Role of epigenetics in paediatric cancer pathogenesis & drug resistance.

Paediatric oncogenesis is tightly intertwined with errors in developmental processes involving cell specification and differentiation, which are governed by intricate temporal epigenetic signals. As paediatric cancers are characterised by a low number of somatic mutations, dysregulated chromatin landscapes are believed to be key drivers of oncogenesis. Epigenetic dysregulation is induced by mutations and aberrant expression of histones and epigenetic regulatory genes, to altered DNA methylation patterns and dysregulated noncoding RNA expression.

PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin.

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC).

Maneuvering through Life with Positivity: Estimating the Effects of Foster Youth's Appraisal on Coping Styles.

Youth in foster care tend to experience a disproportional number of adverse life experiences and demonstrate high rates of emotional and behavioral difficulties. According to the transactional model of stress and coping, how youth appraise their experiences influences the type of coping strategies they use in response to adversity, and these relations are key components to understanding later adjustment. However, few studies have examined potential effects of appraisal on coping for youth in foster care.

Histone variant H3.3 promotes metastasis in alveolar rhabdomyosarcoma.

The relatively quiet mutational landscape of rhabdomyosarcoma (RMS) suggests that epigenetic deregulation could be central to oncogenesis and tumour aggressiveness. Histone variants have long been recognised as important epigenetic regulators of gene expression. However, the role of histone variants in RMS has not been studied hitherto.

Mitochondrial calcium uptake regulates tumour progression in embryonal rhabdomyosarcoma.

Embryonal rhabdomyosarcoma (ERMS) is characterised by a failure of cells to complete skeletal muscle differentiation. Although ERMS cells are vulnerable to oxidative stress, the relevance of mitochondrial calcium homoeostasis in oncogenesis is unclear. Here, we show that ERMS cell lines as well as primary tumours exhibit elevated expression of the mitochondrial calcium uniporter (MCU).

Mitochondrial Dysfunction at the Center of Cancer Therapy.

Mitochondria undergo constant morphological changes through fusion, fission, and mitophagy. As the key organelle in cells, mitochondria are responsible for numerous essential cellular functions such as metabolism, regulation of calcium (Ca), generation of reactive oxygen species, and initiation of apoptosis. Unsurprisingly, mitochondrial dysfunctions underlie many pathologies including cancer.

Genetics, epigenetics and redox homeostasis in rhabdomyosarcoma: Emerging targets and therapeutics.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma accounting for 5-8% of malignant tumours in children and adolescents. Children with high risk disease have poor prognosis. Anti-RMS therapies include surgery, radiation and combination chemotherapy.

Sexual Passion in Committed Relationships: Measurement and Conceptual Issues.

The purpose of this study is to discuss the need for a new triadic model of sexual passion in relationships and to present the preliminary psychometric properties of a scale designed to measure these three approaches to passion (harmonious, obsessive, and inhibited) for use in clinical and scholarly work. Existing theory and measures of general passion are based on a dualistic model of passion that includes the harmonious and obsessive approaches to passion. We added the inhibited approach to passion from the sexuality research and develop measures for assessing sexual passion in relationships.