Eldorado - Repositorium der TU Dortmund
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Aktuellste Veröffentlichungen
Item type:Item, Morphological transformations of SARS‐CoV‐2 nucleocapsid protein biocondensates mediated by antimicrobial peptides(Wiley, 2024-03-14) Campanile, Marco; Kurtul, Emine Dila; Dec, Robert; Möbitz, Simone; Del Vecchio, Pompea; Petraccone, Luigi; Tatzelt, Jörg; Oliva, Rosario; Winter, RolandRecently, the discovery of antimicrobial peptides (AMPs) as excellent candidates for overcoming antibiotic resistance has attracted significant attention. AMPs are short peptides active against bacteria, cancer cells, and viruses. It has been shown that the SARS-CoV-2 nucleocapsid protein (N−P) undergoes liquid-liquid phase separation in the presence of RNA, resulting in biocondensate formation. These biocondensates are crucial for viral replication as they concentrate the viral RNA with the host cell‘s protein machinery required for viral protein expression. Thus, N−P biocondensates are promising targets to block or slow down viral RNA transcription and consequently virion assembly. We investigated the ability of three AMPs to interfere with N−P/RNA condensates. Using microscopy techniques, supported by biophysical characterization, we found that the AMP LL–III partitions into the condensate, leading to clustering. Instead, the AMP CrACP1 partitions into the droplets without affecting their morphology but reducing their dynamics. Conversely, GKY20 leads to the formation of fibrillar structures after partitioning. It can be expected that such morphological transformation severely impairs the normal functionality of the N−P droplets and thus virion assembly. These results could pave the way for the development of a new class of AMP-based antiviral agents targeting biocondensates.Item type:Item, Molecular networking‐guided discovery of kyonggic acids in Massilia spp.(Wiley, 2024-03-21) Steinmetz, Till; Lindig, Anton; Lütz, Stephan; Nett, MarkusIn recent years, bacteria of the genus Massilia have been identified as promising sources of bioactive natural products. In this study, we used mass spectrometry (MS)-based molecular networking for the first comprehensive analysis of the secondary metabolome of these microorganisms. Annotation of the detected metabolite clusters with a mass fragmentation database revealed several compounds not previously known to be produced by Massilia species. To secure sufficient material for further structural analyses as well as biological testing, we selected the most promising producer strains from our molecular networking analysis and subjected them to larger-scale cultivation. Following extraction and UV-directed isolation, we obtained five metabolites in milligram quantities. In addition to a cyclic dipeptide, we elucidated the structures of four acyl amino acids that are related to thalassotalic acid C from the marine bacterium Thalassotalea sp. The Massilia-derived kyonggic acids were found to inhibit the enzyme tyrosinase, which is involved in melanin biosynthesis influencing skin and hair pigmentation. This study illustrates the value of combining spectroscopic and computational tools in natural product discovery in order to detect and guide the isolation of previously overlooked bioactive compounds.Item type:Item, Amtliche Mitteilungen der Technischen Universität Dortmund Nr. 17/2026(Technische Universität Dortmund, 2026-07-29)Item type:Item, Mathematical analysis of a mesoscale model for multiphase membranes(Wiley, 2024-08-10) Fuchs, Jakob; Röger, MatthiasIn this article, we introduce a mesoscale continuum model for membranes made of two different types of amphiphilic lipids. The model extends work by Peletier and the second author (Arch. Ration. Mech. Anal. 193, 2009) for the one-phase case. We present a mathematical analysis of the asymptotic reduction to the macroscale when a key length parameter becomes arbitrarily small. We identify two main contributions in the energy: one that can be connected to bending of the overall structure and a second that describes the cost of the internal phase separations. We prove the Γ-convergence towards a perimeter functional for the phase separation energy and construct, in two dimensions, recovery sequences for the convergence of the full energy towards a 2D reduction of the Jülicher–Lipowsky bending energy with a line tension contribution for phase separated hypersurfaces.Item type:Item, Incompletely observed nonparametric factorial designs with repeated measurements: a wild bootstrap approach(Wiley, 2024-11-23) Amro, Lubna; Konietschke, Frank; Pauly, MarkusIn many life science experiments or medical studies, subjects are repeatedly observed and measurements are collected in factorial designs with multivariate data. The analysis of such multivariate data is typically based on multivariate analysis of variance (MANOVA) or mixed models, requiring complete data, and certain assumption on the underlying parametric distribution such as continuity or a specific covariance structure, for example, compound symmetry. However, these methods are usually not applicable when discrete data or even ordered categorical data are present. In such cases, nonparametric rank-based methods that do not require stringent distributional assumptions are the preferred choice. However, in the multivariate case, most rank-based approaches have only been developed for complete observations. It is the aim of this work to develop asymptotic correct procedures that are capable of handling missing values, allowing for singular covariance matrices and are applicable for ordinal or ordered categorical data. This is achieved by applying a wild bootstrap procedure in combination with quadratic form-type test statistics. Beyond proving their asymptotic correctness, extensive simulation studies validate their applicability for small samples. Finally, two real data examples are analyzed.
