Project description:Abstract: The imbalance of prenatal micronutrients may perturb one-carbon (C1) metabolism and increase the risk for neuropsychiatric disorders. Prenatal excessive methionine (MET) produces in mice behavioral phenotypes reminiscent of human schizophrenia. Whether in-utero programming or early life caregiving mediate these effects is, however, unknown. Here, we show that the behavioral deficits of MET are independent of the early life mother-infant interaction. We also show that MET produces in early life profound changes in the brain C1 pathway components as well as glutamate transmission, mitochondrial function, and lipid metabolism. Bioinformatics analysis integrating metabolomics and transcriptomic data reveal dysregulations of glutamate transmission and lipid metabolism, and identify perturbed pathways of methylation and redox reactions. Our transcriptomics Linkage analysis of MET mice and schizophrenia subjects reveals master genes involved in inflammation and myelination. Finally, we identify potential metabolites as early biomarkers for neurodevelopmental defects and suggest new therapeutic targets for schizophrenia.
Project description:To determine gene expression differences in the olfactory epithelium of sea lamprey between sequential yet behaviorally distinct adult life history stages 2 samples: parasitic adults removed from fish in northern Lake Huron and Lake Michigan in February and March, and reproductive adults collected from Lake Huron and Lake Michigan tributaries in June
Project description:The International Space Exploration Coordination Group has set a roadmap whose long-range strategy envisions the first human settlements on Mars by 2040. In this scenario, finding ways to exploit the local resources for the provision of food, construction materials, propellants, pharmaceuticals is an urgent need. Plants are important resources for deep space manned missions because they produce phytochemicals of pharmaceutical relevance, are sources of food and perform photosynthesis, thus providing oxygen which is crucial in bioregenerative life support systems (BLSS). Growth analysis and plant biomass yield have been previously evaluated on Martian regolith simulants, but molecular studies, such as gene expression analysis and protein profiling are still missing. The present work aims at filling this gap by providing molecular data on a representative member of the Poaceae, Lolium multiflorum Lam., grown on normal soil and Martian regolith simulant (MMS-1). The molecular data were complemented with optical microscopy of root/leaf tissues and soil physico-chemical analyses.
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: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.