Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas

RNA polymerase III (Pol-III) transcribes tRNAs and other small RNAs essential for protein synthesis and cell growth. Pol-III is deregulated during carcinogenesis; however, its role in vivo has not been studied. To address this issue, we manipulated levels of Brf1, a Pol-III transcription factor that is essential for recruitment of Pol-III holoenzyme at tRNA genes in vivo. Knockout of Brf1 led to embryonic lethality at blastocyst stage. In contrast, heterozygous Brf1 mice were viable, fertile and of a normal size. Conditional deletion of Brf1 in gastrointestinal epithelial tissues, intestine, liver and pancreas, was incompatible with organ homeostasis. Deletion of Brf1 in adult intestine and liver induced apoptosis. However, Brf1 heterozygosity neither had gross effects in these epithelia nor did it modify tumorigenesis in the intestine or pancreas. Overexpression of BRF1 rescued the phenotypes of Brf1 deletion in intestine and liver but was unable to initiate tumorigenesis. Thus, Brf1 and Pol-III activity are absolutely essential for normal homeostasis during development and in adult epithelia. However, Brf1 overexpression or heterozygosity are unable to modify tumorigenesis, suggesting a permissive, but not driving role for Brf1 in the development of epithelial cancers of the pancreas and gut

Parenting and late adolescents’ well-being in Greece, Norway, Poland and Switzerland : associations with individuation from parents

Cross-cultural studies focusing on individuation and parent-child relationships during late adolescence in the European context are sparse. This study investigated relationships between maternal and paternal responsiveness, demandingness and autonomy granting and late adolescents subjective well-being in Greece, Norway, Poland, and Switzerland. Additionally, the role of psychological, functional, and financial aspects of adolescents’ individuation in these relationships were assessed. Late adolescents (18-20-years-old, N=745) reported on their parents’ behaviors and themselves. Structural models with latent constructs were applied to test the hypothesized relationships. Results showed that in all four countries, maternal and paternal autonomy granting and responsiveness were positively associated with adolescents’ well-being. No significant results were found for demandingness. Further, the study found that psychological and functional connectedness with mothers and financial connectedness with fathers partially explained the associations between parenting behaviors and adolescents’ well-being. The results indicate more similarities than differences across Europe in the associations between parenting on late adolescents’ outcomes. More importantly, the study points out that maternal and paternal parenting may play different roles in late adolescenc