Publications by authors named "Claudia Escher"

Article Synopsis
  • Circulating proteomes can reveal the body's response to diseases like COVID-19 and treatments like tocilizumab, which is used to mitigate severe symptoms.
  • In a study involving 28 hospitalized COVID-19 patients treated with tocilizumab, researchers collected serum samples to analyze changes in protein levels before and after treatment and assessed patient outcomes for 30 days.
  • Findings indicated that specific proteins related to the complement system and Fc-epsilon receptor signaling could predict treatment success and mortality, where high complement activation linked to worse outcomes and certain signaling pathways showed lower mortality rates.
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Adeno-associated virus 5 (AAV5)-human factor VIII-SQ (hFVIII-SQ; valoctocogene roxaparvovec) is an AAV-mediated product under evaluation for treatment of severe hemophilia A, which contains a B-domain-deleted hFVIII (hFVIII-SQ) transgene and a hybrid liver-specific promotor (HLP). To increase FVIII-SQ expression and reduce the vector dose required, a stronger promoter may be considered. However, because FVIII-SQ is a protein known to be difficult to fold and secrete, this could potentially induce endoplasmic reticulum (ER) stress.

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Three-Dimensional (3D) liver microtissues, specifically prepared from primary human hepatocytes (PHH) in coculture with nonparenchymal cells (NPCs), have been shown to be a valuable tool for toxicology. However, a lack of thorough characterization on a functional, transcriptomic, and proteomic level of such models during long-term cultivation is evident. By integrating multiple omics technologies, we provide in this study an in-depth long-term characterization of 3D microtissues composed of PHH from three different donors cocultured with primary NPCs.

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Membrane proteins are challenging targets for crystallization and structure determination by X-ray crystallography. Hurdles can be overcome by antibody-mediated crystallization. More than 25 unique structures of membrane protein:antibody complexes have already been determined.

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The data-independent acquisition (DIA) approach has recently been introduced as a novel mass spectrometric method that promises to combine the high content aspect of shotgun proteomics with the reproducibility and precision of selected reaction monitoring. Here, we evaluate, whether SWATH-MS type DIA effectively translates into a better protein profiling as compared with the established shotgun proteomics. We implemented a novel DIA method on the widely used Orbitrap platform and used retention-time-normalized (iRT) spectral libraries for targeted data extraction using Spectronaut.

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To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super-resolution microscopy approach to determine the absolute stoichiometry of the human nuclear pore complex (NPC), possibly the largest eukaryotic protein complex. We show that the human NPC has a previously unanticipated stoichiometry that varies across cancer cell types, tissues and in disease.

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Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known.

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The definite molecular diagnosis in patients with muscular dystrophies often requires the assessment of muscular expression of multiple proteins in small amounts of muscle tissue. The sample material obtained in muscle biopsies is limited and the measurement of multiple proteins is often restricted to conventional, non-quantitative assays, i.e.

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Transmembrane signaling by receptor tyrosine kinases typically involves a dynamic receptor monomer-dimer equilibrium in which ligand binding to soluble extracellular domains triggers receptor dimerization and subsequent signaling events. Although the role in signal transduction of the single transmembrane helices of individual receptors, which connect the extracellular with the intracellular protein domains, is not understood in detail, we show here that the single transmembrane domains of all 58 human receptor tyrosine kinases alone have an intrinsic propensity to form stable dimeric structures within a membrane. Thus, defined interactions of the transmembrane domains are most likely generally involved in signaling by all human receptor tyrosine kinases.

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Members of the ErbB/HER family of epidermal growth factor receptor tyrosine kinases cross a membrane with a single transmembrane (TM) helix. ErbB receptors form diverse homo- and heterodimers, which substantially increases the signaling potential of ErbB receptors. The involvement of the ErbB TM domains in homo- and heterodimerization is largely enigmatic.

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There is need for a better understanding of the ecotoxicity of pharmaceuticals present in aquatic systems as only little is known about their potential acute and chronic toxicity to aquatic organisms. In our work, we evaluate the in vitro cytotoxicity of 34 common pharmaceuticals from different classes and with different modes of action using the mitochondrial MTT reduction and neutral red uptake assays in the two fish cell lines, PLHC-1 and RTG-2. Cytotoxicity was found for 21 pharmaceuticals with EC50-values ranging from 2.

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Pharmaceuticals enter aquatic environments in unchanged form or as metabolites. Little is known about their potential hormonal activity, which is of particular interest due to potential long-term effects on fertility and reproduction in aquatic organisms. Moreover, there is a need to assess the combined activity of pharmaceutical mixtures.

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