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Improved Detection By Ensemble-Decision Aliquot Ranking Of Circulating Tumor Cells With Low Numbers Of A Targeted Surface Antigen, Eleanor S. Johnson, Robbyn K. Anand, Daniel T. Chiu
Improved Detection By Ensemble-Decision Aliquot Ranking Of Circulating Tumor Cells With Low Numbers Of A Targeted Surface Antigen, Eleanor S. Johnson, Robbyn K. Anand, Daniel T. Chiu
Robbyn Anand
Circulating tumor cells (CTCs) are shed from a solid tumor into the bloodstream and can seed new metastases. CTCs hold promise for cancer diagnosis and prognosis and to increase our understanding of the metastatic process. However, their low numbers in blood and varied phenotypic characteristics make their detection and isolation difficult. One source of heterogeneity among CTCs is molecular: When they leave the primary tumor, these cells must undergo a molecular transition, which increases their mobility and chance of survival in the blood. During this molecular transition, the cells lose some of their epithelial character, which is manifested by the …
Large Interdomain Rearrangement Triggered By Suppression Of Micro- To Millisecond Dynamics In Bacterial Enzyme I, Vincenzo Venditti, Vitali Tugarinov, Charles D. Schwieters, Alexander Grishaev, G. Marius Clore
Large Interdomain Rearrangement Triggered By Suppression Of Micro- To Millisecond Dynamics In Bacterial Enzyme I, Vincenzo Venditti, Vitali Tugarinov, Charles D. Schwieters, Alexander Grishaev, G. Marius Clore
Vincenzo Venditti
Enzyme I (EI), the first component of the bacterial phosphotransfer signal transduction system, undergoes one of the largest substrate-induced interdomain rearrangements documented to date. Here we characterize the perturbations generated by two small molecules, the natural substrate phosphoenolpyruvate and the inhibitor a-ketoglutarate, on the structure and dynamics of EI using NMR, small-angle X-ray scattering and biochemical techniques. The results indicate unambiguously that the open-to-closed conformational switch of EI is triggered by complete suppression of micro- to millisecond dynamics within the C-terminal domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to a more rigid conformational state …