Notch receptors transmit signals between adjacent cells. Signaling is initiated when ligand binding induces metalloprotease cleavage of Notch within an extracellular negative regulatory region (NRR). We present here the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited conformation. Extensive interdomain interactions within the NRR bury the metalloprotease site, showing tha...

Fast-twitch skeletal muscles are specialized for in vivo motor functions that require high power (mastication and load lifting), high speed (eyelid blink), or a combination of the two (withdrawal reflexes and escape responses). Those functions that rely on high power often involve tetanic stimulation of the effector muscles, resulting in sustained force generation even during tetani that are no...

The migration patterns of naive and activated T cells are associated with the expression of distinct sets of chemokine receptors, but the molecular basis for this regulation is unknown. Here we identify Krupple-like factor 2 (KLF2) as a key transcriptional factor needed to prevent naive T cells from expressing inflammatory chemokine receptors and acquiring the migration patterns of activated T ...

Fast-twitch skeletal muscles are specialized for in vivo motor functions that require high power (mastication and load lifting), high speed (eyelid blink), or a combination of the two (withdrawal reflexes and escape responses). Those functions that rely on high power often involve tetanic stimulation of the effector muscles, resulting in sustained force generation even during tetani that are no...

We developed an adenoviral vector, in which Yamanaka’s four reprogramming factors (RFs) were controlled by individual CMV promoters in a single cassette (Ad-SOcMK). This permitted coordinated expression of RFs (SOX2, OCT3/4, c-MYC and KLF4) in a cell for a transient period of time, synchronizing the reprogramming process with the majority of transduced cells assuming induced pluripotent stem ce...

Fast-twitch skeletal muscles are specialized for in vivo motor functions that require high power (mastication and load lifting), high speed (eyelid blink), or a combination of the two (withdrawal reflexes and escape responses). Those functions that rely on high power often involve tetanic stimulation of the effector muscles, resulting in sustained force generation even during tetani that are no...

INTRODUCTION Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 t...