Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1) gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

Maternal separation followed by isolation-housing differentially affects prepulse inhibition of the acoustic startle response in C57BL/6 mice

Exposure to chronic stress is associated with an increased incidence of neuropsychiatric dysfunction. The current study evaluated two competing hypotheses, the cumulative stress and the match/mismatch hypothesis of neuropsychiatric dysfunction, using two paradigms relating to exposure to “stress”: pre-weaning maternal separation and post-weaning isolation-housing. C57BL/6 offspring were reared under four conditions: typical animal facility rearing (AFR, control), early handling (EH, daily 15 min separation from dam), maternal separation (MS, daily 4 hr separation from dam), and maternal and peer separation (MPS, daily 4 hr separation from dam and from littermates). After weaning, mice were either housed socially (2–3/cage) or in isolation (1/cage) and then tested for prepulse inhibition in adulthood. Isolation-housed MPS subjects displayed greater deficits in prepulse inhibition relative to socially-housed MPS subjects while socially-housed AFR subjects displayed greater deficits in prepulse inhibition relative to isolation-housed AFR subjects. The results indicate that these treatment conditions represent a potentially valuable model for evaluating the match/mismatch hypothesis in regards to neuropsychiatric dysfunction.

Treatment of combined sewer overflows by high gradient magnetic separation : on-site testing with mobile pilot plant trailer /

Mode of access: Internet.

Source separation collection and processing equipment : final report.

"January 1981"--Cover.

Source separation : the community awareness program in Somerville and Marblehead, Massachusetts /

Mode of access: Internet.

Magnetic separation : recovery of saleable iron and steel from municipal solid waste /

Mode of access: Internet.

Study of activated sludge separation by dynamic straining /

Mode of access: Internet.

Oil/water separation : state-of-the-art /

Mode of access: Internet.

Isotope separation by gaseous diffusion and centrifugation : a literature search /

"Stable Isotope Separation."

Upon whom rests the guilt of the war? Separation: war without end.

Caption title: Disunion: degradation without remedy.

Investigation of driver reactions to tread separation scenarios in the National Advanced Driving Simulator (NADS).

Decreasing vehicle understeer was strongly associated with the likelihood of control loss following both the unexpected and expected tire failures. Knowledge of the imminent tread separation reduced the overall probability of control loss from 55% to 20% and had a significant effect on how quickly drivers responded as well as on the nature of their initial responses (i.e., steering orbraking). Driver age was marginally associated with increased likelihood of vehicle control loss, but only on unexpected trials. Vehicle speed at the time of first steering input also contributed to the probability of control loss. Neither the location of the tire that failed (left rear vs. right rear) nor the specific instructions about how best to respond to the tread separation influenced the probability of control loss. Differences associated with vehicle understeer conditions observed in the present study were large and consistent, independent of driver expectations and across driver age groups. It is thus fair to conclude that in the event of a complete rear-tire detread, the increased difficulty in vehicle handling and the associated increased likelihood of loss of vehicle control with decreasing vehicle understeer generalize to real-world driving.

Experiment in assessing color separation techniques for identifying small density variations in tires. Interim report.

National Highway Traffic Safety Administration, Research Institute, Washington, D.C.