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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 Aug 2015

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 …


Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena Jun 2015

Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena

Ryan C. Smith

Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of …


Repeated Stressors In Adulthood Increase The Rate Of Biological Ageing, Michaela Hau, Mark F. Haussmann, Timothy J. Greives, Christa Matlack, David Costantini, Michael Quetting, James S. Adelman, Ana C. Miranda, Jesko Partecke Jan 2015

Repeated Stressors In Adulthood Increase The Rate Of Biological Ageing, Michaela Hau, Mark F. Haussmann, Timothy J. Greives, Christa Matlack, David Costantini, Michael Quetting, James S. Adelman, Ana C. Miranda, Jesko Partecke

James S. Adelman

Individuals of the same age can differ substantially in the degree to which they have accumulated tissue damage, akin to bodily wear and tear, from past experiences. This accumulated tissue damage reflects the individual’s biological age and may better predict physiological and behavioural performance than the individual‘s chronological age. However, at present it remains unclear how to reliably assess biological age in individual wild vertebrates. We exposed hand-raised adult Eurasian blackbirds (Turdus merula) to a combination of repeated immune and disturbance stressors for over one year to determine the effects of chronic stress on potential biomarkers of biological ageing including …


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 Jan 2015

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 …