Dissecting Hippo Interactions: The Hippo signaling pathway plays key roles in many processes, from cell proliferation and cell death to regulation of stem cells and cancer cells. Kwon et al. (p. 737 , published 10 October) attempted to systematically identify all components of the pathway. A protein-protein interaction screen identified more than 200 interactions among approximately 150 proteins. A protein identified in the screen, Leash, restrained the activity of the transcriptional coactivator Yorkie, which regulates gene expression in response to Hippo signaling.

This study characterizes a subset of clock neurons known as large lateral-ventral neurons and their dopaminergic/octopaminergic input circuitry in balancing light-mediated wakefulness in Drosophila. How animals maintain proper amounts of sleep yet remain flexible to changes in environmental conditions remains unknown. We found that environmental light suppressed the wake-promoting effects of dopamine in fly brains. The ten large lateral-ventral neurons (l-LNvs), a subset of clock neurons, are wake-promoting and respond to dopamine, octopamine and light. Behavioral and imaging analyses suggested that dopamine is a stronger arousal signal than octopamine. Notably, light exposure not only suppressed l-LNv responses, but also synchronized responses of neighboring l-LNvs. This regulation occurred by distinct mechanisms: light-mediated suppression of octopamine responses was regulated by the circadian clock, whereas light regulation of dopamine responses occurred by upregulation of inhibitory dopamine receptors. Plasticity therefore alters the relative importance of diverse cues on the basis of the environmental mix of stimuli. The regulatory mechanisms described here may contribute to the control of sleep stability while still allowing behavioral flexibility.

A growing number of US adults have Alzheimer disease and related dementias (ADRD).^1-3 As dementia progresses, patients frequently receive interventions that can add to this burden,^4,5 including tube feeding^6,7 and hospital transfers.⁸ These treatments, if unhelpful in achieving patient and family goals, can potentially contribute to poor quality of life and family dissatisfaction,⁹ while also driving higher health care expenditures at the end of life.^10-12 Early palliative care interventions hold promise in the population with ADRD,^13,14 because the delivery of palliative care improves patient care and family bereavement outcomes and results in more appropriate use of health care resources in other patient populations.^15-20 As such, national organizations are intensifying calls for increasing the reach of palliative care to more patients.^21,22 However, knowing which patients may benefit from palliative care and when is difficult and remains a key barrier to expanding reach. Data suggest that patients with ADRD receive palliative care late in life, possibly interfering with accrual of benefit to patients and families.²³ A predictive tool improving the timeliness of palliative care interventions in patients with ADRD could help to optimally target scarce resources and improve patient care.