective “zeitgeber” that synchronizes biological rhythms. For animals facing seasonal environmental challenges and energetic bottlenecks, daily torpor and hibernation are two metabolic strategies that can save energy. In the wild, the dwarf lemurs of Madagascar are obligate hibernators, hibernating between 3 and 7 months a year. In captivity, however, dwarf lemurs generally express torpor for periods far shorter than the hibernation season in Madagascar. We investigated whether fat-tailed dwarf lemurs (Cheirogaleus medius) housed at the Duke Lemur Center (DLC) could hibernate, by subjecting 8 individuals to husbandry conditions more in accord with those in Madagascar, including alternating photoperiods, low ambient temperatures, and food restriction. All dwarf lemurs displayed daily and multiday torpor bouts, including bouts lasting ~ 11 days. Ambient temperature was the greatest predictor of torpor bout duration, and food ingestion and night length also played a role. Unlike their wild counterparts, who rarely leave their hibernacula and do not feed during hibernation, DLC dwarf lemurs sporadically moved and ate. While demonstrating that captive dwarf lemurs are physiologically capable of hibernation, we argue that facilitating their hibernation serves both husbandry and research goals: first, it enables lemurs to express the biphasic phenotypes (fattening and fat depletion) that are characteristic of their wild conspecifics; second, by “renaturalizing” dwarf lemurs in captivity, they will emerge a better model for understanding both metabolic extremes in primates generally and metabolic disorders in humans specifically.

Performance of horned puffins (Fratercula corniculata) on an object permanence task

Cognition influences how individuals interact with the environment, affecting the ecology of species. Gaining insight into the proficiency of relevant cognitive abilities provides an indication of the processes necessary for a species’ survival and reproduction. Many birds have “slow” life-histories and complex social environments suggestive of high cognitive ability. Little, however, is known about the cognition of most birds with these traits, thus studying cognition in seabirds with these traits provides insight into how slow life-histories and complex social environments relate more generally to predicting cognitive ability. Object permanence is a cognitive ability shared by highly intelligent animals and could be an ecologically relevant ability for many seabirds. I used a simple experimental setup in a semi-controlled environment to test object permanence in captive horned puffins (Fratercula corniculata) by hiding a reward to be retrieved, first partially and then completely. I discovered that the horned puffins performed poorly on the object permanence task when the reward was hidden completely. I discuss briefly how the slow life-histories of many seabirds probably evolved due to the stochastic conditions associated with their marine environment, which in turn may cause an energetic bottleneck that limits the allocation of resources to certain cognitive abilities.

CO2 reduction driven by a pH gradient.

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog-and proposed evolutionary predecessor-of the Wood-Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO-), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.

Habitat modification effects on anuran food webs in the Colombian tropical dry forest

Habitat loss and transformation are major threats to biodiversity and ecosystem functioning, but their effects on species interaction are often poorly understood. We evaluated effects of habitat transformation and seasonality on anuran-prey food webs in Colombian dry-forests. We asked whether anthropic transformation (anthropic vs natural) and/or seasonality (dry, minor and major rain seasons) affect predator load on arthropods, the occurrence of energetic bottlenecks, and the diet overlap of anurans. We selected six dry forest sites in the Caribbean of Colombia, sampled anurans, and identified their stomach contents to construct anuran-prey food webs. We show that the global structure of food webs was affected by disturbance and seasonality, but not by their interaction. Prey vulnerability was higher in anthropic habitats. Habitat transformation enhanced diet overlap among predators, but there was not a differential effect of habitat type according to seasonality for network metrics. Our study shows a strong effect of natural vegetation modification in tropical dry forest on anuran-prey food webs, while seasonality did not seem to further mediate these effects.

Effects of body size, sex, parental care and moult strategies on auk diving behaviour outside the breeding season

Information on seabird foraging behaviour outside the breeding season is currently limited. This knowledge gap is critical as this period is energetically demanding due to post‐fledging parental care, feather moult and changing environmental conditions. Based on species’ body size, post‐fledging parental strategy and primary moult schedule we tested predictions for key aspects of foraging behaviour (maximum dive depth (MDD), daily time submerged (DTS) and diurnal dive activity (DDA)) using dive depth data collected from three seabird species (common guillemot Uria aalge, razorbill Alca torda and Atlantic puffin Fratercula arctica) from the end of the breeding season (July) to mid‐winter (January). We found partial support for predictions associated with body size; guillemots had greater MDD than razorbills but MDD did not differ between razorbills and puffins, despite the former being 35% heavier. In accordance with sexual monomorphism in all three species, MDD did not differ overall between the sexes. However, in guillemots and razorbills there were sex‐specific differences, such that male guillemots made deeper dives than females, and males of both species had higher DTS. In contrast, there were no marked sex differences in dive behaviour of puffins in July and August in accordance with their lack of post‐fledging parental care and variable moult schedule. We found support for the prediction that diving effort would be greater in mid‐winter compared to the period after the breeding season. Despite reduced daylight in mid‐winter, this increase in DTS occurred predominantly during the day and only guillemots appeared to dive nocturnally to any great extent. In comparison to diving behaviour of these species recorded during the breeding season, MDD was shallower and DTS was greater during the non‐breeding period. Such differences in diving behaviour during the post‐breeding period are relevant when identifying potential energetic bottlenecks, known to be key drivers of seabird population dynamics.

Computational Study of Protein-Ligand Unbinding for Enzyme Engineering.

The computational prediction of unbinding rate constants is presently an emerging topic in drug design. However, the importance of predicting kinetic rates is not restricted to pharmaceutical applications. Many biotechnologically relevant enzymes have their efficiency limited by the binding of the substrates or the release of products. While aiming at improving the ability of our model enzyme haloalkane dehalogenase DhaA to degrade the persistent anthropogenic pollutant 1,2,3-trichloropropane (TCP), the DhaA31 mutant was discovered. This variant had a 32-fold improvement of the catalytic rate toward TCP, but the catalysis became rate-limited by the release of the 2,3-dichloropropan-1-ol (DCP) product from its buried active site. Here we present a computational study to estimate the unbinding rates of the products from DhaA and DhaA31. The metadynamics and adaptive sampling methods were used to predict the relative order of kinetic rates in the different systems, while the absolute values depended significantly on the conditions used (method, force field, and water model). Free energy calculations provided the energetic landscape of the unbinding process. A detailed analysis of the structural and energetic bottlenecks allowed the identification of the residues playing a key role during the release of DCP from DhaA31 via the main access tunnel. Some of these hot-spots could also be identified by the fast CaverDock tool for predicting the transport of ligands through tunnels. Targeting those hot-spots by mutagenesis should improve the unbinding rates of the DCP product and the overall catalytic efficiency with TCP.

Water-deficit priming of papaya reduces high-light stress through oxidation avoidance rather than anti-oxidant activity

The mechanisms for tolerance of various abiotic stresses in plants are often considered to be similar, but there are also specific traits responsible for acclimation that differ according to the type and extent of stress. Water-deficit priming is the imposition of a period of moderate drought stress to induce tolerance to a subsequent stress. We hypothesized that priming improves papaya (Carica papaya L.) response to high light intensity. We tested the effects of water-deficit priming on photoinhibition upon shade removal. We assessed morphological and physiological variables associated with priming responses. Priming reduced the intensity and duration of photoinhibition upon shade removal and increased mean leaf area compared to non-primed plants. Photochemical responses to priming included reduced absorption and increased efficiencies of electron transfer from plastoquinone through photosystem I. Photosynthetic responses included upregulation of Rubisco and Ribulose 1,5-bisphosphate regeneration. Morphological responses included increased stomatal density and size. Anti-oxidant capacity was not affected by priming or prior shade treatment. We conclude that water-deficit priming improves papaya response to high light by different physiological mechanisms than shade-to-light acclimation itself. Rather than anti-oxidant upregulation, priming reduces energetic bottlenecks, thereby reducing oxidative stress during shade-to-high-light transitions.

BATS RECOVERING FROM WHITE-NOSE SYNDROME ELEVATE METABOLIC RATE DURING WING HEALING IN SPRING.

Host responses to infection with novel pathogens are costly and require trade-offs among physiologic systems. One such pathogen is the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) and has led to mass mortality of hibernating bats in eastern North America. Although infection with Pd does not always result in death, we hypothesized that bats that survive infection suffer significant consequences that negatively impact the ability of females to reproduce. To understand the physiologic consequences of surviving infection with Pd, we assessed differences in wing damage, mass-specific resting metabolic rate, and reproductive rate between little brown myotis ( Myotis lucifugus) that survived a winter in captivity after inoculation with Pd (WNS survivors) and comparable, uninfected bats. Survivors of WNS had significantly more damaged wing tissue and displayed elevated mass-specific metabolic rates compared with Pd-uninfected bats after emergence from hibernation. The WNS survivors and Pd-uninfected bats did not significantly differ in their reproductive capacity, at least in captivity. However, our metabolic data demonstrated greater energetic costs during spring in WNS survivors compared with uninfected bats, which may have led to other consequences for postpartum fitness. We suggest that, after surviving the energetic constraints of winter, temperate hibernating bats infected with Pd faced a second energetic bottleneck after emerging from hibernation.

Experimental bond dissociation energies of benzylpyridinium thermometer ions determined by threshold-CID and RRKM modeling

Benzylpyridinium salts (BPs) have often been used as thermometer ions to obtain an energy calibration of mass spectrometric experiments (in particular to determine internal energy distributions of ions after the ionization process). Fragmentation of BP+ molecular ions is characterized by specific Bond Dissociation Energies (BDE) which depend on the substituent group and its location on the benzyl ring. Although those BDE values are regularly re-evaluated by quantum chemical calculations, their experimental determination is still missing from the literature. In this paper, a modified Quadrupole-hexapole-Quadrupole (QhQ) mass spectrometer is used to obtain such values on 4 BP+ molecular ions (characterized by a wide range of CN bond strengths) using Threshold Collision-Induced Dissociations (TCID) and Rice–Ramsperger–Kassel–Marcus (RRKM) kinetic modeling. It is found that experimental values are systematically 0.5eV lower than their most recent theoretical evaluations. Despite this shift, the absolute critical energy values are maintained in the same order (pOMe<pMe<pCl<pCN), and the relative energy differences are in very good agreement. We argue that the observed 0.5eV shift relates to the energy dependence of the Transition State’s number of states that is typical for barrier-less fragmentation processes and, relates to a kinetic rather than an energetic bottleneck. Notably, by taking into account the bond elongations characterizing the transition states and their corresponding calculated critical energies (E0), close agreement is found with experimentally obtained E0 values. We thus conclude that much care should be taken when describing the transition state during an internal energy calibration procedure where the involved energy is lower than 3–4eV.

Seasonal Control of Mammalian Energy Balance: Recent Advances in the Understanding of Daily Torpor and Hibernation.

Endothermic mammals and birds require intensive energy turnover to sustain high body temperatures and metabolic rates. To cope with the energetic bottlenecks associated with the change of seasons, and to minimise energy expenditure, complex mechanisms and strategies are used, such as daily torpor and hibernation. During torpor, metabolic depression and low body temperatures save energy. However, these bouts of torpor, lasting for hours to weeks, are interrupted by active 'euthermic' phases with high body temperatures. These dynamic transitions require precise communication between the brain and peripheral tissues to defend rheostasis in energetics, body mass and body temperature. The hypothalamus appears to be the major control centre in the brain, coordinating energy metabolism and body temperature. The sympathetic nervous system controls body temperature by adjustments of shivering and nonshivering thermogenesis, with the latter being primarily executed by brown adipose tissue. Over the last decade, comparative physiologists have put forward integrative studies on the ecophysiology, biochemistry and molecular regulation of energy balance in response to seasonal challenges, food availability and ambient temperature. Mammals coping with such environments comprise excellent model organisms for studying the dynamic regulation of energy metabolism. Beyond the understanding of how animals survive in nature, these studies also uncover general mechanisms of mammalian energy homeostasis. This research will benefit efforts of translational medicine aiming to combat emerging human metabolic disorders. The present review focuses on recent advances in the understanding of energy balance and its neuronal and endocrine control during the most extreme metabolic fluctuations in nature: daily torpor and hibernation.

Leptin levels, seasonality and thermal acclimation in the Microbiotherid marsupial Dromiciops gliroides: Does photoperiod play a role?

Mammals of the Neotropics are characterized by a marked annual cycle of activity, which is accompanied by several physiological changes at the levels of the whole organism, organs and tissues. The physiological characterization of these cycles is important, as it gives insight on the mechanisms by which animals adjust adaptively to seasonality. Here we studied the seasonal changes in blood biochemical parameters in the relict South American marsupial Dromiciops gliroides (“monito del monte” or “little mountain monkey”), under semi-natural conditions. We manipulated thermal conditions in order to characterize the effects of temperature and season on a battery of biochemical parameters, body mass and adiposity. Our results indicate that monitos experience an annual cycle in body mass and adiposity (measured as leptin levels), reaching a maximum in winter and a minimum in summer. Blood biochemistry confirms that the nutritional condition of animals is reduced in summer instead of winter (as generally reported). This was coincident with a reduction of several biochemical parameters in summer, such as betahydroxybutyrate, cholesterol, total protein concentration and globulins. Monitos seem to initiate winter preparation during autumn and reach maximum body reserves in winter. Hibernation lasts until spring, at which time they use fat reserves and become reproductively active. Sexual maturation during summer would be the strongest energetic bottleneck, which explains the reductions in body mass and other parameters in this season. Overall, this study suggests that monitos anticipate the cold season by a complex interaction of photoperiodic and thermal cues.