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- Skowronek, T., et al.
(författare)
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Reissscheiben from shipwrecks as an indicator for copper qualities produced in the major middle and North European mining districts during the late medieval and early modern period 15th-17th Century AD
- 2021
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Ingår i: Journal of Archaeological Science-Reports. - : Elsevier BV. - 2352-409X. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- Major advances in maritime archaeology in the last 20 years resulted in the discovery of several shipwrecks carrying copper slab ingots, so-called Reissscheiben. With the interest in early modern metal trade growing, geochemical analysis of these raw copper ingots represents invaluable merit for understanding the various qualities produced in the major mining regions in Europe. Here, we present ICP-MS trace elemental and lead isotope data for 52 Reissscheiben ingots salvaged at three different findspots in northern European waters dating to the 15th and 16th century. Our results reveal the Reissscheiben to originate from two different mining centres, Slovakia and the southern Harz foreland. Copper produced in these regions shows significantly different trace elemental patterns probably affected by both different kinds of copper ores used and smelting processes applied. The analytical results reveal the difficulties that early modern copper smelters may have had to deal with when processing sulfidic copper ores, as it seems that refining processes were not understood sufficiently. On the other hand, the written historical sources suggest that early modern brass makers already had a proper understanding of which regions produced the most suitable copper qualities. This paper underlines the potential of using geochemical characterisation of early modern period metals for solving historical questions.
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- Gapińska, Marta, et al.
(författare)
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Structure-functional characterization of Lactococcus AbiA phage defense system
- 2024
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Ingår i: Nucleic Acids Research. - 1362-4962. ; 52:8, s. 4723-4738
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK and Abi-P2 are abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi RTs apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in a template- and primer-independent manner. Structures of AbiK and Abi-P2 representatives have recently been determined, but there are no structural data available for AbiA. Here, we report the crystal structure of Lactococcus AbiA polymerase in complex with a single-stranded polymerization product. AbiA comprises three domains: an RT-like domain, a helical domain that is typical for Abi polymerases, and a higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain that is common for many antiviral proteins. AbiA forms a dimer that distinguishes it from AbiK and Abi-P2, which form trimers/hexamers. We show the DNA polymerase activity of AbiA in an in vitro assay and demonstrate that it requires the presence of the HEPN domain which is enzymatically inactive. We validate our biochemical and structural results in vivo through bacteriophage infection assays. Finally, our in vivo results suggest that AbiA-mediated phage defense may not rely on AbiA-mediated cell death.
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- Rath, Matthias, et al.
(författare)
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Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells
- 2022
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 79:6
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral cavernous malformations (CCM) are low-flow vascular lesions prone to cause severe hemorrhage-associated neurological complications. Pathogenic germline variants in CCM1, CCM2, or CCM3 can be identified in nearly 100% of CCM patients with a positive family history. In line with the concept that tumor-like mechanisms are involved in CCM formation and growth, we here demonstrate an abnormally increased proliferation rate of CCM3-deficient endothelial cells in co-culture with wild-type cells and in mosaic human iPSC-derived vascular organoids. The observation that NSC59984, an anticancer drug, blocked the abnormal proliferation of mutant endothelial cells further supports this intriguing concept. Fluorescence-activated cell sorting and RNA sequencing revealed that co-culture induces upregulation of proangiogenic chemokine genes in wild-type endothelial cells. Furthermore, genes known to be significantly downregulated in CCM3(-/-) endothelial cell mono-cultures were upregulated back to normal levels in co-culture with wild-type cells. These results support the hypothesis that wild-type ECs facilitate the formation of a niche that promotes abnormal proliferation of mutant ECs. Thus, targeting the cancer-like features of CCMs is a promising new direction for drug development.
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