Selective metabolic regulations by p53 mutant variants in pancreatic cancer.

Background: Approximately half of all human cancers harbour mutations in the p53 gene, leading to the generation of neomorphic p53 mutant proteins. These mutants can exert gain-of-function (GOF) effects, potentially promoting tumour progression. However, the clinical significance of p53 GOF mutations, as well as the selectivity of individual variants, remains controversial and unclear.

TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis.

Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function.

Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis.

Cell death is a fundamental process in health and disease. Emerging research shows the existence of numerous distinct cell death modalities with similar and intertwined signaling pathways, but resulting in different cellular outcomes, raising the need to understand the decision-making steps during cell death signaling. Paracetamol (Acetaminophen, APAP)-induced hepatocyte death includes several apoptotic processes but eventually is executed by oncotic necrosis without any caspase activation.

Deciphering the significance of p53 mutant proteins.

Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage.

Lasing in Non-Hermitian Flat Bands: Quantum Geometry, Coherence, and the Fate of Kardar-Parisi-Zhang Physics.

We show that lasing in flat-band lattices can be stabilized by means of the geometrical properties of the Bloch states, in settings where the single-particle dispersion is flat in both its real and imaginary parts. We illustrate a general projection method and compute the collective excitations, which display a diffusive behavior ruled by quantum geometry through a peculiar coefficient involving gain, losses and interactions, and entailing resilience against modulational instabilities. Then, we derive an equation of motion for the phase dynamics and identify a Kardar-Parisi-Zhang term of geometric origin.