Sociocultural and Parenting Factors Affect Children\u27s Cognitive Development Through Mastery Motivation

Human development involves multiple, dynamic interactions between a person and their environment. Children’s environment has a significant impact on their current behavior and future development.1,2 Serving as a main component of this environment, parenting behavior influences a child’s development, encouraging certain behavioral patterns, personality traits, and mental dispositions.1,3 Key subcomponents of parenting behavior include level of parental control and intrusiveness, involvement in child play, parenting style, and the amount of attention provided to the child.3,4,5 Two primary factors shape these child-rearing practices: 1) cultural values, which indirectly guide the establishment of customs and behavioral norms such as child-rearing, and 2) socioeconomic status, which affects the amount of resources and stimulation a child receives.1,3,6 One specific developmental outcome affected by parenting is mastery motivation, a psychological force describing an individual\u27s independent, persistent attempts to solve or master a challenging task.7 Although mastery motivation is intrinsic and relatively stable, it is still malleable to multiple environmental influences, especially parental factors.2,7,8 In general, less parental control and more allowance of exploratory play stimulate opportunities for more optimal development.2,5 Previous research on infants and young children linked mastery motivation to increased self-regulation and persistence in challenging tasks, heightened belief in self, encouragement of autonomy, and improved sensorimotor skills as a result of practice.2,7,8 Importantly, the latter are positively related to children\u27s future cognitive development and academic outcomes.4,6,

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca2+ signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological-or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca(2+)calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour-stroma interaction