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  • Author: Holger Berg x
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Abstract

The chronological charts from the eighteenth and nineteenth centuries are generally recognised as precursors of the graph and the timeline. While the modern timeline is of ‘breadthless length’ and thus fulfils Euclid’s definition, breadth is crucial to the lines on chronological charts. These charts used the axes of time and spatio-political power to provide a visual overview of world history in the form of a delta, The Stream of Time. While the History of the Timeline by David Rosenberg and Anthony Grafton has tracked overall developments in Latin Christendom from Eusebius until our day, the flourishing of chronological charts in the nineteenth century has yet to be mapped and explored. My article addresses this gap through a case-study of three chronological charts that were produced in Denmark between 1817 and 1841. The lines in the three charts are analysed along with the concepts of time and space expressed in the text companions. The analysis uncovers significant variation and shows why it makes sense to speak of ‘time columns’ instead of timelines. A final section on the production of chronological charts and their adaptation in teaching shows how charts had a major impact on notions of time and history. The conclusion relates the findings to Ingold’s overarching theses on lines and adds some necessary historical nuance. The outlook also connects the Danish chronological charts to the two alternative teaching aids, historical atlases and chronological tables.

Fatty acids are essential components of almost all biological membranes. Additionally, they are important in energy storage, as second messengers during signal transduction, and in post-translational protein modification. De novo synthesis of fatty acids is essential for almost all organisms, and entails the iterative elongation of the growing fatty acid chain through a set of reactions conserved in all kingdoms. During our work on the biosynthesis of secondary metabolites, a 450-kDa protein was detected by SDS-PAGE of enriched fractions from mycelial lysates from the basidiomycete Omphalotus olearius. Protein sequencing of this protein band revealed the presence of peptides with homology to both α and β subunits of the ascomycete fatty acid synthase (FAS) family. The FAS encoding gene of O. olearius was sequenced. The positions of its predicted 21 introns were verified. The gene encodes a 3931 amino acids single protein, with an equivalent of the ascomycetous β subunit at the N-terminus and the α subunit at the C-terminus. This is the first report on an FAS protein from a homobasidiomycete and also the first fungal FAS which is comprised of a single polypeptide.

Abstract

Abstract Molecular detection of herpes simplex virus (HSV) DNA is recognized as reference standard assay for the sensitive and specific diagnosis of central nervous system and genital infections caused by HSV. In this study, a qualitative molecular assay based on automated DNA extraction on the MagNA Pure LC (Roche Applied Science, Mannheim, Germany) and a commercially available kit, the LightCycler – HSV 1/2 Detection Kit (Roche), were evaluated. This kit includes a homologous internal control. The accuracy and the detection limit of the new molecular assay were determined with samples from European Union Concerted Action HSV Proficiency Panels. A total of 153 clinical specimens including cerebrospinal fluids, genital swabs, and oral swabs were investigated and the results were compared to those obtained from a home-brew molecular assay based on manual DNA extraction and real-time polymerase chain reaction (PCR). When the accuracy of the new molecular assay was tested, all positive samples except for the one containing 3.0 × 102–9.0 × 102 HSV type 1 (HSV-1) genome equivalents (GE) per ml could be detected. All negative samples tested negative. When the detection limit was determined, 6.0 × 102–1.8 × 103 HSV-1 GE per ml, i.e. 12 to 36 GE per LightCycler (LC) capillary and 2.0 × 102–6.0 × 102 HSV type 2 (HSV-2) GE per ml, i.e. 4 to 12 GE per LC capillary could consistently be detected. Results obtained from clinical specimens corresponded to 100% to those obtained by the molecular assay based on manual DNA extraction and real-time PCR. In seven clinical samples, an unexpected melting peak was detected. In conclusion, the new molecular assay allows rapid detection of HSV-1 and HSV-2 DNA in the routine diagnostic laboratory. The inclusion of a homologous internal control ensures accurate interpretation of negative results.

Abstract

Secretory peptides and proteins are frequently modified by pyroglutamic acid (pE, pGlu) at their N-terminus. This modification is catalyzed by the glutaminyl cyclases QC and isoQC. Here, we decipher the roles of the isoenzymes by characterization of IsoQC-/- mice. These mice show a significant reduction of glutaminyl cyclase activity in brain and peripheral tissue, suggesting ubiquitous expression of the isoQC enzyme. An assay of substrate conversion in vivo reveals impaired generation of the pGlu-modified C-C chemokine ligand 2 (CCL2, MCP-1) in isoQC-/- mice. The pGlu-formation was also impaired in primary neurons, which express significant levels of QC. Interestingly, however, the formation of the neuropeptide hormone thyrotropin-releasing hormone (TRH), assessed by immunohistochemistry and hormonal analysis of hypothalamic-pituitary-thyroid axis, was not affected in isoQC-/-, which contrasts to QC-/-. Thus, the results reveal differential functions of isoQC and QC in the formation of the pGlu-peptides CCL2 and TRH. Substrates requiring extensive prohormone processing in secretory granules, such as TRH, are primarily converted by QC. In contrast, protein substrates such as CCL2 appear to be primarily converted by isoQC. The results provide a new example, how subtle differences in subcellular localization of enzymes and substrate precursor maturation might influence pGlu-product formation.