Reviews & Analysis

Cryo-electron microscopy (cryo-EM) imaging of DNA replication origin activation explains the role of Mcm10, a minichromosome maintenance (MCM) protein homolog, during initiation. Mcm10 acts as a wedge to split the two MCM hexamers of the activated replicative helicase. Diverging replication forks are then established, with changes in the MCM hexamers that promote the topological separation of two DNA strands.

NAD(H) redox homeostasis has a fundamental role in cellular metabolism. We screened for potential modulators of NAD(H) using a genome-scale RNA interference (RNAi) approach combined with SoNar, a high-performance sensor that is sensitive to the redox state of NAD(H). Our analysis identified HES4 as a negative regulator of the NADH/NAD⁺ ratio that influences pyrimidine biosynthesis and exerts a potent oncogenic effect.

Targeted biologics delivery requires programming multicomponent protein nanomaterials to enable selective targeting and response to environment changes in a single unified framework. A novel protein nanoparticle platform has been designed to modulate cell-surface target specificity, cargo packaging, and pH-dependent release of encapsulated cargo, providing exciting possibilities in biologics delivery.

Systemic RNA interference (RNAi) in Caenorhabditis elegans is initiated by SID-1-mediated double-stranded RNA (dsRNA) internalization. By combining cryo-electron microscopy (cryo-EM), in vitro and in vivo assays, we show how SID-1 specifically recognizes dsRNA and provide important insights into dsRNA internalization by SID-1.

Cryo-electron microscopy of brain tissue from two individuals with Down syndrome showed amyloid-β (Aβ) and tau filaments identical to those found in individuals with sporadic or dominantly inherited Alzheimer disease (AD), but also two types of Aβ₄₀ filaments with distinct structures different from those previously reported in AD and cerebral amyloid angiopathy.