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Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier

9 months ago
The blood-brain barrier (BBB) restricts the passage of protein-rich fluids through tight junctions (TJs) formed between brain endothelial cells (BECs). BBB restrictiveness diminishes with aging, but the underlying mechanisms remain unclear. BECs establish physical contact with pericytes via N-cadherin homophilic adhesion. In cortex tissue from young and middle-aged patients, the age-related loss of vascular N-cadherin corresponds with the disruption of occludin TJs. Genetic deletion of...
Quinn Lee

CDADC1 is a vertebrate-specific dCTP deaminase that metabolizes gemcitabine and decitabine to prevent cellular toxicity

9 months ago
Cancer therapy is limited by resistance to standard-of-care chemotherapeutic and/or by treatment-associated toxicity. Identifying molecular mechanisms that modulate cellular toxicity is crucial for enhancing treatment efficacy. We characterize CDADC1, a vertebrate-specific orphan enzyme, as an unprecedented eukaryotic dCTP deaminase. CDADC1 catalyzes the conversion of dCTP into dUTP. While bacteria use this activity to sustain proliferation, CDADC1 evolved independently and is not required for...
Marcelo M Rodriguez

Impact of sarcopenia and obesity on skeletal muscle size, gene expression, and mitochondrial function

9 months ago
Skeletal muscle is a primary tissue of dysfunction during both aging and obesity. Recently, the coincidence of obesity and aging has gained attention due to the intersection of the obesity epidemic with an aging demographic. Both aging and obesity are associated with marked defects in skeletal muscle metabolic health. Despite these findings, we have a poor understanding of how obesity and aging may interact to impact skeletal muscle mass and metabolic health. Therefore, we investigated the...
Hector G Paez

Impact of lifestyle factors on quantitative motor and cognitive performance: insights from a longitudinal study on healthy ageing

9 months ago
The process of ageing is extremely variable in progression and phenotypic features including significant variations in disease milestones, such as cognitive impairment, frailty, or recurrent falls. Our aim was to analyze the influence of lifestyle factors on motor and cognitive performance in a longitudinal ageing study in older people on healthy ageing. We conducted a longitudinal analysis in a cohort of 744 older participants (mean 70 years) over an 8-year period. Cognitive performance was...
Milan Zimmermann

Aberrant basal cell clonal dynamics shape early lung carcinogenesis

9 months ago
Science, Volume 388, Issue 6752, June 2025.
Sandra Gómez-López, Ahmed S. N. Alhendi, Moritz J. Przybilla, Ignacio Bordeu, Zoe E. Whiteman, Timothy Butler, Maral J. Rouhani, Lukas Kalinke, Imran Uddin, Kate E. J. Otter, Deepak P. Chandrasekharan, Marta Lebrusant-Fernandez, Abigail Y. L. Shurr,…

A metabolite-based resistance mechanism against malaria

9 months ago
Science, Volume 388, Issue 6752, June 2025.
Ana Figueiredo, Sonia Trikha Rastogi, Susana Ramos, Fátima Nogueira, Katherine De Villiers, António G. Gonçalves de Sousa, Lasse Votborg-Novél, Cäcilie von Wedel, Pinkus Tober-Lau, Elisa Jentho, Sara Pagnotta, Miguel Mesquita, Silvia Cardoso, Giulia…