Project description:We present the analysis of an osseous finger ring from an early Neolithic context in Denmark. To characterise the artefact and identify the raw material used for its manufacture, we performed micro-computed tomography (Micro CT) scanning, zooarchaeology by mass spectrometry (ZooMS) peptide mass fingerprinting, as well as protein sequencing by liquid chromatography tandem mass spectrometry (LC-MS/MS). We found that the ring was made from long bone or antler due to the presence of osteons (Haversian canals). Subsequent ZooMS analysis of the collagen present indicated that it was made from either elk (Alces alces) or red deer (Cervus elaphus) material. We then used LC-MS/MS analysis to refine our species identification, confirming that the ring was made from red deer, and to examine other proteins present. This study demonstrates the potential of ancient proteomics for species identification of prehistoric artefacts made from osseous material.
Project description:Huntington’s disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27 acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.
Project description:Treponeme-associated hoof disease (TAHD) is an emerging disease of elk (Cervus canadensis) in the U.S. Pacific West. Because environmental epigenetics is the primary molecular process that mediates environmental factor impacts on a host organism and disease, the role of epigenetics in TAHD etiology was examined. The current study was designed to examine potential effects of TAHD on systemic epigenetic modifications in infected elk over a range of TAHD lesion severity. Leg tendons that contain predominantly fibroblast connective tissue cells were used to isolate fibroblast cells for epigenetic analysis in unaffected and TAHD-positive male and female Roosevelt and Rocky Mountain elk. DNA methylation in the tendon cells in the different groups was examined. Differential DNA methylation regions (DMRs) between the unaffected and TAHD-positive were identified for both female and male elk. The presence of TAHD was associated with alteration of the connective tissue cell epigenetics and DMR associated genes identified. Therefore, the infected elk were found to have a systemic epigenetic alteration that was associated with the disease despite TAHD pathology being generally limited to feet. Other cell populations with the elk are also anticipated to be affected, and if the elk germline epigenetics is altered then generational transmission of susceptibility to TAHD may impact subsequent generations through epigenetic inheritance. This first study of epigenetic changes associated with disease in elk suggests that TAHD promotes a systemic effect on the elk epigenetics which could exert health impacts on the elk.