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  • 1.
    Andersson, Richard L.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Martinez-Abad, Antonio
    Lagaron, Jose M.
    Gedde, Ulf W.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Mallon, Peter E.
    Olsson, Richard T.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Hedenqvist, Mikael S.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Antibacterial Properties of Tough and Strong Electrospun PMMA/PEO Fiber Mats Filled with Lanasol-A Naturally Occurring Brominated Substance2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 9, p. 15912-15923Article in journal (Refereed)
    Abstract [en]

    A new type of antimicrobial, biocompatible and toughness enhanced ultra-thin fiber mats for biomedical applications is presented. The tough and porous fiber mats were obtained by electrospinning solution-blended poly (methyl methacrylate) (PMMA) and polyethylene oxide (PEO), filled with up to 25 wt % of Lanasol-a naturally occurring brominated cyclic compound that can be extracted from red sea algae. Antibacterial effectiveness was tested following the industrial Standard JIS L 1902 and under agitated medium (ASTM E2149). Even at the lowest concentrations of Lanasol, 4 wt %, a significant bactericidal effect was seen with a 4-log (99.99%) reduction in bacterial viability against S. aureus, which is one of the leading causes of hospital-acquired (nosocomial) infections in the world. The mechanical fiber toughness was insignificantly altered up to the maximum Lanasol concentration tested, and was for all fiber mats orders of magnitudes higher than electrospun fibers based on solely PMMA. This antimicrobial fiber system, relying on a dissolved antimicrobial agent (demonstrated by X-ray diffraction and Infrared (IR)-spectroscopy) rather than a dispersed and "mixed-in" solid antibacterial particle phase, presents a new concept which opens the door to tougher, stronger and more ductile antimicrobial fibers.

  • 2.
    Blom, Hans
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Hassler, Kai
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Chmyrov, Andriy
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Electrostatic Interactions of Fluorescent Molecules with Dielectric Interfaces Studied by Total Internal Reflection Fluorescence Correlation Spectroscopy2010In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 11, no 2, p. 368-406Article in journal (Refereed)
    Abstract [en]

    Electrostatic interactions between dielectric surfaces and different fluorophoresused in ultrasensitive fluorescence microscopy are investigated using objective-based TotalInternal Reflection Fluorescence Correlation Spectroscopy (TIR-FCS). The interfacialdynamics of cationic rhodamine 123 and rhodamine 6G, anionic/dianionic fluorescein,zwitterionic rhodamine 110 and neutral ATTO 488 are monitored at various ionic strengthsat physiological pH. As analyzed by means of the amplitude and time-evolution of theautocorrelation function, the fluorescent molecules experience electrostatic attraction orrepulsion at the glass surface depending on their charges. Influences of the electrostaticinteractions are also monitored through the triplet-state population and triplet relaxationtime, including the amount of detected fluorescence or the count-rate-per-moleculeparameter. These TIR-FCS results provide an increased understanding of how fluorophoresare influenced by the microenvironment of a glass surface, and show a promising approachfor characterizing electrostatic interactions at interfaces.

  • 3.
    Dahlsson Leitao, Charles
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Rinne, S. S.
    Mitran, B.
    Vorobyeva, A.
    Andersson, Ken Gösta
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Tolmachev, V.
    Ståhl, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Löfblom, John
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Orlova, A.
    Molecular Design of HER3-Targeting Affibody Molecules: Influence of Chelator and Presence of HEHEHE-Tag on Biodistribution of 68 Ga-Labeled Tracers2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 5Article in journal (Refereed)
    Abstract [en]

    Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE)₃-tag) and two different gallium-68/chelator-complexes on the biodistribution of Z08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE)₃-Z08698-X and Z08698-X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE)₃-Z08698-X than for non-tagged variants. The neutral [68Ga]Ga-NODAGA complex reduced the hepatic uptake of Z08698 compared to positively charged [68Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE)3-tag. In conclusion, hydrophilic (HE)₃-tag and neutral charge of the [68Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z08698. [68Ga]Ga-(HE)₃-Z08698-NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.

  • 4. Guerriero, Gea
    et al.
    Silvestrini, Lucia
    Obersriebnig, Michael
    Hausman, Jean-Francois
    Strauss, Joseph
    Ezcurra, Inés
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    A WDR gene is a conserved member of a chitin synthase gene cluster and influences the cell wall in Aspergillus nidulans2016In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 17, no 7, p. 1031-Article in journal (Refereed)
    Abstract [en]

    WD40 repeat (WDR) proteins are pleiotropic molecular hubs. We identify a WDR gene that is a conserved genomic neighbor of a chitin synthase gene in Ascomycetes. The WDR gene is unique to fungi and plants, and was called Fungal Plant WD (FPWD). FPWD is within a cell wall metabolism gene cluster in the Ascomycetes (Pezizomycotina) comprising chsD, a Chs activator and a GH17 glucanase. The FPWD, AN1556.2 locus was deleted in Aspergillus nidulans strain SAA.111 by gene replacement and only heterokaryon transformants were obtained. The re-annotation of Aspergilli genomes shows that AN1556.2 consists of two tightly linked separate genes, i.e., the WDR gene and a putative beta-flanking gene of unknown function. The WDR and the beta-flanking genes are conserved genomic neighbors localized within a recently identified metabolic cell wall gene cluster in genomes of Aspergilli. The heterokaryons displayed increased susceptibility to drugs affecting the cell wall, and their phenotypes, observed by optical, confocal, scanning electron and atomic force microscopy, suggest cell wall alterations. Quantitative real-time PCR shows altered expression of some cell wall-related genes. The possible implications on cell wall biosynthesis are discussed.

  • 5.
    Liebmann, Thomas
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden..
    Fritz, Nicolas
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kruusmaegi, Markus
    Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden..
    Westin, Linda
    Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden..
    Bernhem, Kristoffer
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences (SCI), Applied Physics. Royal Inst Technol, Dept Appl Phys, Sci Life Lab, S-17121 Solna, Sweden..
    Bondar, Alexander
    Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia..
    Aperia, Anita
    Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden..
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden..
    Regulation of Neuronal Na,K-ATPase by Extracellular Scaffolding Proteins2018In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 8, article id 2214Article in journal (Refereed)
    Abstract [en]

    Neuronal activity leads to an influx of Na+ that needs to be rapidly cleared. The sodium-potassium ATPase (Na,K-ATPase) exports three Na+ ions and imports two K+ ions at the expense of one ATP molecule. Na,K-ATPase turnover accounts for the majority of energy used by the brain. To prevent an energy crisis, the energy expense for Na+ clearance must provide an optimal effect. Here we report that in rat primary hippocampal neurons, the clearance of Na+ ions is more efficient if Na,K-ATPase is laterally mobile in the membrane than if it is clustered. Using fluorescence recovery after photobleaching and single particle tracking analysis, we show that the ubiquitous alpha 1 and the neuron-specific alpha 3 catalytic subunits as well as the supportive beta 1 subunit of Na,K-ATPase are highly mobile in the plasma membrane. We show that cross-linking of the beta 1 subunit with polyclonal antibodies or exposure to Modulator of Na,K-ATPase (MONaKA), a secreted protein which binds to the extracellular domain of the beta subunit, clusters the alpha 3 subunit in the membrane and restricts its mobility. We demonstrate that clustering, caused by cross-linking or by exposure to MONaKA, reduces the efficiency in restoring intracellular Na+. These results demonstrate that extracellular interactions with Na,K-ATPase regulate the Na+ extrusion efficiency with consequences for neuronal energy balance.

  • 6. Ma, Zhanyu
    et al.
    Teschendorff, Andrew E.
    Yu, Hong
    Taghia, Jalil
    KTH, School of Electrical Engineering (EES), Communication Theory.
    Guo, Jun
    Comparisons of Non-Gaussian Statistical Models in DNA Methylation Analysis2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 6, p. 10835-10854Article in journal (Refereed)
    Abstract [en]

    As a key regulatory mechanism of gene expression, DNA methylation patterns are widely altered in many complex genetic diseases, including cancer. DNA methylation is naturally quantified by bounded support data; therefore, it is non-Gaussian distributed. In order to capture such properties, we introduce some non-Gaussian statistical models to perform dimension reduction on DNA methylation data. Afterwards, non-Gaussian statistical model-based unsupervised clustering strategies are applied to cluster the data. Comparisons and analysis of different dimension reduction strategies and unsupervised clustering methods are presented. Experimental results show that the non-Gaussian statistical model-based methods are superior to the conventional Gaussian distribution-based method. They are meaningful tools for DNA methylation analysis. Moreover, among several non-Gaussian methods, the one that captures the bounded nature of DNA methylation data reveals the best clustering performance.

  • 7.
    Muneer, Faraz
    et al.
    Swedish Univ Agr Sci, Dept Plant Breeding, Box 101, SE-23053 Alnarp, Sweden..
    Johansson, Eva
    Swedish Univ Agr Sci, Dept Plant Breeding, Box 101, SE-23053 Alnarp, Sweden..
    Hedenqvist, Mikael S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Plivelic, Tomas S.
    Lund Univ, MAX IV Lab, Box 118, SE-22100 Lund, Sweden..
    Kuktaite, Ramune
    Swedish Univ Agr Sci, Dept Plant Breeding, Box 101, SE-23053 Alnarp, Sweden..
    Impact of pH Modification on Protein Polymerization and Structure-Function Relationships in Potato Protein and Wheat Gluten Composites2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 1, article id 58Article in journal (Refereed)
    Abstract [en]

    Wheat gluten (WG) and potato protein (PP) were modified to a basic pH by NaOH to impact macromolecular and structural properties. Films were processed by compression molding (at 130 and 150 degrees C) of WG, PP, their chemically modified versions (MWG, MPP) and of their blends in different ratios to study the impact of chemical modification on structure, processing and tensile properties. The modification changed the molecular and secondary structure of both protein powders, through unfolding and re-polymerization, resulting in less cross-linked proteins. The beta-sheet formation due to NaOH modification increased for WG and decreased for PP. Processing resulted in cross-linking of the proteins, shown by a decrease in extractability; to a higher degree for WG than for PP, despite higher beta-sheet content in PP. Compression molding of MPP resulted in an increase in protein cross-linking and improved maximum stress and extensibility as compared to PP at 130 degrees C. The highest degree of cross-linking with improved maximum stress and extensibility was found for WG/MPP blends compared to WG/PP and MWG/MPP at 130 degrees C. To conclude, chemical modification of PP changed the protein structures produced under harsh industrial conditions and made the protein more reactive and attractive for use in bio-based materials processing, no such positive gains were seen for WG.

  • 8.
    Quehenberger, Julian
    et al.
    Research Division Biochemical Engineering, Institute of Chemical, Environmental and Bioscience Engineering, Faculty of Technical Chemistry, TU Wien, Vienna, 1060, Austria.
    Reichenbach, Tom
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Baumann, Niklas
    Research Division Biochemical Engineering, Institute of Chemical, Environmental and Bioscience Engineering, Faculty of Technical Chemistry, TU Wien, Vienna, 1060, Austria.
    Rettenbacher, Lukas
    Research Division Biochemical Engineering, Institute of Chemical, Environmental and Bioscience Engineering, Faculty of Technical Chemistry, TU Wien, Vienna, 1060, Austria.
    Divne, Christina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Spadiut, Oliver
    Research Division Biochemical Engineering, Institute of Chemical, Environmental and Bioscience Engineering, Faculty of Technical Chemistry, TU Wien, Vienna, 1060, Austria.
    Kinetics and Predicted Structure of a Novel Xylose Reductase from Chaetomium thermophilum.2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 1, article id E185Article in journal (Refereed)
    Abstract [en]

    While in search of an enzyme for the conversion of xylose to xylitol at elevated temperatures, a xylose reductase (XR) gene was identified in the genome of the thermophilic fungus Chaetomium thermophilum. The gene was heterologously expressed in Escherichia coli as a His6-tagged fusion protein and characterized for function and structure. The enzyme exhibits dual cofactor specificity for NADPH and NADH and prefers D-xylose over other pentoses and investigated hexoses. A homology model based on a XR from Candida tenuis was generated and the architecture of the cofactor binding site was investigated in detail. Despite the outstanding thermophilicity of its host the enzyme is, however, not thermostable.

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