Perturbing Dynamin Reveals Potent Effects on the Drosophila Circadian Clock

BACKGROUND: Transcriptional feedback loops are central to circadian clock function. However, the role of neural activity and membrane events in molecular rhythms in the fruit fly Drosophila is unclear. To address this question, we expressed a temperature-sensitive, dominant negative allele of the fly homolog of dynamin called shibire(ts1) (shi(ts1)), an active component in membrane vesicle scission. PRINCIPAL FINDINGS: Broad expression in clock cells resulted in unexpectedly long, robust periods (>28 hours) comparable to perturbation of core clock components, suggesting an unappreciated role of membrane dynamics in setting period. Expression in the pacemaker lateral ventral neurons (LNv) was necessary and sufficient for this effect. Manipulation of other endocytic components exacerbated shi(ts1)'s behavioral effects, suggesting its mechanism is specific to endocytic regulation. PKA overexpression rescued period effects suggesting shi(ts1) may downregulate PKA pathways. Levels of the clock component PERIOD were reduced in the shi(ts1)-expressing pacemaker small LNv of flies held at a fully restrictive temperature (29 degrees C). Less restrictive conditions (25 degrees C) delayed cycling proportional to observed behavioral changes. Levels of the neuropeptide PIGMENT-DISPERSING FACTOR (PDF), the only known LNv neurotransmitter, were also reduced, but PERIOD cycling was still delayed in flies lacking PDF, implicating a PDF-independent process. Further, shi(ts1) expression in the eye also results in reduced PER protein and per and vri transcript levels, suggesting that shibire-dependent signaling extends to peripheral clocks. The level of nuclear CLK, transcriptional activator of many core clock genes, is also reduced in shi(ts1) flies, and Clk overexpression suppresses the period-altering effects of shi(ts1). CONCLUSIONS: We propose that membrane protein turnover through endocytic regulation of PKA pathways modulates the core clock by altering CLK levels and/or activity. These results suggest an important role for membrane scission in setting circadian period

Optimization of Fixed-Bed Methanation Reactors: Safe and Efficient Operation under Transient and Steady-State Conditions

ACLInternational audienceDesigning and optimizing packed-bed methanation reactors for power-to-gas leads to conflicting issues. Because of the high exothermicity of the reaction, it might be inefficient (low Gas Hourly Space Velocity), or unsafe (runaway, thermal degradation). Dynamically operating reactors are thus particularly difficult to design. In this paper, the behavior of a reactor with multiple catalyst-dilution zones is studied numerically. Simulations of a dynamic sequence (reactor startup) are carried out. The effect of catalyst dilution profile on steady state and transient efficiency is analyzed. We introduce a method to maximize GHSV, while guarantying safe operation during both transient and steady state operation. A proper catalyst dilution profile can increase the steady state efficiency and stability of the reactor. However, the results of the present study show that this dilution profile can have a negative impact on transient efficiency and stability. \textcopyright 2018 Elsevier Lt