The cerebellar nuclei form the main output structures of the cerebellum and are composed of a deeply conserved set of cell types. Two excitatory cell classes, Class-A and -B, are present in each cerebellar nucleus and mediate all excitatory output of the cerebellum. To provide genetic access to these cell types, here we identified Acan […]

Neurodegenerative diseases such as Parkinson disease (PD) result from complex interactions between neuronal stress and the surrounding tissue environment, yet the determinants that govern this interplay remain incompletely understood. While neuronal responses to mitochondrial dysfunction and proteotoxic stress have been extensively characterized, the contribution of microglial state to disease progression remains unclear. Here, we identify […]

Therapeutics fused to brain shuttles that exploit endogenous receptor-mediated transport at the blood brain barrier (BBB) offer a promising strategy to deliver large molecule drugs and biologics to the CNS. A fundamental but untested assumption underlying their clinical development is that their endothelial receptor targets are consistently expressed between individuals and between patient populations. Here, […]

Somatic copy-number alterations (CNAs) accumulate with age and contribute to age-related pathologies, but their systematic characterization at single-cell resolution has been limited by the throughput-resolution trade-off in single-cell whole-genome sequencing. Here, we developed ultra-CNA, a high-resolution single-cell analysis pipeline that extends CNA detection to 10-kb bin resolution and jointly profiles copy-number and single-nucleotide variation (SNV). […]

Major Depressive Disorder (MDD) frequently follows a recurrent trajectory of episodes and remissions, often culminating in treatment-resistance. Molecular differences defining state-specific changes during episode and remission have been explored. However, progressive differences–defined here as cross-sectional linear trends across clinical stages from first to recurrent episodes or remissions, reflecting increasing illness burden over time–remain poorly understood, […]

BACKGROUND: Variation in pubertal maturation relative to same-age, same-sex peers (pubertal timing) has been linked to increased risk for depressive symptoms during adolescence. This developmental period is also characterized by substantial reorganization of functional brain networks. However, how pubertal timing relates to resting-state functional connectivity (rsFC) changes and depression risk remains unclear. METHODS: We examined […]

Flowering time and monocarpic senescence are tightly environmentally and genetically controlled. Typically, ‘early’ flowering and staygreen traits are associated with opposing life-history strategies; stress avoidance versus adaptation; with flowering time an overarching regulator of crop cycle length. We developed RIL populations segregating for Ppd-1 and NAM-1 variation, which are otherwise isogenic. Multi-year field experiments enabled […]

C4photosynthesis improves light, water and nitrogen-use efficiencies and can raise yieldby50% compared with the ancestral C3pathway.Engineering C4traits into C3crops could substantially boost food production but requires coordinated modifications to leaf anatomy and cell-specific photosynthetic function. For example, C4leaves contain morenumerous, shorter bundle sheath cells that are photosynthetically active. In searching for transcriptional regulators of bundle […]

Many agricultural soils are deficient in key macronutrients needed for healthy plant development. Relying on highly water-soluble commercial fertilizers for long durations can be costly and environmentally harmful. This study investigates a phosphorus-loaded Mg/Fe layered double hydroxide (LDH) dispersed on Douglas fir biochar (Mg/Fe-LDH biochar) as a controlled-release fertilizer and evaluates its impact on bush […]

Diurnal changes in light availability are a defining feature of life on Earth. Photoautotrophic organisms therefore store reduced carbon during the day to sustain energy metabolism at night. In cyanobacteria, glycogen is the primary carbon storage compound and supports both energy homeostasis and stress responses. Although glycogen-deficient Synechocystis strains have been studied previously, how these […]

Post-translational control of circadian period can involve changes in protein intracellular localization to affect clock function. Many clock proteins rely on a nuclear presence for their activity. As the primary gateway regulating the movement of molecules between the cytosol and the nucleus, the nuclear pore may assist in circadian system maintenance. We describe roles for […]