The changes in power requirements and muscle efficiency during elevated force production in the fruit fly Drosophila melanogaster

The limits of flight performance have been estimated in tethered Drosophila melanogaster by modulating power requirements in a 'virtual reality' flight arena. At peak capacity, the flight muscles can sustain a mechanical power output of nearly 80 W kg^(-1) muscle mass at 24 °C, which is sufficient to generate forces of approximately 150% of the animal's weight. The increase in flight force above that required to support body weight is accompanied by a rise in wing velocity, brought about by an increase in stroke amplitude and a decrease in stroke frequency. Inertial costs, although greater than either profile or induced power, would be minimal with even modest amounts of elastic storage, and total mechanical power energy should be equivalent to aerodynamic power alone. Because of the large profile drag expected at low Reynolds numbers, the profile power was approximately twice the induced power at all levels of force generation. Thus, it is the cost of overcoming drag, and not the production of lift, that is the primary requirement for flight in Drosophila melanogaster. By comparing the estimated mechanical power output with respirometrically measured total power input, we determined that muscle efficiency rises with increasing force production to a maximum of 10%. This change in efficiency may reflect either increased crossbridge activation or a favorable strain regime during the production of peak forces

The control of wing kinematics and flight forces in fruit flies (Drosophila spp.)

By simultaneously measuring flight forces and stroke kinematics in several species of fruit flies in the genus Drosophila, we have investigated the relationship between wing motion and aerodynamic force production. We induced tethered flies to vary their production of total flight force by presenting them with a vertically oscillating visual background within a closed-loop flight arena. In response to the visual motion, flies modulated their flight force by changing the translational velocity of their wings, which they accomplished via changes in both stroke amplitude and stroke frequency. Changes in wing velocity could not, however, account for all the modulation in flight force, indicating that the mean force coefficient of the wings also increases with increasing force production. The mean force coefficients were always greater than those expected under steady-state conditions under a variety of assumptions, verifying that force production in Drosophila spp. must involve non-steady-state mechanisms. The subtle changes in kinematics and force production within individual flight sequences demonstrate that flies possess a flexible control system for flight maneuvers in which they can independently control the stroke amplitude, stroke frequency and force coefficient of their wings. By studying four different-sized species, we examined the effects of absolute body size on the production and control of aerodynamic forces. With decreasing body size, the mean angular wing velocity that is required to support the body weight increases. This change is due almost entirely to an increase in stroke frequency, whereas mean stroke amplitude was similar in all four species. Despite the elevated stroke frequency and angular wing velocity, the translational velocity of the wings in small flies decreases with the reduction in absolute wing length. To compensate for their small size, D. nikananu must use higher mean force coefficients than their larger relatives

The production of elevated flight force compromises manoeuvrability in the fruit fly Drosophila melanogaster

In this study, we have investigated how enhanced total flight force production compromises steering performance in tethered flying fruit flies, Drosophila melanogaster. The animals were flown in a closed-loop virtual-reality flight arena in which they modulated total flight force production in response to vertically oscillating visual patterns. By simultaneously measuring stroke amplitude and stroke frequency, we recorded the ability of each fly to modulate its wing kinematics at different levels of aerodynamic force production. At a flight force that exactly compensates body weight, the temporal deviations with which fruit flies vary their stroke amplitude and frequency are approximately 27° and 4.8 Hz of their mean value, respectively. This variance in wing kinematics decreases with increasing flight force production, and at maximum force production fruit flies are restricted to a unique combination of stroke amplitude, stroke frequency and mean force coefficient. This collapse in the kinematic envelope during peak force production could greatly attenuate the manoeuvrability and stability of animals in free flight

The scaling of carbon dioxide release and respiratory water loss in flying fruit flies (Drosophila spp.)

By simultaneously measuring carbon dioxide release, water loss and flight force in several species of fruit flies in the genus Drosophila, we have investigated respiration and respiratory transpiration during elevated locomotor activity. We presented tethered flying flies with moving visual stimuli in a virtual flight arena, which induced them to vary both flight force and energetic output. In response to the visual motion, the flies altered their energetic output as measured by changes in carbon dioxide release and concomitant changes in respiratory water loss. We examined the effect of absolute body size on respiration and transpiration by studying four different-sized species of fruit flies. In resting flies, body-mass-specific CO(2) release and water loss tend to decrease more rapidly with size than predicted according to simple allometric relationships. During flight, the mass-specific metabolic rate decreases with increasing body size with an allometric exponent of -0.22, which is slightly lower than the scaling exponents found in other flying insects. In contrast, the mass-specific rate of water loss appears to be proportionately greater in small animals than can be explained by a simple allometric model for spiracular transpiration. Because fractional water content does not change significantly with increasing body size, the smallest species face not only larger mass-specific energetic expenditures during flight but also a higher risk of desiccation than their larger relatives. Fruit flies lower their desiccation risk by replenishing up to 75 % of the lost bulk water by metabolic water production, which significantly lowers the risk of desiccation for animals flying under xeric environmental conditions

The active control of wing rotation by Drosophila

This paper investigates the temporal control of a fast wing rotation in flies, the ventral flip, which occurs during the transition from downstroke to upstroke. Tethered flying Drosophila actively modulate the timing of these rapid supinations during yaw responses evoked by an oscillating visual stimulus. The time difference between the two wings is controlled such that the wing on the outside of a fictive turn rotates in advance of its contralateral partner. This modulation of ventral-flip timing between the two wings is strongly coupled with changes in wing-stroke amplitude. Typically, an increase in the stroke amplitude of one wing is correlated with an advance in the timing of the ventral flip of the same wing. However, flies do display a limited ability to control these two behaviors independently, as shown by flight records in which the correlation between ventral-flip timing and stroke amplitude transiently reverses. The control of ventral-flip timing may be part of an unsteady aerodynamic mechanism that enables the fly to alter the magnitude and direction of flight forces during turning maneuvers

Density of states of helium droplets

Accurate analytical expressions for the state densities of liquid He-4 droplets are derived, incorporating the ripplon and phonon degrees of freedom. The microcanonical temperature and the ripplon angular momentum level density are also evaluated. The approach is based on inversions and systematic expansions of canonical thermodynamic properties.Comment: 20 pages, 5 figure

Intrathecal B-cell activation in LGI1 antibody encephalitis.

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies

Activation of interferon regulatory factor 3 by replication-competent Vaccinia viruses improves antitumor efficacy mediated by T-cell responses

Recently, oncolytic vaccinia viruses (VACVs) have shown their potential to provide for clinically effective cancer treatments. The reason for this clinical usefulness is not only the direct destruction of infected cancer cells but also activation of immune responses directed against tumor antigens. For eliciting a robust antitumor immunity, a dominant T helper 1 (Th1) cell differentiation of the response is preferred, and such polarization can be achieved by activating the Toll-like receptor 3 (TLR3)-interferon regulatory factor 3 (IRF3) signaling pathway. However, current VACVs used as oncolytic viruses to date still encode several immune evasion proteins involved in the inhibition of this signaling pathway. By inactivating genes of selected regulatory virus proteins, we aimed for a candidate virus with increased potency to activate cellular antitumor immunity but at the same time with a fully maintained replicative capacity in cancer cells. The removal of up to three key genes (C10L, N2L, and C6L) from VACV did not reduce the strength of viral replication, both in vitro and in vivo, but resulted in the rescue of IRF3 phosphorylation upon infection of cancer cells. In syngeneic mouse tumor models, this activation translated to enhanced cytotoxic T lymphocyte (CTL) responses directed against tumor-associated antigens and neo-epitopes and improved antitumor activity