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Genetic influences on haematopoiesis

1 week 6 days ago
Haematopoiesis has long been a paradigm for understanding how human genetic variation can influence physiology in health and disease, ranging from the genetic characterization of Mendelian blood diseases to population-scale genomic studies of blood cell phenotypes and diseases. More recently, advances in single-cell genomics and variant-to-function mapping are enabling mechanistic insights into how genetic variation shapes blood cell development. Alongside inherited variation, the...
Michael Poeschla

Adaptor protein supersaturation drives innate immune signaling and cell fate

1 week 6 days ago
How minute pathogenic signals trigger decisive immune responses is a fundamental question in biology. Classical signaling often relies on ATP-driven enzymatic cascades, but innate immunity frequently employs death fold domain (DFD) self-assembly. The energetic basis of this assembly is unknown. Here, we show that specific DFDs function as energy reservoirs through metastable supersaturation. Characterizing all 109 human DFDs, we identified sequence-encoded nucleation barriers specifically in the...
Alejandro Rodriguez Gama

Role of Succinate Dehydrogenase in Age-Related Th17 Inflammation

1 week 6 days ago
Age-related cellular changes negatively impact CD4^(+) T cell function. Our prior work showed that mitochondrial complex II (succinate dehydrogenase [SDH]) expression was upregulated in T cells from older (O) adults (60-80 years old). T cells from older adults also produced higher amounts of cytokines generally considered proinflammatory, such as Th17 cytokines IL-17A/F and IL-21, and the Th-17-supportive cytokine IL-6, compared to T cells from younger (Y) adults (25-40 years old). The objective...
Evelyn Ocegueda

Aging is not a disease: an evolutionary and comparative biological reappraisal

2 weeks ago
The question of whether aging should be classified as a disease has gained prominence in geroscience, fueled by advances in molecular biology and the aspiration to develop interventions that mitigate age-associated functional decline. However, evolutionary models describe aging as an emergent consequence of declining selection gradients and life-history trade-offs rather than as a deviation from species-typical function. Comparative data across taxa reveal substantial heterogeneity in aging...
Bruno César Feltes