The embodiment of status in the Mississippian component of the Perry site (1Lu25)

This thesis assesses the ways in which social status was embodied by the Mississippian period occupants of the Perry site (1LU25). Status, as indicated by various facets of mortuary goods, is examined alongside a suite of skeletal indicators of behavior including: linear enamel hypoplasia, stature, cribra orbitalia, porotic hyperostosis, dental caries, tibial periostitis, entheseal changes, degenerative joint disease, traumatic injuries, and cranial modification. In most cases there is no relationship between mortuary goods and skeletal indicators; however, dental caries and cranial modification do present significant statistical relationships with mortuary goods. These results suggest that Mississippian period occupants of the Perry site participated in a hierarchical socio-political organization that was embodied via daily practices. (Published By University of Alabama Libraries

Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe2O3-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term

Chromium: binding studies with transferrin and peptide eeeegdd and its effect on colorectal cancer

Chromium as the trivalent ion has been proposed as an essential element for decades. Although that status has recently been discredited, doses of Cr3+ have been shown to generate improvements in insulin sensitivity and blood cholesterol levels in animals that have problems with their glucose and lipid metabolism systems, especially in type 2 diabetic rodent models. The mechanism for these effects at a molecular level is unknown. Transferrins are a class of protein that can reversibly bind 2 equivalents of metal ions. Biologically, transferrins are the main iron transport proteins in plasma. A role for transferrin in the delivery Cr3+ from plasma to tissues has been proposed. Studies have shown that Cr3+ readily binds to the two metal-binding sites in the two lobes of apotransferrin. The Cr3+ binding is accompanied by intense changes in the transferrin’s ultraviolet spectrum. This intense changes arises from chromic ion binding to two tyrosine residues in the two iron-binding sites of transferrin and allow the binding of Cr3+ to transferrin to be monitored. The rate at which Cr3+ binds to transferrin and the stability of Cr-transferrin recently has received considerable attention. In vitro spectroscopic studies previously found that the generation of Cr2-transferrin needs two weeks to guarantee a stoichiometric amount of Cr3+ binding. However, this study indicates that in the presence of 25 mM (bi)carbonate, the concentration in human blood, two Cr3+ ions bind rapidly and tightly to apotransferrin. Glycation of transferrin alters how tightly the protein binds iron and may alter the conformation of diferric transferrin, presumably changing its ability to deliver the iron to tissues. Given that Cr3+ complexes has been proposed as nutritional supplements to improve symptoms of type 2 diabetic subjects, understanding the ability of glycated transferrin to bind and transport Cr is significant, especially for determining the appropriate dose of Cr. This study examined the binding ability of Cr3+ to glycated serum transferrin and the transport of Cr in vivo by glycated transferrin. The results suggest that glycation of transferrin in subjects with elevated blood glucose levels should lower the ability of Cr from pharmacological agents to enter tissues. Additionally, these studies with glycated transferrin also indicate that heat treatment of transferrin makes dramatic change on its conformation and Cr binding ability. (Published By University of Alabama Libraries

Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors.

PURPOSE: Modulation of vascular endothelial growth factor-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors. METHODS: Eligible patients had metastatic renal cell carcinoma (RCC), endometrial cancer, squamous cell carcinoma of the head and neck (SCCHN), melanoma, non-small-cell lung cancer (NSCLC), or urothelial cancer. The primary objective of phase Ib was to determine the maximum tolerated dose (MTD) for lenvatinib plus pembrolizumab (200 mg intravenously every 3 weeks). In the preplanned phase II cohort expansion, the primary objective was objective response rate at week 24 (ORR RESULTS: Overall, 137 patients were enrolled during phase Ib (n = 13) and the initial phase II expansion (n = 124). Two dose-limiting toxicities (DLTs; grade 3 arthralgia and grade 3 fatigue) were reported in the initial dose level (lenvatinib 24 mg/d plus pembrolizumab). No DLTs were observed in the subsequent dose-de-escalation cohort, establishing the MTD and recommended phase II dose at lenvatinib 20 mg/d plus pembrolizumab. ORR CONCLUSION: Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types