Project description:Paget disease of bone (PDB) is a chronic skeletal disorder with contemporary cases characterised by one or a few affected bones in individuals over 55 years of age. PDB-like changes have been noted in archaeological remains as old as Roman although accurate diagnoses and knowledge of the natural history of ancient forms of the disease are lacking. Previous macroscopic and radiographic analyses of six skeletons from a collection of 130 excavated at Norton Priory in Cheshire, UK, and dating to late Medieval times, noted unusually extensive pathological changes resembling PDB affecting up to 75% of individual skeletons. Here we report the prevalence of the disease in the collection is also remarkably high (at least 15.8% of the adult sample) with age-at-death estimations as low as 35 years. Despite these profound phenotypic differences paleoproteomic analyses identified SQSTM1/p62 (p62), a protein central to the pathological milieu of classical PDB, as one of the few non-collagenous human sequences preserved in skeletal samples, indicating that the disorder was likely an ancient precursor of contemporary PDB. Western blotting indicated abnormal migration of ancient p62 protein, with subsequent targeted proteomic analyses detecting more than 60% of the p62 primary sequence and directing sequencing analyses of ancient DNA that excluded contemporary PDB-associated SQSTM1 mutations. Together our observations indicate the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated (UBA) domain. Ancient miRNAs were also remarkably well preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression changes consistent with that reported in contemporary PDB-associated bone tumours. Our work demonstrates the potential of proteomics to inform diagnoses of ancient disease and supports the proposal that Medieval Norton Priory was a ‘hotspot’ for an ancient form of PDB, with unusual features presumably potentiated by as yet unidentified environmental or genetic factors.
Project description:To investigate dairy consumption in ancient Mongolia, we analysed dental calculus samples from four Late Bronze Age (LBA, 1500-1000 BCE) individuals for proteomic evidence of milk proteins. As many archaeological sites before Mongolia's Iron Age suffer from a dearth of occupational materials, looking to biomolecular markers of dietary intake can open new investigational avenues into ancient economies. In this case, we use a previously established method of extracting proteins from calculus to explore the consumption of dairy products at LBA Khirigsuur sites in northern Mongolia's Hovsgol Aimag. Seven of nine individual's calculus contained peptides from the whey protein Beta-lactoglobulin from Ovis, Capra hircus, Bos, and general Bovidae species. Aside from proteomics, these and 16 other individuals from the site were analysed for aDNA. We found that 18 of the 20 were primarily from one genetic ancestral group, and Ancient North Eurasian (ANE). One of the outliers represents a combination of ANE and Western Steppe Herder (WSH), with the other a combination of ANE and Eastern Asian (EE). This finding, while important in its own right, evidences the earliest known dairy consumption in Mongolia, and supports a widely held assumption that pastoralism was a primary subsistence strategy in the ancient Eastern Steppes. The combined proteomic and DNA evidence suggest that Western Steppe dairy animals and technology entered Mongolia before genetic admixture.
Project description:Archaeological dental calculus has emerged as a rich source of ancient biomolecules, including proteins. Previous analyses of proteins extracted from ancient dental calculus revealed the presence of the dietary milk protein β-lactoglobulin, providing direct evidence of dairy consumption in the archaeological record. However, the potential for calculus to preserve other food-related proteins has not yet been systematically explored. Here we analyse shotgun metaproteomic data from 100 archaeological dental calculus samples ranging from the Iron Age to the post-medieval period (8thC BC - 19thC AD) in Britain, as well as dental calculus from contemporary dental patients and recently deceased individuals, to characterise the range and extent of dietary proteins preserved in dental calculus. In addition to milk proteins, we detected proteomic evidence of foodstuffs such as cereals and plant products, as well as the digestive enzyme salivary amylase. We discuss the importance of optimized protein extraction methods, data analysis approaches, and authentication strategies in the identification of dietary proteins from archaeological dental calculus. Our ability to detect dietary proteins, although limited, demonstrates the potential of these methods to robustly identify foodstuffs in the archaeological record that are under-represented due to their poor preservation.
2018-07-18 | PXD009603 | Pride
Project description:Ancient human genomes from Late Bronze Age Mongolia
Project description:For thousands of years, the Eurasian steppe has been a centre for human migrations and cultural changes. To understand its population history following the Bronze Age migrations, 137 ancient humans were sequenced. These ancient DNA sequences were notably compared to the genetic data of present-day populations from Eurasia. Besides already published data, 502 individuals currently living in Inner Asia and Jordania were sampled and newly genotyped on diverse DNA-arrays. These new data, merged as a single dataset of 242,406 autosomal SNPs, are included in the present ENA study.
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.