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  • 1. Agnarsdottir, Margret
    et al.
    Sooman, Linda
    Bolander, Asa
    Stromberg, Sara
    Rexhepaj, Elton
    Bergqvist, Michael
    Ponten, Fredrik
    Gallagher, William
    Lennartsson, Johan
    Ekman, Simon
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hedstrand, Hakan
    SOX10 expression in superficial spreading and nodular malignant melanomas2010In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, no 6, p. 468-478Article in journal (Refereed)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P = 0.008). The staining intensity was also inversely correlated with T-stage (Spearman's rho = -0.261, P = 0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (rho = -0.173, P = 0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P <= 0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn. Melanoma Res 20:468-478

  • 2. Agostinho, Ana
    et al.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van Schendel, Robin
    Hernandez-Hernandez, Abrahan
    Kouznetsova, Anna
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höög, Christer
    High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation2016In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 17, no 6, p. 901-913Article in journal (Refereed)
    Abstract [en]

    During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.

  • 3.
    Ahrenstedt, Lage
    KTH, School of Biotechnology (BIO).
    Surface modification of cellulose materials: from wood pulps to artificial blood vessels2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This thesis describes the improvement of two radically different cellulose materials, paper and artificial blood vessels, constructed from two diverse cellulose sources, wood pulp and Acetobacter xylinum. The improvement of both materials was possible due to the natural affinity of the hemicellulose xyloglucan for cellulose.

    Chemical and mechanical pulps were treated with xyloglucan in the wet-end prior to hand sheet formation or by spray application of dry hand sheets, loading a comparable amount of xyloglucan. The tensile strength increases for the wet-end treatment and spray application were 28% and 71% respectively for bleached soft wood, compared to untreated sheets (20.7 Nm/g). The corresponding strength increases for hand sheets made of thermo-mechanical pulp were 6% and 13% respectively compared to untreated sheets (42.4 Nm/g). The tendency for chemical pulp to be superior to mechanical pulp with respect to strength increase was valid even for tear strength and Scott-Bond. These results suggest, in agreement with other studies, that adhesion of xyloglucan to wood fibres is dependent on their degree of surface lignification.

    Also, a method was developed to increase the blood compatibility of artificial blood vessels constructed of bacterial cellulose. Xyloglucan was covalently linked to the endothelial cell adhesion motif (Arg-Gly-Asp). To obtain this, new solid-phase coupling chemistry was developed. Xyloglucan oligosaccharides (XGO) were transformed into XGO-succinamic acid via the corresponding XGO--NH2 derivative prior to coupling with the N-terminus of the solid-phase synthesised Gly-Arg-Gly-Asp-Ser peptide. The resin-bound glyco-peptide was then cleaved and enzymatically re-incorporated into high molecular weight xyloglucan. The glyco-peptide was further adsorbed onto bacterial cellulose scaffolds, increasing the adhesion and proliferation of endothelial cells and therefore blood compatibility.

  • 4.
    Akhras, Michael S.
    KTH, School of Biotechnology (BIO).
    Nucleic Acid Based Pathogen Diagnostics2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Pathogenic organisms are transmitted to the host organism through all possible connected pathways, and cause a myriad of diseases states. Commonly occurring curable infectious diseases still impose the greatest health impacts on a worldwide perspective. The Bill & Melinda Gates Foundation partnered with RAND Corporation to form the Global Health Diagnostics Forum, with the goal of establishing and interpreting mathematical models for what effects a newly introduced point-of-care pathogen diagnostic would have in developing countries. The results were astonishing, with potentially millions of lives to be saved on an annual basis.

    Golden standard for diagnostics of pathogenic bacteria has long been cultureable medias. Environmental biologists have estimated that less than 1% of all bacteria are cultureable. Genomic-based approaches offer the potential to identify all microbes from all the biological kingdoms. Nucleic acid based pathogen diagnostics has evolved significantly over the past decades. Novel technologies offer increased potential in sensitivity, specificity, decreased costs and parallel sample management. However, most methods are confined to core laboratory facilities. To construct an ultimate nucleic acid based diagnostic for use in areas of need, potential frontline techniques need to be identified and combined.

    The research focus of this doctoral thesis work has been to develop and apply nucleic acid based methods for pathogen diagnostics. Methods and assays were applied to the two distinct systems i) screening for antibiotic resistance mutations in the bacterial pathogen Neisseria gonorrhoeae, and ii) genotype determination of the cancer causative Human Papillomavirus (HPV). The first part of the study included development of rapid, direct and multiplex Pyrosequencing nucleic acid screenings. With improved methodology in the sample preparation process, we could detect an existence of multiple co-infecting HPV genotypes at greater sensitivities than previously described, when using the same type of methodology. The second part of the study focused on multiplex nucleic acid amplification strategies using Molecular Inversion Probes with end-step Pyrosequencing screening. The PathogenMip assay presents a complete detection schematic for virtually any known pathogenic organism. We also introduce the novel Connector Inversion Probe, a padlock probe capable of complete gap-fill reactions for multiplex nucleic acid amplifications.

  • 5.
    Akkuratov, Evgeny E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab. St Petersburg State Univ, Inst Translat Biomed, St Petersburg, Russia.
    Gelfand, Mikhail S.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia.;Natl Res Univ, Higher Sch Econ, Fac Comp Sci, Moscow, Russia.;MM Lomonosov Moscow State Univ, Dept Bioengn & Bioinformat, Moscow, Russia..
    Khrameeva, Ekaterina E.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia..
    Neanderthal and Denisovan ancestry in Papuans: A functional study2018In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 16, no 2, article id 1840011Article in journal (Refereed)
    Abstract [en]

    Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.

  • 6.
    Albertsson, Ann-Christine
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Voepel, Jens
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Edlund, Ulrica
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Dahlman, Olof
    Soderqvist-Lindblad, Margaretha
    Design of Renewable Hydrogel Release Systems from Fiberboard Mill Wastewater2010In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, no 5, p. 1406-1411Article in journal (Refereed)
    Abstract [en]

    A new route for the design of renewable hydrogels is presented. The soluble waste from masonite production was isolated, fractionized, and upgraded. The resulting hemicellulose rich fraction was alkenyl-functionalized and used in the preparation of covalently cross-linked hydrogels capable of sustained release of incorporated agents. Said hydrogels showed a Fickian diffusion-based release of incorporated bovine serum albumin. Also, a method for the coating of seeds with hydrogel was developed. The sustained release of incorporated growth retardant agents from the hydrogel coating on rape seeds was shown to enable the temporary inhibition of germination.

  • 7.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lee, Woojoo
    Pernemalm, Maria
    Guegan, Justin
    Dessen, Philippe
    Lazar, Vladimir
    Lehtio, Janne
    Pawitan, Yudi
    Network enrichment analysis: extension of gene-set enrichment analysis to gene networks2012In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 13, p. 226-Article in journal (Refereed)
    Abstract [en]

    Background: Gene-set enrichment analyses (GEA or GSEA) are commonly used for biological characterization of an experimental gene-set. This is done by finding known functional categories, such as pathways or Gene Ontology terms, that are over-represented in the experimental set; the assessment is based on an overlap statistic. Rich biological information in terms of gene interaction network is now widely available, but this topological information is not used by GEA, so there is a need for methods that exploit this type of information in high-throughput data analysis. Results: We developed a method of network enrichment analysis (NEA) that extends the overlap statistic in GEA to network links between genes in the experimental set and those in the functional categories. For the crucial step in statistical inference, we developed a fast network randomization algorithm in order to obtain the distribution of any network statistic under the null hypothesis of no association between an experimental gene-set and a functional category. We illustrate the NEA method using gene and protein expression data from a lung cancer study. Conclusions: The results indicate that the NEA method is more powerful than the traditional GEA, primarily because the relationships between gene sets were more strongly captured by network connectivity rather than by simple overlaps.

  • 8.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schmitt, Thomas
    Tjärnberg, Andreas
    Stockholm University, Science for Life Laboratory.
    Guala, Dmitri
    Stockholm University, Science for Life Laboratory.
    Frings, Oliver
    Stockholm University, Science for Life Laboratory.
    Sonnhammer, Erik L. L.
    Stockholm University, Science for Life Laboratory.
    Comparative interactomics with Funcoup 2.02012In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no D1, p. D821-D828Article in journal (Refereed)
    Abstract [en]

    FunCoup (http://FunCoup.sbc.su.se) is a database that maintains and visualizes global gene/protein networks of functional coupling that have been constructed by Bayesian integration of diverse high-throughput data. FunCoup achieves high coverage by orthology-based integration of data sources from different model organisms and from different platforms. We here present release 2.0 in which the data sources have been updated and the methodology has been refined. It contains a new data type Genetic Interaction, and three new species: chicken, dog and zebra fish. As FunCoup extensively transfers functional coupling information between species, the new input datasets have considerably improved both coverage and quality of the networks. The number of high-confidence network links has increased dramatically. For instance, the human network has more than eight times as many links above confidence 0.5 as the previous release. FunCoup provides facilities for analysing the conservation of subnetworks in multiple species. We here explain how to do comparative interactomics on the FunCoup website.

  • 9. Allerbring, Eva B.
    et al.
    Duru, Adil D.
    Chadderton, Jesseka
    Markov, Natalia
    Uchtenhagen, Hannes
    Popov, Alexander
    Madhurantakam, Chaithanya
    Sandalova, Tatyana
    Turner, Stephen J.
    Nygren, Per-Åke
    KTH, School of Biotechnology (BIO), Protein Technology.
    Achour, Adnane
    Structural and thermodynamic basis underlying in vivo reestablishment of T-cell recognition of a viral escape mutant2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 68, no 2, p. 151-151Article in journal (Other academic)
  • 10.
    Alm, Tove
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Introducing the Affinity Binder Knockdown Initiative-A public-private partnership for validation of affinity reagents2016In: EuPA Open Proteomics, ISSN 0014-2328, E-ISSN 2212-9685, Vol. 10, p. 56-58Article in journal (Refereed)
    Abstract [en]

    The newly launched Affinity Binder Knockdown Initiative encourages antibody suppliers and users to join this public-private partnership, which uses crowdsourcing to collect characterization data on antibodies. Researchers are asked to share validation data from experiments where gene-editing techniques (such as siRNA or CRISPR) have been used to verify antibody binding. The initiative is launched under the aegis of Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies towards human protein targets. What is known about an antibody is the foundation of the scoring and ranking system in Antibodypedia.

  • 11.
    Alm, Tove
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    von Feilitzen, Kalle
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sivertsson, Åsa
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    A Chromosome-Centric Analysis of Antibodies Directed toward the Human Proteome Using Antibodypedia2014In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 3, p. 1669-1676Article in journal (Refereed)
    Abstract [en]

    Antibodies are crucial for the study of human proteins and have been defined as one of the three pillars in the human chromosome-centric Human Proteome Project (CHPP). In this article the chromosome-centric structure has been used to analyze the availability of antibodies as judged by the presence within the portal Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies toward human protein targets. This public database displays antibody data from more than one million antibodies toward human protein targets. A summary of the content in this knowledge resource reveals that there exist more than 10 antibodies to over 70% of all the putative human genes, evenly distributed over the 24 human chromosomes. The analysis also shows that at present, less than 10% of the putative human protein-coding genes (n = 1882) predicted from the genome sequence lack antibodies, suggesting that focused efforts from the antibody-based and mass spectrometry-based proteomic communities should be encouraged to pursue the analysis of these missing proteins. We show that Antibodypedia may be used to track the development of available and validated antibodies to the individual chromosomes, and thus the database is an attractive tool to identify proteins with no or few antibodies yet generated.

  • 12.
    Alm, Tove
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Yderland, Louise
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Nilvebrant, Johan
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Halldin, Anneli
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    A small bispecific protein selected for orthogonal affinity purification2010In: BIOTECHNOL J, ISSN 1860-6768, Vol. 5, no 6, p. 605-617Article in journal (Refereed)
    Abstract [en]

    A novel protein domain with dual affinity has been created by randomization and selection. The small alkali-stabilized albumin-binding domain (ABD(star)), used as scaffold to construct the library, has affinity to human serum albumin (HSA) and is constituted of 46 amino acids of which 11 were randomized. To achieve a dual binder, the binding site of the inherent HSA affinity was untouched and the randomization was made on the opposite side of the molecule. Despite its small size and randomization of almost a quarter of its amino acids, a bifunctional molecule, ABDz1, with ability to bind to both HSA and the Z(2) domain/protein A was successfully selected using phage display. Moreover, the newly selected variant showed improved affinity for HSA compared to the parental molecule. This novel protein domain has been characterized regarding secondary structure and affinity to the two different ligands. The possibility for affinity purification on two different matrices has been investigated using the two ligands, the HSA matrix and the protein A-based, MabSelect SuRe matrix, and the new protein domain was purified to homogeneity. Furthermore, gene fusions between the new domain and three different target proteins with different characteristics were made. To take advantage of both affinities, a purification strategy referred to as orthogonal affinity purification using two different matrices was created. Successful purification of all three versions was efficiently carried out using this strategy.

  • 13.
    Almquist, Ann-Charlotte
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Fäldt, Jenny
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Yart, A.
    Chevet, Y.
    Sauvard, D.
    Lieutier, F.
    Borg-Karlson, Anna Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Host selection in Tomicus piniperda L.: Composition of monoterpene hydrocarbons in relation to attack frequency in the shoot feeding phase2006In: Zeitschrift fur Naturforschung - Section C Journal of Biosciences, ISSN 0939-5075, Vol. 61, no 5-6, p. 439-444Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the host selection capacity of the pine shoot beetle, Tomicus piniperda, in the shoot-feeding phase and analyze the chiral and non-chiral host volatiles by means of GC-MS and 2D-GC in five Pinus species originating from France (Pinus sylvestris, P. halepensis, P. nigra laricio, P. pinaster maritima, P. pinaster mesogeensis). Dominating monoterpenes were (-)-α-pinene, (+)-α-pinene, (-)-β-pinene and (+)-3-carene. The amounts of the enantiomers varied considerably within and among the species. In a principal component analysis-plot, based on the absolute amounts of 18 monoterpene hydrocarbons, separation of the pine species into two groups was obtained. P. halepensis and P. sylvestris were grouped according to the amount of (+)-α-pinene and (+)-3-carene, while P. nigra laricio, P. pinaster maritima and P. pinaster mesogeensis were grouped according to (-)-α-pinene and (-)-β-pinene. P. nigra laricio was the species most attacked and P. halepensis the one least attacked by T. piniperda.

  • 14.
    Alneberg, Johannes
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bjarnason, Brynjar Smári
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    de Bruijn, Ino
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Bioinformatics Infrastructure for Life Sciences (BILS), Sweden.
    Schirmer, Melanie
    Quick, Joshua
    Ijaz, Umer Z.
    Lahti, Leo
    Loman, Nicholas J.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Quince, Christopher
    Binning metagenomic contigs by coverage and composition2014In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 11, no 11, p. 1144-1146Article in journal (Refereed)
    Abstract [en]

    Shotgun sequencing enables the reconstruction of genomes from complex microbial communities, but because assembly does not reconstruct entire genomes, it is necessary to bin genome fragments. Here we present CONCOCT, a new algorithm that combines sequence composition and coverage across multiple samples, to automatically cluster contigs into genomes. We demonstrate high recall and precision on artificial as well as real human gut metagenome data sets.

  • 15. Altai, M.
    et al.
    Wallberg, H.
    Honarvar, H.
    Strand, J.
    Orlova, A.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Varasteh, Z.
    Sandström, M.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Re-188-Z(HER2: V2), a promising targeting agent against HER2-expressing tumors: in vitro and in vivo assessment2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, p. S119-S119Article in journal (Other academic)
  • 16. Altai, Mohamed
    et al.
    Strand, Joanna
    Rosik, Daniel
    Selvaraju, Ram Kumar
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Orlova, Anna
    Tolmachev, Vladimir
    Influence of Nuclides and Chelators on Imaging Using Affibody Molecules: Comparative Evaluation of Recombinant Affibody Molecules Site-Specifically Labeled with Ga-68 and In-111 via Maleimido Derivatives of DOTA and NODAGA2013In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, no 6, p. 1102-1109Article in journal (Refereed)
    Abstract [en]

    Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more of personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use should increase sensitivity of HER2 imaging. The chemical nature of the generator-produced positron-emitting radionuclide Ga-68 of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant Z(HER2:2395) HER2-binding Affibody molecule with Ga-68. DOTA and NODAGA were site-specifically conjugated to the Z(HER2:2395) Affibody molecule having a C-terminal cysteine and labeled with Ga-68 and In-111. All labeled conjugates retained specificity to HER2 in vitro. Most of the cell-associated activity was membrane-bound with a minor difference in internalization rate. All variants demonstrated specific targeting of xenografts and a high tumor uptake. The xenografts were dearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for Ga-68 than for In-111. The tumor uptake of Ga-68-NODAGA-Z(HER2:2395) and Ga-68-NODAGA-Z(HER2:2395) and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for Ga-68-NODAGA- Z(HER2:2395) (8 +/- 2 vs 5.0 +/- 0.3) offering the advantage of better liver metastases visualization. In conclusion, influence of chelators on biodistribution of Affibody molecules depends on the radionuclides and reoptimization of labeling chemistry is required when a radionuclide label is changed.

  • 17. Altai, Mohamed
    et al.
    Wållberg, Helena
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Orlova, Anna
    Rosestedt, Maria
    Hosseinimehr, Seyed Jalal
    Tolmachev, Vladimir
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of Tc-99m-labeled recombinant Affibody molecules2012In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 42, no 5, p. 1975-1985Article in journal (Refereed)
    Abstract [en]

    Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide Tc-99m. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of Tc-99m-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied Tc-99m-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of Tc-99m. The biodistribution of all Tc-99m-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of Tc-99m was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates.

  • 18.
    Ampomah, Osei Yaw
    et al.
    University of Tromso.
    Jensen, John Beck
    University of Tromso.
    Bhuvaneswari, T V
    University of Tromso.
    Lack of trehalose catabolism in Sinorhizobium species increases their nodulation competitiveness on certain host genotypes2008In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 179, no 2, p. 495-504Article in journal (Refereed)
    Abstract [en]

    The role of host and bacterial genotypes in determining the competitiveness of trehalose utilization mutants of Sinorhizobium meliloti and Sinorhizobium medicae was investigated here. Trehalose utilization mutants of S. meliloti and S. medicae were obtained by mutagenesis of their trehalose utilization gene thuB. The mutant strains and the wild type were coinoculated on three cultivars of alfalfa (Medicago sativa) and two cultivars of Medicago truncatula and assessed for competitiveness in root colonization, and nodule occupancy. The thuB mutants formed more nodules than their parent strains on two of the three alfalfa lines tested and on one of the two M. truncatula lines tested. They were not more competitive on the other alfalfa and M. truncatula lines. Their competitiveness for nodule occupancy did not correlate positively with their ability to colonize these roots but correlated with the extent of thuB induction in the infection threads. Induction of thuB was shown to be dependent on the concentration of trehalose in the environment. These results suggest a direct role for host trehalose metabolism in early plant-symbiont interactions and show that the ability to manage host-induced stresses during infection, rather than the ability to colonize the root, is critical for competitive nodulation.

  • 19.
    An, Junxue
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Dédinaité, Andra
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Nilsson, Anki
    Holgersson, Jan
    Claesson, Per M.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Comparison of a Brush-with-Anchor and a Train-of-Brushes Mucin on Poly(methyl methacrylate) Surfaces: Adsorption, Surface Forces, and Friction2014In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, no 4, p. 1515-1525Article in journal (Refereed)
    Abstract [en]

    Interfacial properties of two types of mucins have been investigated at the aqueous solution/poly(methyl methacrylate) (PMMA) interface. One is commercially available bovine submaxillary mucin, BSM, which consists of alternating glycosylated and nonglycosylated regions. The other one is a recombinant mucin-type fusion protein, PSGL-1/mIgG(2b), consisting of a glycosylated mucin part fused to the Fc part of an immunoglobulin. PSGL-1/mIgG(2b) is mainly expressed as a (timer upon production. A quartz crystal microbalance with dissipation was used to study the adsorption of the mucins to PMMA surfaces. The mass of the adsorbed mucin layers, including the adsorbed mucin and water trapped in the layer, was found to be significantly higher for PSGL-1/mIgG(2b) than for BSM. Atomic force microscopy with colloidal probe was employed to study interactions and frictional forces between mucin-coated PMMA surfaces. Purely repulsive forces of steric origin were Observed between PSGL-1/mIgG(2b) mucin layers, whereas a small adhesion was detected between BSM layers and attributed to bridging. Both mucin layers reduced the friction force between PMMA surfaces in aqueous solution. The reduction was, however, significantly more pronounced for PSGL-1/mIgG(2b). The effective friction coefficient between PSGL-1/mIgG(2b)-coated PMMA surfaces is as low as 0.02 at low loads, increasing to 0.24 at the highest load explored, 50 nN. In contrast, a friction coefficient of around 0.7 was obtained between BSM-coated PMMA surfaces. The large differences in interfacial properties for the two mucins are discussed in relation to their structural differences.

  • 20. Anderbrant, Olle
    et al.
    Matteson, Donald S.
    Unelius, C. Rikard
    Pharazyn, Philip S.
    Santangelo, Ellen M.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Schlyter, Fredrik
    Birgersson, Goran
    Pheromone of the elm bark beetle Scolytus laevis (Coleoptera Scolytidae): stereoisomers of 4-methyl-3-heptanol reduce interspecific competition2010In: Chemoecology, ISSN 0937-7409, E-ISSN 1423-0445, Vol. 20, no 3, p. 179-187Article in journal (Refereed)
    Abstract [en]

    Stereoisomers of 4-methyl-3-heptanol (MH) are pheromone components of several Scolytus bark beetles. The elm bark beetle Scolytus laevis (Coleoptera: Scolytidae) has in previous studies been caught in traps baited with commercial MH containing all four stereoisomers, but the lure has been considered a weak attractant. In this study, we addressed the question whether stereospecific responses by S. laevis to stereoisomers of MH might contribute to its niche separation from other sympatric Scolytus species. Using GC-MS, we analyzed extracts of hindguts and abdomens from male and female S. laevis and the sympatric S. triarmatus. We also tested all four MH-stereoisomers individually and in combinations in the field to determine their role for S. laevis. All four stereoisomers were synthesized via a boronic ester method with 1,2-dicyclohexylethanediol as chiral director. In addition, the (3S,4R)-stereoisomer of MH was prepared through enantioselective, lipase-mediated transesterification of a mixture of the four stereoisomers of MH. Females of both species contained small amounts of syn-MH, and males contained trace amounts of anti-MH. The anti stereoisomer (3R,4S)-MH was attractive to male and female S. laevis, whereas the syn stereoisomer (3S,4S)-MH acted as an inhibitor or deterrent and reduced the catch when added to the attractive isomer. The syn isomer is the main aggregation pheromone component of the larger and sympatric S. scolytus and possibly also of S. triarmatus. The avoidance response of S. laevis to the (3S,4S)-stereoisomer may reduce interspecific competition for host trees.

  • 21.
    Andersen, Malin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Engström, Pär
    Lithwick, Stuart
    Arenillas, David
    Eriksson, Per
    Lenhard, Boris
    Wasserman, Wyeth
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO), Gene Technology.
    In silico detection of sequence variations modifying transcriptional regulation2008In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 4, no 1, p. e5-Article in journal (Refereed)
    Abstract [en]

    Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN ( regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

  • 22.
    Andersen, Malin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Lenhard, Boris
    Whatling, Carl
    Eriksson, Per
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO), Gene Technology.
    Alternative promoter usage of the membrane glycoprotein CD362006In: BMC Molecular Biology, ISSN 1471-2199, E-ISSN 1471-2199, Vol. 7, p. 8-Article in journal (Refereed)
    Abstract [en]

    Background: CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation.

    Results: We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters.

    Conclusion: Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  • 23.
    Anderson, Mattias
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Amine Transaminases in Multi-Step One-Pot Reactions2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Amine transaminases are enzymes that catalyze the mild and selective formation of primary amines, which are useful building blocks for biologically active compounds and natural products. In order to make the production of these kinds of compounds more efficient from both a practical and an environmental point of view, amine transaminases were incorporated into multi-step one-pot reactions. With this kind of methodology there is no need for isolation of intermediates, and thus unnecessary work-up steps can be omitted and formation of waste is prevented. Amine transaminases were successfully combined with other enzymes for multi-step synthesis of valuable products: With ketoreductases all four diastereomers of a 1,3-amino alcohol could be obtained, and the use of a lipase allowed for the synthesis of natural products in the form of capsaicinoids. Amine transaminases were also successfully combined with metal catalysts based on palladium or copper. This methodology allowed for the amination of alcohols and the synthesis of chiral amines such as the pharmaceutical compound Rivastigmine. These examples show that the use of amine transaminases in multi-step one-pot reactions is possible, and hopefully this concept can be further developed and applied to make industrial processes more sustainable and efficient in the future.

  • 24. Andersson, E.
    et al.
    Stenrup, Michael
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Eland, J.H.D.
    Hedin, L.
    Berglund, M.
    Karlsson, L.
    Larson, Åsa
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Rubensson, Jan Erik
    Feifel, Raimund
    Single-photon core-valence double ionization of molecular oxygen2008In: Physical Review A. Atomic, Molecular, and Optical Physics, ISSN 1050-2947, E-ISSN 1094-1622, Vol. 78, no 2, p. 023409-Article in journal (Refereed)
    Abstract [en]

    Single-photon core-valence double ionization of molecular oxygen has been studied using a magnetic bottle time-of-flight electron coincidence spectrometer. The K-1 V-1 double ionization electron spectrum of O2 is reported and is assigned with the aid of ab initio calculations. A direct comparison of the core-valence double ionization electron spectra with the conventional valence band photoelectron spectrum is made. The lowest core-valence double ionization energy is found to be 571.6 eV and is associated with a Π3 dicationic state.

  • 25.
    Andersson, Helene
    et al.
    KTH, Superseded Departments, Biotechnology.
    van den Berg, A.
    Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities2004In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 4, no 2, p. 98-103Article, review/survey (Refereed)
    Abstract [en]

    An introductory overview of the use of microfluidic devices for tissue engineering is presented. After a brief description of the background of tissue engineering, different application areas of microfluidic devices are examined. Among these are methods for patterning cells, topographical control over cells and tissues, and bioreactors. Examples where microfluidic devices have been employed are presented such as basal lamina, vascular tissue, liver, bone, cartilage and neurons. It is concluded that until today, microfluidic devices have not been used extensively in tissue engineering. Major contributions are expected in two areas. The first is growth of complex tissue, where microfluidic structures ensure a steady blood supply, thereby circumventing the well-known problem of providing larger tissue structures with a continuous flow of oxygen and nutrition, and withdrawal of waste products. The second, and probably more important function of microfluidics, combined with micro/nanotechnology, lies in the development of in vitro physiological systems for studying fundamental biological phenomena.

  • 26.
    Andersson, Helene
    et al.
    KTH, Superseded Departments, Signals, Sensors and Systems.
    van den Berg, A.
    Microtechnologies and nanotechnologies for single-cell analysis2004In: Current Opinion in Biotechnology, ISSN 0958-1669, E-ISSN 1879-0429, Vol. 15, no 1, p. 44-49Article, review/survey (Refereed)
    Abstract [en]

    Many efforts are currently underway to try and mimic the properties of single cells with the aim of designing chips that are as efficient as cells. However, cells are nature's nanotechnology engineering at the scale of atoms and molecules, and it might be better to envision a microchip that utilizes a single cell as an experimentation platform. A novel, so-called laboratory-in-a-cell concept has been described, where advantage is taken of micro-and nanotechnological tools to enable precise control of the biochemical cellular environment; these tools also offer the possibility to analyse the composition of single cells. Methods for single-cell handling and analysis are being developed and will be required for this concept to progress further.

  • 27.
    Andersson, Ken G.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Combinatorial Protein Engineering Of Affibody Molecules Using E. Coli Display And Rational Design Of Affibody-Based Tracers For Medical Imaging2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Directed evolution is today an established strategy for generation of new affinity proteins. This thesis describes the development of a cell-display method using Escherichia coli for directed evolution of Affibody molecules. Further, the thesis describes rational design of Affibody-based tracers, intended for future patient stratification using medical imaging. Fusing recombinant proteins to various autotransporters is a promising approach for efficient surface display on the surface of E. coli, as well as for construction of high-complexity libraries. In paper I, we successfully engineered an expression vector for display of Affibody molecules using the autotransporter AIDA-I. In paper II, a large Affibody library of 2.3x109 variants was constructed and screening using FACS resulted in new specific binders in the nanomolar range. In paper III, we demonstrated Sortase-mediated secretion and conjugation of binders directly from the E. coli surface. 

    The three following studies describe rational design of Affibody-based tracers against two cancer-associated targets for molecular imaging. First, anti-HER3 Affibody molecules were labelled with 111In, and SPECT imaging showed that the conjugates specifically targeted HER3-expressing xenografts. Furthermore, labeling with 68Ga for PET imaging showed that tumor uptake correlated with HER3 expression, suggesting that the tracers have potential for patient stratification. The last study describes the development and investigation of anti-EGFR Affibody-based imaging agents. Labeled with 89Zr, the Affibody tracer demonstrated higher tumor uptake at 3 h post injection than the anti-EGFR antibody cetuximab at 48 h post injection. 

    In conclusion, this thesis describes new tools and knowledge that will hopefully contribute to the development of affinity proteins for biotechnology, therapy and medical imaging in the future. 

     

  • 28.
    Andersson, Ken G.
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Persson, Jonas
    KTH, School of Biotechnology (BIO), Protein Technology. Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Autotransporter-mediated display of a naïve Affibody library on the outer membrane of E. coliManuscript (preprint) (Other academic)
    Abstract [en]

    Development of new affinity proteins using combinatorial protein engineering is today established for generation of monoclonal antibodies and also essential for discovery of binders that are based on non-immunoglobulin proteins. Phage display is the most frequently used method, but yeast display is becoming increasingly popular, partly due to the option of utilizing fluorescence-activated cell sorting (FACS) for isolation of new candidates. Escherichia coli have several properties that are valuable for library applications and then in particular the high transformation efficiency. Although the first studies on display of recombinant peptides and proteins on E. coli were reported over 25 years ago, the method is still not fully established for directed evolution of affinity proteins. More recently, the use of various autotransporters and intimins for secretion and anchoring on the outer membrane have shown promising results and in particular for directed evolution of different enzymes. Here, we report on display of a large naïve Affibody library on the outer membrane of E. coli using the autotransporter AIDA-I. The expression cassette was first engineered by removing non-essential sequences, followed by introduction of an Affibody library, comprising more than 109 variants, into the new display vector. Selections by FACS against five different target molecules resulted in a panel of binders with down to nanomolar affinities.

  • 29.
    Andersson, Ken G.
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Sjöstrand, Nanna
    KTH, School of Biotechnology (BIO), Protein Technology.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Coupled release and site-specific conjugation of Affibody molecules from the surface of E. coli using Sortase AManuscript (preprint) (Other academic)
    Abstract [en]

    Combinatorial protein engineering using libraries displayed on various microorganisms is a powerful method forgeneration of new affinity proteins. Successful efforts often result in broad panels of isolated binders, which are thentypically subcloned, produced, purified and characterized in various assays. Many such assays also require conjugation tofor example reporters or other functional molecules and the downstream production and modification thus tends to be verylaborious and limits the number of candidates that can be screened. Staphylococcal sortase A is a natural transpeptidasethat catalyzes the ligation between a LPXTG motif and N-terminal glycines and is today used in a variety of applicationsfor site-specific conjugation of different molecules to recombinant proteins. We have previously developed a surfacedisplay method for combinatorial protein engineering of Affibody molecules on the outer membrane of E. coli usingautodisplay. Here, we introduced a sortase-A recognition motif into the displayed recombinant proteins and evaluatedsortase-mediated release and specific conjugation of various reporters to Affibody molecules. The approach has potentialto significantly increase the flexibility and throughput of downstream characterization of affinity proteins after directedevolution using cell display and FACS.

  • 30.
    Andersson, Robert
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology.
    Boutonnet, Magali
    KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Chemical Technology.
    Järås, Sven
    KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology.
    On-line gas chromatographic analysis of higher alcohol synthesis products from syngas2012In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1247, p. 134-145Article in journal (Refereed)
    Abstract [en]

    An on-line gas chromatographic (GC) system has been developed for rapid and accurate product analysis in catalytic conversion of syngas (a mixture of H-2 and CO) to alcohols, so called "higher alcohol synthesis (HAS)". Conversion of syngas to higher alcohols is an interesting second step in the route of converting coal, natural gas and possibly biomass to liquid alcohol fuel and chemicals. The presented GC system and method are developed for analysis of the products formed from syngas using alkali promoted MoS2 catalysts, however it is not limited to these types of catalysts. During higher alcohol synthesis not only the wanted short alcohols (similar to C-2-C-5) are produced, but also a great number of other products in smaller or greater amounts, they are mainly short hydrocarbons (olefins, paraffins, branched, non-branched), aldehydes, esters and ketones as well as CO2, H2O. Trace amounts of sulfur-containing compounds can also be found in the product effluent when sulfur-containing catalysts are used and/or sulfur-containing syngas is feed. In the presented GC system, most of them can be separated and analyzed within 60 min without the use of cryogenic cooling. Previously, product analysis in "higher alcohol synthesis" has in most cases been carried out partly on-line and partly off-line, where the light gases (gases at room temp) are analyzed on-line and liquid products (liquid at room temp) are collected in a trap for later analysis off-line. This method suffers from many drawbacks compared to a complete on-line GC system. In this paper an on-line system using an Agilent 7890 gas chromatograph equipped with two flame ionization detectors (FID) and a thermal conductivity detector (TCD), together with an Agilent 6890 with sulfur chemiluminescence dual plasma detector (SCD) is presented. A two-dimensional GC system with Deans switch (heart-cut) and two capillary columns (HP-FFAP and HP-Al2O3) was used for analysis of the organic products on the FIDs. Light inorganic gases (H-2, CO, CO2, N-2) and methane were separated on packed columns and quantified with the TCD. The "sulfur GC" was optimized for on-line trace level sulfur analysis in hydrocarbon matrices and used to understand to which degree sulfur is released from the catalyst and incorporated into the liquid product, and if so in which form. The method provides excellent quantitative measurements with a carbon material balance near 99.5% (carbon in/carbon out) for individual measurement points.

  • 31.
    Andersson Svahn, Helene
    et al.
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). University of Twente, Netherlands .
    Van Den Berg, A.
    Single cells or large populations?2007In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 7, no 5, p. 544-546Article in journal (Refereed)
  • 32. Andõn, F. T.
    et al.
    Kapralov, A. A.
    Yanamala, N.
    Feng, W.
    Baygan, Arjang
    Karolinska Institutet.
    Chambers, B. J.
    Hultenby, K.
    Ye, Fei
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.
    Toprak, Muhammet S.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.
    Brandner, B. D.
    Fornara, Andrea
    Institute for Surface Chemistry, Stockholm.
    Klein-Seetharaman, J.
    Kotchey, G. P.
    Star, A.
    Shvedova, Anna A.
    West Virginia University, USA.
    Fadeel, B.
    Kagan, V. E.
    Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase2013In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 9, no 16, p. 2721-2729Article in journal (Refereed)
    Abstract [en]

    Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes.

  • 33.
    Ansari, Farhan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Berglund, Lars A.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Toward Semistructural Cellulose Nanocomposites: The Need for Scalable Processing and Interface Tailoring2018In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 7, p. 2341-2350Article in journal (Refereed)
    Abstract [en]

    Cellulose nanocomposites can be considered for semistructural load-bearing applications where modulus and strength requirements exceed 10 GPa and 100 MPa, respectively. Such properties are higher than for most neat polymers but typical for molded short glass fiber composites. The research challenge for polymer matrix biocomposites is to develop processing concepts that allow high cellulose nanofibril (CNF) content, nanostructural control in the form of well-dispersed CNF, the use of suitable polymer matrices, as well as molecular scale interface tailoring to address moisture effects. From a practical point of view, the processing concept needs to be scalable so that large-scale industrial processing is feasible. The vast majority of cellulose nanocomposite studies elaborate on materials with low nanocellulose content. An important reason is the challenge to prevent CNF agglomeration at high CNF content. Research activities are therefore needed on concepts with the potential for rapid processing with controlled nanostructure, including well-dispersed fibrils at high CNF content so that favorable properties are obtained. This perspective discusses processing strategies, agglomeration problems, opportunities, and effects from interface tailoring. Specifically, preformed CNF mats can be used to design nanostructured biocomposites with high CNF content. Because very few composite materials combine functional and structural properties, CNF materials are an exception in this sense. The suggested processing concept could include functional components (inorganic clays, carbon nanotubes, magnetic nanoparticles, among others). In functional three-phase systems, CNF networks are combined with functional components (nanoparticles or fibril coatings) together with a ductile polymer matrix. Such materials can have functional properties (optical, magnetic, electric, etc.) in combination with mechanical performance, and the comparably low cost of nanocellulose may facilitate the use of large nanocomposite structures in industrial applications.

  • 34.
    Ansari, Farhan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Salajkova, Michaela
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites. KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Wood Chemistry and Pulp Technology.
    Zhou, Qi
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Lars, Berglund
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Strong surface treatment effects on reinforcement efficiency in biocomposites based on cellulose nanocrystals in poly(vinyl acetate) matrix2015In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 16, no 12, p. 3916-3924Article in journal (Refereed)
    Abstract [en]

    In this work, the problem to disperse cellulose nanocrystals (CNC) in hydrophobic polymer matrices has been addressed through application of an environmentally friendly chemical modification approach inspired by clay chemistry. The objective is to compare the effects of unmodified CNC and modified CNC (modCNC) reinforcement, where degree of CNC dispersion is of interest. Hydrophobic functionalization made it possible to disperse wood-based modCNC in organic solvent and cast well-dispersed nanocomposite films of poly(vinyl acetate) (PVAc) with 1-20 wt % CNC. Composite films were studied by infrared spectroscopy (FT-IR), UV-vis spectroscopy, dynamic mechanical thermal analysis (DMTA), tensile testing, and field-emission scanning electron microscopy (FE-SEM). Strongly increased mechanical properties were observed for modCNC nanocomposites. The reinforcement efficiency was much lower in unmodified CNC composites, and specific mechanisms causing the differences are discussed.

  • 35.
    Apostolov, Rossen
    et al.
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Yonezawa, Yasushige
    Standley, Daron M
    Kikugawa, Gota
    Takano, Yu
    Nakamura, Haruki
    Membrane attachment facilitates ligand access to the active site in monoamine oxidase A2009In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 48, no 25, p. 5864-5873Article in journal (Refereed)
    Abstract [en]

    Monoamine oxidase membrane enzymes are responsible for the catalytic breakdown of extra- and intracellular neurotransmitters and are targets for the development of central nervous system drugs. We analyzed the dynamics of rat MAOA by performing multiple independent molecular dynamics simulations of membrane-bound and membrane-free forms to clarify the relationship between the mechanics of the enzyme and its function, with particular emphasis on the significance of membrane attachment. Principal component analysis of the simulation trajectories as well as correlations in the fluctuations of the residues pointed to the existence of three domains that define the global dynamics of the protein. Interdomain anticorrelated movements in the membrane-bound system facilitated the relaxation of interactions between residues surrounding the substrate cavity and induced conformational changes which expanded the active site cavity and opened putative pathways for substrate uptake and product release. Such events were less pronounced in the membrane-free system due to differences in the nature of the dominant modes of motion. The presence of the lipid environment is suggested to assist in decoupling the interdomain motions, consistent with the observed reduction in enzyme activity under membrane-free conditions. Our results are also in accordance with mutational analysis which shows that modifications of interdomain hinge residues decrease the activity of rat MAOA in solution.

  • 36. Araujo, Rafael B.
    et al.
    Chakraborty, Sudip
    Ahuja, Rajeev
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering, Applied Material Physics. Uppsala University, Sweden .
    Unveiling the charge migration mechanism in Na2O2: implications for sodium-air batteries2015In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 17, no 12, p. 8203-8209Article in journal (Refereed)
    Abstract [en]

    Metal-air batteries have become promising candidates for modern energy storage due to their high theoretical energy density in comparison to other storage devices. The lower overpotential of Na compared with Li makes Na-air batteries more efficient in terms of battery lifetime. Additionally, the abundance of Na over Li is another advantage for Na batteries compared to Li batteries. Na2O2 is one of the main products of sodium-air battery reactions. The efficiency of air cells is always related to the charge transport mechanisms in the formed product. To unveil these diffusion mechanisms in one of the main products of the cell reaction Na-O-2 we systematically investigate the mobility of charge carriers as well as the electronic structural properties of sodium peroxide. The framework of the density functional theory based on hybrid functional approach is used to study the mobility of charge carriers and intrinsic defects in Na2O2. Our calculations reveal that the formation of small electron and hole polarons is preferentially occurring over the delocalized state in the crystal structure of Na2O2. The migration of these small polarons displays activation energies of about 0.92 eV and 0.32 eV for the electron and hole polarons respectively, while the analysis of the charged sodium vacancy mobility reveals an activation energy of about 0.5 eV. These results suggest that the charge transport in sodium peroxide would mainly occur through the diffusion of hole polarons.

  • 37.
    Arias, Veluska
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Höglund, Anders
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Odelius, Karin
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Albertsson, Ann-Christine
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Tuning the Degradation Profiles of Poly(L-lactide)-Based Materials through Miscibility2014In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, no 1, p. 391-402Article in journal (Refereed)
    Abstract [en]

    The effective use of biodegradable polymers relies on the ability to control the onset of and time needed for degradation. Preferably, the material properties should be retained throughout the intended time frame, and the material should degrade in a rapid and controlled manner afterward. The degradation profiles of polyester materials were controlled through their miscibility. Systems composed of PLLA blended with poly[(R,S)-3-hydroxybutyrate] (a-PHB) and polypropylene adipate (PPA) with various molar masses were prepared through extrusion. Three different systems were used: miscible (PLLA/a-PHB5 and PLLA/a-PHB20), partially miscible (PLLA/PPA5/comp and PLLA/PPA20/comp), and immiscible (PLLA/PPA5 and PLLA/PPA20) blends. These blends and their respective homopolymers were hydrolytically degraded in water at 37 degrees C for up to I year. The blends exhibited entirely different degradation profiles but showed no diversity between the total degradation times of the materials. PLLA presented a two-stage degradation profile with a rapid decrease in molar mass during the early stages of degradation, similar to the profile of PLLA/a-PHB5. PLLA/a-PHB20 presented a single, constant linear degradation profile. PLLA/PPA5 and PLLA/PPA20 showed completely opposing degradation profiles relative to PLLA, exhibiting a slow initial phase and a rapid decrease after a prolonged degradation time. PLLA/PPA5/comp and PLLA/PPA20/comp had degradation profiles between those of the miscible and the immiscible blends. The molar masses of the materials were approximately the same after 1 year of degradation despite their different profiles. The blend composition and topographical images captured at the last degradation time point demonstrate that the blending component was not leached out during the period of study. The hydrolytic stability of degradable polyester materials can be tailored to obtain different and predetermined degradation profiles for future applications.

  • 38. Ariza, A.
    et al.
    Eklöf, Jens
    KTH, School of Biotechnology (BIO), Glycoscience.
    Spadiut, Oliver
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Offen, W.A.
    Roberts, S.M.
    Wilson, K.S.
    Brumer, Harry
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Davies, G.J.
    Structure and Activity of a Paenibacillus polymyxa Xyloglucanase from Glycoside Hydrolase Family 442011In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 39, p. 33890-33900Article in journal (Refereed)
    Abstract [en]

    The enzymatic degradation of plant polysaccharides is emerging as one of the key environmental goals of the early 21st century, impacting on many processes in the textile and detergent industries as well as biomass conversion to biofuels. One of the well known problems with the use of nonstarch (nonfood)-based substrates such as the plant cell wall is that the cellulose fibers are embedded in a network of diverse polysaccharides, including xyloglucan, that renders access difficult. There is therefore increasing interest in the "accessory enzymes," including xyloglucanases, that may aid biomass degradation through removal of "hemicellulose" polysaccharides. Here, we report the biochemical characterization of the endo-beta-1,4-(xylo)glucan hydrolase from Paenibacillus polymyxa with polymeric, oligomeric, and defined chromogenic aryl-oligosaccharide substrates. The enzyme displays an unusual specificity on defined xyloglucan oligosaccharides, cleaving the XXXG-XXXG repeat into XXX and GXXXG. Kinetic analysis on defined oligosaccharides and on aryl-glycosides suggests that both the -4 and +1 subsites show discrimination against xylose-appended glucosides. The three-dimensional structures of PpXG44 have been solved both in apo-form and as a series of ligand complexes that map the -3 to -1 and +1 to +5 subsites of the extended ligand binding cleft. Complex structures are consistent with partial intolerance of xylosides in the -4' subsites. The atypical specificity of PpXG44 may thus find use in industrial processes involving xyloglucan degradation, such as biomass conversion, or in the emerging exciting applications of defined xyloglucans in food, pharmaceuticals, and cellulose fiber modification.

  • 39. Armbrecht, L.
    et al.
    Dincer, C.
    Kling, A.
    Horak, Josef
    KTH, School of Biotechnology (BIO), Protein Technology. University of Freiburg, Germany.
    Kieninger, J.
    Urban, G.
    Self-assembled magnetic bead chains for sensitivity enhancement of microfluidic electrochemical biosensor platforms2015In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 22, p. 4314-4321Article in journal (Refereed)
    Abstract [en]

    In this paper, we present a novel approach to enhance the sensitivity of microfluidic biosensor platforms with self-assembled magnetic bead chains. An adjustable, more than 5-fold sensitivity enhancement is achieved by introducing a magnetic field gradient along a microfluidic channel by means of a soft-magnetic lattice with a 350 mu m spacing. The alternating magnetic field induces the self-assembly of the magnetic beads in chains or clusters and thus improves the perfusion and active contact between the analyte and the beads. The soft-magnetic lattices can be applied independent of the channel geometry or chip material to any microfluidic biosensing platform. At the same time, the bead-based approach achieves chip reusability and shortened measurement times. The bead chain properties and the maximum flow velocity for bead retention were validated by optical microscopy in a glass capillary. The magnetic actuation system was successfully validated with a biotin-streptavidin model assay on a low-cost electrochemical microfluidic chip, fabricated by dry-film photoresist technology (DFR). Labelling with glucose oxidase (GOx) permits rapid electrochemical detection of enzymatically produced H2O2.

  • 40. Asplund, A.
    et al.
    Edqvist, P. -HD.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Antibodies for profiling the human proteome-The Human Protein Atlas as a resource for cancer research2012In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 12, no 13, p. 2067-2077Article in journal (Refereed)
    Abstract [en]

    In this review, we present an update on the progress of the Human Protein Atlas, with an emphasis on strategies for validating immunohistochemistry-based protein expression patterns and on the possibilities to extend the map of protein expression patterns for cancer research projects. The objectives underlying the Human Protein Atlas include (i) the generation of validated antibodies toward a major isoform of all proteins encoded by the human genome, (ii) creating an information database of protein expression patterns in normal human tissues, in cells, and in cancer, and (iii) utilizing generated antibodies and protein expression data as tools to identify clinically useful biomarkers. The success of such an effort is dependent on the validity of antibodies as specific binders of intended targets in applications used to map protein expression patterns. The development of strategies to support specific target binding is crucial and remains a challenge as a large fraction of proteins encoded by the human genome is poorly characterized, including the approximately one-third of all proteins lacking evidence of existence. Conceivable methods for validation include the use of paired antibodies, i.e. two independent antibodies targeting different and nonoverlapping epitopes on the same protein as well as comparative analysis of mRNA expression patterns with corresponding proteins.

  • 41. Avesson, L.
    et al.
    Reimegård, Johan
    Uppsala University.
    Wagner, E. G. H.
    Söderbom, F.
    MicroRNAs in Amoebozoa: Deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs2012In: RNA: A publication of the RNA Society, ISSN 1355-8382, E-ISSN 1469-9001, Vol. 18, no 10, p. 1771-1782Article in journal (Refereed)
    Abstract [en]

    The RNA interference machinery has served as a guardian of eukaryotic genomes since the divergence from prokaryotes. Although the basic components have a shared origin, silencing pathways directed by small RNAs have evolved in diverse directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein-coding genes and play vital roles in plants and animals, but less is known about their functions in other organisms. Here, we report, for the first time, deep sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA from growing single-cell amoebae as well as from two multicellular developmental stages was sequenced. Computational analyses combined with experimental data reveal the expression of miRNAs, several of them exhibiting distinct expression patterns during development. To our knowledge, this is the first report of miRNAs in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is dependent on the Dicer-like protein DrnB, further supporting the presence of miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin structures originating from an intron as well as from a class of repetitive elements. We believe that these repetitive elements are sources for newly evolved miRNAs.

  • 42.
    Axelsson, Karolin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Chemical signals in interactions between Hylobius abietis and associated bacteria2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pine weevil (Hylobius abietis L.) is one of the two topmost economically important insect pests in Swedish conifer forests. The damage increase in areas were the silvicultural practice is to use clear cuttings were the insects gather and breed. During egglaying the female protects her offspring by creating a cave in roots and stumps were she puts her egg and covers it with frass, a mixture of weevil feces and chewed bark. Adult pine weevils have been observed to feed on the other side of the egg laying site and antifeedant substance has been discovered in the feces of the pine weevil. We think it is possible that microorganisms present in the frass contribute with antifeedant/repellent substances. Little is known about the pine weevils associated bacteria community and their symbiotic functions. In this thesis the bacterial community is characterized in gut and frass both from pine weevils in different populations across Europe as well as after a 28 day long diet regime on Scots pine, silver birch or bilberry. Volatile substances produced by isolated bacteria as well as from a consortium of microorganisms were collected with solid phase micro extraction (SPME) and analyzed with GC-MS. The main volatiles were tested against pine weevils using a two-choice test. Wolbachia, Rahnella aquatilis, Serratia and Pseudomonas syringae was commonly associated with the pine weevil. 2-Methoxyphenol, 2-phenylethanol, 3-methyl-1-butanol were found in the headspace from Rahnella aquatilis when grown in substrate containing pine bark. 2-Methoxyphenol and 3-methyl-1-butanol, phenol and methyl salicylate were found in pine feces. Birch and bilberry feces emitted mainly linalool oxides and bilberry emitted also small amounts of 2-phenylethanol.

    A second part of the thesis discusses the role of fungi in forest insect interactions and the production of oxygenated monoterpenes as possible antifeedants. Spruce bark beetles (Ips typhographus L.) aggregate with the help of pheromones and with collected forces they kill weakened adult trees as a result of associated fungi growth and larval development. A fungi associated with the bark beetle, Grosmannia europhoides, was shown to produce de novo 2-methyl-3-buten-2-ol, the major component of the spruce bark beetle aggregation pheromone. Chemical defense responses against Endoconidiophora polonica and Heterobasidion parviporum were investigated using four clones of Norway spruce with different susceptibility to Heterobasidion sp. Clone specific differences were found in induced mono-, sesqui and diterpenes. A number of oxygenated monoterpenes which are known antifeedants for the pine weevil were produced in the infested areas.

  • 43.
    Ayoglu, Burcu
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Birgersson, Elin
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mezger, Anja
    Nilsson, Mats
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Multiplexed protein profiling by sequential affinity capture2016In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 16, no 8, p. 1251-1256Article in journal (Refereed)
    Abstract [en]

    Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off-target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi-automated sequential capture assay. This novel bead-based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read-out by a secondary capture bead array. We demonstrate in a proof-of-concept setting that target detection via two sequential affinity interactions reduced off-target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA-based signal amplification, and demonstrate the applicability of the dual capture bead-based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond.

  • 44.
    Ayoglu, Burcu
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Häggmark, Anna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khademi, M.
    Olsson, T.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Autoantibody profiling in multiple sclerosis using arrays of human protein fragments2013In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 12, no 9, p. 2657-2672Article in journal (Refereed)
    Abstract [en]

    Profiling the autoantibody repertoire with large antigen collections is emerging as a powerful tool for the identification of biomarkers for autoimmune diseases. Here, a systematic and undirected approach was taken to screen for profiles of IgG in human plasma from 90 individuals with multiple sclerosis related diagnoses. Reactivity pattern of 11,520 protein fragments (representing ̃38% of all human protein encoding genes) were generated on planar protein microarrays built within the Human Protein Atlas. For more than 2,000 antigens IgG reactivity was observed, among which 64% were found only in single individuals. We used reactivity distributions among multiple sclerosis subgroups to select 384 antigens, which were then reevaluated on planar microarrays, corroborated with suspension bead arrays in a larger cohort (n = 376) and confirmed for specificity in inhibition assays. Among the heterogeneous pattern within and across multiple sclerosis subtypes, differences in recognition frequencies were found for 51 antigens, which were enriched for proteins of transcriptional regulation. In conclusion, using protein fragments and complementary high-throughput protein array platforms facilitated an alternative route to discovery and verification of potentially disease-associated autoimmunity signatures, that are now proposed as additional antigens for large-scale validation studies across multiple sclerosis biobanks.

  • 45.
    Ayoglu, Burcu
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Antigen arrays for profiling autoantibody repertoires2016In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 8, no 10, p. 1105-1126Article, review/survey (Refereed)
    Abstract [en]

    Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed assays based on antigen arrays hold a great potential and provide possibilities to analyze hundreds of body fluid samples for their reactivity pattern against thousands of antigens in parallel. Here, we provide an overview of the available technologies for producing antigen arrays, highlight some of the technical and methodological considerations and discuss their applications as discovery tools. Together with recent studies utilizing antigen arrays, we give an overview on how the different types of antigen arrays have and will continue to deliver novel insights into autoimmune diseases among several others.

  • 46. Azarias, Guillaume
    et al.
    Kruusmagi, Markus
    Connor, Siobhan
    Akkuratov, Evgeny E.
    Liu, Xiao-Li
    Lyons, David
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Broberger, Christian
    Aperia, Anita
    A Specific and Essential Role for Na,K-ATPase alpha 3 in Neurons Co-expressing alpha 1 and alpha 32013In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 4, p. 2734-2743Article in journal (Refereed)
    Abstract [en]

    Most neurons co-express two catalytic isoforms of Na,K-ATPase, the ubiquitous alpha 1, and the more selectively expressed alpha 3. Although neurological syndromes are associated with alpha 3 mutations, the specific role of this isoform is not completely understood. Here, we used electrophysiological and Na+ imaging techniques to study the role of alpha 3 in central nervous system neurons expressing both isoforms. Under basal conditions, selective inhibition of alpha 3 using a low concentration of the cardiac glycoside, ouabain, resulted in a modest increase in intracellular Na+ concentration ([Na+](i)) accompanied by membrane potential depolarization. When neurons were challenged with a large rapid increase in [Na+](i), similar to what could be expected following suprathreshold neuronal activity, selective inhibition of alpha 3 almost completely abolished the capacity to restore [Na+](i) in soma and dendrite. Recordings of Na, K-ATPase specific current supported the notion that when [Na+](i) is elevated in the neuron, alpha 3 is the predominant isoform responsible for rapid extrusion of Na+. Low concentrations of ouabain were also found to disrupt cortical network oscillations, providing further support for the importance of alpha 3 function in the central nervous system. The alpha isoforms express a well conserved protein kinase A consensus site, which is structurally associated with an Na+ binding site. Following activation of protein kinase A, both the alpha 3-dependent current and restoration of dendritic [Na+](i) were significantly attenuated, indicating that alpha 3 is a target for phosphorylation and may participate in short term regulation of neuronal function.

  • 47.
    Azeem, Muhammad
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Kuttuva Rajarao, Gunaratna
    KTH, School of Biotechnology (BIO), Environmental Microbiology (closed September 2009).
    Nordenhem, Henrik
    SLU, Uppsala.
    Nordlander, Göran
    SLU, Uppsala.
    Borg-Karlson, Anna Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Penicillium expansum Volatiles Reduce Pine Weevil Attraction to Host Plants2013In: Journal of Chemical Ecology, ISSN 0098-0331, E-ISSN 1573-1561, Vol. 39, no 1, p. 120-128Article in journal (Refereed)
    Abstract [en]

    The pine weevil Hylobius abietis (L.) is a severe pest of conifer seedlings in reforested areas of Europe and Asia. To identify minimally toxic and ecologically sustainable compounds for protecting newly planted seedlings, we evaluated the volatile metabolites produced by microbes isolated from H. abietis feces and frass. Female weevils deposit feces and chew bark at oviposition sites, presumably thus protecting eggs from feeding conspecifics. We hypothesize that microbes present in feces/frass are responsible for producing compounds that deter weevils. Here, we describe the isolation of a fungus from feces and frass of H. abietis and the biological activity of its volatile metabolites. The fungus was identified by morphological and molecular methods as Penicillium expansum Link ex. Thom. It was cultured on sterilized H. abietis frass medium in glass flasks, and volatiles were collected by SPME and analyzed by GC-MS. The major volatiles of the fungus were styrene and 3-methylanisole. The nutrient conditions for maximum production of styrene and 3-methylanisole were examined. Large quantities of styrene were produced when the fungus was cultured on grated pine bark with yeast extract. In a multi-choice arena test, styrene significantly reduced male and female pine weevils' attraction to cut pieces of Scots pine twigs, whereas 3-methylanisole only reduced male weevil attraction to pine twigs. These studies suggest that metabolites produced by microbes may be useful as compounds for controlling insects, and could serve as sustainable alternatives to synthetic insecticides.

  • 48.
    Azizi Samir, M. A. S.
    et al.
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures. Université Joseph Fourier, France.
    Alloin, F.
    Dufresne, A.
    Review of recent research into cellulosic whiskers, their properties and their application in nanocomposite field2005In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 6, no 2, p. 612-626Article in journal (Refereed)
    Abstract [en]

    There are numerous examples where animals or plants synthesize extracellular high-performance skeletal biocomposites consisting of a matrix reinforced by fibrous biopolymers. Cellulose, the world's most abundant natural, renewable, biodegradable polymer, is a classical example of these reinforcing elements, which occur as whiskerlike microfibrils that are biosynthesized and deposited in a continuous fashion. In many cases, this mode of biogenesis leads to crystalline microfibrils that are almost defect-free, with the consequence of axial physical properties approaching those of perfect crystals. This quite "primitive" polymer can be used to create high performance nanocomposites presenting outstanding properties. This reinforcing capability results from the intrinsic chemical nature of cellulose and from its hierarchical structure. Aqueous suspensions of cellulose crystallites can be prepared by acid hydrolysis of cellulose. The object of this treatment is to dissolve away regions of low lateral order so that the water-insoluble, highly crystalline residue may be converted into a stable suspension by subsequent vigorous mechanical shearing action. During the past decade, many works have been devoted to mimic biocomposites by blending cellulose whiskers from different sources with polymer matrixes.

  • 49. Babrzadeh, Farbod
    et al.
    Jalili, Roxana
    Wang, Chunlin
    Shokralla, Shadi
    Pierce, Sarah
    Robinson-Mosher, Avi
    Nyrén, Pål
    KTH, School of Biotechnology (BIO), Biochemistry.
    Shafer, Robert W.
    Basso, Luiz C.
    de Amorim, Henrique V.
    de Oliveira, Antonio J.
    Davis, Ronald W.
    Ronaghi, Mostafa
    Gharizadeh, Baback
    Stambuk, Boris U.
    Whole-genome sequencing of the efficient industrial fuel-ethanol fermentative Saccharomyces cerevisiae strain CAT-12012In: Molecular Genetics and Genomics, ISSN 1617-4615, E-ISSN 1617-4623, Vol. 287, no 6, p. 485-494Article in journal (Refereed)
    Abstract [en]

    The Saccharomyces cerevisiae strains widely used for industrial fuel-ethanol production have been developed by selection, but their underlying beneficial genetic polymorphisms remain unknown. Here, we report the draft whole-genome sequence of the S. cerevisiae strain CAT-1, which is a dominant fuel-ethanol fermentative strain from the sugarcane industry in Brazil. Our results indicate that strain CAT-1 is a highly heterozygous diploid yeast strain, and the similar to 12-Mb genome of CAT-1, when compared with the reference S228c genome, contains similar to 36,000 homozygous and similar to 30,000 heterozygous single nucleotide polymorphisms, exhibiting an uneven distribution among chromosomes due to large genomic regions of loss of heterozygosity (LOH). In total, 58 % of the 6,652 predicted protein-coding genes of the CAT-1 genome constitute different alleles when compared with the genes present in the reference S288c genome. The CAT-1 genome contains a reduced number of transposable elements, as well as several gene deletions and duplications, especially at telomeric regions, some correlated with several of the physiological characteristics of this industrial fuel-ethanol strain. Phylogenetic analyses revealed that some genes were likely associated with traits important for bioethanol production. Identifying and characterizing the allelic variations controlling traits relevant to industrial fermentation should provide the basis for a forward genetics approach for developing better fermenting yeast strains.

  • 50.
    Balamurugan, Kanagasabai
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Langström, Bengt
    Nordberg, Agneta
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. Siberian Federal University, Russian Federation.
    Effect of Alzheimer Familial Chromosomal Mutations on the Amyloid Fibril Interaction with Different PET Tracers: Insight from Molecular Modeling Studies2017In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 8, no 12, p. 2655-2666Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide, it poses a great challenge for the society and health care. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the fi region of the amyloid precursor protein, which is referred to as autosomal dominant AD (ADAD). These mutations may cause changes in the secondary structure of the amyloid fi fibrils and may alter the fibrillization rate leading to changes in the disease development and could also affect the binding to tracers used in diagnosis. In particular, from some recent clinical studies using PET tracers for detection of fibrillar amyloids, it is evident that in ADAD patients with Arctic mutation no amyloid plaque binding can be detected with the "C Pittsburgh Compound B (C-11-PIB). However, for in vitro conditions, significant binding of H-3-PIB has been reported for the amyloid fibrils carrying the Arctic mutation. The aim of the present study is to investigate if there is any mutation specific binding of commonly used amyloid tracers, namely, florbetaben, florbetapir, FPIB, AZD4694, and AZD2184, by means of molecular modeling techniques. Other than Arctic, ADAD mutations, such as the Dutch, Italian, Iowa, and Flemish mutations, are considered in this study. We report that all tracers except florbetapir show reduced binding affinity toward amyloid beta fibrils with the Arctic mutation when compared to the native type. Moreover, florbetapir is the only tracer that binds to all mutants with increased affinity when compared to the native fibril. The results obtained from these studies could increase the understanding of the structural changes caused by mutation and concomitant changes in the interaction pattern of the PET tracers with the mutated variants, which in turn can be useful in selecting the appropriate tracers for the purpose of diagnosis as well as for designing new tracers with desirable properties.

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