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Sijilmâsa (south‐east Morocco) was one of the most strategic cities in a far‐reaching exchange network, that is, the Trans‐Saharan trade, linking the Maghreb with West Africa during the medieval period (from the 8th to the 15th century CE). It was also one of the most important gold and silver monetary workshops at the time. If gold came from West Africa, we know from written sources that silver was produced in Morocco, although archaeological evidence of silver mining and smelting has remained elusive. Thanks to a thorough analysis of the lead isotopic data from silver mining districts in Morocco and from ores and slags of our study, we were able to refine the tracing of our materials and provide tangible evidence of medieval mining in the close hinterland of Sijilmâsa city. [ABSTRACT FROM AUTHOR]

Background: Inflammatory activation of CD8 + T cells can, when left unchecked, drive severe immunopathology. Hyperstimulation of CD8 + T cells through a broad set of triggering signals can precipitate hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disorder., Objective: The mechanism linking CD8 + T-cell hyperactivation to pathology is controversial, with excessive production of IFN-γ and, more recently, excessive consumption of IL-2, which are proposed as competing hypotheses. We formally tested the proximal mechanistic events of each pathway in a mouse model of HLH., Methods: In addition to reporting a complete autosomal recessive IFN-γ receptor 1-deficient patient with multiple aspects of HLH pathology, we used the mouse model of perforin (Prf1) KO mice infected with lymphocytic choriomeningitis virus to genetically eliminate either IFN-γ production or CD25 expression and assess the immunologic, hematologic, and physiologic disease measurement., Results: We found a striking dichotomy between the mechanistic basis of the hematologic and inflammatory components of CD8 + T cell-mediated pathology. The hematologic features of HLH were completely dependent on IFN-γ production, with complete correction after loss of IFN-γ production without any role for CD8 + T cell-mediated IL-2 consumption. By contrast, the mechanistic contribution of the immunologic features was reversed, with no role for IFN-γ production but substantial correction after reduction of IL-2 consumption by hyperactivated CD8 + T cells. These results were complemented by the characterization of an IFN-γ receptor 1-deficient patients with HLH-like disease, in whom multiple aspects of HLH pathology were observed in the absence of IFN-γ signaling., Conclusion: These results synthesize the competing mechanistic models of HLH pathology into a dichotomous pathogenesis driven through discrete pathways. A holistic model provides a new paradigm for understanding HLH and, more broadly, the consequences of CD8 + T-cell hyperactivation, thereby paving the way for clinical intervention based on the features of HLH in individual patients., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)