A mechanosensory pathway to the Drosophila circadian clock

Circadian clocks attune the physiology of virtually all living organisms to the diurnal cycles of their environments. In metazoan animals, multiple sensory input pathways have been linked to clock synchronization with the environmental cycle (entrainment). Extrinsic entrainment cues include light and temperature. We show that (12-hour:12-hour) cycles of vibration and silence (VS) are sufficient to synchronize the daily locomotor activity of wild-type Drosophila melanogaster. Behavioral synchronization to VS cycles required a functional clock and functional chordotonal organs and was accompanied by phase-shifts of the daily oscillations of PERIOD protein concentrations in brain clock neurons. The feedback from mechanosensory-and particularly, proprioceptive-organs may help an animal to keep its circadian clock in sync with its own, stimulus-induced activities

Temperature Entrainment of Drosophila's Circadian Clock Involves the Gene nocte and Signaling from Peripheral Sensory Tissues to the Brain

Circadian clocks are synchronized by the natural day/night and temperature cycles. Our previous work demonstrated that synchronization by temperature is a tissue autonomous process, similar to synchronization by light. We show here that this is indeed the case, with the important exception of the brain. Using luciferase imaging we demonstrate that brain clock neurons depend on signals from peripheral tissues in order to be synchronized by temperature. Reducing the function of the gene nocte in chordotonal organs changes their structure and function and dramatically interferes with temperature synchronization of behavioral activity. Other mutants known to affect the function of these sensory organs also interfere with temperature synchronization, demonstrating the importance of nocte in this process and identifying the chordotonal organs as relevant sensory structures. Our work reveals surprising and important mechanistic differences between light- and temperature-synchronization and advances our understanding of how clock resetting is accomplished in nature

Light Dominates Peripheral Circadian Oscillations in Drosophila melanogaster During Sensory Conflict

In Drosophila, as in other animals, the circadian clock is a singular entity in name and concept only. In reality, clock functions emerge from multiple processes and anatomical substrates. One distinction has conventionally been made between a central clock (in the brain) and peripheral clocks (e.g., in the gut and the eyes). Both types of clock generate robust circadian oscillations, which do not require external input. Furthermore, the phases of these oscillations remain exquisitely sensitive to specific environmental cues, such as the daily changes of light and temperature. When these cues conflict with one another, the central clock displays complex forms of sensory integration; how peripheral clocks respond to conflicting input is unclear. We therefore explored the effects of light and temperature misalignments on peripheral clocks. We show that under conflict, peripheral clocks preferentially synchronize to the light stimulus. This photic dominance requires the presence of the circadian photoreceptor, Cryptochrome

Mathematical Identification of Critical Reactions in the Interlocked Feedback Model

Dynamic simulations are necessary for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. Sensitivity analysis allows the linking of robustness to network structure. However, it yields only local properties regarding a particular choice of plausible parameter values, because it is hard to know the exact parameter values in vivo. Global and firm results are needed that do not depend on particular parameter values. We propose mathematical analysis for robustness (MAR) that consists of the novel evolutionary search that explores all possible solution vectors of kinetic parameters satisfying the target dynamics and robustness analysis. New criteria, parameter spectrum width and the variability of solution vectors for parameters, are introduced to determine whether the search is exhaustive. In robustness analysis, in addition to single parameter sensitivity analysis, robustness to multiple parameter perturbation is defined. Combining the sensitivity analysis and the robustness analysis to multiple parameter perturbation enables identifying critical reactions. Use of MAR clearly identified the critical reactions responsible for determining the circadian cycle in the Drosophila interlocked circadian clock model. In highly robust models, while the parameter vectors are greatly varied, the critical reactions with a high sensitivity are uniquely determined. Interestingly, not only the per-tim loop but also the dclk-cyc loop strongly affect the period of PER, although the dclk-cyc loop hardly changes its amplitude and it is not potentially influential. In conclusion, MAR is a powerful method to explore wide parameter space without human-biases and to link a robust property to network architectures without knowing the exact parameter values. MAR identifies the reactions critically responsible for determining the period and amplitude in the interlocked feedback model and suggests that the circadian clock intensively evolves or designs the kinetic parameters so that it creates a highly robust cycle

Bumblebee foraging rhythms under the midnight sun measured with radiofrequency identification

<p>Abstract</p> <p>Background</p> <p>In the permanent daylight conditions north of the Arctic circle, there is a unique opportunity for bumblebee foragers to maximise intake, and therefore colony growth, by remaining active during the entire available 24-h period. We tested the foraging rhythms of bumblebee (<it>Bombus terrestris </it>and <it>B. pascuorum</it>) colonies in northern Finland during the summer, when the sun stays above the horizon for weeks. We used fully automatic radio-frequency identification to monitor the foraging activity of more than 1,000 workers and analysed their circadian foraging rhythms.</p> <p>Results</p> <p>Foragers did not use the available 24-h foraging period but exhibited robust diurnal rhythms instead. A mean of 95.2% of the tested <it>B. terrestris </it>workers showed robust diurnal rhythms with a mean period of 23.8 h. Foraging activity took place mainly between 08:00 and 23:00, with only low or almost no activity during the rest of the day. Activity levels increased steadily during the morning, reached a maximum around midday and decreased again during late afternoon and early evening. Foraging patterns of native <it>B. pascuorum </it>followed the same temporal organisation, with the foraging activity being restricted to the period between 06:00 and 22:00.</p> <p>Conclusions</p> <p>The results of the present study indicate that the circadian clock of the foragers must have been entrained by some external cue, the most prominent being daily cycles in light intensity and temperature. Daily fluctuations in the spectral composition of light, especially in the UV range, could also be responsible for synchronising the circadian clock of the foragers under continuous daylight conditions.</p

An Efficient Bi-Level Surrogate Approach for Optimizing Shock Control Bumps under Uncertainty

The assessment of uncertainties is essential in aerodynamic shape optimization problems in order to come up with configurations that are more robust. The influence of aleatory fluctuations in flight conditions and manufacturing tolerances is of primary concern when designing shock control bumps, as their effectiveness is highly sensitive to the shock wave location. However, exploring the stochastic design space for the global robust optimum increases the computational cost, especially when dealing with nonconvex design spaces and multiple local optima. The aim of this paper is to develop a framework for efficient aerodynamic shape optimization under uncertainty by means of a bi-level surrogate approach and to apply it to the robust design of a retrofitted shock control bump over an airfoil. The framework combines a surrogate-based optimization algorithm with an efficient surrogate-based approach for uncertainty quantification. The surrogate-based optimizer efficiently finds the global optimum of a given quantile of the drag coefficient. It outperforms traditional evolutionary algorithms by effectively balancing exploration and exploitation through the combination of adaptive sampling and a moving trust region. At each iteration of the optimization, the surrogate-based uncertainty quantification uses an active infill criterion in order to accurately quantify the quantile of the drag at a reduced number of function evaluations. Two different quantiles of the drag are chosen, the 95% to increase the robustness at off-design conditions, and the 50% for a configuration that is best for day to day operations. In both cases, the optimum configurations lead to an airfoil that is more robust to geometrical and operational uncertainties, compared to the configuration obtained through classical deterministic optimization

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Genomic characterization of a repetitive motif strongly associated with developmental genes in Drosophila

BACKGROUND: Non-coding DNA represents a high proportion of all metazoan genomes. Although an undetermined fraction of this DNA may be considered devoid of any function, it also contains important information residing in specific cis-regulatory sequences. RESULTS: We report a 27 bp motif that is overrepresented within the fly genome. This motif does not show any significant similarity with transposon sequences and is strongly associated with genes involved in development and/or signal transduction. The 27 bp motif is preferentially located within introns, and has a tendency to be present in multiple copies around genes. Furthermore, it is often found embedded in known non-coding regulatory regions. The regulatory network defined by this motif is partially shared in D. pseudoobscura. CONCLUSION: We have identified a 27 bp cis-regulatory sequence widely distributed within the Drosophila genome in association with developmental genes. This motif may be very useful towards the annotation of functional regulatory regions within the Drosophila genome and the construction of regulatory networks of Drosophila development

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex