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The circadian rhythm of adult emergence (aka eclosion) of the fruit fly Drosophila is a classic behavioural read-out that served in the first characterisation of the key features of circadian clocks and was also used for the identification of the first clock genes. Rhythmic eclosion requires the central clock in the brain, as well as a peripheral clock in the steroidogenic prothoracic gland. Here, we review recent findings on the timing and neuroendocrine coupling mechanisms of the two clocks. These findings identify rhythmic prothoracicotropic hormone and downstream ERK signalling as the main coupling pathway and show that the two clocks impose daily rhythmicity to the temporal pattern of eclosion by regulating the timing of the very last steps in metamorphosis., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of this review., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Circadian clocks impose daily periodicities to behavior, physiology, and metabolism. This control is mediated by a central clock and by peripheral clocks, which are synchronized to provide the organism with a unified time through mechanisms that are not fully understood. Here, we characterized in Drosophila the cellular and molecular mechanisms involved in coupling the central clock and the peripheral clock located in the prothoracic gland (PG), which together control the circadian rhythm of emergence of adult flies. The time signal from central clock neurons is transmitted via small neuropeptide F (sNPF) to neurons that produce the neuropeptide Prothoracicotropic Hormone (PTTH), which is then translated into daily oscillations of Ca 2+ concentration and PTTH levels. PTTH signaling is required at the end of metamorphosis and transmits time information to the PG through changes in the expression of the PTTH receptor tyrosine kinase (RTK), TORSO, and of ERK phosphorylation, a key component of PTTH transduction. In addition to PTTH, we demonstrate that signaling mediated by other RTKs contributes to the rhythmicity of emergence. Interestingly, the ligand to one of these receptors (Pvf2) plays an autocrine role in the PG, which may explain why both central brain and PG clocks are required for the circadian gating of emergence. Our findings show that the coupling between the central and the PG clock is unexpectedly complex and involves several RTKs that act in concert and could serve as a paradigm to understand how circadian clocks are coordinated., Competing Interests: Competing interests statement:The authors declare no competing interest.

Medical schools are increasingly utilising remote learning. Remote learning can take many forms such as online lectures, small group tutorials, virtual clinical skills sessions, and online case presentations. Remote learning presents both challenges and opportunities for students globally. This article shares twelve tips from senior medical students, based on the author's personal experience of remote learning and the relevant literature, to help others maximise the benefits of both synchronous and asynchronous remote learning. The authors include guidance on how to approach the remote format, embrace the use of technology, detail helpful open-access resources, and encourage students to become independent learners.

Autism Spectrum Disorder (ASD) is characterized by impaired social communication, restricted interests, and repetitive and stereotyped behaviors. The TRPC6 (transient receptor potential channel 6) represents an ASD candidate gene under an oligogenic/multifactorial model based on the initial description and cellular characterization of an individual with ASD bearing a de novo heterozygous mutation disrupting TRPC6, together with the enrichment of disruptive TRPC6 variants in ASD cases as compared to controls. Here, we perform a clinical re-evaluation of the initial non-verbal patient, and also present eight newly reported individuals ascertained for ASD and bearing predicted loss-of-function mutations in TRPC6. In order to understand the consequences of mutations in TRPC6 on nervous system function, we used the fruit fly, Drosophila melanogaster, to show that null mutations in transient receptor gamma (trpγ; the fly gene most similar to TRPC6), cause a number of behavioral defects that mirror features seen in ASD patients, including deficits in social interactions (based on courtship behavior), impaired sleep homeostasis (without affecting the circadian control of sleep), hyperactivity in both young and old flies, and defects in learning and memory. Some defects, most notably in sleep, differed in severity between males and females and became normal with age. Interestingly, hyperforin, a TRPC6 agonist and the primary active component of the St. John's wort antidepressant, attenuated many of the deficits expressed by trpγ mutant flies. In summary, our results provide further evidence that the TRPC6 gene is a risk factor for ASD. In addition, they show that the behavioral defects caused by mutations in TRPC6 can be modeled in Drosophila, thereby establishing a paradigm to examine the impact of mutations in other candidate genes., (© 2022. The Author(s).)

There is ongoing and rapid advancement in approaches to modelling the fate of exhaled particles in different environments relevant to disease transmission. It is important that models are verified by comparison with each other using a common set of input parameters to ensure that model differences can be interpreted in terms of model physics rather than unspecified differences in model input parameters. In this paper, we define parameters necessary for such benchmarking of models of airborne particles exhaled by humans and transported in the environment during breathing and speaking., (© 2022 The Authors.)

Coupled Wells-Riley (WR) and Computational Fluid Dynamics (CFD) modelling (WR-CFD) facilitates a detailed analysis of COVID-19 infection probability (IP). This approach overcomes issues associated with the WR 'well-mixed' assumption. The WR-CFD model, which makes uses of a scalar approach to simulate quanta dispersal, is applied to Chinese long-distance trains (G-train). Predicted IPs, at multiple locations, are validated using statistically derived (SD) IPs from reported infections on G-trains. This is the first known attempt to validate a coupled WR-CFD approach using reported COVID-19 infections derived from the rail environment. There is reasonable agreement between trends in predicted and SD IPs, with the maximum SD IP being 10.3% while maximum predicted IP was 14.8%. Additionally, predicted locations of highest and lowest IP, agree with those identified in the statistical analysis. Furthermore, the study demonstrates that the distribution of infectious aerosols is non-uniform and dependent on the nature of the ventilation. This suggests that modelling techniques neglecting these differences are inappropriate for assessing mitigation measures such as physical distancing. A range of mitigation strategies were analysed; the most effective being the majority (90%) of passengers correctly wearing high efficiency masks (e.g. N95). Compared to the base case (40% of passengers wearing low efficiency masks) there was a 95% reduction in average IP. Surprisingly, HEPA filtration was only effective for passengers distant from an index patient, having almost no effect for those in close proximity. Finally, as the approach is based on CFD it can be applied to a range of other indoor environments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Neuromodulators, such as neuropeptides, can regulate and reconfigure neural circuits to alter their output, affecting in this way animal physiology and behavior. The interplay between the activity of neuronal circuits, their modulation by neuropeptides, and the resulting behavior, is still poorly understood. Here, we present a quantitative framework to study the relationships between the temporal pattern of activity of peptidergic neurons and of motoneurons during Drosophila ecdysis behavior, a highly stereotyped motor sequence that is critical for insect growth. We analyzed, in the time and frequency domains, simultaneous intracellular calcium recordings of peptidergic CCAP (crustacean cardioactive peptide) neurons and motoneurons obtained from isolated central nervous systems throughout fictive ecdysis behavior induced ex vivo by Ecdysis triggering hormone. We found that the activity of both neuronal populations is tightly coupled in a cross-frequency manner, suggesting that CCAP neurons modulate the frequency of motoneuron firing. To explore this idea further, we used a probabilistic logistic model to show that calcium dynamics in CCAP neurons can predict the oscillation of motoneurons, both in a simple model and in a conductance-based model capable of simulating many features of the observed neural dynamics. Finally, we developed an algorithm to quantify the motor behavior observed in videos of pupal ecdysis, and compared their features to the patterns of neuronal calcium activity recorded ex vivo. We found that the motor activity of the intact animal is more regular than the motoneuronal activity recorded from ex vivo preparations during fictive ecdysis behavior; the analysis of the patterns of movement also allowed us to identify a new post-ecdysis phase., Competing Interests: The authors have declared that no competing interests exist.

In animals, neuropeptidergic signaling is essential for the regulation of survival and reproduction. In insects, Orcokinins are poorly studied, despite their high level of conservation among different orders. In particular, there are currently no reports on the role of Orcokinins in the experimental insect model, the fruit fly, Drosophila melanogaster. In the present work, we made use of the genetic tools available in this species to investigate the role of Orcokinins in the regulation of different innate behaviors including ecdysis, sleep, locomotor activity, oviposition, and courtship. We found that RNAi-mediated knockdown of the orcokinin gene caused a disinhibition of male courtship behavior, including the occurrence of male to male courtship, which is rarely seen in wildtype flies. In addition, orcokinin gene silencing caused a reduction in egg production. Orcokinin is emerging as an important neuropeptide family in the regulation of the physiology of insects from different orders. In the case of the fruit fly, our results suggest an important role in reproductive success., (Copyright © 2021 Elsevier Ltd. All rights reserved.)