Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.

To gain further insights into the importance of the unsaturated 1,4-ketoaldehyde moiety of ophiobolin A (OpA) for the potency and selectivity observed toward cancer stem cells, several derivatives were synthesized through controlled reduction and oxidations of the unsaturated aldehyde and ketone moieties. Structure elucidation of these new OpA derivatives was achieved through detailed NMR studies and comparison to OpA and known isolated congeners possessing variations in these regions. The relative stereochemistry of the newly generated stereocenters was determined by coupling constants in conjunction with conformational analyses (DFT) of the synthetic derivatives.

Twist-Induced Epithelial-to-Mesenchymal Transition Confers Specific Metabolic and Mitochondrial Alterations.

Cells undergo significant epigenetic and phenotypic change during the epithelial-to-mesenchymal transition (EMT), a process observed in development, wound healing, and cancer metastasis. EMT confers several advantageous characteristics, including enhanced migration and invasion, resistance to cell death, and altered metabolism. In disease, these adaptations could be leveraged as therapeutic targets.

Family and Home Environment Predictors of Children's 24-Hour Movement Guideline Adherence: A Mixed-Methods Study.

During summer, children may meet fewer 24 hours Movement Guidelines (24 hr-MGs) [moderate-vigorous physical activity (PA): ≥60 minutes/day, screen time: ≤2 hours/day, sleep: 9-11 hours/day) compared with the school year. Structured environments within community settings (, summer programs) support guideline adherence. Information about the relationship between structured home environments and 24 hr-MGs is needed.

Covalent inhibitors of the RAS binding domain of PI3Kα impair tumor growth driven by RAS and HER2.

Genetic disruption of the RAS binding domain (RBD) of PI 3-kinase (PI3K) prevents the growth of mutant RAS driven tumors in mice and does not impact PI3K's role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3K interaction may represent an attractive strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3K lipid kinase activity such as alpelisib. Here we report compounds that bind covalently to cysteine 242 in the RBD of PI3K p110α and block the ability of RAS to activate PI3K activity.

Hybrid performances in sport: Cybathlon spectatorship for critically imagining technologies for disability futures.

Disabled bodies have been historically marginalised in sporting arenas and spectacles. Assistive technologies have been increasingly featuring in, and changing, sporting landscapes. In some ways recent shifts have made disability more present and visible across many (para) sporting cultures, and yet sport continues to operate on a tiered system that assumes a normative able body.