First, the Co/TPP/RGO complex allows improved tooth bleaching and shorter treatment times. Second, because the Co/TPP/RGO complex bleached D&C Red 34 at a similar rate and to a similar degree as tea and other natural agents stain teeth, it is a convenient staining agent for studying many vital aspects of tooth bleaching. (J Esthet Restor Dent 28:321-329, 2016).
The ability to identify and characterize individual biomarker protein molecules in patient blood samples could enable diagnosis of diseases at an earlier stage, when treatment is typically more effective. Single-molecule imaging offers a promising approach to accomplish this goal. However, thus far single-molecule imaging methods have only been used to monitor protein molecules in solutions or cell lysates, and have not been translated into the clinical arena. Furthermore, the detection limit of these methods has been confined to the picomolar (10-12 M) range. In many diseases, the circulating concentrations of biomarker proteins fall several orders of magnitude below this range. Here we describe Single-Molecule Augmented Capture (SMAC), a single-molecule imaging technique to visualize, quantify, and characterize individual protein molecules of interest down to the subfemtomolar (<10-15 M) range, even in complex biologic fluids. We demonstrate SMAC in a wide variety of applications with human blood samples, including the analysis of disease-associated secreted proteins, membrane proteins, and rare intracellular proteins. Using ovarian cancer as a model, a lethal malignancy in which high-grade disease is driven almost universally by alterations in the TP53 gene and frequently only diagnosed at a late, incurable stage, we found that mutant pattern p53 proteins are released into the blood in patients at an early stage in disease progression. SMAC opens the door to the application of single-molecule imaging in non-invasive disease profiling and allows for the analysis of circulating mutant proteins as a new class of highly specific disease biomarkers. The SMAC platform can be adapted to multiplex or high-throughput formats to characterize heterogeneous biochemical and structural features of circulating proteins-of-interest.
drug discovery is their immature state relative to the adult myocardium. In this research, 3D cardiac microtissues (CMTs) were generated using hiPSC-CMs to recapitulate the structural, functional and metabolic properties of normal and diseased adult ventricular myocardium. CMTs were treated with ontologically defined biochemical interventions (thyroid hormone, dexamethasone and insulin-like growth factor, TDI) to promote the maturation of hiPSC-CMs. The effects of TDI treatment on both structural and functional (biomechanical, Ca2þ handling and electrophysiology) properties at the tissue level were characterized. Also, the molecular correlates of maturation of the hiPSC-CMs in the CMTs were studied by gene expression, proteomics studies. Our data demonstrate that TDI treatment improves both the structure and function of CMTs. Structurally, the hiPSC-CMs show improved alignment and longer sarcomere length, as shown by immunofluorescence and confocal microscopy. Functionally, CMTs' static and dynamic force both increase following TDI treatment, and cardiac electrophysiology assessed by optical mapping showing that the CMTs are electrically coupled. TDI-treated CMTs exhibited both chronotropic and inotropic response to isoproterenol treatment. The enhanced functional properties that this maturation approach yields have the potential to yield improved hiPSC derived cardiac model systems that can advance both mechanistic studies and the development of new therapies for the treatment of cardiac diseases.
Antiviral treatment for human cytomegalovirus (HCMV) is limited and suffers from the selection of drug-resistant viruses. Several cellular pathways have been shown to modulate HCMV replication.
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