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Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood–brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

Summary During DNA double strand break (DSB) repair, the ring-shaped Ku70/80 complex becomes trapped on DNA and needs to be actively extracted, but it has remained unclear what provides the required energy. By means of reconstitution of DSB repair on beads, we demonstrate here that DNA-locked Ku rings are released by the AAA-ATPase, p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the Ufd1-Npl4 ubiquitin adapter complex and specifically targets Ku80 that is modified by K48-linked ubiquitin chains. In U2OS cells, chemical inhibition of p97, or siRNA-mediated depletion of p97 or its adapters impairs Ku80 removal after non-homologous end-joining of DSBs. Moreover, it attenuates early steps in homologous recombination consistent with p97-driven Ku release also affecting repair pathway choice. Thus, our data solve a central question regarding regulation of Ku in DSB repair, and illustrate the ability of p97 to segregate even tightly bound protein complexes for release from DNA.

Charged up: Three-dimensional architectures constructed from graphene/MoS2 nanoflake arrays have been successfully fabricated by a one-step hydrothermal method. MoS2 nanoflakes with thicknesses less than 13 nm grow vertically on both sides of graphene sheets (see figure), which allows the architectures to be more stable during charging and discharging. Even at a high current density of 8000 mA g(-1), their discharge capacity is still up to 516 mA h g(-1).