ABE-ultramax for high-efficiency biallelic adenine base editing in zebrafish.

Advancements in CRISPR technology, particularly the development of base editors, revolutionize genetic variant research. When combined with model organisms like zebrafish, base editors significantly accelerate and refine in vivo analysis of genetic variations. However, base editors are restricted by protospacer adjacent motif (PAM) sequences and specific editing windows, hindering their applicability to a broad spectrum of genetic variants.

Translational modulator ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome.

Fragile X syndrome (FXS) is caused by the loss of fragile X messenger ribonucleoprotein (FMRP), a translational regulator that binds the transcripts of proteins involved in synaptic function and plasticity. Dysregulated protein synthesis is a central effect of FMRP loss, however, direct translational modulation has not been leveraged in the treatment of FXS. Thus, we examined the effect of the translational modulator integrated stress response inhibitor (ISRIB) in treating synaptic and behavioral symptoms of FXS.

The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders.

Individuals with neurodevelopmental disorders experience persistent sleep deficits, and there is increasing evidence that sleep dysregulation is an underlying cause, rather than merely an effect, of the synaptic and behavioral defects observed in these disorders. At the molecular level, dysregulation of the synaptic proteome is a common feature of neurodevelopmental disorders, though the mechanism connecting these molecular and behavioral phenotypes is an ongoing area of investigation. A role for eIF2α in shifting the local proteome in response to changes in the conditions at the synapse has emerged.

Phylogenetic conservation of the interdependent homeostatic relationship of sleep regulation and redox metabolism.

Sleep is an essential and evolutionarily conserved process that affects many biological functions that are also strongly regulated by cellular metabolism. The interdependence between sleep homeostasis and redox metabolism, in particular, is such that sleep deprivation causes redox metabolic imbalances in the form of over-production of ROS. Likewise (and vice versa), accumulation of ROS leads to greater sleep pressure.

Sleep deficiency as a driver of cellular stress and damage in neurological disorders.

Neurological disorders encompass an extremely broad range of conditions, including those that present early in development and those that progress slowly or manifest with advanced age. Although these disorders have distinct underlying etiologies, the activation of shared pathways, e.g.