John Dewey

Jan 2, 2025 | nature.com | John Dewey |Gloria Alvarado |Jesse Kooistra |Agata M. Parsons |Aaron Zebolsky |Seth Byrne | +3 more

The “secondhit” pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele is joined by somatic mutation of the remaining functional allele. The mechanisms are unresolved, but the human PKD1 tumor suppressor is a good experimental model for identifying the molecular determinants. Inactivation of PKD1 results in autosomal dominant polycystic kidney disease, a very common disorder characterized by the accumulation of fluid-filled cysts and end-stage renal disease. Since human PKD1 follows second hit and mouse Pkd1 heterozygotes do not, we reasoned that there is likely a molecular difference that explains the elevated mutagenesis of the human gene. Here we demonstrate that guanine quadruplex DNA structures are abundant throughout human, but not mouse, PKD1 where they activate the DNA damage response. Our results suggest that guanine quadruplex DNAs provoke DNA breaks in PKD1, providing a potential mechanism for cystogenesis in autosomal dominant polycystic kidney disease specifically and for the inactivation of guanine quadruplex-rich tumor suppressors generally. In humans, ADPKD can develop from “second hit” mutations in the PKD1 gene. Here, the authors show that human PKD1 contains guanine quadruplex structures that cause mutagenic double stranded breaks.

Jan 7, 2024 | citylights.com | John Dewey

Based on John Dewey’s lectures on esthetics, delivered as the first William James Lecturer at Harvard in 1932, Art as Experience has grown to be considered internationally as the most distinguished work ever written by an American on the formal structure and characteristic effects of all the arts: architecture, sculpture, painting, music, and literature. Read More

Jul 12, 2023 | americanthinker.com | Dana E. Abizaid |John Dewey

Over the past two decades the classroom has been hijacked by an army of ideologues trumpeting empty slogans like “mindfulness,” “caring”, and “celebrating diversity.” Combined with recent “diversity, equity and inclusion” policies forced on teachers and students, American education has devolved into an unhealthy “totalitarianism of compassion” that oftentimes is anything but compassionate and inclusive.