Synapses connect neurons together to form the circuits of the brain, and their molecular composition controls innate and learned behavior. We analyzed the molecular and morphological diversity of 5 billion excitatory synapses at single-synapse resolution across the mouse brain from birth to old age. A continuum of changes alters synapse composition in all brain regions across the life span....
Chromatin instability and mitochondrial decline are conserved processes that contribute to cellular aging. Although both processes have been explored individually in the context of their distinct signaling pathways, the mechanism that determines which process dominates during aging of individual cells is unknown. We show that interactions between the chromatin silencing and mitochondrial pathways...
Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome-wide data from 26 ancient individuals from northern and southern East Asia spanning 9500 to 300 years ago. Genetic differentiation in this region was higher in the past than the present, which reflects a major episode of admixture involving northern East Asian ancestry spreading across...
Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn serum contains abundant autoantibodies, suggesting that B cell tolerance during gestation is not yet fully established. To investigate this apparent paradox, we evaluated the reactivities of more than 450 antibodies cloned from single B cells from...
Isomerization-based strategies to enable the stereodivergent construction of complex polyenes from geometrically defined alkene linchpins remain conspicuously underdeveloped. Mitigating the thermodynamic constraints inherent to isomerization is further frustrated by the considerations of atom efficiency in idealized low–molecular weight precursors. In this work, we report a general...
The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)–filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM)...