Long Pritchard (pumpdish35)

Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation of alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations associated with nucleosome instability. Through analyses of existing cancer genomics datasets, we find aberrant sH2A upregulation in a broad array of cancers, which manifest splicing patterns consistent with global nucleosome destabilization. We posit that short H2As are a class of "ready-made" oncohistones, whose inappropriate expression contributes to chromatin dysfunction in cancer.Photomediated-reversible-deactivation radical polymerisation (photo-RDRP) has a limited scope of available photocatalysts (PCs) due to multiple stringent requirements for PC properties, limiting options for performing efficient polymerisations under long wavelengths. Here we report an oxygen-mediated reductive quenching pathway (O-RQP) for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerisation. The highly efficient polymerisations that are performed in the presence of ambient air enable an expanded scope of available PCs covering a much-broadened absorption spectrum, where the oxygen tolerance of PET-RAFT allows high-quality polymerisation by preventing the existence of O2 in large amounts and efficient O-RQP is permitted due to its requirement for only catalytic amounts of O2. Initially, four different porphyrin dyes are investigated for their ability to catalyse PET-RAFT polymerisation via an oxidative quenching pathway (OQP), reductive quenching pathway (RQP) and O-RQP. Thermodynamic studies with the aid of (time-dependent) density functional theory calculations in combination with experimental studies, enable the identification of the thermodynamic constraints within the OQP, RQP and O-RQP frameworks. This knowledge enables the identification of four phthalocyanine photocatalysts, that were previously thought to be inert for PET-RAFT, to be successfully used for photopolymerisations via O-RQP. Well-controlled polymerisations displaying excellent livingness are performed at wavelengths in the red to near-infrared regions. The existence of this third pathway O-RQP provides an attractive pathway to further expand the scope of photocatalysts compatible with the PET-RAFT process and facile access to photopolymerisations under long wavelengths.Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins that transport cargo, and the mechanisms regulating their localization and function are poorly understood. Here, we report a single-particle cryo-EM reconstruction of a three-headed axonemal dynein natively bound to doublet microtubules isolated from cilia. The slanted conformation of the axonemal dynein causes interaction of its motor domains with the neighboring dynein complex. Our structure shows how a heterotrimeric docking complex specifically localizes the linear array of axonemal dyneins to the doublet microtubule by directly interacting with the heavy chains. Our structural analysis establishes the arrangement of conserved heavy, intermediate and light chain subunits, and provides a framework to understand the roles of individual subunits and the interactions between dyneins during ciliary waveform generation.In seismically-active regions, mapping active and potentially-active faults is the first step to assess seismic hazards and site selection for paleoseismic studies that will estimate recurrence rates. Here, we present a comprehensive database of active and potentially-active continental faults in Chile based on existing studies and new mapping at 125,000 scale using geologic and geomorphic criter