Manuring and stable nitrogen isotope ratios in cereals and pulses: towards a new archaeobotanical approach to the inference of land use and dietary practices

This paper explores the impact of animal manure application on the δ15N values of a broad range of crops (cereals and pulses), under a range of manuring levels/regimes and at a series of locations extending from northwest Europe to the eastern Mediterranean. We included both agricultural field experiments and areas where ‘traditional’ farming is practised. Our aim is to ground-truth interpretation of δ15N values in archaeobotanical crop remains as evidence of past growing conditions and husbandry practices. The results confirm the potentially radical impact of manuring on δ15N values in cereals, depending on manuring level, but indicate only a slight effect on pulses, which can fix atmospheric nitrogen. The expected geographical trend towards greater δ15N with increasing climatic aridity is not apparent, probably because the growing conditions for crops are ‘buffered’ through crop management. Each of these observations has fundamental implications for archaeobotanical interpretation of δ15N values as evidence of land use practices and (together with analysis of bone collagen/tooth enamel in potential consumers) palaeodiet

Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia

Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors constituted a highly aberrant, disease-defining compartment: their gene expression and differentiation state affected both the chemotherapy response and leukemia's ability to differentiate into transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers misregulated specifically in leukemic cells. Taken together, CloneTracer reveals a differentiation landscape that mimics its healthy counterpart and may determine biology and therapy response in AML