Supramolecular nanostructures with tunable properties can have applications in medicine, pharmacy, and biotechnology. In this work, we show that the self-assembly behavior of peptide amphiphiles (PAs) can be effectively tuned by replacing the carboxylic acids exposed to the aqueous media with isosteres, functionalities that share key physical or chemical properties with another chemical group. Transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering studies indicated that the nanostructure’s morphologies are responsive to the ionization states of the side chains, which are related to their pK a values. Circular dichroism studies revealed the effect of the isosteres on the internal arrangement of the nanostructures. The interactions between diverse surfaces and the nanostructures and the effect of salt concentration and temperature were assessed to further understand the properties of these self-assembled systems. These results indicate that isosteric replacements allow the pH control of supramolecular morphology by manipulating the pK a of the charged groups located on the nanostructure’s surface. Theoretical studies were performed to understand the morphological transitions that the nanostructures underwent in response to pH changes, suggesting that the transitions result from alterations in the Coulomb forces between PA molecules. This work provides a strategy for designing biomaterials that can maintain or change behaviors based on the pH differences found within cells and tissues.

BACKGROUND AND OBJECTIVES: Within the field of pediatric hospital medicine, physicians can choose to work at community-based or university-based centers. The factors that motivate pediatric hospitalists to work specifically at community sites have not yet been fully explored. Our objective with this study was to elucidate the motivators for pediatric hospitalists to begin and continue work at community sites. METHODS: A qualitative study was performed via phone-based focus groups. Physicians were included if they were able to attend 1 of the offered group sessions and they self-identified as spending the majority of their time working as community-based pediatric hospitalists. Data were analyzed through a constant comparative analysis. RESULTS: Five themes emerged regarding factors that motivate pediatricians to begin and continue their careers as hospitalists in the community. The themes were (1) professional impact, (2) scope of practice, (3) personal and professional satisfaction, (4) community involvement, and (5) job availability.

we utilize single-molecule microscopy to localize and track fluorescently labeled chaperone and effector proteins in live Yersinia enterocolitica cells, a human pathogen in which the three phases of secretion can be physically and chemically controlled. By combining single-molecule tracking with bacterial genetics, we determine the prevalent diffusive states of chaperone proteins and chaperone:effector protein complexes in the presence and absence of their (putative) cytosolic binding partners. The results allow us to test whether the temporal hierarchy of secretion is regulated by cytosolic T3SS components that interact with chaperone:effector substrates either at the injectisome or while diffusing freely in the cytosol. Understanding the mechanism of temporally-ordered secretion may reveal new strategies for targeted anti-virulence therapies and enable the controlled use of T3SSs for therapeutic purposes.

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50,000 deaths each year. Despite major advances in treatment (i.e., surgery, radiation therapy, chemotherapy, biologic/immune therapy) and resultant improved outcomes over time, it has been demonstrated that failure of treatment in patients with metastatic breast cancer portends a poor prognosis. As the number of potential FDA-approved cancer drugs increases, the likelihood of identifying effective combination strategies tailored to an individual patient's tumor increases. Therefore, to provide significant advances in cancer treatment and enable the most effective chemotherapy, development of more quantitative and objective means for assessing drug sensitivity of an individual patient's tumor that is safer, faster, sensitive and capable for single-or multidrug testing is urgently needed for advancing personalized therapies. To develop such an approach, fluorescence spectroscopic technologies may serve as a non-invasive means of revealing cell health. We applied phasorfluorescence lifetime imaging microscopy (phasor-FLIM) to measure drug response using human colorectal cancer cell line HCT116 and patient samples. FLIM can be served as a promising new approach for reading the metabolic states of cancer cells treated with anti-cancer therapeutics and identified specific alterations of metabolic states that are early indicators of irreversible cell demise and that such metabolic changes can be detected using a labelfree imaging assay for single-cell drug testing of rare and/or heterogeneous cancer cells. Based on these findings, we apply the label-free imaging platform to measure drug response using patient samples.