ABSTRACT
In this work, we have developed an ESIPT-based benzimidazole platform (MO-E1 and MO-E2) for the two-photon cell imaging of ONOO- and a potential ONOO--activated theranostic scaffold (MO-E3). Each benzimidazole platform, MO-E1-3, were shown to rapidly detect ONOO- at micromolar concentrations (LoD = 0.28 µM, 6.53 µM and 0.81 µM respectively). The potential theranostic MO-E3 was shown to release the parent fluorophore and drug indomethacin in the presence of ONOO- but unfortunately did not perform well in vitro due to low solubility. Despite this, the parent scaffold MO-E2 demonstrated its effectiveness as a two-photon imaging tool for the ratiometric detection of endogenous ONOO- in RAW264.7 macrophages and rat hippocampus tissue. These results demonstrate the utility of this ESIPT benzimidazole-based platform for theranostic development and bioimaging applications.
ABSTRACT
Understanding childhood experiences of health and well-being is essential to reconstructing ancient life-ways. Here, archaeological hair samples from five juveniles from Cahuachi and near Huaca del Loro in the Nasca Region, Peru, are analyzed for their carbon- and nitrogen-isotope compositions and cortisol levels. Stable isotopic data are used to investigate dietary change and nitrogen metabolism, and cortisol levels are used to infer exposure to stress. Using a case study approach, we determined that juveniles have distinct, individualized experiences of diet and morbidity, which are, in some cases, similar to adult experiences in the same region. Overall, Nasca Region juveniles have high systemic cortisol levels (1444±402ng/g) compared to Peruvian adults (281±35ng/g; Webb et al., 2010). Younger juveniles have comparatively high δ15N values that decrease over several months, suggesting transition from breast milk to a weaning diet. Older juveniles exhibit patterns of dietary shifting similar to those determined for adults in the region, or suggestive of particular socioeconomic roles. This study demonstrates the value of applying biomolecular methods to juvenile mummified remains to better understand the life histories of children in archaeological contexts.
ABSTRACT
Archeological hair from 14 adults from the Nasca Region, Peru (c. AD1-1000) was analyzed for carbon and nitrogen isotopic compositions and cortisol levels. We investigated the relationship between isotopic compositions, which reflect diet, and cortisol, which reflects biogenic cortisol production and chronic stress. Using a case study approach, we determined that there are consistent changes in cortisol production associated with the rapid dietary change characteristic of local mobility. Moreover, changes in nitrogen- and carbon-isotope compositions, when integrated with cortisol levels, enabled inferences to be made about nitrogen metabolism and carbon routing, and elucidated the nature of potential stressors in the months before death. The isotopic and cortisol data suggested a relatively high rate of exposure to stress that is consistent with what is known about the Nasca Region social and physical environments. Of the 14 adults included in this study, six likely suffered from illness/trauma before death, and a further three experienced stress without an observable associated change in isotopic composition. Five individuals also experienced increased stress related to local mobility, inferred from co-occurring changes in cortisol production and dietary shifting. The integration of cortisol and isotopic data revealed individual characteristics of hidden frailty and risk that would not be apparent using more traditional methods of evaluating health status. This approach will provide a powerful enhancement to the understanding of stress, morbidity, and well-being developed through skeletal analysis.