Fishes regulate tail-beat kinematics to minimize speed-specific cost of transport

Energetic expenditure is an important factor in animal locomotion. Here we test the hypothesis that fishes control tail-beat kinematics to optimize energetic expenditure during undulatory swimming. We focus on two energetic indices used in swimming hydrodynamics, cost of transport and Froude efficiency. To rule out one index in favour of another, we use computational-fluid dynamics models to compare experimentally observed fish kinematics with predicted performance landscapes and identify energy-optimized kinematics for a carangiform swimmer, an anguilliform swimmer and larval fishes. By locating the areas in the predicted performance landscapes that are occupied by actual fishes, we found that fishes use combinations of tail-beat frequency and amplitude that minimize cost of transport. This energy-optimizing strategy also explains why fishes increase frequency rather than amplitude to swim faster, and why fishes swim within a narrow range of Strouhal numbers. By quantifying how undulatory-wave kinematics affect thrust, drag, and power, we explain why amplitude and frequency are not equivalent in speed control, and why Froude efficiency is not a reliable energetic indicator. These insights may inspire future research in aquatic organisms and bioinspired robotics using undulatory propulsion.

Hyperactive HRAS dysregulates energetic metabolism in fibroblasts from patients with Costello syndrome via enhanced production of reactive oxidizing species

Germline activating mutations in HRAS cause Costello Syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via ROS-dependent AMPKα and p38 hyperactivation, occurs in CS, resulting in accelerated glycolysis, and increased fatty acid synthesis and storage as lipid droplets in primary fibroblasts. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.

Relationships between endogenous circadian period, physiological and cognitive parameters and sex in aged non-human primates

The biological clock exhibits circadian rhythms, with an endogenous period tau close to 24h. The circadian resonance theory proposes that lifespan is reduced when endogenous period goes far from 24h. It has been suggested that daily resetting of the circadian clock to the 24h external photoperiod might induce marginal costs that would accumulate over time and forward accelerate aging and affect fitness. In this study, we aimed to evaluate the link between the endogenous period and biomarkers of aging in order to investigate the mechanisms of the circadian resonance theory. We studied 39 middle-aged and aged Microcebus murinus, a nocturnal non-human primate whose endogenous period is about 23.1h, measuring the endogenous period of locomotor activity, as well as several physiological and behavioral parameters (rhythm fragmentation and amplitude, energetic expenditure, oxidative stress, insulin-like growth factor-1 (IGF-1) concentrations and cognitive performances) in both males and females. We found that aged males with tau far from 24h displayed increased oxidative stress. We also demonstrated a positive correlation between tau and IGF-1 concentrations, as well as learning performances, in males and females. Together these results suggest that a great deviation of tau from 24h leads to increased biomarkers of age-related impairments.

Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy

The malignant energetic demands are satisfied through glycolysis, glutaminolysis and de novo synthesis of fatty acids, while the host curses with a state of catabolism and systemic inflammation. The concurrent inhibition of both, tumor anabolism and host catabolism, and their effect upon tumor growth and whole animal metabolism, have not been evaluated. We aimed to evaluate in colon cancer cells a combination of six agents directed to block the tumor anabolism (orlistat + lonidamine + DON) and the host catabolism (growth hormone + insulin + indomethacin). Treatment reduced cellular viability, clonogenic capacity and cell cycle progression. These effects were associated with decreased glycolysis and oxidative phosphorylation, leading to a quiescent energetic phenotype, and with an aberrant transcriptomic landscape showing dysregulation in multiple metabolic pathways. The in vivo evaluation revealed a significant tumor volume inhibition, without damage to normal tissues. The six-drug combination preserved lean tissue and decreased fat loss, while the energy expenditure got decreased. Finally, a reduction in gene expression associated with thermogenesis was observed. Our findings demonstrate that the simultaneous use of this six-drug combination has anticancer effects by inducing a quiescent energetic phenotype of cultured cancer cells. Besides, the treatment is well-tolerated in mice and reduces whole animal energetic expenditure and fat loss.

Novel active magnetorheological knee prosthesis presents low energy consumption during ground walking

This study analyses the energy consumption of an active magnetorheological knee (AMRK) actuator that was designed for transfemoral prostheses. The system was developed as an operational motor unit (MU), which consists of an EC motor, a harmonic drive and a magnetorheological (MR) clutch, that operates in parallel with an MR brake. The dynamic models of the MR brake and MU were used to simulate the system’s energetic expenditure during over-ground walking under three different working conditions: using the complete AMRK; using just its motor-reducer, to operate as a common active knee prosthesis (CAKP), and using just the MR brake, to operate as a common semi-active knee prosthesis (CSAKP). The results are used to compare the MR devices power consumptions with that of the motor-reducer. As previously hypothesized, to use the MR brake in the swing phase is more energetically efficient than using the motor-reducer to drive the joint. Even if using the motor-reducer in regenerative braking mode during the stance phase, the differences in power consumption among the systems are remarkable. The AMRK expended 16.3 J during a gait cycle, which was 1.6 times less than the energy expenditure of the CAKP (26.6 J), whereas the CSAKP required just 6.0 J.

Blood as fuel: the metabolic cost of pedestrian locomotion in Rhodnius prolixus

Active searching for vertebrate blood is a necessary activity for haematophagous insects, and it can be assumed that this search should also be costly in terms of energetic expenditure. Either if it is by swimming, walking, running or flying, active movement requires energy, increasing metabolic rates relative to resting situations. We analysed the respiratory pattern and the energetic cost of pedestrian locomotion in the blood-sucking bug Rhodnius prolixus using flow-through respirometry, by measuring carbon dioxide emission and water loss before, during and after walking. We observed an increase of up to 1.7-fold in the metabolic rate during walking as compared to resting in male R. prolixus and 1.5-fold in females, as well as a change in their respiratory pattern. The last switched from cyclic during resting to continuous, when the insects started to walk, remaining this condition unchanged during locomotion and for several minutes after stopping. Walking induced a significant loss of weight in both, males and females. This can be explained by the increase in both, the metabolic rate and the water loss during walking. These data constitute the first metabolic measures of active hematophagous insects and provide the first insights on the energetic expenditure associated to the active search for blood in this group.

Social hierarchy reveals thermoregulatory trade-offs in response to repeated stressors

ABSTRACTCoping with stressors can require substantial energetic investment, and when resources are limited, such investment can preclude simultaneous expenditure on other biological processes. Among endotherms, energetic demands of thermoregulation can also be immense, yet our understanding of whether a stress response is sufficient to induce changes in thermoregulatory investment is limited. Using the black-capped chickadee as a model species, we tested a hypothesis that stress-induced changes in surface temperature (Ts), a well-documented phenomenon across vertebrates, stem from trade-offs between thermoregulation and stress responsiveness. Because social subordination is known to constrain access to resources in this species, we predicted that Ts and dry heat loss of social subordinates, but not social dominants, would fall under stress exposure at low ambient temperatures (Ta), and rise under stress exposure at high Ta, thus permitting a reduction in total energetic expenditure toward thermoregulation. To test our predictions, we exposed four social groups of chickadees to repeated stressors and control conditions across a Ta gradient (n=30 days/treatment/group), whilst remotely monitoring social interactions and Ts. Supporting our hypothesis, we show that: (1) social subordinates (n=12), who fed less than social dominants and alone experienced stress-induced mass-loss, displayed significantly larger changes in Ts following stress exposure than social dominants (n=8), and (2) stress-induced changes in Ts significantly increased heat conservation at low Ta and heat dissipation at high Ta among social subordinates alone. These results suggest that chickadees adjust their thermoregulatory strategies during stress exposure when resources are limited by ecologically relevant processes.

Physiological and cognitive consequences of a daily 26 h photoperiod in a primate : exploring the underlying mechanisms of the circadian resonance theory

The biological clock expresses circadian rhythms, whose endogenous period (tau) is close to 24 h. Daily resetting of the circadian clock to the 24 h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26 h photoperiodic regimen compared to the classical 24 h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances) in males of a non-human primate ( Microcebus murinus ), a nocturnal species whose endogenous period is about 23.5 h. We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26 h. Together these results suggest that a great deviation of external cycles from tau leads to daily greater energetic expenditure, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.

A temperate endotherm trades thermoregulation for self-preservation: stress-induced changes in surface temperature as thermoregulatory trade-offs

Coping with stressors can require substantial energetic investment, and when resources are limited, such investment can preclude simultaneous expenditure on other biological processes. Among endotherms, energetic demands of thermoregulation can be immense, yet whether a stress response is sufficient to induce changes in thermoregulatory investment appears unexplored. We tested the hypothesis that stress-induced changes in surface temperature, a well-documented phenomenon across vertebrates, stem from a trade-off between thermoregulation and stress responsiveness, whereby individuals seek to reduce energetic expenditure on thermoregulation in challenging environments (the "Thermoprotective Hypothesis"). We predicted that surface temperature and dry heat loss of individuals that are resource-limited would fall under stress exposure at low ambient temperatures and rise under stress exposure at high ambient temperatures when compared with non-resource limited individuals. To test our predictions, we exposed Black-capped Chickadees to rotating stressors and control treatments (ndays/treatment = 30; paired treatments) across an ambient temperature gradient whilst remotely monitoring both feeding behaviour and surface temperature. Supporting the Thermoprotective Hypothesis, our results showed that: 1) social subordinates (n = 12), who fed less than social dominants and alone suffered stress-induced declines in mass, displayed significantly larger changes in surface temperature following stress exposure than social dominants (n = 8), and 2) stress-induced changes in surface temperature significantly increased heat conservation at low ambient temperatures, and heat dissipation at high ambient temperatures among social subordinates alone. These results suggest that Black-capped Chickadees adjust their thermoregulatory strategies under stress when resources are limited and support the hypothesis that stress-induced changes in temperature are functionally significant.

Physiological and cognitive consequences of a daily 26h photoperiod in a primate (M. murinus)

Daily resetting of the circadian clock to the 24h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory by Pittendrigh in 1972. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26h photoperiodic regimen compared to the classical 24h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances). We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26h. Together these results suggest that a great deviation of external cycles from 24h leads to daily greater synchronization costs, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.