Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate.

Neural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrains NSCs to a self-renewing state and prevents neurosphere formation. Ncf1-dependent oxidation of Igfbp2 promotes neurogenesis by NSCs in vitro and in vivo while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1-/- and Igfbp2-/- NSCs favor the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induces DDSBs and is sufficient to rescue the ability of Ncf1-/- and Igfbp2-/- NSCs to lineage-commit to form neurospheres and neurons. NSC lineage commitment is dependent on the oxidizable cysteine-43 residue of Igfbp2. Our study highlights the role of DNA damage/repair in orchestrating NSC fate decisions downstream of redox-regulated Igfbp2.

Effects of 1 MHz Therapeutic Ultrasound on Limb Blood Flow and Microvascular Reactivity: A Randomized Pilot Trial.

A randomized, double-blind, placebo-controlled, cross-over study where continuous therapeutic ultrasound (CUS; at 0.4 W/cm2), pulsed therapeutic ultrasound (PUS; at 20% duty cycle, 0.08 W/cm2), both at 1 MHz, and placebo (equipment on, no energy provided) were randomized and applied over the forearm of the non-dominant arm for 5 min in 10 young, healthy individuals. Absolute and peak forearm blood flow (FBF) were measured via Venous Occlusion Plethysmography. FBF was measured before, halfway, and after (immediately and 5 min after) the therapeutic ultrasound (TUS) intervention. Post-ischemic peak FBF was measured 10 min before and 10 min after the TUS intervention. A two-way repeated measures ANOVA (group × time) was selected to assess differences in FBF before, during, and after TUS treatment, and for peak FBF before and after TUS treatment. FBF increased 5 min after TUS in CUS compared to placebo (2.96 ± 1.04 vs. 2.09 ± 0.63 mL/min/100 mL of tissue, p < 0.05). PUS resulted in the greatest increase in Peak FBF at 10 min after US (Δ = 3.96 ± 2.02 mL/min/100 mL of tissue, p = 0.06). CUS at 1 MHz was an effective treatment modality for increasing FBF up to 5 min after intervention, but PUS resulted in the greatest increase in peak FBF at 10 min after intervention.