Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Belonging: a review of conceptual issues, an integrative framework, and directions for future research

OBJECTIVE: A sense of belonging-the subjective feeling of deep connection with social groups, physical places, and individual and collective experiences-is a fundamental human need that predicts numerous mental, physical, social, economic, and behavioural outcomes. However, varying perspectives on how belonging should be conceptualised, assessed, and cultivated has hampered much-needed progress on this timely and important topic. To address these critical issues, we conducted a narrative review that summarizes existing perspectives on belonging, describes a new integrative framework for understanding and studying belonging, and identifies several key avenues for future research and practice. METHOD: We searched relevant databases, including Google Scholar, PubMed, Scopus, PsycInfo, and ClinicalTrials.gov, for articles describing belonging, instruments for assessing belonging, and interventions for increasing belonging. RESULTS: By identifying the core components of belonging, we introduce a new integrative framework for understanding, assessing, and cultivating belonging that focuses on four interrelated components: competencies, opportunities, motivations, and perceptions. CONCLUSION: This integrative framework enhances our understanding of the basic nature and features of belonging, provides a foundation for future interdisciplinary research on belonging and belongingness, and highlights how a robust sense of belonging may be cultivated to improve human health and resilience for individuals and communities worldwide

Why do children worry about their academic achievement? An expectancy-value perspective on elementary students’ worries about their mathematics and reading performance

Children’s worrying about their academic performance has profound implications for their learning and wellbeing in school. Understanding the contextual and psychological antecedents of students’ worry thus represents an important area of research. Drawing on Eccles and colleagues’ expectancy-value theory and Pekrun’s control-value theory and using data from the Childhood and Beyond Study, we examined the motivational underpinnings of elementary students’ worries about performing poorly in the domains of mathematics and reading (N=805, grades 3, 4 and 6). With one exception, the analyses confirmed that children’s expectations of success in and valuing of mathematics and reading interacted in predicting children’s worry about these domains. Children’s worry was strongest when they rated their subjective abilities and expected success in mathematics and reading as relatively low but perceived these subjects as valuable. Moderated mediation analyses further suggested that when children’s self-concepts of mathematics and reading ability were low to moderate, students’ perceived parental valuing of their performance in these subjects indirectly positively predicted children’s worry via its positive impact on children’s own subjective valuing of mathematics and reading. Thus, when children perceive high academic performance as potentially difficult to attain, perceived parental valuing might negatively impact their wellbeing in school (by increasing not only their valuing of mathematics and reading, but also their performance-related worrying). Children’s gender, grade level, teacher-rated mathematics and reading aptitude, and prior self-reported worry about mathematics and reading performance were included as control variables in all analyses

Structural effects of the antimicrobial peptide maculatin 1.1 on supported lipid bilayers

The interactions of the antimicrobial peptide maculatin 1.1 (GLFGVLAKVAAHVVPAIAEHF-NH2) with model phospholipid membranes were studied by use of dual polarisation interferometry and neutron reflectometry and dimyristoylphosphatidylcholine (DMPC) and mixed DMPC–dimyristoylphosphatidylglycerol (DMPG)-supported lipid bilayers chosen to mimic eukaryotic and prokaryotic membranes, respectively. In DMPC bilayers concentration-dependent binding and increasing perturbation of bilayer order by maculatin were observed. By contrast, in mixed DMPC–DMPG bilayers, maculatin interacted more strongly and in a concentration-dependent manner with retention of bilayer lipid order and structure, consistent with pore formation. These results emphasise the importance of membrane charge in mediating antimicrobial peptide activity and emphasise the importance of using complementary methods of analysis in probing the mode of action of antimicrobial peptides