Short-Term,Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension

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Ocean migration and behavior of steelhead Oncorhynchus mykiss kelts from the Situk River,Alaska

Environmental Biology of Fishes - Although steelhead (Oncorhynchus mykiss) is an iconic species found throughout the North Pacific rim, little is known about its ocean ecology. To provide insights...     

Dietary Modulation of Drosophila Sleep-Wake Behaviour

Background

A complex relationship exists between diet and sleep but despite its impact on human health, this relationship remains uncharacterized and poorly understood. Drosophila melanogaster is an important model for the study of metabolism and behaviour, however the effect of diet upon Drosophila sleep remains largely unaddressed.

Methodology/Principal Findings

Using automated behavioural monitoring, a capillary feeding assay and pharmacological treatments, we examined the effect of dietary yeast and sucrose upon Drosophila sleep-wake behaviour for three consecutive days. We found that dietary yeast deconsolidated the sleep-wake behaviour of flies by promoting arousal from sleep in males and shortening periods of locomotor activity in females. We also demonstrate that arousal from nocturnal sleep exhibits a significant ultradian rhythmicity with a periodicity of 85 minutes. Increasing the dietary sucrose concentration from 5% to 35% had no effect on total sucrose ingestion per day nor any affect on arousal, however it did lengthen the time that males and females remained active. Higher dietary sucrose led to reduced total sleep by male but not female flies. Locomotor activity was reduced by feeding flies Metformin, a drug that inhibits oxidative phosphorylation, however Metformin did not affect any aspects of sleep.

Conclusions

We conclude that arousal from sleep is under ultradian control and regulated in a sex-dependent manner by dietary yeast and that dietary sucrose regulates the length of time that flies sustain periods of wakefulness. These findings highlight Drosophila as an important model with which to understand how diet impacts upon sleep and wakefulness in mammals and humans.     

Cyclophilin A is a damage-associated molecular pattern molecule that mediates acetaminophen-induced liver injury

The immune system is alerted to cell death by molecules known as damage-associated molecular patterns (DAMPs). These molecules partly mediate acetaminophen-induced liver injury, an archetypal experimental model of sterile cell death and the commonest cause of acute liver failure in the western world. Cyclophilin A (CypA) is an intracellular protein that is proinflammatory when released by cells. We hypothesized that CypA is released from necrotic liver cells and acts as a DAMP to mediate acetaminophen-induced liver injury. Our data demonstrated that mice lacking CypA (Ppia(-/-)) were resistant to acetaminophen toxicity. Antagonism of the extracellular receptor for CypA (CD147) also reduced acetaminophen-induced liver injury. When injected into a wild-type mouse, necrotic liver from Ppia(-/-) mice induced less of an inflammatory response than did wild-type liver. Conversely, the host inflammatory response was increased when CypA was injected with necrotic liver. Antagonism of CD147 also reduced the inflammatory response to necrotic liver. In humans, urinary CypA concentration was significantly increased in patients with acetaminophen-induced liver injury. In summary, CypA is a DAMP that mediates acetaminophen poisoning. This mechanistic insight presents an opportunity for a new therapeutic approach to a disease that currently has inadequate treatment options.