Slave Subsistence Strategies at Thomas Jefferson’s Monticello Plantation: Paleoethnobotanical Analysis and Interpretation of the Site 8 (44AB442) Macrobotanical Assemblage

Throughout the seventeenth to nineteenth centuries, millions of enslaved Africans and African Americans were crucial to the success of plantations in the American South, but despite their numbers little exists in the written record to provide an accurate history for the African American slave community. However, archaeological and historic research shows that even under the constraints of slavery, enslaved African Americans were active in forming their own families and communities, countering ill-treatment and nutritional deprivation, maintaining their cultural and spiritual identities, and establishing ways to enhance their well-being. The research presented in this study emphasizes the utility of studying carbonized plant remains recovered from slave quarters to draw conclusions that contribute to our understanding of the lifeways of the enslaved in late eighteenth-century Virginia. The primary focus of this study is Site 8 (44AB442), a late eighteenth-century slave quarter occupied by the field laborers of Thomas Jefferson’s Monticello plantation. Jefferson transformed Monticello from a tobacco plantation to a wheat plantation in the early 1790s, resulting in major alterations to both the landscape and the labor system. Agricultural labor systems implemented by planters and overseers largely impacted slaves’ free time, and consequently affected their domestic pursuits. Theories borrowed from human behavioral ecology have been applied to this study to interpret the Site 8 macrobotanical assemblage in order to better understand how the agricultural shift from commercial tobacco production to commercial wheat production affected the subsistence behaviors of the Site 8 occupants. Borrowing from Tucker (2006), a model based on future discounting theory is applied to the Site 8 macrobotanical assemblage to explain observable patterns pointing to a mixed foraging/low-investment horticulture subsistence strategy employed by the Site 8 occupants to balance nutritional stress and add variety to their diets

A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists

High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical charac teristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect

Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts

Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial. Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by cross-polymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using student's t-test or two-way ANOVA. Results: We succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%. Conclusion: In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies. © 2019 The Author(s)

Morphodynamic controls for growth and evolution of a rubble coral island

Rubble islands are dynamic sedimentary features present on reef platforms that evolve under a variety of morphodynamic processes and controlling mechanisms. They provide valuable inhabitable land for small island nations, critical habitat for numerous species, and are threatened by climate change. Aiming to investigate the controlling mechanisms dictating the evolution of One Tree Island (OTI), a rubble island in the Southern Great Barrier Reef, we combined different remotely-sensed data across varying timescales with wave data extracted from satellite altimetry and cyclone activity. Our findings show that (1) OTI had expanded by 7% between 1978 and 2019, (2) significant gross planform decadal adjustments were governed by the amount, intensity, proximity, and relative position of cyclones as well as El Niño Southern Oscillation (ENSO) phases, and (3) the mechanisms of island growth involve rubble spits delivering and redistributing rubble to the island through alongshore sediment transport and wave overtopping. Frequent short-term monitoring of the island and further research coupling variations in the different factors driving island change (i.e., sediment availability, reef-wave interactions, and extreme events) are needed to shed light on the future trajectory of OTI and other rubble islands under a climate change scenario

A Food Frequency Questionnaire for the Assessment of Calcium, Vitamin D and Vitamin K: A Pilot Validation Study

The study objective was to validate a food frequency questionnaire (FFQ) to assess calcium, vitamin D and vitamin K intakes in overweight and obese postmenopausal community-dwelling women. The FFQ was validated against intakes derived from a 5-day diet record (5DDR) that also included assessment of supplement intake. Strong correlations between methods were observed for all nutrients (r = 0.63, 0.89, 0.54 for calcium, vitamin D and vitamin K, respectively) and cross-classification analyses demonstrated no major misclassification of participants into intake quartiles. Bland-Altman analysis showed that the FFQ overestimated intakes for calcium, by 576 mg/day (95% CI, −668 to 1,821 mg/day), for vitamin D by 75 IU/day (95% CI, −359 to 510 IU/day), and forvitamin K by 167 mcg/day (95% CI, −233 to 568 mcg/day). This pilot study showed promising validation evidence for the use of this FFQ, which focuses on calcium, vitamin D and vitamin K intakes in postmenopausal women, as a screening tool in clinicaland research settings

Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability

Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy

Tumor-derived lactic acid inhibits T and natural killer (NK) cell function and, thereby, tumor immunosurveillance. Here, we report that melanoma patients with high expression of glycolysis-related genes show a worse progression free survival upon anti-PD1 treatment. The non-steroidal anti-inflammatory drug (NSAID) diclofenac lowers lactate secretion of tumor cells and improves anti-PD1-induced T cell killing in vitro. Surprisingly, diclofenac, but not other NSAIDs, turns out to be a potent inhibitor of the lactate transporters monocarboxylate transporter 1 and 4 and diminishes lactate efflux. Notably, T cell activation, viability, and effector functions are preserved under diclofenac treatment and in a low glucose environment in vitro. Diclofenac, but not aspirin, delays tumor growth and improves the efficacy of checkpoint therapy in vivo. Moreover, genetic suppression of glycolysis in tumor cells strongly improves checkpoint therapy. These findings support the rationale for targeting glycolysis in patients with high glycolytic tumors together with checkpoint inhibitors in clinical trials