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  • 301.
    Bergkvist, Liza
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandin, Linnea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    A beta PP processing results in greater toxicity per amount of A beta(1-42) than individually expressed and secreted A beta(1-42) in Drosophila melanogaster2016Inngår i: BIOLOGY OPEN, ISSN 2046-6390, Vol. 5, nr 8, s. 1030-1039Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aggregation of the amyloid-beta (A beta) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimers disease (AD). A beta peptides are generated from proteolytic processing of the transmembrane A beta precursor protein (A beta PP) via sequential proteolysis through the beta-secretase activity of beta-site A beta PP-cleaving enzyme (BACE1) and by the intramembranous enzyme gamma-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the A beta peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human A beta PP is co-expressed with human BACE1, resulting in production of the A beta peptide through the processing of A beta PP by BACE1 and by endogenous fly gamma-secretase. Here, we performed a parallel study of flies that expressed the A beta(1-42) peptide alone or that co-expressed A beta PP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the A beta(1-42), A beta(1-40) and A beta(1-38) peptides were examined. Our data reveal that the toxic effect per amount of detected A beta(1-42) peptide was higher in the flies co-expressing A beta PP and BACE1 than in the A beta(1-42)-expressing flies, and that the co-existence of A beta(1-42) and A beta(1-40) in the flies co-expressing A beta PP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the A beta(1-42) peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research.

  • 302.
    Berglin, Lena
    Högskolan i Borås, Institutionen Textilhögskolan.
    Interactive Textile Structures: Creating Multifunctional Textiles based on Smart Materials2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Textiles of today are materials with applications in almost all our activities. We wear clothes all the time and we are surrounded with textiles in almost all our environments. The integration of multifunctional values in such a common material has become a special area of interest in recent years. Smart Textile represents the next generation of textiles anticipated for use in several fashion, furnishing and technical textile applications. The term smart is used to refer to materials that sense and respond in a pre-defined manner to environmental stimuli. The degree of smartness varies and it is possible to enhance the intelligence further by combining these materials with a controlling unit, for example a microprocessor. As an interdisciplinary area Smart Textile includes design spaces from several areas; the textile design space, the information technology design space and the design space of material science. This thesis addresses how Smart Textiles affect the textile design space; how the introduction of smart materials and information technology affects the creation of future textile products. The aim is to explore the convergence between textiles, smart materials and information technology and to contribute to providing a basis for future research in this area. The research method is based on a series of interlinked experiments designed through the research questions and the research objects. The experiments are separated into two different sections: interactive textile structures and health monitoring. The result is a series of basic methods for how interactive textile structures are created and a general system for health monitoring. Furthermore the result consists of a new design space, advanced textile design. In advanced textile design the focus is set on the relation between the different natures of a textile object: its physical structure and its structure in the context of design and use.

  • 303.
    Berglund, Anna-Karin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Dual Targeting of Proteins to Mitochondria and Chloroplasts2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The vast majority of mitochondrial and chloroplastic proteins are nuclear encoded, synthesized in the cytosol and imported into the respective organelle using an N-terminal extension, the targeting peptide (TP). After import into the organelle, the TP is cleaved off and degraded by the Presequence protease (PreP). The import process is thought to be highly specific, however there is a group of proteins that are localised to both mitochondria and chloroplasts, using an ambiguous, dual targeting peptide (dTP). The aim of this thesis was to investigate targeting properties of dTPs. Analysis of the amino acid content of all currently known dually targeted proteins revealed that the dTPs are enriched in hydroxylated, hydrophobic and positively charged residues, lacking acidic residues, whereas the content of serine, arginine and proline is intermediary in comparison to the mitochondrial and chloroplastic TPs. dTPs do not form amphiphilic a-helices, characteristic of the mitochondrial TPs, but the helical structure can be induced in membrane mimetic environment, as revealed by spectroscopic studies of a dTP of an aminoacyl- tRNA-synthetase (aaRS). In vitro and in vivo import experiments of fusion constructs containing N-terminal truncations of seven aaRS-dTPs coupled to green fluorescent protein (GFP) demonstrated different organisation of targeting determinants showing that the N-terminal portion of dTPs was crucial for import into both organelles or at least one organelle for different constructs. In addition, studies of targeting capacity of the TPs of PreP homologues from plant, mammal and yeast (AtPreP, hPreP and Mop112) showed species dependent intra-mitochondrial localisation of the coupled GFP and demonstrated functional complementation of an intermembrane space located Mop112 with a matrix located AtPreP. The studies presented here contribute to understanding of the intracellular and intra-mitochondrial sorting process of proteins in the eukaryotic cell.

  • 304. Berglund, Elias
    The effects of probiotics on sleep and fatty acids2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Probiotics are dietary supplements that contain bacteria that are potentially beneficial for the intestinal flora. The positive effects of probiotics are however not limited to the intestine. The use of probiotics is becoming more and more common and therefore needs to be studied more closely.The purpose of this study is to see how healthy individuals, in the age between 18 and 28 years old and with a BMI between 20 and 25, respond to the probiotic LactiPlus (also called FF8).Blood samples were collected before and after the subjects have eaten a standardized meal. The subject´s glucometabolic responses to food, sleep patterns and their fatty acid profile was analyzed in relation to the probiotic composition.Due to difficulties including study subjects, three subject completed the participation in the study. The three study subjects had similar sleeping habits, one had slightly higher fruit intake, the word and number memory were similar, but it was not possible to relate any data to the use of probiotics. It can be summarized that inclusion additional study subjects is needed.

  • 305.
    Berglund, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Pollard, Katherine S.
    Webster, Matthew T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hotspots of biased nucleotide substitutions in human genes2009Inngår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 7, nr 1, s. e26-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.

  • 306.
    Berglund, Sara
    Karlstads universitet.
    AB0-blodgruppens betydelse i trombocyttransfusionssammanhäng.2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 307.
    Berglund, Sofia
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Gaballa, Ahmed
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Sawaisorn, Piamsiri
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Mahidol Univ, Fac Med Technol, Ctr Res & Innovat, Bangkok, Thailand..
    Sundberg, Berit
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Uhlin, Michael
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.; Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden..
    Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility2018Inngår i: STEM CELLS INTERNATIONAL, ISSN 1687-966X, artikkel-id 8529104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gammadelta (gamma delta) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of gamma delta T cells in umbilical cord blood (UCB) is low, and the majority express delta 1, in contrast to blood, whereas the main subset is delta 2 gamma 9 T cells. UCB gamma delta T cells are functionally immature, which together with their scarcity complicates the development of UCB gamma delta T cell therapies. We aimed to develop an effective expansion protocol for UCB gamma delta T cells based on zoledronate and IL-2. We found that culture with 5 mu M zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were gamma 9 delta 2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal gamma delta T cell repertoire and the main memory subset was central memory (CD45RO(+) CD27(+)). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB gamma delta T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.

  • 308. Bergmann, Olaf
    et al.
    Zdunek, Sofia
    Felker, Anastasia
    Salehpour, Mehran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Alkass, Kanar
    Bernard, Samuel
    Sjostrom, Staffan L.
    Szewczykowska, Mirosawa
    Jackowska, Teresa
    dos Remedios, Cris
    Malm, Torsten
    Andrae, Michaela
    Jashari, Ramadan
    Nyengaard, Jens R.
    Possnert, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi.
    Jovinge, Stefan
    Druid, Henrik
    Frisen, Jonas
    Dynamics of Cell Generation and Turnover in the Human Heart2015Inngår i: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 161, nr 7, s. 1566-1575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived C-14 revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart.

  • 309.
    Bergner, Helén
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Screening för virus i myggor insamlade sommaren 2017 i Västerbotten2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 310.
    Bergquist, Helen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Inturi, Raviteja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Zain, Rula
    Punga, Tanel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    RNA triplex formation in human adenovirus type 4 VA RNAI and its implication on virus growthArtikkel i tidsskrift (Fagfellevurdert)
  • 311.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Proteomics to Understand the Degenerative Matter2014Inngår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 75, s. S10-S10Artikkel i tidsskrift (Annet vitenskapelig)
  • 312.
    Bergqvist, Annica
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper (from 2013).
    Validering av ADMA direct ELISA för bestämning av ADMA i EDTAplasma och serum2018Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
  • 313.
    Bergqvist, Simon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Preanalytisk stabilitet för 25(OH)-vitamin D i koagulerat blod och serum2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 314.
    Bergsten, Niklas
    Högskolan i Skövde, Institutionen för vård och natur.
    PDIA3 and Prostate Cancer: Do changes in nucleotidesequence correspond tomalignancy?2012Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    PDIA3 interacts with the lectin chaperons; calnexin and calreticulin to surveythe folding of newly synthesized glycoproteins by the addition of N-linkedglycans. PDIA3 is also involved in transcaltachia signaling cascades andimmunogenicity. The purpose was to determine if there were any changespresent in the nucleotide sequence of the Pdia3 gene. To study this, fourprostate cell lines were examined by Sanger sequencing, two malignant(LNCaP, PC3) and two normal (PNT1A, PNT2). These were to be compared tothe nucleotide sequence from nine formalin fixed paraffin-embedded (FFPE)samples of different Gleason score and the sequence from three FFPE samplesof normal prostate tissue chosen from the Örebro Radical Cohort. The obtainedsequences were then analysed with several bioinformatics tools to determine ifthere were any changes present. The nucleotide sequence obtained from thesequencing indicated that none of the cell lines expressed the most redundantisofrom; CRA_c, but instead CRA_a and CRA_b. Surprisingly, the two normalcell lines (PNT1A and PNT2) produced similar scores in BLAST search forboth the CRA_a and the CRA_b isoforms. Software analysis of the translatedsequences predicted that LNCaP expressed a membrane bound form PDIA3while PC3 expressed a cytoplasmic variant of the protein. To confirm this,another sequencing reaction was performed. The second results indicated thatall cell lines expressed the same isoform, but that the isoforms were localizedto different intracellular compartments.

  • 315.
    Bergström, Joakim
    et al.
    Veryst Engineering, LLCNeedhamUSA.
    Hayman, Danika
    An Overview of Mechanical Properties and Material Modeling of Polylactide (PLA) for Medical Applications2016Inngår i: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 44, nr 2, s. 330-340Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article provides an overview of the connection between the microstructural state and the mechanical response of various bioresorbable polylactide (PLA) devices for medical applications. PLLA is currently the most commonly used material for bioresorbable stents and sutures, and its use is increasing in many other medical applications. The non-linear mechanical response of PLLA, due in part to its low glass transition temperature (T g ≈ 60 °C), is highly sensitive to the molecular weight and molecular orientation field, the degree of crystallinity, and the physical aging time. These microstructural parameters can be tailored for specific applications using different resin formulations and processing conditions. The stress-strain, deformation, and degradation response of a bioresorbable medical device is also strongly dependent on the time history of applied loads and boundary conditions. All of these factors can be incorporated into a suitable constitutive model that captures the multiple physics that are involved in the device response. Currently developed constitutive models already provide powerful computations simulation tools, and more progress in this area is expected to occur in the coming years.

  • 316.
    Bergström, Rosita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Savary, Katia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Morén, Anita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Guibert, Sylvain
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Heldin, Carl-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Ohlsson, Rolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Transforming growth factor β promotes complexes between Smad proteins and the CCCTC-binding factor on the H19 imprinting control region chromatin2010Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 285, nr 26, s. 19727-19737Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whether signal transduction pathways regulate epigenetic states in response to environmental cues remains poorly understood. We demonstrate here that Smad3, signaling downstream of transforming growth factor beta, interacts with the zinc finger domain of CCCTC-binding factor (CTCF), a nuclear protein known to act as "the master weaver of the genome." This interaction occurs via the Mad homology 1 domain of Smad3. Although Smad2 and Smad4 fail to interact, an alternatively spliced form of Smad2 lacking exon 3 interacts with CTCF. CTCF does not perturb well established transforming growth factor beta gene responses. However, Smads and CTCF co-localize to the H19 imprinting control region (ICR), which emerges as an insulator in cis and regulator of transcription and replication in trans via direct CTCF binding to the ICR. Smad recruitment to the ICR requires intact CTCF binding to this locus. Smad2/3 binding to the ICR requires Smad4, which potentially provides stability to the complex. Because the CTCF-Smad complex is not essential for the chromatin insulator function of the H19 ICR, we propose that it can play a role in chromatin cross-talk organized by the H19 ICR.

  • 317.
    Bergström, Sven
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Zückert, Wolfram R
    Structure, function and biogenesis of the Borrelia cell envelope2010Inngår i: Borrelia, molecular biology, host interactions and pathogenesis / [ed] Eds DS Samuels and JD Radolf, Norfolk, UK: Caister Academic Press , 2010, s. 139-166Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 318.
    Bergström, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Modeling Neural Stem Cell and Glioma Biology2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis is focused on neural stem cell (NSC) and glioma biology. I discuss how NSCs interact with extracellular matrix (ECM) proteins in the stem cell niche, and investigate the consequences of deregulated Platelet-derived growth factor (PDGF) signaling for embryonic NSCs in transgenic mice. Furthermore I present cell cultures of human glioblastoma multiforme (GBM) that models human disease, taking into account the heterogeneity of GBM. Finally, interactions between brain tumors and mast cells are studied using the glioma cultures.

    In paper I, the importance of NSC interactions with the ECM in the stem cell niche during development is discussed. Contacts between NSCs and the ECM in the subventricular zone (SVZ) are emerging as important regulatory mechanisms. We show that early postnatal neural stem and progenitor cells (NSPC) attach to collagen I, and that the adhesion is explained by higher expression of collagen receptor integrins compared to adult NSPC. Further, blood vessels in the SVZ express collagen I, indicating a possible functional relationship.

    Growth factors, e.g. PDGF, regulate NSC proliferation and differentiation. Aberrant activation of growth factor signaling pathways also plays a role in brain tumor formation. Paper II demonstrates that transgenic mice expressing PDGF-B at high levels in embryonic NSCs displayed mild neurological defects but no hyperplasia or brain tumors. This suggests that a high level of PDGF is not sufficient to induce brain tumors from NSCs without further mutations.

    Paper III presents a novel panel of human glioma stem cell (GSC) lines from GBM that display NSC markers in vitro and form secondary orthotopic tumors in vivo. GBM has recently been categorized in molecular subclasses and we demonstrate, for the first time, that these subclasses can be retained in vitro by stem cell culture conditions. We have thus generated models for research and drug development aiming at a focused treatment depending on GBM subtype.

    Interactions with the immune system are integral parts of tumorigenesis. Mast cells are found in glioma and in paper IV we demonstrate that the grade-dependent infiltration of mast cells is in part mediated by macrophage migration inhibitory factor and phosphorylation of STAT5.

     

     

  • 319.
    Bergström, Valentina
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper.
    Effekt av extrakt från kråkbär, grönt te, Rooibos te och kakao på prostaglandin E2-bildning i humana monocyter och makrofager2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 320.
    Berkeby Banérsson, Emilia
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Hållbarhetsstudier och granskning av automatvalidering av analysresultat vid analys av prostataspecifikt antigen Hållbarhetsstudier och granskning av automatvalidering av analysresultat vid analys av prostataspecifikt antigen2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Prostatacancer är den vanligaste orsaken till cancerdöd hos män i Sverige. Cirka 9500 patienter får diagnosen prostatacancer varje år. Prostatacancer diagnostiseras med hjälp av analys av tumörmarkören prostataspecifikt antigen (PSA) i plasma.

    Syftet med den aktuella studien var att undersöka den preanalytiska stabiliteten av PSA i plasma och att undersöka hur förändrade provtagningsanvisningar och provtagningsrutiner påverkade analysresultat, arbetsförhållanden och patientsäkerhet.

    Analysmetoden som användes vid studien var electrochemiluminiscence immunoassay (ECLIA), vilken nyttjar ljus för detektion av antigen-/antikroppskomplex.

    I en första studie visades att centrifugerade PSA-prover med icke avhälld plasma, förvarade i 6o C, kan analyseras upp till 5 dagar efter provtagning. Detta till skillnad från nuvarande metodbeskrivning som kräver avhälld plasma vid analys 24 timmar efter provtagning. En andra studie visade att PSA-prov, förvarat i 6o C, centrifugerat och analyserat 24 timmar efter provtagning gav oförändrade PSA-värden jämfört med PSA-prov som centrifugerats och analyserats direkt efter provtagning. Detta till skillnad från nuvarande metodbeskrivning där prov skall centrifugeras inom 2 timmar och att ocentrifugerat prov skall förvaras i rumstemperatur.

    Nya automatvalideringsgränser och införandet av laboratoriedataprogrammet Delta-check gav en halvering av antalet analysresultat som ej automatvalideras.

    Studien visar att PSA var mer stabilt än tidigare förmodats och att förändrade rutiner vid analys av PSA och införande av automatvalidering med Delta-check kan leda till ett förbättrat och mer effektivt arbete för personalen på laboratoriet och ge ökad patientsäkerhet.

  • 321.
    Berndtson, E.
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Emanuelson, U.
    Swedish Association for Livestock Breeding and Production, Eskilstuna, Sweden .
    Engvall, A.
    Department of Epizootiology, National Veterinary Institute, Uppsala, Sweden .
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    A 1-year epidemiological study of campylobacters in 18 Swedish chicken farms1996Inngår i: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 26, nr 3-4, s. 167-185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Broiler chickens are often intestinal carriers of Campylobacter. During processing, Campylobacter may be spread over the carcass. Thus, undercooked chicken meat, or other foods contaminated by raw chicken can act as a source of infection to humans. This study was conducted to identify risk factors for chicken flocks being colonized with Campylobacter. Eighteen chicken farms with altogether 62 chicken compartments were studied for 1 year with visits during each growing period and sampling of chicken caecal contents at slaughter. Four to six subsequent flocks were raised in each compartment during the study. A detailed questionnaire was used to record farm parameters such as building materials, feed and water equipment, hygiene and management routines. Campylobacter prevalence varied between farms, between growing periods within the farms and also during the year, with lowest prevalence during the spring. Campylobacters were isolated from 27% out of 287 flocks. Only two farms were negative at all samplings. Often the flock following a positive flock in a compartment was negative, indicating that normal cleaning and disinfecting routines are sufficient for eliminating the bacteria from the house. Usually only one serotype was found in each positive flock. Campylobacter occurrence increased with the age of the chickens at slaughter, and also with flock size.

    Univariable chi-square tests were done of the association between possible risk factors and Campylobacter prevalence. Factors associated with higher Campylobacter prevalence in flocks were lack of or diffuse hygiene barriers, increasing flock size, increasing age at slaughter, short vs. long empty periods, wet litter beds, other poultry nearby or staff handling other poultry, flocks divided before slaughter, staff loading to slaughter at several farms and occurrence of mice. Under Swedish conditions, water does not seem to be a source of infection for chickens. Origin and handling of day-old chickens, feed additives, houses and litter were not associated with higher Campylobacter prevalence.

  • 322.
    Berner-Branzell, Filip
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Carbohydrate Binding Specificity of a Variant Heliocobacter pylori BabA Adhesin2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 323.
    Bernzen, Noel
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap.
    Noellator: Vinterrollator2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Idag är det en hög andel av äldre personer, främst kvinnor, som använder rollatorer. De blir allt fler med tiden, då genomsnittsåldern av befolkningen blir allt högre. För att öka livskvalitet för de äldre, är det rekommenderat att promenera utomhus så ofta som möjligt, exempelvis med hjälp av en rollator. Ett problem som uppstår är att ingen rollator är anpassad för användning under vintern. I detta examensarbete har ett rollator-koncept tagits fram, speciellt anpassat för ”fyra årstider”. Detta innebär att konceptet har allt som en vanligt rollator har men även tillbehör som är användarvänliga i vilket väder som helst, såväl vid snö- som isförhållanden. Det innebär en komplettering med specialdesignade tillbehör som är enkla att byta oberoende av väderslag. En årstidsoberoende rollator blir dyrare än en vanligt rollator, men samtidigt skapas ett hjälpmedel som gör det lättare för användaren att vara en del av samhället och förbättra sin hälsa, vilket faktiskt är såväl viktigt som aktuellt

  • 324.
    Berts, Ida
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fragneto, Giovanna
    Institut Laue-Langevin.
    Frisk, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Rennie, Adrian. R
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Polymeric Smart Coating Strategy for Titanium Implants2014Inngår i: Advanced Engineering Materials, ISSN 1438-1656, E-ISSN 1527-2648, Vol. 16, nr 11, s. 1340-1350Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hyaluronan based hydrogel coatings can mimic extracellular matrix components and incorporate growth factors that can be released during a progressive degradation while new tissue regenerates. This paper describes a structural characterization of a hydrogel coating made of modified hyaluronan polymers and how these coatings interact with bone morphogenetic protein-2 (BMP-2). Quartz crystal microbalance and neutron reflectivity measurements were used for in-situ, real-time measurements of the adsorption properties of polymers and proteins on smooth titanium oxide surfaces that mimic implant products in orthopedics. The adsorption of BMP-2 on a bare titanium oxide surface is compared to that on titanium oxide coated with different chemically modified hyaluronan, the most important being hyaluronan with bisphosphonate groups (HA-BP). The subsequent release of the BMP-2 from these hydrogel coatings could be triggered by calcium ions. The amount of adsorbed protein on the surfaces as well as the amount of released protein both depend on the type of hyaluronan coating. We conclude that HA-BP coated titanium oxide surfaces provide an excellent material for growth factor delivery in-vivo.

  • 325. Bestas, Burcu
    et al.
    Moreno, Pedro M. D.
    Blomberg, K. Emelie M.
    Mohammad, Dara K.
    Saleh, Amer F.
    Sutlu, Tolga
    Nordin, Joel Z.
    Guterstam, Peter
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
    Gustafsson, Manuela O.
    Kharazi, Shabnam
    Piatosa, Barbara
    Roberts, Thomas C.
    Behlke, Mark A.
    Wood, Matthew J. A.
    Gait, Michael J.
    Lundin, Karin E.
    EL Andaloussi, Samir
    Mansson, Robert
    Berglof, Anna
    Wengel, Jesper
    Smith, C. I. Edvard
    Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model2014Inngår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 124, nr 9, s. 4067-4081Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.

  • 326.
    Bett, Bernard
    et al.
    Int Livestock Res Inst, Nairobi, Kenya..
    Said, Mohammed Y.
    Int Livestock Res Inst, Nairobi, Kenya..
    Sang, Rosemary
    Kenya Govt Med Res Ctr, Nairobi, Kenya..
    Bukachi, Salome
    Univ Nairobi, Inst Anthropol Gender & African Studies, Nairobi, Kenya..
    Wanyoike, Salome
    Minist Agr, Dept Vet Serv, Nairobi, Kenya..
    Kifugo, Shem C.
    Int Livestock Res Inst, Nairobi, Kenya..
    Otieno, Fredrick
    Int Livestock Res Inst, Nairobi, Kenya..
    Ontiri, Enoch
    Int Livestock Res Inst, Nairobi, Kenya..
    Njeru, Ian
    Kenyatta Natl Hosp, Minist Publ Hlth & Sanitat, Div Dis Surveillance & Response, Nairobi, Kenya..
    Lindahl, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Int Livestock Res Inst, Nairobi, Kenya.;Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Grace, Delia
    Int Livestock Res Inst, Nairobi, Kenya..
    Effects of flood irrigation on the risk of selected zoonotic pathogens in an arid and semi-arid area in the eastern Kenya2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 5, artikkel-id e0172626Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To investigate the effects of irrigation on land cover changes and the risk of selected zoonotic pathogens, we carried out a study in irrigated, pastoral and riverine areas in the eastern Kenya. Activities implemented included secondary data analyses to determine land use and land cover (LULC) changes as well as human, livestock and wildlife population trends; entomological surveys to characterize mosquitoes population densities and species distribution by habitat and season; and serological surveys in people to determine the risk of Rift Valley fever virus (RVFV), West Nile fever virus (WNV), dengue fever virus (DFV), Leptospira spp. and Brucella spp. Results demonstrate a drastic decline in vegetation cover over R approximate to 25 years particularly in the irrigated areas where cropland increased by about 1,400% and non-farm land (under closed trees, open to closed herbaceous vegetation, bushlands and open trees) reduced by 30-100%. The irrigated areas had high densities of Aedes mcintoshi, Culexspp. and Mansonia spp. (important vectors for multiple arboviruses) during the wet and dry season while pastoral areas had high densities of Ae. tricholabis specifically in the wet season. The seroprevalences of RVFV, WNV and DFV were higher in the irrigated compared to the pastoral areas while those for Leptospira spp and Brucella spp. were higher in the pastoral compared to the irrigated areas. It is likely that people in the pastoral areas get exposed to Leptospira spp by using water fetched from reservoirs that are shared with livestock and wildlife, and to Brucella spp. by consuming raw or partially cooked animal source foods such as milk and meat. This study suggests that irrigation increases the risk of mosquito-borne infections while at the same time providing a protective effect against zoonotic pathogens that thrive in areas with high livestock population densities.

  • 327.
    Beven, Laure
    et al.
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Charenton, Claire
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Dautant, Alain
    Univ Bordeaux, Bordeaux, France ; IBMC, CNRS, Bordeaux, France.
    Bouyssou, Guillaume
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Labroussaa, Fabien
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Sköllermo, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Persson, Anja
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Blanchard, Alain
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Sirand-Pugnet, Pascal
    Univ Bordeaux, Villenave Dornon, France ; INRA Villenave Dornon, France .
    Specific Evolution of F-1-Like ATPases in Mycoplasmas2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38793-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    F1F0 ATPases have been identified in most bacteria, including mycoplasmas which have very small genomes associated with a host-dependent lifestyle. In addition to the typical operon of eight genes encoding genuine F1F0 ATPase (Type 1), we identified related clusters of seven genes in many mycoplasma species. Four of the encoded proteins have predicted structures similar to the alpha, beta, gamma and e subunits of F-1 ATPases and could form an F-1-like ATPase. The other three proteins display no similarity to any other known proteins. Two of these proteins are probably located in the membrane, as they have three and twelve predicted transmembrane helices. Phylogenomic studies identified two types of F-1-like ATPase clusters, Type 2 and Type 3, characterized by a rapid evolution of sequences with the conservation of structural features. Clusters encoding Type 2 and Type 3 ATPases were assumed to originate from the Hominis group of mycoplasmas. We suggest that Type 3 ATPase clusters may spread to other phylogenetic groups by horizontal gene transfer between mycoplasmas in the same host, based on phylogeny and genomic context. Functional analyses in the ruminant pathogen Mycoplasma mycoides subsp. mycoides showed that the Type 3 cluster genes were organized into an operon. Proteomic analyses demonstrated that the seven encoded proteins were produced during growth in axenic media. Mutagenesis and complementation studies demonstrated an association of the Type 3 cluster with a major ATPase activity of membrane fractions. Thus, despite their tendency toward genome reduction, mycoplasmas have evolved and exchanged specific F-1-like ATPases with no known equivalent in other bacteria. We propose a model, in which the F-1-like structure is associated with a hypothetical X-0 sector located in the membrane of mycoplasma cells.

  • 328.
    Bhushan, Shashi
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Kuhn, Claus
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Berglund, Anna-Karin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Roth, Christian
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Glaser, Elzbieta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    The role of the N-terminal domain of chloroplast targeting peptides in organellar protein import and miss-sorting2006Inngår i: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 580, nr 16, s. 3966-3972Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have analysed 385 mitochondrial and 567 chloroplastic signal sequences of proteins found in the organellar proteomes of Arabidopsis thaliana. Despite overall similarities, the first 16 residues of transit peptides differ remarkably. To test the hypothesis that the N-terminally truncated transit peptides would redirect chloroplastic precursor proteins to mitochondria, we studied import of the N-terminal deletion mutants of ELIP, PetC and Lhcb2.1. The results show that the deletion mutants were neither imported into chloroplasts nor miss-targeted to mitochondria in vitro and in vivo, showing that the entire transit peptide is necessary for correct targeting as well as miss-sorting.

  • 329.
    Bhushan, Shashi
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Pavlov, Pavel F
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Rudhe, Charlotta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Glaser, Elzbieta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    In vitro and in vivo methods to study protein import into plant mitochondria.2007Inngår i: Methods Mol Biol, ISSN 1064-3745, Vol. 390, s. 131-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plant mitochondria contain about 1000 proteins, 90-99% of which in different plant species are nuclear encoded, synthesized on cytosolic polyribosomes, and imported into the organelle. Most of the nuclear-encoded proteins are synthesized as precursors containing an N-terminal extension called a presequence or targeting peptide that directs the protein to the mitochondria. Here we describe in vitro and in vivo methods to study mitochondrial protein import in plants. In vitro synthesized precursor proteins can be imported in vitro into isolated mitochondria (single organelle import). However, missorting of chloroplast precursors in vitro into isolated mitochondria has been observed. A novel dual import system for simultaneous import of proteins into isolated mitochondria and chloroplasts followed by reisolation of the organelles is superior over the single import system as it abolishes the mistargeting. Precursor proteins can also be imported into the mitochondria in vivo using an intact cellular system. In vivo approaches include import of transiently expressed fusion constructs containing a presequence or a full-length precursor protein fused to a reporter gene, most commonly the green fluorescence protein (GFP) in protoplasts or in an Agrobacterium-mediated system in intact tobacco leaves.

  • 330.
    Biasiotto, Roberta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Akusjärvi, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Regulation of Human Adenovirus Alternative RNA Splicing by the Adenoviral L4-33K and L4-22K Proteins2015Inngår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, nr 2, s. 2893-2912Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular protein kinases Protein Kinase A (PKA) and DNA-dependent protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral protein that binds the cellular protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich protein activity by inducing SR protein dephosphorylation. The L4-33K, and most likely also the L4-22K protein, are highly phosphorylated in vivo. Here we will review the function of these viral proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential protein kinases phosphorylating the L4-33K and/or L4-22K proteins.

  • 331.
    Biava, Pier M.
    et al.
    Scientific Institute of Research and Care Multimedica, Milano, Italy.
    Canaider, Silvia
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Facchin, Federica
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Bianconi, Eva
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Ljungberg, Liza
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Rotilio, Domenico
    Department of Haematology, Ospedali Riuniti BMM, Reggio Calabria, Italy.
    Burigana, Fabio
    Associazione Medicina e Complessità (AMEC), Trieste, Italy.
    Ventura, Carlo
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy; Stem Wave Institute for Tissue Healing (SWITH), Gruppo Villa Maria (GVM) Care & Research - Ettore Sansavini Health Science Foundation, Lugo (Ravenna), Italy.
    Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells2015Inngår i: Current Pharmaceutical Biotechnology, ISSN 1389-2010, E-ISSN 1873-4316, Vol. 16, nr 9, s. 782-792Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In spite of the growing body of evidence on the biology of the Zebrafish embryo and stem cells, including the use of Stem Cell Differentiation Stage Factors (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics, comparatively little is known about the possibility to use these factors to modulate the homeostasis of normal human stem cells or to modulate the behavior of cells involved in different pathological conditions. In the present review we recall in a synthetic way the most important researches about the use of SCDSFs in reprogramming cancer cells and in modulating the high speed of multiplication of keratinocytes which is characteristic of some pathological diseases like psoriasis. Moreover we add here the results about the capability of SCDSFs in modulating the homeostasis of human adipose-derived stem cells (hASCs) isolated from a fat tissue obtained with a novel-non enzymatic method and device. In addition we report the data not yet published about a first protein analysis of the SCDSFs and about their role in a pathological condition like neurodegeneration.

  • 332.
    Biberfeld, G
    et al.
    National bacteriological laboratory.
    Thorstensson, R
    National bacteriological laboratory.
    Bergström, M
    National bacteriological laboratory.
    Naucler, A
    National bacteriological laboratory.
    Costa, C M
    National bacteriological laboratory.
    Enzyme immunoassays for the demonstration of antibodies to HIV-2SBL-6669 and HTLV-IV (SIVmac).1988Inngår i: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 2, nr 3, s. 195-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Enzyme-linked immunosorbent assays (ELISA) were developed for the demonstration of antibodies to HIV-2 using disrupted virions of the SBL-6669 isolate of HIV-2 and the so-called human T-lymphotropic virus type IV (HTLV-IV), recently found to be identical with the simian immunodeficiency virus (SIVmac), as antigens. Three hundred sera from West African subjects, attending an outward clinic in Bissau for examination of suspected tuberculosis, were tested by these two assays as well as by a commercially available anti-HIV-2 ELISA (ELAVIA II). Fifty of these sera were positive in all three ELISAs as well as in Western blot tests against HTLV-IV. Thirty-eight of these positive sera were also tested by an anti-HIV-2 Western blot kit (LAV-Blot II) with positive results. The ELISAs based on SBL-6669 and HTLV-IV antigens had a specificity of 99.6% (one false positive among 250 negative sera) whereas the specificity of ELAVIA II was 94.6% using the recommended cut-off value and 98.4% using a higher cut-off value. Another 58 sera from West African patients, clinically suspected of having AIDS or HIV-related disease, were tested for HIV-2/HTLV-IV antibodies by Western blot and by ELISA against SBL-6669 and HTLV-IV antigens; all of the 30 sera which were positive by Western blot were found to be positive in both ELISAs.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 333.
    Bicer, Baver
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper (from 2013).
    Delegation till biomedicinsk analytiker för warfarindosering2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 334.
    Bild, Filippa
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Utvärdering av BD Vacutainer® Rapid Serum Tube vid analys av S-Paracetamol och S-Etanol2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Avdelningen för klinisk kemi vid Länssjukhuset i Kalmar analyserar läkemedel och alkoholer med BD Vacutainer® Plus Plastic Serum Tube (Serum Tube), som kräver en koagulationstid i upp till 60 minuter. BD Vacutainer® Rapid Serum Tube (RST™) innehåller trombin och kräver en koagulationstid på endast 5 minuter. Syftet med studien var att undersöka möjligheten att förkorta den preanalytiska väntetiden före centrifugering vid intoxikationsanalyser i serumrör från akutmottagningen. Studien utfördes genom att jämföra RST™ med Serum Tube vid analys av S-Paracetamol och S-Etanol. Totalt analyserades 70 prover för S-Paracetamol, varav 35 RST™ och 35 Serum Tube från 35 patienter. Analys av S-Etanol utfördes på 60 prover, varav 30 RST™ och 30 Serum Tube från 30 patienter. RST™ centrifugerades efter 5 minuter och Serum Tube efter 50 minuter, före kolorimetrisk analys på analysinstrumentet VITROS® 5,1 FS. Resultaten för S-Paracetamol var inom intervallet 74,9 – 198,7 µmol/L för RST™ och inom 76,6 – 195,3 µmol/L för Serum Tube. Resultaten för S-Etanol var inom intervallet 7,5 – 74,5 mmol/L för RST™ och inom 7,5 – 74,8 mmol/L för Serum Tube. Pearsons korrelationskoefficient var 0,9977 för S-Paracetamol och 0,9980 för S-Etanol och det fanns en liten positiv bias vid analys med RST™ för båda analyterna, men ingen signifikant skillnad (p>0,05) mellan provrören påvisades. Användning av RST™ på akutmottagningen medför en förkortad preanalytisk väntetid och en snabbare turnaround time (TAT). Hypotesen att S-Paracetamol och S-Etanol kan analyseras med RST™ på VITROS® 5,1 FS stämmer, med undantag för höga koncentrationer av S-Paracetamol som inte kunde utvärderas. För att RST™ ska kunna användas rutinmässigt bör därför ytterligare studier utföras.

  • 335.
    Bin Kaderi, Mohamed Arifin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Hematologi och immunologi.
    Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL.

    In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL.

    In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results.

    In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.

  • 336.
    Bisevac, Maida
    Högskolan Kristianstad, Sektionen för lärande och miljö.
    Jämförelse av Vibrio parahaemolyticus överlevnad i marint och artificiellt saltvatten samt jämförelse av fyra kit för RNA-extrahering från V. parahaemolyticus 2015Independent thesis Basic level (university diploma), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Vibrio parahaemolyticus är en marin bakterie som människan kan få i sig via fisk och skaldjur eller genom att bada i vattnet med höga koncentrationer av denna bakterie och som kan orsaka mag- och tarminfektioner, öroninfektioner, sårinfektioner och till och med blodförgiftningar. Bakterien är patogen även för marina organismer. Eftersom ökad koldioxidhalt leder till havsförsurningen som kommer att försvaga immunsystem hos marina organismer är det viktigt att studera genuttrycket hos V. parahaemolyticus vid lägre pH för att få kunskap om den blir lika virulent. Syftet med denna studie är att jämföra bakteriens överlevnad i marint vatten och artificiellt vatten (ASW) eftersom det senare ofta används i laborativa studier av marina bakteriers egenskaper och funktion, samt att jämföra fyra kommersiella kit (TRIzol Max Bacterial RNA Isolation Kit Life Technologies), RNeasy Mini Kit (Qiagen), NucleoSpin RNA Plus (Macherey-Nagel) och SV Total RNA Isolation Kit (Promega)) för RNA extrahering både från bakterier i log-fasen vid rekommenderat bakterieantal och marint vatten vid lågt bakterieantal. Bakterierna överlevde lika bra i båda sorters vatten. När det gäller RNA extrahering gav TRIzol högst RNA-mängd, men sämre kvalitet, speciellt i extraherat från marint vatten. NucleoSpin gav lite högre RNA-mängd än Qiagen, men kvalitet hos RNA extraherat med Qiagen uppskattades som lite bättre när provet kördes ut på gel. Detta och mycket kort extraheringstid, samt bättre säkerhet och enklare steg kan göra att man föredrar NucleoSpin och Qiagen framför TRIzol.

  • 337.
    Bivik Stadler, Caroline
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Genetic pathways controlling CNS development: The role of Notch signaling in regulating daughter cell proliferation in Drosophila2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The human central nervous system (CNS) displays the greatest cellular diversity of any organ system, consisting of billions of neurons, of numerous cell sub-types, interconnected in a vast network. Given this enormous complexity, decoding the genetic programs controlling the multistep process of CNS development remains a major challenge. While great progress has been made with respect to understanding sub-type specification, considerably less is known regarding how the generation of the precise number of each sub-type is controlled.

    The aim of this thesis was to gain deeper knowledge into the regulatory programs controlling cell specification and proliferation. To address these questions I have studied the Drosophila embryonic CNS as a model system, to thereby be able to investigate the genetic mechanisms at high resolution. Despite the different size and morphology between the Drosophila and the mammalian CNS, the lineages of their progenitors share similarity. Importantly for this thesis, both species progenitors show elaborate variations in their proliferation modes, either giving rise to daughters that can directly differentiate into neurons or glia (type 0), divide once (type I), or multiple times (type II).

    The studies launched off with a comprehensive chemical forward genetic screen, for the very last born cell in the well-studied lineage of progenitor NB5-6T: the Ap4 neuron, which expresses the neuropeptide FMRFa. NB5-6T is a powerful model to use, because it undergoes a programmed type I>0 daughter cell proliferation switch. An FMRF-eGFP transgenic reporter was utilized as readout for successful terminal differentiation of Ap4/FMRFa and thereby proper lineage progression of the ∼20 cells generated. The strongest mutants were mapped to genes with both known and novel essential functions e.g., spatial and temporal patterning, cell cycle control, cell specification and chromatin modification. Subsequently, we focused on some of the genes that showed a loss of function phenotype with an excess of lineage cells. We found that Notch is critical for the type I>0 daughter cell proliferation switch in the NB5-6T lineage and globally as well. When addressing the broader relevance of these findings, and to further decipher the Notch pathway, we discovered that selective groups of E(spl) genes is controlling the switch in a close interplay with four key cell cycle factors: Cyclin E, String, E2F and Dacapo, in most if not all embryonic progenitors. The Notch mediation of the switch is likely to be by direct transcriptional regulation. Furthermore, another gene identified in the screen, sequoia, was investigated. The analysis revealed that sequoia is also controlling the daughter cell switch in the CNS, and this partly through context dependent interactions with the Notch pathway.

    Taken together, the findings presented in this thesis demonstrate that daughter cell proliferation switches in Drosophila neural lineages are genetically programmed, and that Notch contributes to the triggering of these events. Given that early embryonic processes is frequently shown to be evolutionary conserved, you can speculate that changeable daughter proliferation programs could be applied to mammals, and contribute to a broader understanding of proliferation processes in humans as well.

     

  • 338.
    Bixo, Mi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Detektion av alloantikroppar hos nyligt transfunderade DAT-positiva patienter: Utvärdering med en experimentell in vitro modell2018Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 339. Bjorklund, Geir
    et al.
    Stejskal, Vera
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Urbina, Mauricio A.
    Dadar, Maryam
    Chirumbolo, Salvatore
    Mutter, Joachim
    Metals and Parkinson's Disease: Mechanisms and Biochemical Processes2018Inngår i: Current Medicinal Chemistry, ISSN 0929-8673, E-ISSN 1875-533X, Vol. 25, nr 19, s. 2198-2214Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Genetic background accounts for only 5 to 10% of the reported cases of Parkinson's disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.

  • 340. Bjornsdottir, Halla
    et al.
    Rudin, Agnes Dahlstrand
    Klose, Felix P.
    Elmwall, Jonas
    Welin, Amanda
    Stylianou, Marios
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Christenson, Karin
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Forsman, Huamei
    Dahlgren, Claes
    Karlsson, Anna
    Bylund, Johan
    Phenol-soluble Modulin α Peptide Toxins from aggressive Staphylococcus aureus induce rapid Formation of neutrophil extracellular Traps through a reactive Oxygen species-independent Pathway2017Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikkel-id 257Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neutrophils have the ability to capture and kill microbes extracellularly through the formation of neutrophil extracellular traps (NETs). These are DNA and protein structures that neutrophils release extracellularly and are believed to function as a defense mechanism against microbes. The classic NET formation process, triggered by, e.g., bacteria, fungi, or by direct stimulation of protein kinase C through phorbol myristate acetate, is an active process that takes several hours and relies on the production of reactive oxygen species (ROS) that are further modified by myeloperoxidase (MPO). We show here that NET-like structures can also be formed by neutrophils after interaction with phenol-soluble modulin alpha (PSM alpha) that are cytotoxic membrane-disturbing peptides, secreted from community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The PSMa-induced NETs contained the typical protein markers and were able to capture microbes. The PSMa-induced NET structures were disintegrated upon prolonged exposure to DNase-positive S. aureus but not on exposure to DNase-negative Candida albicans. Opposed to classic NETosis, PSMa-triggered NET formation occurred very rapidly, independently of ROS or MPO, and was also manifest at 4 degrees C. These data indicate that rapid NETs release may result from cytotoxic membrane disturbance by PSMa peptides, a process that may be of importance for CA-MRSA virulence.

  • 341.
    Bjurhager, Ingela
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Gamstedt, E. Kristofer
    Keunecke, Daniel
    Niemz, Peter
    Berglund, Lars A.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Biokompositer. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Mechanical performance of yew (Taxus baccata L.) from a longbow perspective2013Inngår i: Holzforschung, ISSN 0018-3830, E-ISSN 1437-434X, Vol. 67, nr 7, s. 763-770Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Yew (Taxus baccata L.) longbow was the preferred weapon in the Middle Ages until the emergence of guns. In this study, the tensile, compression, and bending properties of yew were investigated. The advantage of yew over the other species in the study was also confirmed by a simple beam model. The superior toughness of yew has the effect that a yew longbow has a higher range compared with bows made from other species. Unexpectedly, the mechanical performance of a bow made from yew is influenced by the juvenile-to-mature wood ratio rather than by the heartwood-to-sapwood ratio. A yew bow is predicted to have maximized performance at a juvenile wood content of 30-50%, and located at the concave side (the compressive side facing the bowyer). Here, the stiffness and yield stress in compression should be as high as possible.

  • 342.
    Bjällmark, Anna
    KTH, Medicinsk teknik.
    New ultrasonographic approaches to monitoring cardiac and vascular function2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Atherosclerotic cardiovascular disease is the leading cause of death worldwide. To decrease mortality and morbidity in cardiovascular disease, the development of accurate, non-invasive methods for early diagnosis of atherosclerotic cardiac and vascular engagement is of considerable clinical interest. Cardiovascular ultrasound imaging is today the cornerstone in the routine evaluation of cardiovascular function and recent development has resulted in two new techniques, tissue velocity imaging (TVI) and speckle tracking, which allow objective quantification of cardiovascular function. TVI and speckle tracking are the basis for three new approaches to cardiac and vascular monitoring presented in this thesis: wave intensity wall analysis (WIWA), two-dimensional strain imaging in the common carotid artery, and the state diagram of the heart.

     

    WIWA uses longitudinal and radial strain rate as input for calculations of wave intensity in the arterial wall. In this thesis, WIWA was validated against a commercially available wave intensity system, showing that speckle tracking-derived strain variables can be useful in wave intensity analysis. WIWA was further tested in patients with end stage renal disease and documented high mortality in cardiovascular disease. The latter study evaluated the effects of a single session of hemodialysis using WIWA and TVI variables and showed improved systolic function after hemodialysis. The results also indicated that preload-adjusted early systolic wave intensity obtained by the WIWA system may contribute in the assessment of left ventricular contractility in this patient category. Two-dimensional strain imaging in the common carotid artery is a new approach showing great potential to detect age-dependent differences in mechanical properties of the common carotid artery. Among the measured strain variables, global circumferential strain had the best discriminating performance and appeared to be superior to conventional measures of arterial stiffness such as elastic modulus and β stiffness index. The state diagram is a visualisation tool that provides a quantitative overview of the temporal interrelationship of mechanical events in the left and right ventricles. Case examples and a small clinical study showed that state diagrams clearly visualize cardiac function and can be useful in the detection of non ST-elevation myocardial infarction (NSTEMI).

     

    Even though WIWA, two-dimensional strain imaging in the common carotid artery and the state diagram show potential to be useful in the evaluation of cardiovascular function, there still remains a considerable amount of work to be done before they can be used in the daily clinical practice.

  • 343.
    Bjällmark, Anna
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik.
    New ultrasonographic approaches to monitoring cardiac and vascular function2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Atherosclerotic cardiovascular disease is the leading cause of death worldwide. To decrease mortality and morbidity in cardiovascular disease, the development of accurate, non-invasive methods for early diagnosis of atherosclerotic cardiac and vascular engagement is of considerable clinical interest. Cardiovascular ultrasound imaging is today the cornerstone in the routine evaluation of cardiovascular function and recent development has resulted in two new techniques, tissue velocity imaging (TVI) and speckle tracking, which allow objective quantification of cardiovascular function. TVI and speckle tracking are the basis for three new approaches to cardiac and vascular monitoring presented in this thesis: wave intensity wall analysis (WIWA), two-dimensional strain imaging in the common carotid artery, and the state diagram of the heart.

     

    WIWA uses longitudinal and radial strain rate as input for calculations of wave intensity in the arterial wall. In this thesis, WIWA was validated against a commercially available wave intensity system, showing that speckle tracking-derived strain variables can be useful in wave intensity analysis. WIWA was further tested in patients with end stage renal disease and documented high mortality in cardiovascular disease. The latter study evaluated the effects of a single session of hemodialysis using WIWA and TVI variables and showed improved systolic function after hemodialysis. The results also indicated that preload-adjusted early systolic wave intensity obtained by the WIWA system may contribute in the assessment of left ventricular contractility in this patient category. Two-dimensional strain imaging in the common carotid artery is a new approach showing great potential to detect age-dependent differences in mechanical properties of the common carotid artery. Among the measured strain variables, global circumferential strain had the best discriminating performance and appeared to be superior to conventional measures of arterial stiffness such as elastic modulus and β stiffness index. The state diagram is a visualisation tool that provides a quantitative overview of the temporal interrelationship of mechanical events in the left and right ventricles. Case examples and a small clinical study showed that state diagrams clearly visualize cardiac function and can be useful in the detection of non ST-elevation myocardial infarction (NSTEMI).

     

    Even though WIWA, two-dimensional strain imaging in the common carotid artery and the state diagram show potential to be useful in the evaluation of cardiovascular function, there still remains a considerable amount of work to be done before they can be used in the daily clinical practice.

  • 344.
    Björk, Josefin
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Erytrocytinnehåll i plasmakomponenter: En jämförelse mellan teststickan Multistix, hematologiinstrumentet Advia 2120 och manuell räkning i mikroskop med Bürkers räknekammare2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Efter tappning av 450 mL helblod från frivilliga blodgivare separeras blodet till plasma, erytrocyter och trombocyter. Kontroller tas för att undersöka komponentframställningens resultat. I plasmaenheterna kontrolleras bland annat att antalet erytrocyter är under 6x109 per liter. Helblod innehåller normalt 4-6x1012 erytrocyter per liter. Massiv blödning är den främsta indikationen för plasmatransfusion. En transfusion är förknippad med risker såsom transfusion related acute lung injury (TRALI) och transfusion associated circulatory overload (TACO). Syftet med examensarbetet var att hitta en beslutsgräns för bestämning av erytrocytinnehållet i plasmakomponenter som framställs vid beredning av blodkomponenter inför transfusion. Gränsen skulle fastställas genom en jämförelse mellan teststickan Multistix 8 SG, Body fluid-programmet i hematologiinstrumentet Advia 2120 samt manuell räkning i Bürkers räknekammare. Analys skedde av 38 prover varav 18 prover fick tillsats av extra erytrocyter för att antingen överstiga kontrollgränsen eller finna övergången till stickans högsta nivå. Medelvärdet och medianen för de kvantitativa resultaten från Bürkers räknekammare för 20 godkända kontrollerna, fördelade efter teststickans kategorier, beräknades. Samtliga resultaten låg mellan 0,063x109/L och 2,08x109/L. Av de 38 prover som analyserades erhöll 37 ett resultat i form <10x109/L på Advia 2120. Utifrån de erhållna resultaten fastslogs gränsen vid vilken en komponentkontroll garanteras ett godkänt resultat till ≤2+ på teststickan. Vid resultat 3+ ska en konfirmerande kvantitativ analys utföras. Den slutsats som kunde dras var att teststickan Multistix 8 SG kan användas som en screeningmetod vid analys av erytrocytinnehållet i de tillverkade plasmakomponenterna. Slutsatsen blev även att det Adviaprogram som användes inte är lämpligt för analys av erytrocytinnehållet i plasma.

  • 345.
    Björkander, Sophia
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Hell, Lena
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Johansson, Maria A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Mata Forsberg, Manuel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lasaviciute, Gintare
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Roos, Stefan
    Holmlund, Ulrika
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Staphylococcus aureus-derived factors induce IL-10, IFN-gamma and IL-17A-expressing FOXP3(+)CD161(+) T-helper cells in a partly monocyte-dependent manner2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 22083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells. Stimulation of PBMC with S. aureus 161:2-cell free supernatant (CFS) induced expression of IL-10, IFN-gamma and IL-17A in FOXP3(+) cells. Further, CD161 and HELIOS separated the FOXP3(+) cells into four distinct populations regarding cytokine-expression. Monocyte-depletion decreased S. aureus 161:2-induced activation of FOXP3(+) cells while pre-stimulation of purified monocytes with S. aureus 161:2-CFS and subsequent co-culture with autologous monocyte-depleted PBMC was sufficient to mediate activation of FOXP3(+) cells. Together, these data show that S. aureus potently induces FOXP3(+) cells and promotes a diverse phenotype with expression of regulatory and pro-inflammatory cytokines connected to increased CD161-expression. This could indicate potent regulation or a contribution of FOXP3(+) cells to inflammation and repression of immune-suppression upon encounter with S. aureus.

  • 346.
    Björkblom, Benny
    et al.
    The Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway ; Center for Organelle Research, University of Stavanger, Stavanger, Norway.
    Maple-Grødem, Jodi
    The Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway ; Center for Organelle Research, University of Stavanger, Stavanger, Norway.
    Puno, Marc Rhyan
    Department of Molecular and Applied Biosciences, University of Westminster, London, United Kingdom.
    Odell, Mark
    Department of Molecular and Applied Biosciences, University of Westminster, London, United Kingdom.
    Larsen, Jan Petter
    The Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
    Møller, Simon Geir
    The Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway ; Department of Biological Sciences, St. John's University, New York, New York, USA.
    Reactive oxygen species-mediated DJ-1 monomerization modulates intracellular trafficking involving karyopherin beta 22014Inngår i: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 34, nr 16, s. 3024-3040Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in DJ-1 are a cause of recessive, early-onset Parkinson's disease (PD). Although oxidative stress and mitochondrial integrity have been implicated in PD, it is largely unknown why neurons degenerate. DJ-1 is involved in oxidative stress-mediated responses and in mitochondrial maintenance; however, its specific function remains vague. Here we show that DJ-1 exhibits neuronal dynamic intracellular trafficking, with dimeric/monomeric cycling modulated by the oxidative environment. We demonstrate that oxidative stress enhances monomerization of wild-type cytosolic DJ-1, leading to nuclear recruitment. The pathogenic DJ-1/E163K variant is unable to homodimerize but is retained in the cytosol upon wild-type DJ-1 heterodimerization. We found that this wild-type/pathogenic heterodimer is disrupted by oxidative stress, leading to DJ-1/E163K mitochondrial translocation. We further demonstrated that endogenously expressed wild-type DJ-1 is imported into neuronal nuclei as a monomer and that nucleo-cytoplasmic transport is oxidative stress mediated. We identified a novel proline-tyrosine nuclear localization signal (PY-NLS) in DJ-1, and we found that nuclear monomeric DJ-1 import is mediated by an oxidative stress-dependent interaction with karyopherin beta 2. Our study provides evidence that oxidative stress-mediated intracellular trafficking of DJ-1, mediated by dynamic DJ-1 dimeric/monomeric cycling, is implicated in PD pathogenesis.

  • 347.
    Björkelund, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Novel Methods for Analysis of Heterogeneous Protein-Cell Interactions: Resolving How the Epidermal Growth Factor Binds to Its Receptor2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cells are complex biological units with advanced signalling systems, a dynamic capacity to adapt to its environment, and the ability to divide and grow. In fact, they are of such high level of complexity that it has deemed extremely difficult or even impossible to completely understand cells as complete units. The search for comprehending the cell has instead been divided into small, relatively isolated research fields, in which simplified models are used to explain cell biology. The result produced through these reductionistic investigations is integral for our current description of biology. However, there comes a time when it is possible to go beyond such simplifications and investigate cell biology at a higher level of complexity. That time is now.

    This thesis describes the development of mathematical tools to investigate intricate biological systems, with focus on heterogeneous protein interactions. By the use of simulations, real-time measurements and kinetic fits, standard assays for specificity measurements and receptor quantification were scrutinized in order to find optimal experimental settings and reduce labour time as well as reagent cost. A novel analysis platform, called Interaction Map, was characterized and applied on several types of interactions. Interaction Map decomposes a time-resolved binding curve and presents information on the kinetics and magnitude of each interaction that contributed to the curve. This provides a greater understanding of parallel interactions involved in the same biological system, such as a cell. The heterogeneity of the epidermal growth factor receptor (EGFR) system was investigated with Interaction Map applied on data from the instrument LigandTracer, together with complementing manual assays. By further introducing disturbances to the system, such as tyrosine kinase inhibitors and variation in temperature, information was obtained about dimerization, internalization and degradation rates.

    In the long term, analysis of binding kinetics and combinations of parallel interactions can improve the understanding of complex biomolecular mechanisms in cells and may explain some of the differences observed between cell lines, medical treatments and groups of patients.

  • 348.
    Björklund, Asa K
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Light, Sara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Hedin, Linnea
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Elofsson, Arne
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Quantitative assessment of the structural bias in protein-protein interaction assays.2008Inngår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 8, nr 22, s. 4657-46667Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    With recent publications of several large-scale protein-protein interaction (PPI) studies, the realization of the full yeast interaction network is getting closer. Here, we have analysed several yeast protein interaction datasets to understand their strengths and weaknesses. In particular, we investigate the effect of experimental biases on some of the protein properties suggested to be enriched in highly connected proteins. Finally, we use support vector machines (SVM) to assess the contribution of these properties to protein interactivity. We find that protein abundance is the most important factor for detecting interactions in tandem affinity purifications (TAP), while it is of less importance for Yeast Two Hybrid (Y2H) screens. Consequently, sequence conservation and/or essentiality of hubs may be related to their high abundance. Further, proteins with disordered structure are over-represented in Y2H screens and in one, but not the other, large-scale TAP assay. Hence, disordered regions may be important both in transient interactions and interactions in complexes. Finally, a few domain families seem to be responsible for a large part of all interactions. Most importantly, we show that there are method-specific biases in PPI experiments. Thus, care should be taken before drawing strong conclusions based on a single dataset.

  • 349.
    Björklund, Kristofer
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Evaluation and optimization of four real-time PCRs, using TaqMan-probes, for detection of and discrimination between barley, oat, rye and wheat2008Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Coeliac disease is a chronic inflammatory disease treated with a gluten-free diet, excluding barley, rye and wheat. Hence, there is a demand for methods able to detect gluten in foods in order to ensure correct labeling of products. According to the Codex Alimentarius Commission, 20ppm gluten is the maximum amount allowed in food labeled gluten-free.

    PCR can detect DNA from cereals in food. Four real-time PCR-systems,

    using TaqMan®-probes for detection of barley, oat, rye and wheat were optimized and evaluated. Evaluations were carried out using seeds. Primers were targeted to genes coding for prolamines, seed storage proteins. PCR-systems targeted to barley, oat and wheat were shown to be specific for the cereals corresponding to each system. The system targeted to rye showed cross-reactions with durum wheat and spelt wheat. Detection limits were 50pg, corresponding to <10 haploid genome copies for each cereal. All systems were able to detect 250ppm amounts of DNA, most likely even smaller amounts are detectable. All systems showed an amplification efficiency of ≥95%.

    Systems for detection of barley, oat and wheat are ready for further evaluation, using food products as samples. The rye system however, needs to be re-designed before further evaluation can take place.

  • 350.
    Björklund, Åsa K.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Ekman, Diana
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Elofsson, Arne
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Expansion of Protein Domain Repeats2006Inngår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 2, nr 8, s. 959-970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e. g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

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