AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1-/- mice.

The SLC6A1 gene encodes the gamma-aminobutyric acid (GABA) transporter GAT-1, the deficiency of which is associated with infantile encephalopathy with intellectual disability. We designed two AAV9 vectors, with either the JeT or MeP promoter, and conducted preclinical gene therapy studies using heterozygous and homozygous Slc6a1 KO mice at different developmental ages and various routes of administration. Neonatal intracerebroventricular administration of either vector resulted in significantly normalized EEG patterns in Slc6a1-/- or Slc6a1+/- mice, as well as improvement in several behavioral phenotypes of Slc6a1-/- mice.

Emplacement of the Franklin large igneous province and initiation of the Sturtian Snowball Earth.

During the Cryogenian (720 to 635 Ma ago) Snowball Earth glaciations, ice extended to sea level near the equator. The cause of this catastrophic failure of Earth's thermostat has been unclear, but previous geochronology has suggested a rough coincidence of glacial onset with one of the largest magmatic episodes in the geological record, the Franklin large igneous province. U-Pb geochronology on zircon and baddeleyite from sills associated with the paleo-equatorial Franklin large igneous province in Arctic Canada record rapid emplacement between 719.

Oral anticoagulation use in non-valvular atrial fibrillation patients in rural setting.

Background: The 2019 ACC/AHA/HRS guidelines established direct oral anticoagulants (DOACs) as first line therapy over warfarin for non-valvular atrial fibrillation (AF).

Methods: Ambulatory clinic patients with non-valvular AF or atrial flutter seen between 10/1/2019-7/12/2020 included. High-risk AF defined as males CHADS-VASc score ≥2 and females ≥3.

Zircon dating of oceanic crustal accretion.

Most of Earth's present-day crust formed at mid-ocean ridges. High-precision uranium-lead dating of zircons in gabbros from the Vema Fracture Zone on the Mid-Atlantic Ridge reveals that the crust there grew in a highly regular pattern characterized by shallow melt delivery. Combined with results from previous dating studies, this finding suggests that two distinct modes of crustal accretion occur along slow-spreading ridges.