Cytokinesis is initiated by the localized assembly of the contractile ring, a dynamic actomyosin structure that generates a membrane furrow between the segregating chromosomal masses to divide a cell into two. Here we show that the stabilization and organization of the cytokinetic furrow is specifically dependent on localized β-actin filament assembly at the site of cytokinesis. β-actin filaments are assembled directly at the furrow by an anillin-dependent pathway that enhances RhoA-dependent activation of the formin DIAPH3, an actin nucleator. DIAPH3 specifically generates homopolymeric filaments of β-actin in vitro. By employing enhancers and activators, cells can achieve acute spatio-temporal control over isoform-specific actin arrays that are required for distinct cellular functions.

In connective tissues, intercellular adhesion is essential for tissue morphogenesis, development and wound healing. However, the signaling mechanisms initiated by cell-cell adhesion in fibroblasts and that regulate it are not known. In this study we tested the hypothesis that intracellular calcium signaling is required to mediate intercellular adhesion between fibroblasts. Fura-2 or fluo-3 labeled human fibroblasts were used to investigate calcium homeostasis during intercellular adhesion. After contact with suspended fibroblasts there was a rise in cytosolic free calcium ([Ca2+]i) and multiple calcium oscillations in substrate-attached cells. Antibodies against the extracellular but not the cytoplasmic domain of cadherin induced a similar calcium response, indicating that these responses were initiated by cadherin binding. As shown by the near-plasma membrane Ca2+ indicator (Fura-C18) and by confocal microscopy of fluo-3-loaded cells, [Ca2+]i transients probably originated at sites of cell-cell contact. Cell-cell adhesion was dependent on both calcium influx through membrane channels and release of Ca2+ from internal calcium stores, because the calcium channel inhibitor LaCl3 or pretreatment of cells with thapsigargin significantly inhibited (>35%) cell-cell attachment. The [Ca2+]i changes induced by cell-cell adhesion were temporally correlated with increased recruitment of intercellular junctional proteins into the cytoskeleton and movement of GFP-actin to sites of cell-cell contact. [Ca2+]i responses induced by intercellular adhesion were essential for both junctional protein recruitment and the establishment of strong cell-cell contacts, as loading cells with BAPTA/AM significantly inhibited cell-cell adhesion and recruitment of cadherins and beta-catenin to the actin cytoskeleton. Actin depolymerization by cytochalasin D dramatically reduced cell-cell adhesion and recruitment of cadherins and catenin to the actin cytoskeleton. These results demonstrate that cadherin-cadherin interaction induces [Ca2+]i transients during cell-cell adhesion in fibroblasts, and these calcium signals regulate cell-cell adhesion through remodeling of cortical actin and recruitment of cadherins and beta-catenin into intercellular junctions.

The post-discharge period is an extremely vulnerable period for patients, particularly for those discharged from inpatient children and adolescent mental health services (CAMHS). Poor discharge practices and discontinuity of care can put children and youth at heightened risk for readmission, among other adverse outcomes. However, there is limited understanding of the structure and effectiveness of interventions to facilitate discharges from CAMHS. As such, a scoping review was conducted to identify the literature on discharge interventions. This scoping review aimed to describe key components, designs, and outcomes of existing discharge interventions from CAMHS. Nineteen documents were included in the final review. Discharge interventions were extracted and summarized for pre-discharge, post-discharge, and bridging elements. Results of this scoping review found that intervention elements included aspects of risk assessment, individualized care, discharge preparation, community linkage, psychoeducation, and follow-up support. Reported outcomes of discharge interventions were also extracted and included positive patient and caregiver satisfaction, improved patient health outcomes, and increased cost effectiveness. Literature on discharge interventions from inpatient CAMHS, while variable in structure, consistently underscore the role of such interventions in minimizing patient and family vulnerability post-discharge. However, findings are limited by inadequate reporting and heterogeneity across studies. There is a need for further research into the design, implementation, and evaluation of interventions to support successful discharges from inpatient child and adolescent mental health care.

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