Biomarker system for studying muscle, stem cells, and cancer in vivo.

Bioluminescent reporter genes are sensitive in situ tools for following disease progression in preclinical models, albeit they are subject to scattering and absorption in deep tissues. We have generated a bicistronic Cre/LoxP reporter mouse line that pairs the expression of firefly luciferase with quantifiable expression of a human placental alkaline phosphatase that is secreted into the serum (SeAP). With the use of this dual-modality bioreporter with a novel, inducible Pax7-CreER line for tracking muscle satellite cells, we demonstrate the longitudinal kinetics of muscle stem cell turnover, accounting for a doubling of the signal from satellite cell and progeny every 3.

Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: a report from the Children's Oncology Group.

Background: Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. In this study we sought to identify gene expression signatures of advanced stage and progressive disease.

Procedure: Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV.

Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not regulated through oligomerization.

Intramembrane cleaving proteases such as site 2 protease, gamma-secretase, and signal peptide peptidase hydrolyze peptide bonds within the transmembrane domain (TMD) of signaling molecules such as SREBP, Notch, and HLA-E, respectively. All three enzymes require a prior cleavage at the juxtamembrane region by another protease. It has been proposed that removing the extracellular domain allows dissociation of substrate TMD, held together by the extracellular domain or loop.