Behavioural microclimate selection and physiological responses to environmental conditions in a hibernating bat

Hibernators adjust the expression of torpor behaviourally and physiologically to balance the benefits of energy conservation in hibernation against the physiological and ecological costs. Small fat-storing species, like many cave-hibernating bats, have long been thought to be highly constrained in their expression of hibernation because they must survive winter relying only on endogenous energy stores. We evaluated behavioural microclimate selection in tri-colored bats (Perimyotis subflavus (Cuvier, 1832)) across a three-month hibernation experiment under laboratory conditions. We also opportunistically tested for evidence of acclimatization in torpid metabolic rate (TMR). When given access to gradients in microclimate, bats tended to choose the warmest temperature available (11°C) while almost completely avoiding the driest condition available (85% relative humidity at 8°C). Further, bats held at different temperatures over the course of the hibernation showed no differences in TMR when measured under common conditions at the end of hibernation. Taken together, our results suggest selective pressures to conserve energy during hibernation are not overwhelmingly strong and further support the proposition that optimal expression of hibernation is something less than the maximal expression of hibernation unless the animal is nearing starvation.

Cortisol and Dexamethasone Mediate Glucocorticoid Actions in the Lesser Spotted Catshark (Scyliorhinus canicula)

Corticosteroids are hormones produced in vertebrates exerting gluco- and mineralocorticoid actions (GC and MC) mediated by specific receptors (GR and MR, respectively). In elasmobranchs, the major circulating corticosteroid is the 1α-hydroxycorticosterone (1α-OHB). This hormone acts as a MC, but to date its role as a GC has not been established. As there is no 1α-OHB standard available, here we employed a set of in vivo and ex vivo approaches to test GC actions of other corticosteroids in the lesser spotted catshark (Scyliorhinus canicula). Dexamethasone (DEX, a synthetic corticosteroid) slow-release implants decreased plasma 1α-OHB levels after 7 days, and modified carbohydrates metabolism in liver and white muscle (energy stores and metabolic enzymes). In addition, ex vivo culture of liver and white muscle explants confirmed GC actions of corticosteroids not naturally present in sharks (cortisol and DEX) by increasing glucose secretion from these tissues. Dose–response curves induced by cortisol and DEX, altogether with the use of specific GR inhibitor mifepristone, confirmed the involvement of GR mediating glucose secretion. This study highlights the influence of corticosteroids in the glucose balance of S. canicula, though the role of 1α-OHB as a GC hormone in sharks should be further confirmed.

The Role of Leptin in the Development of Energy Homeostatic Systems and the Maintenance of Body Weight

LEP is a pleiotropic gene and the actions of leptin extend well beyond simply acting as the signal of the size of adipose tissue stores originally proposed. This is a discussion of the multi-system interactions of leptin with the development of the neural systems regulating energy stores, and the subsequent maintenance of energy stores throughout the lifespan. The prenatal, perinatal, and later postnatal effects of leptin on systems regulating body energy stores and on the energy stores themselves are heavily influenced by the nutritional environment which leptin exposure occurs. This review discusses the prenatal and perinatal roles of leptin in establishing the neuronal circuitry and other systems relevant to the adiposity set-point (or “threshold”) and the role of leptin in maintaining weight homeostasis in adulthood. Therapeutic manipulation of the intrauterine environment, use of leptin sensitizing agents, and identification of specific cohorts who may be more responsive to leptin or other means of activating the leptin signaling pathway are ripe areas for future research.

Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress

Toxoplasma gondii has evolved different developmental stages for disseminating during acute infection (i.e. tachyzoites) and for establishing chronic infection (i.e. bradyzoites). Calcium ion (Ca2+) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motility to drive egress and cell invasion. However, the roles of Ca2+ signaling pathways in bradyzoites remain largely unexplored. Here we show that Ca2+ responses are highly restricted in bradyzoites and that they fail to egress in response to agonists. Development of dual-reporter parasites revealed dampened Ca2+ responses and minimal microneme secretion by bradyzoites induced in vitro or harvested from infected mice and tested ex vivo. Ratiometric Ca2+ imaging demonstrated lower Ca2+ basal levels, reduced magnitude, and slower Ca2+ kinetics in bradyzoites compared with tachyzoites stimulated with agonists. Diminished responses in bradyzoites were associated with down-regulation of Ca2+-ATPases involved in intracellular Ca2+ storage in the endoplasmic reticulum (ER) and acidocalcisomes. Once liberated from cysts by trypsin digestion, bradyzoites incubated in glucose plus Ca2+ rapidly restored their intracellular Ca2+ and ATP stores leading to enhanced gliding. Collectively, our findings indicate that intracellular bradyzoites exhibit dampened Ca2+ signaling and lower energy levels that restrict egress, and yet upon release they rapidly respond to changes in the environment to regain motility.

Convergent energy state-dependent antagonistic signalling by CART and NPY modulates the plasticity of forebrain neurons to regulate feeding in zebrafish

Dynamic re-configuration of circuit function subserves the flexibility of innate behaviours tuned to physiological states. Internal energy stores adaptively regulate feeding-associated behaviours by integrating opposing hunger and satiety signals at the level of neural circuits. Across vertebrate lineages, the neuropeptides CART and NPY have potent anorexic and orexic functions, respectively, and show energy state-dependent expression in interoceptive neurons. However, how the antagonistic activities of these peptides modulate circuit plasticity remain unclear. Using behavioural, neuroanatomical and activity analysis in adult zebrafish, along with pharmacological interventions, we show that CART and NPY activities converge on a population of neurons in the dorsomedial telencephalon (Dm). While CART facilitates glutamatergic neurotransmission at the Dm, NPY dampens the response to glutamate. In energy-rich states, CART enhances NMDA receptor (NMDAR) function by PKA/PKC mediated phosphorylation of the NR1 subunit of the NMDAR complex. Conversely, starvation triggers NPY-mediated reduction in phosphorylated NR1 via calcineurin activation and inhibition of cAMP production leading to reduced responsiveness to glutamate. Our data identify convergent integration of CART and NPY inputs by the Dm neurons to generate nutritional state-dependent circuit plasticity that is correlated with the behavioural switch induced by the opposing actions of satiety and hunger signals.

Lipid droplet evolution gives insight into polyaneuploid cancer cell lipid droplet functions

Lipid droplets (LDs) are found throughout all phyla across the tree of life. Originating as pure energy stores in the most basic organisms, LDs have evolved to fill various roles as regulators of lipid metabolism, signaling, and trafficking. LDs have been noted in cancer cells and have shown to increase tumor aggressiveness and chemotherapy resistance. A certain transitory state of cancer cell, the polyaneuploid cancer cell (PACC), appears to have higher LD levels than the cancer cell from which they are derived. PACCs are postulated to be the mediators of metastasis and resistance in many different cancers. Utilizing the evolutionarily conserved roles of LDs to protect from cellular lipotoxicity allows PACCs to survive otherwise lethal stressors. By better understanding how LDs have evolved throughout different phyla we will identify opportunities to target LDs in PACCs to increase therapeutic efficiency in cancer cells.

How recreational marathon runners hit the wall: A large-scale data analysis of late-race pacing collapse in the marathon

Introduction In the marathon, how runners pace and fuel their race can have a major impact on race outcome. The phenomenon known as hitting the wall (HTW) refers to the iconic hazard of the marathon distance, in which runners experience a significant slowing of pace late in the race, typically after the 20-mile mark, and usually because of a depletion of the body’s energy stores. Aim This work investigates the occurrence of significant late-race slowing among recreational marathoners, as a proxy for runners hitting the wall, to better understand the likelihood and nature of such slowdowns, and their effect on race performance. Methods Using pacing data from more than 4 million race records, we develop a pacing-based definition of hitting the wall, by identifying runners who experience a sustained period of slowing during the latter stages of the marathon. We calculate the cost of these slowdowns relative to estimates of the recent personal-best times of runners and compare slowdowns according to runner sex, age, and ability. Results We find male runners more likely to slow significantly (hit the wall) than female runners; 28% of male runners hit the wall compared with 17% of female runners, χ2(1, N = 1, 928, 813) = 27, 693.35, p < 0.01, OR = 1.43. Such slowdowns are more frequent in the 3 years immediately before and after a recent personal-best (PB) time; for example, 36% of all runners hit the wall in the 3 years before a recent PB compared with just 23% in earlier years, χ2(1, N = 509, 444) = 8, 120.74, p < 0.01, OR = 1.31. When runners hit the wall, males slow more than females: a relative slowdown of 0.40 vs. 0.37 is noted, for male and female runners, when comparing their pace when they hit the wall to their earlier race (5km-20km) pace, with t(475, 199) = 60.19, p < 0.01, d = 0.15. And male runners slow over longer distances than female runners: 10.7km vs. 9.6km, respectively, t(475, 199) = 68.44, p < 0.01, d = 0.17. Although, notably the effect size of these differences is small. We also find the finish-time costs of hitting the wall (lost minutes) to increase with ability; r2(7) = 0.91, p < 0.01 r2(7) = 0.81, p < 0.01 for male and female runners, respectively. Conclusions While the findings from this study are consistent with qualitative results from earlier single-race or smaller-scale studies, the new insights into the risk and nature of slowdowns, based on the runner sex, age, and ability, have the potential to help runners and coaches to better understand and calibrate the risk/reward trade-offs that exist as they plan for future races.

Detection of Voltage Unbalance in Microgrids using Artificial Neural Networks

This work proposes a methodology for detecting voltage imbalance using the OpenDSS software and its COM interface. The proposal is to detect voltage imbalance using the communication between OpenDSS and MATLAB through a Perceptron Multilayer Artificial Neural Network. For that, tests were carried out in a distribution network with distributed generators and energy stores. The studies were conducted on an IEEE 13 bus test system.

Glycolytically impaired glial cells fuel neural metabolism via β-oxidation

Neuronal function is highly energy demanding and thus requires efficient and constant metabolite delivery. Like their mammalian counterparts Drosophila glia are highly glycolytic and provide lactate to fuel neuronal metabolism. However, flies are able to survive for several weeks in the absence of glial glycolysis1. Here, we study how glial cells maintain sufficient nutrient supply to neurons under conditions of carbohydrate restriction. We show that glycolytically impaired glia switch to fatty acid breakdown via β-oxidation and provide ketone bodies as an alternate neuronal fuel. Moreover, flies also rely on glial β-oxidation under starvation conditions with glial loss of β-oxidation increasing susceptibility to starvation. Further, we show that glial cells act as a metabolic sensor in the brain and can induce mobilization of peripheral energy stores to ensure brain metabolic homeostasis. In summary, our study gives pioneering evidence on the importance of glial β-oxidation and ketogenesis for brain function, and survival, under adverse conditions, like malnutrition. The glial capacity to utilize lipids as an energy source seems to be conserved from flies to humans.