fridafo

• Palinkas, Sabina Strmic; Forsberg, Frida; Pedersen, Rolf B.; Stubseid, Håvard Hallås; McClenaghan, Seán H. & Spangenberg, Jorge E. (2024). Metallogenic model of the Lykling ophiolite-hosted lode Au deposit, Scandinavian Caledonides: Insight from fluid inclusions, mineral chemistry and stable isotope geochemistry. Ore Geology Reviews. ISSN 0169-1368. 173. doi: 10.1016/j.oregeorev.2024.106227. Full text in Research Archive Show summary

  The Lykling lode Au deposit represents a unique example of gold mineralization in the Upper Allochthone of the Scandinavian Caledonides. The mineralization is hosted by the Early Ordovician Lykling Ophiolite Complex and the intruding trondhjemite unit and spatially associated with two generations of mafic dykes that crosscut both the ophiolitic complex and trondhjemite. Field observations indicate that the mafic dykes did not play an active role in the emplacement of Au at Lykling, however their contacts with the immediate host rocks (i.e., gabbro and trondhjemite) may have focused ore-forming fluids. Three main stages in the evolution of the hydrothermal system in the Lykling area are documented by two generations of auriferous quartz veins: 1) older quartz-carbonate veins hosted by moderately angled brittle-ductile shear zones and 2) younger quartz-sulfide veins that fill steeply dipping brittle faults. Stage 1 resulted in deposition of barren quartz and gold-free pyrite from moderately saline NaCl-CaCl2-H2O ± CO2 fluids at temperatures between ∼310–330 °C and pressures in the range from 2.7 to 3.5 kbars. Under the given physicochemical conditions Au was mobile in the form of its chloride complexes. Stage 2 is associated with multiple episodes of ductile deformation punctuated by concomitant brecciation reflecting brittle-ductile transition processes. Fluid inclusion data reveals a decrease in temperature and pressure that may result in the formation of stable Au-bisulfide complexes and making the hydrothermal mobility of Au sensitive to changes in pressure. Consequently, the fluctuation in pressure controlled by the development of brittle-ductile structures likely resulted in the precipitation of native gold in quartz veins. Stage 3 represents a pure brittle event which is accompanied by a significant decrease in the fCO2/fS2 ratio. Mixing of higher-temperature and moderate-salinity fluids with cooler fluids has been recognized as the principal trigger for deposition of sulfides and a paragenetically late phase of native gold in the Lykling hydrothermal system. The Lykling ophiolite-hosted lode Au deposit shows numerous similarities with orogenic gold deposits elsewhere, including structural controls during mineralizing events, deposition from moderately to low salinity CO2-bearing aqueous solutions, deposition from a focused fluid flow along trans-crustal fault zones with a mixed brittle-ductile character and the spatial association with regionally metamorphosed terranes. In contrast to the great majority of the known orogenic gold deposits, the Lykling ophiolite-hosted lode Au deposit records a magmatic origin of volatiles. Therefore, taking into consideration field relationships and the regional setting of the Lykling deposit, we argue that its formation is concomitant with emplacement of the Sunnhordland Batholith during post-collisional thinning of the crust and associated localized uplift within the Lykling Ophiolite Complex

• Engelfriet, Melanie Lianne; Malecki, Jedrzej Mieczyslaw; Forsberg, Frida; Falnes, Pål & Ciosk, Rafal (2023). Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans. PLOS ONE. 18(6), p. 1–16. doi: 10.1371/journal.pone.0287558. Full text in Research Archive Show summary

  The methyltransferase-like protein 13 (METTL13) methylates the eukaryotic elongation factor 1 alpha (eEF1A) on two locations: the N-terminal amino group and lysine 55. The absence of this methylation leads to reduced protein synthesis and cell proliferation in human cancer cells. Previous studies showed that METTL13 is dispensable in non-transformed cells, making it potentially interesting for cancer therapy. However, METTL13 has not been examined yet in whole animals. Here, we used the nematode Caenorhabditis elegans as a simple model to assess the functions of METTL13. Using methyltransferase assays and mass spectrometry, we show that the C . elegans METTL13 (METL-13) methylates eEF1A (EEF-1A) in the same way as the human protein. Crucially, the cancer-promoting role of METL-13 is also conserved and depends on the methylation of EEF-1A, like in human cells. At the same time, METL-13 appears dispensable for animal growth, development, and stress responses. This makes C . elegans a convenient whole-animal model for studying METL13-dependent carcinogenesis without the complications of interfering with essential wild-type functions.

• Brunet, Annaëlle; Forsberg, Anna Frida; Fan, Qiong; Sæther, Thomas & Collas, Philippe (2019). Nuclear lamin B1 interactions with chromatin during the circadian cycle are uncoupled from periodic gene expression. Frontiers in Genetics. 10. doi: 10.3389/fgene.2019.00917. Full text in Research Archive Show summary

  Many mammalian genes exhibit circadian expression patterns concordant with periodic binding of transcription factors, chromatin modifications, and chromosomal interactions. Here we investigate whether chromatin periodically associates with nuclear lamins. Entrainment of the circadian clock is accompanied, in mouse liver, by a net gain of lamin B1–chromatin interactions genome-wide, after which the majority of lamina-associated domains (LADs) are conserved during the circadian cycle. By tailoring a bioinformatics pipeline designed to identify periodic gene expression patterns, we also observe hundreds of variable lamin B1-chromatin interactions among which oscillations occur at 64 LADs, affecting one or both LAD extremities or entire LADs. Only a small subset of these oscillations however exhibit highly significant 12, 18, 24, or 30 h periodicity. These periodic LADs display oscillation asynchrony between their 5′ and 3′ borders, and are uncoupled from periodic gene expression within or in the vicinity of these LADs. Periodic gene expression is also unrelated to variations in gene-to-nearest LAD distances detected during the circadian cycle. Accordingly, periodic genes, including central clock-control genes, are located megabases away from LADs throughout circadian time, suggesting stable residence in a transcriptionally permissive chromatin environment. We conclude that periodic LADs are not a dominant feature of variable lamin B1–chromatin interactions during the circadian cycle in mouse liver. Our results also suggest that periodic hepatic gene expression is not regulated by rhythmic chromatin associations with the nuclear lamina.

• Forsberg, Frida; Brunet, Annaëlle; Ali, Tharvesh Moideen Liyakat & Collas, Philippe (2019). Interplay of lamin A and lamin B LADs on the radial positioning of chromatin. Nucleus. ISSN 1949-1034. 10(1), p. 7–20. doi: 10.1080/19491034.2019.1570810. Full text in Research Archive Show summary

  Immunosuppressive drugs such as cyclosporin A (CsA) can elicit hepatotoxicity by affecting gene expression. Here, we address the link between CsA and large-scale chromatin organization in HepG2 hepatocarcinoma cells. We show the existence of lamina-associated domains (LADs) interacting with lamin A, lamin B, or both. These ‘A-B’, ‘A-only’ and ‘B-only’ LADs display distinct fates after CsA treatment: A-B LADs remain constitutive or lose A, A-only LADs mainly lose A or switch to B, and B-only LADs remain B-only or acquire A. LAD rearrangement is overall uncoupled from changes in gene expression. Three-dimensional (3D) genome modeling predicts changes in radial positioning of LADs as LADs switch identities, which are corroborated by fluorescence in situ hybridization. Our results reveal interplay between A- and B-type lamins on radial locus positioning, suggesting complementary contributions to large-scale genome architecture. The data also unveil a hitherto unsuspected impact of cytotoxic drugs on genome conformation. Abbreviations: ChIP-seq: chromatin immunoprecipitation sequencing; CsA: cyclosporin A; FISH; fluorescence in situ hybridization; ICMT: isoprenylcysteine methyltransferase; LAD: lamina-associated domain; TAD: topologically-associated domain

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