Institut für Chemie und Bioanalytik
Dauerhafte URI für die Sammlunghttps://irf.fhnw.ch/handle/11654/24
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6 Ergebnisse
Ergebnisse nach Hochschule und Institut
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, RudiAdhesive 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 ZeitschriftPublikation An origami like 3D patterned cellulose-based scaffold for bioengineering cardiovascular applications(Springer, 2023) Rodriguez, Gabriela Melo; Trueb, Donata; Köser, Joachim; Schoelkopf, Joachim; Gullo, MaurizioIn 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 ZeitschriftPublikation 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 LucíaThe 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 ZeitschriftPublikation 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, AidaMotivation: 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 ZeitschriftPublikation 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, Gabriele01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Plasmonic photothermal activation of an organosilica shielded cold-adapted lipase co-immobilised with gold nanoparticles on silica particles(Royal Society of Chemistry, 01.01.2023) Giunta, Carolina; Nazemi, Seyed Amirabbas; Olesińska, Magdalena; Shahgaldian, PatrickGold nanoparticles (AuNPs), owing to their intrinsic plasmonic properties, are widely used in applications ranging from nanotechnology and nanomedicine to catalysis and bioimaging. Capitalising on the ability of AuNPs to generate nanoscale heat upon optical excitation, we designed a nanobiocatalyst with enhanced cryophilic properties. It consists of gold nanoparticles and enzyme molecules, co-immobilised onto a silica scaffold, and shielded within a nanometre-thin organosilica layer. To produce such a hybrid system, we developed and optimized a synthetic method allowing efficient AuNP covalent immobilisation on the surface of silica particles (SPs). Our procedure allows to reach a dense and homogeneous AuNP surface coverage. After enzyme co-immobilisation, a nanometre-thin organosilica layer was grown on the surface of the SPs. This layer was designed to fulfil the dual function of protecting the enzyme from the surrounding environment and allowing the confinement, at the nanometre scale, of the heat diffusing from the AuNPs after surface plasmon resonance photothermal activation. To establish this proof of concept, we used an industrially relevant lipase enzyme, namely Lipase B from Candida Antarctica (CalB). Herein, we demonstrate the possibility to photothermally activate the so-engineered enzymes at temperatures as low as −10 °C.01A - Beitrag in wissenschaftlicher Zeitschrift