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Identifying Methylation Patterns in Dental Pulp Aging: Application to Age-at-Death Estimation in Forensic AnthropologyAge-at-death estimation constitutes one of the key parameters for identification of human remains in forensic investigations. However, for applications in forensic anthropology, many current methods are not sufficiently accurate for adult individuals, leading to chronological age estimates erring by ±10 years. Based on recent trends in aging studies, DNA methylation has great potential as a solution to this problem. However, there are only a few studies that have been published utilizing DNA methylation to determine age from human remains. The aim of the present study was to expand the range of this work by analyzing DNA methylation in dental pulp from adult individuals. Healthy erupted third molars were extracted from individuals aged 22–70. DNA from pulp was isolated and bisulfite converted. Pyrosequencing was the chosen technique to assess DNA methylation. As noted in previous studies, we found that ELOVL2 and FHL2 CpGs played a role in age estimation. In addition, three new markers were evaluated—NPTX2, KLF14, and SCGN. A set of CpGs from these five loci was used in four different multivariate regression models, providing a Mean Absolute Error (MAE) between predicted and chronological age of 1.5–2.13 years. The findings from this research can improve age estimation, increasing the accuracymore »
α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraineDespite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure–function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization. Furthermore, while CGRP and/or amylin monomers reduce the secretion of both mouse Ins1 and Ins2 proteins, CGRP oligomers have a reverse effect on Ins1. Genetically reduced Ins2, the orthologous version of human insulin, has been shown to enhance insulin sensitivity and extend the life-span in old female mice. Beyond the mechanistic insights, our data suggest that CGRP regulates insulin secretion and lowers the risk of T2DM. Our result rationalizes how migraine might be protective against T2DM. We envision the new paradigm of CGRP : amylin interactions as a pivotal aspect for T2DM diagnostics and therapeutics. Maintaining a low level of amylin while increasing the level of CGRP could become a viable approach toward T2DM prevention and treatment.