Acute ischemic stroke on anti-Xa inhibitors: Pharmacokinetics and outcomes.

Background And Purpose: Direct oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use.

Methods: This is a single center retrospective study of consecutive patients with AIS within 4.

Synergistic interactions with PI3K inhibition that induce apoptosis.

Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a mutant human breast cancer cell.

LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation.

LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors.

Molecular basis for interaction of let-7 microRNAs with Lin28.

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis.