| 1. |
- Azinas, Stavros, et al.
(författare)
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Membrane-containing virus particles exhibit the mechanics of a composite material for genome protection
- 2018
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Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 10:16, s. 7769-7779
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Tidskriftsartikel (refereegranskat)abstract
- The protection of the viral genome during extracellular transport is an absolute requirement for virus survival and replication. In addition to the almost universal proteinaceous capsids, certain viruses add a membrane layer that encloses their double-stranded (ds) DNA genome within the protein shell. Using the membrane-containing enterobacterial virus PRD1 as a prototype, and a combination of nanoindentation assays by atomic force microscopy and finite element modelling, we show that PRD1 provides a greater stability against mechanical stress than that achieved by the majority of dsDNA icosahedral viruses that lack a membrane. We propose that the combination of a stiff and brittle proteinaceous shell coupled with a soft and compliant membrane vesicle yields a tough composite nanomaterial well-suited to protect the viral DNA during extracellular transport.
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| 4. |
- Bano, Fouzia, et al.
(författare)
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Single-molecule unbinding forces between the polysaccharide hyaluronan and its binding proteins
- 2018
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Ingår i: Biophysical Journal. - : Biophysical society. - 0006-3495 .- 1542-0086. ; 114:12, s. 2910-2922
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Tidskriftsartikel (refereegranskat)abstract
- The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices.
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| 5. |
- Bano, Fouzia, et al.
(författare)
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Unraveling the complexity of the interactions of DNA nucleotides with gold by single molecule force spectroscopy
- 2015
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Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 7:46, s. 19528-19533
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Tidskriftsartikel (refereegranskat)abstract
- Addressing the effect of different environmental factors on the adsorption of DNA to solid supports is critical for the development of robust miniaturized devices for applications ranging from biosensors to next generation molecular technology. Most of the time, thiol-based chemistry is used to anchor DNA on gold – a substrate commonly used in nanotechnology – and little is known about the direct interaction between DNA and gold. So far there have been no systematic studies on the direct adsorption behavior of the deoxyribonucleotides (i.e., a nitrogenous base, a deoxyribose sugar, and a phosphate group) and on the factors that govern the DNA–gold bond strength. Here, using single molecule force spectroscopy, we investigated the interaction of the four individual nucleotides, adenine, guanine, cytosine, and thymine, with gold. Experiments were performed in three salinity conditions and two surface dwell times to reveal the factors that influence nucleotide–Au bond strength. Force data show that, at physiological ionic strength, adenine–Au interactions are stronger, asymmetrical and independent of surface dwell time as compared to cytosine–Au and guanine–Au interactions. We suggest that in these conditions only adenine is able to chemisorb on gold. A decrease of the ionic strength significantly increases the bond strength for all nucleotides. We show that moderate ionic strength along with longer surface dwell period suggest weak chemisorption also for cytosine and guanine.
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| 7. |
- Malmros, Karin, et al.
(författare)
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Comparison of antibiotic treatment guidelines for urinary tract infections in 15 European countries : Results of an online survey
- 2019
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 54:4, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- Appropriate antibiotic use for urinary tract infections (UTIs) is important in order to provide effective and safe treatment while minimising the risk of antimicrobial resistance development. This survey was carried out to compare existing national guidelines for UTIs in Europe. Experts in 37 European countries were asked to participate. An electronic questionnaire was used to obtain information on treatment recommendations, factors considered important when setting guidelines, acceptable resistance rates for empirical therapy, evidence grading, and existing resistance surveillance for uropathogens. Treatment guidelines and antimicrobial susceptibility data were collected. In total, 22 experts (59%) responded to the survey. National guidelines were missing in four countries and data were incomplete in three cases. Fifteen national guidelines published between 2004 and 2017 were included in the analysis. Great variability was found between guidelines in the selection of antibiotics, dosing regimens and treatment duration. For example, 10 different antibiotics were recommended as first-line therapy for uncomplicated cystitis. National surveillance data on antimicrobial susceptibility of uropathogens were available in 13 of 15 countries. Resistance epidemiology could not explain the observed differences between guidelines, and comparison of resistance rates was hampered by variations in methods. This study revealed major differences in treatment guidelines for UTIs within Europe, indicating that there are opportunities for improvement. More clinical research and a more systematic and stratified approach to resistance surveillance, including also antibiotics that are currently not available in all countries, is needed.
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