TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis.

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.

Integrated family and individual therapy for bipolar disorder: results of a treatment development study.

BACKGROUND: Several studies have established the efficacy of psychosocial interventions as adjuncts to pharmacotherapy in the symptom maintenance of bipolar disorder. This study concerned a new psychosocial approach - integrated family and individual therapy (IFIT) - that synthesizes family psychoeducational sessions with individual sessions of interpersonal and social rhythm therapy. METHOD: Shortly after an acute illness episode, 30 bipolar patients (DSM-IV criteria) were assigned to open treatment with IFIT (up to 50 weekly sessions of family and individual therapy) and mood-stabilizing medications in the context of a treatment development study. Their outcomes over 1 year were compared with the outcomes of 70 patients from a previous trial who received standard community care, consisting of 2 family educational sessions, mood-stabilizing medications, and crisis management (CM). Patients in both samples were evaluated as to symptomatic functioning at entry into the project and then every 3 months for 1 year. RESULTS: Patients in IFIT had longer survival intervals (time without relapsing) than patients in CM. They also showed greater reductions in depressive symptoms over 1 year of treatment relative to their baseline levels. The results could not be explained by group differences in baseline symptoms or pharmacologic treatment regimens. CONCLUSION: Combining family and individual therapy with medication may protect episodic bipolar patients from early relapse and ongoing depressive symptoms. Further examination of this integrative model within randomized controlled trials is warranted.