Hierarchical integration of mitochondrial and nuclear positioning pathways by the Num1 EF hand.

Positioning organelles at the right place and time is critical for their function and inheritance. In budding yeast, mitochondrial and nuclear positioning require the anchoring of mitochondria and dynein to the cell cortex by clusters of Num1. We have previously shown that mitochondria drive the assembly of cortical Num1 clusters, which then serve as anchoring sites for mitochondria and dynein. When mitochondrial inheritance is inhibited, mitochondrial-driven assembly of Num1 in buds is disrupted and defects in dynein-mediated spindle positioning are observed. Using a structure-function approach to dissect the mechanism of mitochondria-dependent dynein anchoring, we found that the EF hand-like motif (EFLM) of Num1 and its ability to bind calcium are required to bias dynein anchoring on mitochondria-associated Num1 clusters. Consistently, when the EFLM is disrupted, we no longer observe defects in dynein activity following inhibition of mitochondrial inheritance. Thus, the Num1 EFLM functions to bias dynein anchoring and activity in nuclear inheritance subsequent to mitochondrial inheritance. We hypothesize that this hierarchical integration of organelle positioning pathways by the Num1 EFLM contributes to the regulated order of organelle inheritance during the cell cycle.

Do survivors of acute neurologic injury remember their stay in the neuroscience intensive care unit?

BACKGROUND: Patients in medical, surgical, and trauma intensive care units (ICUs) are at risk for later development of symptoms of post-traumatic stress disorder (PTSD). Because acute brain injury can impair recall; we sought to show that neuroscience patients undergoing prolonged neuroscience ICU admission have limited memory of their ICU stay and thus are less likely to develop symptoms of PTSD. METHODS: We surveyed patients >18 years admitted for 10 days or more to our neuroscience ICU over a 10-year period. RESULTS: The survey response rate was 50.5% (47/93). Forty percent (19/47) of respondents presented with coma. Recall of details of the ICU admission was limited. Fewer than 10% of patients who required mechanical ventilation recalled being on a ventilator. Only five patients (11%) had responses suggestive of possible post-traumatic stress syndrome. The most commonly experienced symptoms following discharge were difficulty sleeping, difficulty with concentration, and memory loss. CONCLUSION: Patients requiring prolonged neuroscience ICU admission do not appear to be traumatized by their ICU stay.