Multi-wavelength quantitative polarization and phase microscope

We introduce a snapshot multi-wavelength quantitative polarization and phase microscope (MQPPM) for measuring spectral dependent quantitative polarization and phase information. The system uniquely integrates a polarized light microscope and a snap-shot quantitative phase microscope in a single system, utilizing a novel full-Stokes camera operating in the red, green, and blue (RGB) spectrum. The linear retardance and fast axis orientation of a birefringent sample can be measured simultaneously in the visible spectra. Both theoretical analysis and experiments have been performed to demonstrate the capability of the proposed microscope. Data from liquid crystal and different biological samples are presented. We believe that MQPPM will be a useful tool in measuring quantitative polarization and phase information of live cells. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing AgreementNational Science Foundation (NSF) [1455630, 1607358]; National Institutes of Health (NIH) [S10OD018061]; TRIF Space Exploration & Optical Sciences (SEOS) of University of ArizonaOpen access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer

BACKGROUND: Recently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC). METHODS: Flow cytometry was used to determine the expression of interferon gamma (IFN-gamma), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-alpha and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-alpha were examined. RESULTS: Th22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-alpha and IL-6 was significantly high in CC patients. CONCLUSIONS: Our results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch

Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb)-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point). We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse- or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths

Curcumin derivative C212 inhibits Hsp90 and eliminates both growing and quiescent leukemia cells in deep dormancy

Background: Relapsed leukemia following initial therapeutic response and remission is difficult to treat and causes high patient mortality. Leukemia relapse is due to residual quiescent leukemia cells that escape conventional therapies and later reemerge. Eliminating not only growing but quiescent leukemia cells is critical to effectively treating leukemia and preventing its recurrence. Such dual targeting therapeutic agents, however, are lacking in the clinic. To start tackling this problem, encouraged by the promising anticancer effects of a set of curcumin derivatives in our earlier studies, we examined in this work the effects of a 4-arylmethyl curcumin derivative (C212) in eliminating both growing and quiescent leukemia cells. Methods: We analyzed the effects of C212 on the growth and viability of growing and quiescent leukemia cells using MTS, apoptosis, cell cycle and cell tracking assays. The effects of C212 on the quiescence depth of leukemia cells were measured using EdU incorporation assay upon growth stimulation. The mechanisms of C212-induced apoptosis and deep dormancy, particularly associated with its inhibition of Hsp90 activity, were studied using molecular docking, protein aggregation assay, and Western blot of client proteins. Results: C212, on the one hand, inhibits growing leukemia cells at a higher efficacy than curcumin by inducing apoptosis and G2/M accumulation; it, on the other hand, eliminates quiescent leukemia cells that are resistant to conventional treatments. Furthermore, C212 drives leukemia cells into and kills them at deep quiescence. Lastly, we show that C212 induces apoptosis and drives cells into deep dormancy at least partially by binding to and inhibiting Hsp90, leading to client protein degradation and protein aggregation. Conclusion: C212 effectively eliminates both growing and quiescent leukemia cells by inhibiting Hsp90. The property of C212 to kill quiescent leukemia cells in deep dormancy avoids the risk associated with awaking therapy-resistant subpopulation of quiescent leukemia cells during treatments, which may lead to the development of novel therapies against leukemia relapse.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Exit from quiescence displays a memory of cell growth and division

Reactivating quiescent cells to proliferate is critical to tissue repair and homoeostasis. Quiescence exit is highly noisy even for genetically identical cells under the same environmental conditions. Deregulation of quiescence exit is associated with many diseases, but cellular mechanisms underlying the noisy process of exiting quiescence are poorly understood. Here we show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history before quiescence entry, and that such a memory is reflected in cell size at a coarse scale. The deterministic memory effects of preceding cell cycle, coupled with the stochastic dynamics of an Rb-E2F bistable switch, jointly and quantitatively explain quiescence-exit heterogeneity. As such, quiescence can be defined as a distinct state outside of the cell cycle while displaying a sequential cell order reflecting preceding cell growth and division variations.NSF [DMS1463137, DMS1418172]; NSF of China and Anhui Province [31500676, 1508085SQC202]; NIH [CA09213, GM084905]; DARPA [WF911NF-14-1-0395]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]