Institut für Chemie und Bioanalytik

Dauerhafte URI für die Sammlunghttps://irf.fhnw.ch/handle/11654/24

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Anfangsdatum: 2022Thema: search.filters.subject.600 - Technik, Medizin, angewandte Wissenschaften

Ergebnisse nach Hochschule und Institut

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    Publikation
    Stochastic chain termination in bacterial pilus assembly
    (Nature, 2023) Giese, Christoph; Puorger, Chasper; Ignatov, Oleksandr; Bečárová, Zuzana; Weber, Marco E.; Schärer, Martin A.; Capitani, Guido; Glockshuber, Rudi
    Adhesive type 1 pili from uropathogenic Escherichia coli strains are filamentous, supramolecular protein complexes consisting of a short tip fibrillum and a long, helical rod formed by up to several thousand copies of the major pilus subunit FimA. Here, we reconstituted the entire type 1 pilus rod assembly reaction in vitro, using all constituent protein subunits in the presence of the assembly platform FimD, and identified the so-far uncharacterized subunit FimI as an irreversible assembly terminator. We provide a complete, quantitative model of pilus rod assembly kinetics based on the measured rate constants of FimD-catalyzed subunit incorporation. The model reliably predicts the length distribution of assembled pilus rods as a function of the ratio between FimI and the main pilus subunit FimA and is fully consistent with the length distribution of membrane-anchored pili assembled in vivo. The results show that the natural length distribution of adhesive pili formed via the chaperone-usher pathway results from a stochastic chain termination reaction. In addition, we demonstrate that FimI contributes to anchoring the pilus to the outer membrane and report the crystal structures of (i) FimI in complex with the assembly chaperone FimC, (ii) the FimI-FimC complex bound to the N-terminal domain of FimD, and (iii) a ternary complex between FimI, FimA and FimC that provides structural insights on pilus assembly termination and pilus anchoring by FimI.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    An origami like 3D patterned cellulose-based scaffold for bioengineering cardiovascular applications
    (Springer, 2023) Rodriguez, Gabriela Melo; Trueb, Donata; Köser, Joachim; Schoelkopf, Joachim; Gullo, Maurizio
    In this work we describe the manufacturing of cellulosic, cell compatible scaffolds with an inherent 3D origami crease pattern for applications in cardiac tissue engineering. Different cellulosic materials were studied, among them cotton linters, fibers obtained from eucalyptus, pine, spruce and lyocell. Formed sheets made of cotton linters were chosen for further study due to the highest biocompatibility and mechanical properties best suited for cardiomyocytes in wet and dry conditions: E - modulus of 0.8 GPa, tensile strength of 4.7 MPa and tensile strength in wet environment of 2.28 MPa. Cell alignment is desired to achieve directional contraction of the cardiac tissue, and several options were investigated to achieve fiber alignment, e.g. a dynamic sheet former and Rapid Köthen sheet former. Although the orientation was minimal, cells cultured on the cellulose fibers grew and aligned along the fibers. Origami inspired crease patterns were applied to the cellulose scaffolds in order to introduce directional flexibility beneficial for cardiac contraction. The transfer of a Miura-ori crease pattern was successfully applied in two ways: folding of the dried sheet between PET foils pre-formed in a 3D printed mold, and in situ wet fiber molding on a 3D-patterned mesh mounted in the sheet former’s sieve section. The latter approach enables upscaling for potential mass production.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    SARS-CoV-2 variants of concern and clinical severity in the mexican pediatric population
    (MDPI, 2023) Maldonado-Cabrera, Anahí; Colin-Vilchis, Jesus Alejandro; Haque, Ubydul; Velazquez, Carlos; Alvarez Villaseñor, Andrea Socorro; Magdaleno-Márquez, Luis Eduardo; Calleros-Muñoz, Carlos Iván; Figueroa-Enríquez, Karen Fernanda; Angulo-Molina, Aracely; Gallego-Hernández, Ana Lucía
    The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) presents global heterogeneity, and their relative effect on pediatric severity is still limited. In this study, we associate VOCs with pediatric clinical severity outcomes in Mexico. Bioinformatics methods were used to characterize VOCs and single amino acid (aa) mutations in 75,348 SARS-CoV-2 genetic sequences from February 2020 to October 2022. High-predominance VOCs groups were calculated and subsequently associated with 372,989 COVID-19 clinical pediatric outcomes. We identified 21 high-frequency mutations related to Omicron lineages with an increased prevalence in pediatric sequences compared to adults. Alpha and the other lineages had a significant increase in case fatality rate (CFR), intensive critical unit (ICU) admission, and automated mechanical ventilation (AMV). Furthermore, a logistic model with age-adjusted variables estimated an increased risk of hospitalization, ICU/AMV, and death in Gamma and Alpha, in contrast to the other lineages. We found that, regardless of the VOCs lineage, infant patients presented the worst severity prognoses. Our findings improve the understanding of the impact of VOCs on pediatric patients across time, regions, and clinical outcomes. Enhanced understanding of the pediatric severity for VOCs would enable the development and improvement of public health strategies worldwide.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    CanIsoNet: a database to study the functional impact of isoform switching events in diseases
    (Oxford University Press, 17.04.2023) Karakulak, Tülay; Szklarczyk, Damian; Saylan, Cemil Can; Moch, Holger; von Mering, Christian; Kahraman, Abdullah; Ouangraoua, Aida
    Motivation: Alternative splicing, as an essential regulatory mechanism in normal mammalian cells, is frequently disturbed in cancer and other diseases. Switches in the expression of most dominant alternative isoforms can alter protein interaction networks of associated genes giving rise to disease and disease progression. Here, we present CanIsoNet, a database to view, browse and search isoform switching events in diseases. CanIsoNet is the first webserver that incorporates isoform expression data with STRING interaction networks and ClinVar annotations to predict the pathogenic impact of isoform switching events in various diseases. Results: Data in CanIsoNet can be browsed by disease or searched by genes or isoforms in annotation-rich data tables. Various annotations for 11 811 isoforms and 14 357 unique isoform switching events across 31 different disease types are available. The network density score for each disease-specific isoform, PFAM domain IDs of disrupted interactions, domain structure visualization of transcripts and expression data of switched isoforms for each sample is given. Additionally, the genes annotated in ClinVar are highlighted in interactive interaction networks. Availability and implementation: CanIsoNet is freely available at https://www.caniso.net. The source codes can be found under a Creative Common License at https://github.com/kahramanlab/CanIsoNet_Web.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Allosteric targeting resolves limitations of earlier LFA-1 directed modalities
    (Elsevier, 05/2023) Mancuso, Riccardo V.; Schneider, Gisbert; Hürzeler Müller, Marianne; Gut, Martin; Zurflüh, Jonas; Breitenstein, Werner; Bouitbir, Jamal; Reisen, Felix; Atz, Kenneth; Ehrhardt, Claus; Duthaler, Urs; Gygax, Daniel; Schmidt, Albrecht G.; Krähenbühl, Stephan; Weitz-Schmidt, Gabriele
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    MTPpilot. An interactive software for visualization of next-generation sequencing results in molecular tumor boards
    (American Society of Clinical Oncology Journal, 25.08.2022) Arnold, Fabian M.; Hanimann, Jacob; Nowak, Marta; Pauli, Chantal; Britschgi, Christian; Moch, Holger; Zoche, Martin; Kahraman, Abdullah
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer
    (Wiley, 30.08.2022) Akhoundova, Dilara; Hussung, Saskia; Sivakumar, Smruthy; Töpfer, Antonia; Rechsteiner, Markus; Arnold, Fabian; Angst, Florian; Britschgi, Christian; Zoche, Martin; Moch, Holger; Weber, Achim; Sokol, Ethan; Fritsch, Ralph M.; Kahraman, Abdullah
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    IsoAligner. Dynamic mapping of amino acid positions across protein isoforms
    (Faculty of 1000, 31.03.2022) Hanimann, Jacob; Moch, Holger; Zoche, Martin; Kahraman, Abdullah
    Aligning protein isoform sequences is often performed in cancer diagnostics to homogenise mutation annotations from different diagnostic assays. However, most alignment tools are fitted for homologous sequences, leading often to alignments of non-identical exonic regions. Here, we present the interactive alignment webservice IsoAligner for exact mapping of exonic protein subsequences. The tool uses a customized Needleman-Wunsch algorithm including an open gap penalty combined with a gene-specific minimal exon length function and dynamically adjustable parameters. As an input, IsoAligner accepts either various gene/transcript/protein IDs from different databases (Ensembl, UniProt, RefSeq) or raw amino acid sequences. The output of IsoAligner consists of pairwise alignments and a table of mapped amino acid positions between the canonical or supplied isoform IDs and all alternative isoforms. IsoAligner’s human isoform library comprises of over 1.3 million IDs mapped on over 120,000 protein sequences. IsoAligner, is a fast and interactive alignment tool for retrieving amino acids positions between different protein isoforms. Its application will allow diagnostic and precision medicine labs to detect inconsistent variant annotations between different assays and databases. Availability: This tool is available as a Webservice on www.isoaligner.org. A REST API is available for programmatic access. The source code for both services can be found at https://github.com/mtp-usz/IsoAligner.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Enhanced formation of nanometric titanium cones by incorporation of titanium, tungsten and/or iron in a helium ion beam
    (Elsevier, 12/2022) Sanchez, Fabien; Steiner, Roland; Latttner, P.; Spicher, J.; Mathys, Daniel; Antunes, Rodrigo; Marcin, Kisiel; Mukkadam, Khaled; Astasov-Fraunhofer, Monika; Kühl, Sebastian; Köser, Joachim; Wagner, Raphael; Marot, Laurent; Meyer, Ernst
    Surface patterning of bio-compatible titanium (Ti) shows a growing interest in the medical field. The engineering of material surfaces can achieve bactericidal properties and osteointegration improvements in order to develop medical implants. Spikes-like surface morphologies have already demonstrated the development of promising bactericidal properties. A barely new method to produce nanometric-sized cones on titanium consists of helium (He) ion irradiation using low energies ( 100 eV) and temperatures comprised between 0.25 T/T 0.5 (with T being the melting temperature of the material). Ti, iron (Fe) and/or tungsten (W) were incorporated in a He beam, and their amounts were quantified using X-ray Photoelectron Spectroscopy (XPS). The He ion energy was varied from 70 and 120 eV, the surface temperatures from 571 to 651 K for fluences approximately equal to 1024 m−2. After irradiation, the surface morphology was characterized using Scanning Electron Microscopy (SEM) and Focused Ion Beam (FIB). This study demonstrated the capability for irradiated Ti surfaces to form cones with tunable density, aspect ratio, and heights with the incorporation of Ti, Fe and/or W in a He ion. Additionally, the growth rate of the cones was enhanced by about 30 times in comparison to pure He irradiation as a function of the chosen materials introduced in the He beam.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Water-soluble optical sensors: keys to detect aluminium in biological environment
    (Royal Society of Chemistry, 01.01.2022) Unniram, Ajmal; Kavyashree, P.; Silswal, Akshay; Koner, Apurba Lal
    Metal ion plays a critical role from enzyme catalysis to cellular health and functions. The concentration of metal ions in a living system is highly regulated. Among the biologically relevant metal ions, the role and toxicity of aluminium in specific biological functions have been getting significant attention in recent years. The interaction of aluminium and the living system is unavoidable due to its high earth crust abundance, and the long-term exposure to aluminium can be fatal for life. The adverse Al3+ toxicity effects in humans result in various diseases ranging from cancers to neurogenetic disorders. Several Al3+ ions sensors have been developed over the past decades using the optical responses of synthesized molecules. However, only limited numbers of water-soluble optical sensors have been reported so far. In this review, we have confined our discussion to water-soluble Al3+ ions detection using optical methods and their utility for live-cell imaging and real-life application.
    01A - Beitrag in wissenschaftlicher Zeitschrift