COVID-19 isolation and containment strategies for ships: Lessons from the USS Theodore Roosevelt outbreak

The control of shipborne disease outbreaks represents a vexing but entirely predictable challenge at the start of any pandemic. Passenger ships, with large numbers of people confined in close quarters, can serve as incubators of disease, seeding the pandemic across the globe as infected passengers return home. Short-term steps taken by local authorities can exacerbate this problem, creating humanitarian crises and worsening the scale of the outbreak. In this work, we have undertaken a model-based examination of the USS Theodore Roosevelt outbreak to understand the dynamics of COVID-19 spread aboard the aircraft carrier. We have used a series of counterfactual "what-if" analyses to better understand the options available to public health authorities in such situations. The models suggest that rapid mass evacuation and widespread surveillance testing can be effective in these settings. Our results lead to a set of generalizable recommendations for disease control that are broadly applicable to the current COVID-19 crisis as well as to future pandemics.

TRAF6 and p62 inhibit amyloid ß-induced neuronal death through p75 neurotrophin receptor.

Amyloid ß (Aß) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient's brain. Aß is known to bind p75 neurotrophin receptor (p75(NTR)) and mediates Aß-induced neuronal death. Recently, we showed that NGF leads to p75(NTR) polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aß stimulation impaired the p75(NTR) polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75(NTR) on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75(NTR) polyubiquitination upon Aß/NGF treatment. Aß significantly reduced NF-κB activity by attenuating the interaction of p75(NTR) with IKKß. p75(NTR) increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aß-mediated inhibition of p75(NTR) polyubiquitination and restored neuronal cell survival.