MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization.

Cancer cell migration during metastasis is mediated by a highly polarized cytoskeleton. MARK2 and its invertebrate homolog Par1B are kinases that regulate the microtubule cytoskeleton to mediate polarization of neurons in mammals and embryos in invertebrates. However, the role of MARK2 in cancer cell migration is unclear. Using osteosarcoma cells, we found that in addition to its known localizations on microtubules and the plasma membrane, MARK2 also associates with the actomyosin cytoskeleton and focal adhesions. Cells depleted of MARK proteins demonstrated that MARK2 promotes phosphorylation of both myosin II and the myosin phosphatase targeting subunit MYPT1 to synergistically drive myosin II contractility and stress fiber formation in cells. Studies with isolated proteins showed that MARK2 directly phosphorylates myosin II regulatory light chain, while its effects on MYPT1 phosphorylation are indirect. Using a mutant lacking the membrane-binding domain, we found that membrane association is required for focal adhesion targeting of MARK2, where it specifically enhances cell protrusion by promoting FAK phosphorylation and formation of focal adhesions oriented in the direction of migration to mediate directionally persistent cell motility. Together, our results define MARK2 as a master regulator of the actomyosin and microtubule cytoskeletal systems and focal adhesions to mediate directional cancer cell migration.

Resilience among a large sample of adult Palestinians in the Gaza Strip: examining contextual sociodemographic factors and emotional response through a social-ecological lens.

OBJECTIVES: Palestinians in the Gaza Strip continue to cope with persistent violations of their social, economic, political, and civil rights. This study sought to measure resilience among adult Palestinians and its relation to contextual factors (sociodemographic variables) and emotional response using a social-ecological framework. STUDY DESIGN: Community-based, cross-sectional. METHODS: Involving 1068 households in the Gaza Strip, individuals (aged ≥18 years) completed (a) a questionnaire on demographics and social construct, (b) 25-item Connor-Davidson Resilience Scale (Cronbach alpha = .91), and (c) Positive and Negative Affect Schedule (PANAS) (Cronbach alpha = .89). Bivariate analysis, Pearson correlations, and step-wise multiple regression were conducted. RESULTS: Gazans scored significantly lower resilience compared to the normative mean in the general population (mean score = 75.9 vs. 80.4). Bivariate analysis revealed that being employed and highly educated were associated with higher resilience scores. Likewise, participants showed statistically lower positive affects (PA) (mean = 33.49, standard deviation [SD] = 7.5: 95% confidence interval [CI] 2.39-1.23, P < 0.00) and higher negative affects (NA) (mean = 22.3, SD = 7.0; 95% CI 3.68-4.73, P < 0.001) compared to normative means. Resilience scores were positively correlated with PA (r = .40, P < 0.001), with much weaker negative correlation with NA (r = -.10, P < 0.001). Only PA and NA were significant predictors of resilience (r2 = 16%); PA recorded a positive and higher beta value (beta = .38, P < 0.001) than NA (beta = -.089, P = 0.017). CONCLUSIONS: Sumud, the Palestinian notion of resilience, is an interactive process that depends on individual assets and contextual resources. Given the political turmoil and high levels of poverty, the employment opportunities must be addressed for this highly educated population to preserve resilience. Providing accessible mental health and social support services is critical.

Psychiatric predictors of surgery non-completion following suitability assessment for bariatric surgery.

BACKGROUND: Bariatric surgery is recognized as a treatment for severe obesity; however, little is known about factors influencing patient surgery non-completion. This study explored the relationship between psychiatric factors and patient non-completion during the pre-bariatric surgery suitability assessment. METHODS: A total of 367 individuals underwent a structured psychiatric interview and were classified as either surgery completers (SC) or surgery non-completers (SNC) if they attended at least one pre-surgery assessment appointment but did not receive surgery. RESULTS: The results showed that in comparison to the SC group, the SNC group had significantly higher rates of overall past Axis I psychiatric disorders (58.1 vs. 46.6 %, p = 0.035), past anxiety disorders (17.4 vs. 9.4 %, p = 0.03), and past substance use disorders (8.7 vs. 3.7 %, p = 0.03). For specific past psychiatric disorders, the SNC group exhibited significantly higher rates of a past post-traumatic stress disorder (PTSD) (5 vs. 1 %, p = 0.029) and past substance dependence disorder (7 vs. 1 %, p = 0.005). Although overall current psychiatric disorders did not significantly differ between groups, the SNC group had significantly higher rates of current PTSD (2 vs. 0 %, p = 0.049) and current generalized anxiety disorder (4 vs. 0 %, p = 0.005). CONCLUSIONS: A past history of an anxiety or substance use disorder may play a role in patients not completing the assessment component of the bariatric surgery process. Additional psychosocial support, such as cognitive behavioral therapy or targeted psychoeducation, may help improve patient completion of the pre-surgery assessment phase.