Stromal-derived factor (SDF)-1 and its G protein–coupled receptor, CXCR4, regulate stem/progenitor cell migration and retention in the marrow and are required for hematopoiesis. We show here an interaction between CXCR4 and the Src-related kinase, Lyn, in normal progenitors. We demonstrate that CXCR4-dependent stimulation of Lyn is associated with the activation of phosphatidylinositol 3-kinase (PI3-kinase). This chemokine signaling, which involves a Src-related kinase and PI3-kinase, appears to be a target for BCR/ABL, a fusion oncoprotein expressed only in leukemia cells. We show that the binding of phosphorylated BCR/ABL to Lyn results in the constitutive activation of Lyn and PI3-kinase, along with a total loss of responsiveness of these kinases to SDF-1 stimulation. Inhibition of BCR/ABL tyrosine kinase with STI571 restores Lyn responsiveness to SDF-1 signaling. Thus, BCR/ABL perturbs Lyn function through a tyrosine kinase-dependent mechanism. Accordingly, the blockade of Lyn tyrosine kinase inhibits both BCR/ABL-dependent and CXCR4-dependent cell movements. Our results demonstrate, for the first time, that Lyn-mediated pathological crosstalk exists between BCR/ABL and the CXCR4 pathway in leukemia cells, which disrupts chemokine signaling and chemotaxis, and increases the ability of immature cells to escape from the marrow. These results define a Src tyrosine kinases-dependent mechanism whereby BCR/ABL (and potentially other oncoproteins) dysregulates G protein–coupled receptor signaling and function of mammalian precursors.
Reinforcement Sensitivity Theory (RST) posits that individual differences in reward and punishment processing predict differences in cognition, behavior, and psychopathology. We performed a quantitative review of the relationships between reinforcement sensitivity, depression and anxiety, in two separate sets of analyses. First, we reviewed 204 studies that reported either correlations between reinforcement sensitivity and self-reported symptom severity or differences in reinforcement sensitivity between diagnosed and healthy participants, yielding 483 effect sizes. Both depression (Hedges' g = .99) and anxiety (g = 1.21) were found to be high on punishment sensitivity. Reward sensitivity negatively predicted only depressive disorders (g =-.21). More severe clinical states (e.g., acute vs remission) predicted larger effect sizes for depression but not anxiety. Next, we reviewed an additional 39 studies that reported correlations between reinforcement sensitivity and both depression and anxiety, yielding 156 effect sizes. We then performed meta-analytic structural equation modeling to simultaneously estimate all covariances and control for comorbidity. Again we found punishment sensitivity to predict depression (β = .37) and anxiety (β = .35), with reward sensitivity only predicting depression (β =-.07). The transdiagnostic role of punishment sensitivity and the discriminatory role of reward sensitivity support a hierarchical approach to RST and psychopathology. Highlights: Sensitivity to punishment positively predicts both depression and anxiety. Sensitivity to reward discriminates between them, negatively predicting depression. This pattern was observed even when directly controlling for comorbidity. Depression's effect sizes are uniquely sensitive to clinical state. Depression's effect sizes are also moderated by method of clinical assessment.
The relationship between context and emotion regulation is currently at the center of a burgeoning area of research. Commonly used emotion regulation questionnaires, however, are predominantly trait-based, and insensitive to situational choice of regulatory strategy. The current work describes the development and validation of the State Emotion Regulation Inventory (SERI), a brief measure of situational use of distraction, reappraisal, brooding and acceptance. In Study 1, an initial item pool was constructed, based on commonly used trait-based emotion regulation surveys. Then, the psychometric properties of the items were examined with a group of 181 participants who recalled a saddening autobiographical event, identified a distressing thought it triggered, and then waited for 3 minutes without instruction, as an opportunity to allow for spontaneous emotion regulation. Participants then completed the initial item pool, and other relevant trait-based scales. Exploratory factor analysis suggested a 4-factor solution, corresponding to the 4 regulatory strategies measured in the SERI. The 4 items to exclusively load highest on each factor were selected for the final measure. Assembled subscales correlated with relevant trait-based subscales in the expected directions. In Study 2, another sample of 155 participants completed the same procedure and the new SERI, and confirmatory factor analysis supported the 4-factor structure of this instrument. As a brief, validated instrument, the SERI may be a useful measure for studies of state emotion regulation, in protocols that use repeated measures in a single session, over the course of multiple sessions, or via ecological momentary assessments. (PsycINFO Database Record
The COVID-19 pandemic has had medical, economic and behavioral implications on a global scale and was argued to have negatively impacted the population’s mental health as well. The current study utilizes longitudinal data to assess such an assertion. An international group of 218 participants completed measures of depression, anxiety, rumination and distress intoler-ance at two baselines six months apart as well as at the height of the COVID-19 pandemic ex-actly 12 months later. Contrary to expectations, depression, rumination, and distress intolerance were at equivalent levels during the pandemic as they were at baseline. Anxiety was reduced by a trivial degree (d = .10). Furthermore, a comparison of quantitative explanatory models indi-cated that symptom severity and pandemic-related environmental stressors predicted pandem-ic-related distress, but pandemic-related distress did not predict symptom severity. These find-ings underscore the necessity of longitudinal designs and diathesis-stress models in the study of mental health during the COVID-19 pandemic.
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