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  • 351. Blau, Axel
    et al.
    Murr, Angelika
    Wolff, Sandra
    Sernagor, Evelyne
    Medini, Paolo
    Iurilli, Giuliano
    Ziegler, Christiane
    Benfenati, Fabio
    Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals2011Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, nr 7, s. 1778-1786Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Microelectrode electrophysiology has become a widespread technique for the extracellular recording of bioelectrical signals. To date, electrodes are made of metals or inorganic semiconductors, or hybrids thereof. We demonstrate that these traditional conductors can be completely substituted by highly flexible electroconductive polymers. Pursuing a two-level replica-forming strategy, conductive areas for electrodes, leads and contact pads are defined as microchannels in poly(dimethylsiloxane) (PDMS) as a plastic carrier and track insulation material. These channels are coated by films of organic conductors such as polystyrenesulfonate-doped poly(3,4-ethylenedioxy-thiophene) (PEDOT:PSS) or filled with a graphite-PDMS (gPDMS) composite, either alone or in combination. The bendable, somewhat stretchable, non-cytotoxic and biostable all-polymer microelectrode arrays (polyMEAs) with a thickness below 500 μm and up to 60 electrodes reliably capture action potentials (APs) and local field potentials (LFPs) from acute preparations of heart muscle cells and retinal whole mounts, in vivo epicortical and epidural recordings as well as during long-term in vitro recordings from cortico-hippocampal co-cultures.

  • 352.
    Blikstad, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Widersten, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Functional characterization of a stereospecific diol dehydrogenase, FucO, from Escherichia coli: substrate specificity, pH dependence, kinetic isotope effects and influence of solvent viscosity2010Inngår i: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 66, nr 1-2, s. 148-155Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    FucO, (S)-1,2-propanediol oxidoreductase, from Escherichia coli is involved in the anaerobic catabolic metabolism of L-fucose and L-rhamnose, catalyzing the interconversion of lactaldehyde to propanediol. The enzyme is specific for the S-enantiomers of the diol and aldehyde suggesting stereospecificity in catalysis. We have studied the enzyme kinetics of FucO with a spectrum of putative alcohol and aldehyde substrates to map the substrate specificity space. Additionally, for a more detailed analysis of the kinetic mechanism, pH dependence of catalysis, stereochemistry in hydride transfer, deuterium kinetic isotope effect of hydride transfer and effect of increasing solvent viscosity were also analyzed. The outcome of this study can be summarized as follows: FucO is highly stereospecific with the highest E-value measured to be 320 for the S-enantiomer of 1,2-propanediol. The enzyme is strictly regiospecific for oxidation of primary alcohols. The enzyme prefers short-chained (2-4 carbons) substrates and does not act on bulkier compounds such as phenyl-substituted alcohols. FucO is an 'A-side' dehydrogenase transferring the pro-R-hydrogen of NADH to the aldehyde substrate. The deuterium KIEs of kcat and kcat/KM were 1.9 and 4.2, respectively, illustrating that hydride transfer is partially rate-limiting but also that other reaction steps contribute to rate limitation of catalysis. Combining the KIE results with the observed effects of increasing medium viscosity proposed a working model for the kinetic mechanism involving slow, rate-limiting, product release and on-pathway conformational changes in the enzyme-nucleotide complexes.

  • 353.
    Blissing, Annica
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Thiopurine S-methyltransferase - characterization of variants and ligand binding2017Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Thiopurine S-methyltransferase (TPMT) belongs to the Class I S-adenosylmethionine-dependent methyltransferase (SAM-MT) super family of structurally related proteins. Common to the members of this large protein family is the catalysis of methylation reactions using S-adenosylmethionine (SAM) as a methyl group donor, although SAM-MTs act on a wide range of different substrates and carry out numerous biologically important functions. While the natural function of TPMT is unknown, this enzyme is involved in the metabolism of thiopurines, a class of pharmaceutical substances administered in treatment of immune-related disorders. Specifically, methylation by TPMT inactivates thiopurines and their metabolic intermediates, which reduces the efficacy of clinical treatment and increases the risk of adverse side effects. To further complicate matters, TPMT is a polymorphic enzyme with over 40 naturally occurring variants known to date, most of which exhibit lowered methylation activity towards thiopurines. Consequently, there are individual variations in TPMTmediated thiopurine inactivation, and the administered dose has to be adjusted prior to clinical treatment to avoid harmful side effects.

    Although the clinical relevance of TPMT is well established, few studies have investigated the molecular causes of the reduced methylation activity of variant proteins. In this thesis, the results of biophysical characterization of two variant proteins, TPMT*6 (Y180F) and TPMT*8 (R215H), are presented. While the properties of TPMT*8 were indistinguishable from those of the wild-type protein, TPMT*6 was found to be somewhat destabilized. Interestingly, the TPMT*6 amino acid substitution did not affect the functionality or folding pattern of the variant protein. Therefore, the decreased in vivo functionality reported for TPMT*6 is probably caused by increased proteolytic degradation in response to the reduced stability of this protein variant, rather than loss of function.

    Also presented herein are novel methodological approaches for studies of TPMT and its variants. Firstly, the advantages of using 8-anilinonaphthalene-1-sulfonic acid (ANS) to probe TPMT tertiary structure and active site integrity are presented. ANS binds exclusively to the native state of TPMT with high affinity (KD ~ 0.2 μm) and a 1:1 ratio. The stability of TPMT was dramatically increased by binding of ANS, which was shown to co-localize with the structurally similar adenine moiety of the cofactor SAM. Secondly, an enzyme activity assay based on isothermal titration calorimetry (ITC) is presented. Using this approach, the kinetics of 6-MP and 6-TG methylation by TPMT has been characterized.

  • 354.
    Block, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    En jämförande neurografisk studie: Hur mätparametrar för utvärdering av neurofysiologisk sjukdom påverkas vid olika vinklar på armbågen2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 355.
    Blokzijl, Andries
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. YUMAB GmbH, Rebenring 33, D-38106 Braunschweig, Germany..
    Zieba, Agata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Hust, Michael
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, Dept Biotechnol, Spielmannstr 7, D-38106 Braunschweig, Germany..
    Schirrmann, Thomas
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, Dept Biotechnol, Spielmannstr 7, D-38106 Braunschweig, Germany.;YUMAB GmbH, Rebenring 33, D-38106 Braunschweig, Germany..
    Helmsing, Saskia
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, Dept Biotechnol, Spielmannstr 7, D-38106 Braunschweig, Germany..
    Grannas, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hertz, Ellen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Morén, Anita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Chen, Lei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Dubel, Stefan
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, Dept Biotechnol, Spielmannstr 7, D-38106 Braunschweig, Germany..
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Single Chain Antibodies as Tools to Study transforming growth factor--Regulated SMAD Proteins in Proximity Ligation-Based Pharmacological Screens2016Inngår i: Molecular & cellular proteomics (online), ISSN 1535-9476, E-ISSN 1535-9484, Vol. 15, nr 6, s. 1848-1856Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cellular heterogeneity seen in tumors, with subpopulations of cells capable of resisting different treatments, renders single-treatment regimens generally ineffective. Accordingly, there is a great need to increase the repertoire of drug treatments from which combinations may be selected to efficiently target sets of pathological processes, while suppressing the emergence of resistance mutations. In this regard, members of the TGF- signaling pathway may furnish new, valuable therapeutic targets. In the present work, we developed in situ proximity ligation assays (isPLA) to monitor the state of the TGF- signaling pathway. Moreover, we extended the range of suitable affinity reagents for this analysis by developing a set of in-vitro-derived human antibody fragments (single chain fragment variable, scFv) that bind SMAD2 (Mothers against decapentaplegic 2), 3, 4, and 7 using phage display. These four proteins are all intracellular mediators of TGF- signaling. We also developed an scFv specific for SMAD3 phosphorylated in the linker domain 3 (p179 SMAD3). This phosphorylation has been shown to inactivate the tumor suppressor function of SMAD3. The single chain affinity reagents developed in the study were fused tocrystallizable antibody fragments (Fc-portions) and expressed as dimeric IgG-like molecules having Fc domains (Yumabs), and we show that they represent valuable reagents for isPLA. Using these novel assays, we demonstrate that p179 SMAD3 forms a complex with SMAD4 at increased frequency during division and that pharmacological inhibition of cyclin-dependent kinase 4 (CDK4)(1) reduces the levels of p179SMAD3 in tumor cells. We further show that the p179SMAD3-SMAD4 complex is bound for degradation by the proteasome. Finally, we developed a chemical screening strategy for compounds that reduce the levels of p179SMAD3 in tumor cells with isPLA as a read-out, using the p179SMAD3 scFv SH544-IIC4. The screen identified two kinase inhibitors, known inhibitors of the insulin receptor, which decreased levels of p179SMAD3/SMAD4 complexes, thereby demonstrating the suitability of the recombinant affinity reagents applied in isPLA in screening for inhibitors of cell signaling.

  • 356.
    Blom, Amanda
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    HSP90- och IAP-inhibitor motverkar cisplatinresistens i lungcancerceller2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 357.
    Blom, Hans
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Experimentell biomolekylär fysik.
    Rönnlund, Daniel
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Experimentell biomolekylär fysik.
    Scott, Lena
    Spicarova, Zuzana
    Rantanen, Ville
    Widengren, Jerker
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Experimentell biomolekylär fysik.
    Aperia, Anita
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Nearest neighbor analysis of dopamine D1 receptors and Na plus -K plus -ATPases in dendritic spines dissected by STED microscopy2012Inngår i: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 75, nr 2, s. 220-228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein localization in dendritic spines is the focus of intense investigations within neuroscience. Applications of super-resolution microscopy to dissect nanoscale protein distributions, as shown in this work with dual-color STED, generate spatial correlation coefficients having quite small values. This means that colocalization analysis to some extent looses part of its correlative impact. In this study we thus introduced nearest neighbor analysis to quantify the spatial relations between two important proteins in neurons, the dopamine D1 receptor and Na+,K+-ATPase. The analysis gave new information on how dense the D1 receptor and Na+,K+-ATPase constituting nanoclusters are located both with respect to the homogenous (self to same) and the heterogeneous (same to other) topology. The STED dissected nanoscale topologies provide evidence for both a joint as well as a separated confinement of the D1 receptor and the Na+,K+-ATPase in the postsynaptic areas of dendritic spines. This confined topology may have implications for generation of local sodium gradients and for structural and functional interactions modulating slow synaptic transmission processes. Microsc. Res. Tech., 2011.

  • 358.
    Blom, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Andersson, Claes R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Predictive Value of Ex Vivo Chemosensitivity Assays for Individualized Cancer Chemotherapy: A Meta-Analysis2017Inngår i: SLAS TECHNOLOGY, ISSN 2472-6303, Vol. 22, nr 3, s. 306-314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Current treatment strategies for chemotherapy of cancer patients were developed to benefit groups of patients with similar clinical characteristics. In practice, response is very heterogeneous between individual patients within these groups. Precision medicine can be viewed as the development toward a more fine-grained treatment stratification than what is currently in use. Cell-based drug sensitivity testing is one of several options for individualized cancer treatment available today, although it has not yet reached widespread clinical use. We present an up-to-date literature meta-analysis on the predictive value of ex vivo chemosensitivity assays for individualized cancer chemotherapy and discuss their current clinical value and possible future developments.

  • 359.
    Blomdahl, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Könsskillnader i progress av hjärtengagemang hos patienter med ärftlig transthyretinamyloidos: En studie över tid2015Independent thesis Basic level (professional degree), 180 hpOppgave
  • 360.
    Blomfeldt, Thomas O. J.
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Kuktaite, Ramune
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Johansson, Eva
    Hedenqvist, Mikael S.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Mechanical Properties and Network Structure of Wheat Gluten Foams2011Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 12, nr 5, s. 1707-1715Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This Article reports the influence of the protein network structure on the mechanical properties of foams produced from commercial wheat gluten using freeze-drying. Foams were produced from alkaline aqueous solutions at various gluten concentrations with or without glycerol, modified with bacterial cellulose nanosized fibers, or both. The results showed that 20 wt % glycerol was sufficient for plasticization, yielding foams with low modulus and high strain recovery. It was found that when fibers were mixed into the foams, a small but insignificant increase in elastic modulus was achieved, and the foam structure became more homogeneous. SEM indicated that the compatibility between the fibers and the matrix was good, with fibers acting as bridges in the cell walls. IR spectroscopy and SE-HPLC revealed a relatively low degree of aggregation, which was highest in the presence of glycerol. Confocal laser scanning microscopy revealed distinct differences in HMW-glutenin subunits and gliadin distributions for all of the different samples.

  • 361.
    Blomgran, Parmis
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Hammerman, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Systemic corticosteroids improve tendon healing when given after the early inflammatory phase2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 12468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammation initiates tendon healing and then normally resolves more or less completely. Unresolved inflammation might disturb the remodeling process. We hypothesized that suppression of inflammation during the early remodeling phase by systemic dexamethasone treatment can improve healing. 36 rats underwent Achilles tendon transection and were randomized to dexamethasone or saline on days 0-4 after surgery (early inflammatory phase), and euthanasia day 7. Another 54 rats received injections days 5-9 (early remodeling phase) and were euthanized day 12 for mechanical, histological and flow cytometric evaluation. Dexamethasone treatment days 0-4 reduced the cross-sectional area, peak force and stiffness by day 7 to less than half (p amp;lt; 0.001 for all), while material properties (peak stress and elastic modulus) were not significantly affected. In contrast, dexamethasone treatment days 5-9 increased peak force by 39% (p = 0.002) and stiffness by 58% (p amp;lt; 0.001). The cross-sectional area was reduced by 42% (p amp;lt; 0.001). Peak stress and elastic modulus were more than doubled (p amp;lt; 0.001 for both). Semi-quantitative histology at day 12 showed that late dexamethasone treatment improved collagen alignment, and flow cytometry revealed reduced numbers of CD8a(+) cytotoxic T cells in the tendon callus. These results suggest that downregulation of lingering inflammation during the early remodeling phase can improve healing.

  • 362.
    Boberg, Andreas
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
    Stålnacke, Alexandra
    Etvax AB, Solna, Sweden.
    Bråve, Andreas
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Wahren, Britta
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
    Carlin, Nils
    Etvax AB, Solna, Sweden.
    Receptor binding by cholera toxin B-subunit and amino acid modification improves minimal peptide immunogenecity2012Inngår i: ISRN Molecular Biology, ISSN 2090-7907, Vol. 2012, artikkel-id 170676Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We increase our understanding of augmenting a cellular immune response, by using an HIV-1 protease-derived epitope (PR7584), and variants thereof, coupled to the C-terminal, of the B subunit of cholera toxin (CTB). Fusion proteins were used for immunizations of HLA-A0201 transgenic C57BL/6 mice. We observed different capacities to elicit a cellular immune response by peptides with additions of five to ten amino acids to the PR epitope. There was a positive correlation between the magnitude of the elicited cellular immune response and the capacity of the fusion protein to bind GM-1. This binding capacity is affected by its ability to form natural pentamers of CTB. Our results suggest that functional CTB pentamers containing a foreign amino acid-modified epitope is a novel way to overcome the limited cellular immunogenicity of minimal peptide antigens. This way of using a functional assay as readout for improved cellular immunogenicity might become highly valuable for difficult immunogens such as short peptides (epitopes).

  • 363.
    Bodén, Ida
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Larsson, William
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Forssell, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindholm-Sethson, Britta
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    In vivo skin measurements with a novel probe head for simultaneous skin impedance and near-infrared spectroscopy2011Inngår i: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 17, nr 4, s. 494-504Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/purpose: Near-infrared (NIR) spectroscopy and skin impedance (IMP) measurements are useful techniques for objective diagnostics of various skin diseases. Here, we present a combined probe head for simultaneous, time-saving NIR spectroscopy and skin impedance measurements. The probe also ensures that both measurements are performed under equal conditions and at the same skin location.

    Methods: Finite element method simulations were performed for evaluation of the impedance. In vivo skin measurements were performed and combined NIR and impedance spectra were analysed by means of multivariate methods with respect to body location, age and gender. The classification rate was determined by a planar discriminant analysis. Reproducibility was investigated by calculation of scatter values and statistical significance between overlapping groups was assessed by the calculation of intra-model distances, q.

    Results: The novel probe yielded rapid reproducible results and was easy to manage. Significant differences between skin locations and to a lesser extent age groups and gender were demonstrated.

    Conclusion: With the novel probe, statistically significant differences between overlapping classes in score plots can be confirmed by calculating intra-model distances. The influence of molecular differences in the skin at different body locations is larger than the influence of gender or age and therefore relevant reference measurements are discussed.

  • 364.
    Boerman, Susanna
    Örebro universitet, Institutionen för hälsovetenskaper.
    Histokemisk och immunhistokemisk detektion av brosktillväxt i en tre-dimensionell odling av hyalint brosk2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 365.
    Bohman, Malin
    Örebro universitet, Institutionen för hälsovetenskaper.
    Kvantitativ analys av DNA-metylering i biomarkörgener för cervixcancer2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 366.
    Boiso, Samuel
    et al.
    Swedish National Forensic Centre, Linköping, Sweden.
    Dalin, Erik
    Swedish National Forensic Centre, Linköping, Sweden.
    Seidlitz, Heidi
    Swedish National Forensic Centre, Linköping, Sweden.
    Sidstedt, Maja
    Swedish National Forensic Centre, Linköping, Sweden / Applied Microbiology, Department of Chemistry, Lund University, Lund, Sweden.
    Trygg, Elias
    Swedish National Forensic Centre, Linköping, Sweden.
    Hedman, Johannes
    Swedish National Forensic Centre, Linköping, Sweden / Applied Microbiology, Department of Chemistry, Lund University, Lund, Sweden.
    Ansell, Ricky
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten. Swedish National Forensic Centre, Linköping, Sweden.
    RapidHIT for the purpose of stain analyses – An interrupted implementation2017Inngår i: Forensic Science International: Genetics Supplement Series, ISSN 1875-1768, E-ISSN 1875-175X, Vol. 6, nr Supplement C, s. e589-e590Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rapid DNA instruments have in recent years been developed, enabling analysis of forensic samples with a minimum of human intervention. Initially intended for fast handling of reference samples, such as samples from suspects in booking suites, attention shifted to include crime scene samples. The aim of this study was to determine whether or not the RapidHIT System (IntegenX) is fit for crime scene samples. The first runs gave very poor results, which was found to be due to an incorrect firmware setting leading to no or just minute amounts of amplicons being injected for electrophoresis. After solving this problem, 28 full runs (seven samples each) applying NGM SElect Express were performed comprising various amounts of blood on cotton swabs. Six of the runs failed completely, four due to cartridge leakage and in two runs the PCR mix was not injected. For 155 samples with 1–5ÎŒL blood (volumes for which complete DNA profiles are expected), 119 samples (77%) gave complete DNA profiles. Among the most serious failures were incorrect allele calling and leakage of DNA extract or PCR product. Other general issues were failure to export results, anode motor breakdown and broken capillary array. Due to the encountered problems with software, hardware and cartridges, together with the low success rate, it was decided not to continue towards implementation of the RapidHIT System in casework.

  • 367.
    Bojmar, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Metastatic Mechanisms in Malignant Tumors2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The ultimate cause of cancer related deaths is metastasis. This thesis is about three of the main human cancers; breast, colorectal and pancreatic cancer, that together account for more than 25% of the cancer-related deaths worldwide. The focus of the thesis is the spread of cancer, metastasis, and the aim was to investigate mechanisms that can be of importance for this process. We analyzed patient samples to validate the role of epithelialto-mesenchymal transition in vivo and found regulations of many related factors. However, these changes tend to fluctuate along the metastatic process, something which makes targeting complicated. We, moreover, focused on the influence of the tumor microenvironment for metastatic spread. In pancreatic cancer, the stroma constitutes the main part of many tumors. We analyzed the crosstalk between tumor and stromal cell and focused on the mediating inflammatory factor interleukin-1 (IL-1) and regulation of microRNAs. The results showed that the most commonly mutated factor in pancreatic cancer, KRAS, associates with the expression of IL-1 and subsequent activation of stromal cells. Blocking KRAS signaling together with IL-1 blockage give a more pronounced effect on in vitro proliferation and migration of cancer cells and suggests the use of a combination therapy. The cancer-associated activation of the stroma was found to be related to changes in microRNA expression. microRNA was analyzed separately in epithelial cells and stromal cells after microdissection of matched samples of primary and secondary tumors of breast and colorectal cancers. miR-214 and miR-199a were upregulated in stroma associated with progressive tumors and in pancreatic cancer stroma we could show that their expression alters the activation of stromal cells and thereby the growth and migratory ability of associated pancreatic tumor cells. In  breast and colorectal cancers we found several common microRNAs to be up- or downregulated in line with progression. We could show that one of these candidates, miR-18a, had a prognostic value in metastatic breast cancer. To further develop these studies we analyzed this microRNA in circulating microvesicles, i.e. exosomes, and investigated their role in the preparation of a pre-metastatic niche. MicroRNAs are stable biomarkers in the circulation, especially protected in exosomes, which can moreover specifically deliver their message to recipient cells. These studies facilitate the understanding of metastatic behavior and suggest new targets to stop cancer metastasis.

  • 368.
    Bojmar, Linda
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 369.
    Boklund, Kajsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jämförelse av citratkoncentration i koagulationsprovtagningsrör: Jämförelse av citratkoncentrationerna 3,8 % och 3,2 % i koagulationsprovtagningsrör och dess effekter på analysresultat i samband med rörposttransport2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 370.
    Boknäs, Niklas
    et al.
    Department of Hematology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Faxälv, Lars
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lindahl, Tomas L.
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders2018Inngår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, nr 5, s. 512-519Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p = 0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.

  • 371. Bolander, Å.
    et al.
    Agnarsdóttir, M.
    Strömberg, S.
    Ponten, F.
    Hesselius, P.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Bergqvist, M.
    The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas2008Inngår i: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 5, nr 6, s. 293-300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. Patients and Methods: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. Results: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). Conclusion: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.

  • 372. Bollampalli, V. P.
    et al.
    Harumi Yamashiro, L.
    Feng, X.
    Bierschenk, D.
    Gao, Y.
    Blom, Hans
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Henriques-Normark, B.
    Nylén, S.
    Rothfuchs, A. G.
    BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming2015Inngår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 11, nr 10, artikkel-id e1005206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The transport of antigen from the periphery to the draining lymph node (DLN) is critical for T-cell priming but remains poorly studied during infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG). To address this we employed a mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from the BCG inoculation site in the skin to the DLN. Detection of BCG in the DLN was concomitant with the priming of antigen-specific CD4+ T cells at that site. We found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport of BCG to the DLN. Migratory skin DCs distributed to the T-cell area of the LN, co-localized with BCG and were found in close apposition to antigen-specific CD4+ T cells. Consequently, blockade of skin DC traffic into DLN dramatically reduced mycobacterial entry into DLN and muted T-cell priming. Interestingly, DC and mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL-12p40. In addition, we found using DC adoptive transfers that the requirement for MyD88 in BCG-triggered migration was not restricted to the migrating DC itself and that hematopoietic expression of MyD88 was needed in part for full-fledged migration. Our observations thus identify a population of DCs that contribute towards the priming of CD4+ T cells to BCG infection by transporting bacilli into the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and -extrinsic requirements for MyD88 in DC migration.

  • 373.
    Bollen, Lise Svendsen
    Uppsala universitet, Institutionen för försöksdjursvetenskap.
    Production of polyclonal antibodies in rabbits and chickens immunised with human immunoglobulin G: A study of the utility of egg yolk antibody production as a substitute for rabbit serum antibody production1997Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The utility of chicken egg yolk antibodies as an alternative to rabbit antisera was studied by comparing antibody and avidity development in immunised animals (15 rabbits and 30 chickens) during a one-year immunisation scheme. Human IgG was used as the model antigen and the efficacy of three adjuvants, Freund's Complete Adjuvant, Freund's Incomplete Adjuvant and Hunter's TiterMax, was compared. Purification procedures for egg yolk antibodies were developed, rendering the harvest and processing time for yolk and serum antibodies comparable. A majoradvantage of producing egg yolk antibodies instead of rabbit antisera is an increased productivity.Although the antibody response was found to be higher in rabbit serum than in egg yolk of chickensimmunised using identical schemes, the volumes of obtainable antibody source were ten timeshigher with egg yolk than with rabbit sera. Depending on the immunisation scheme and, inparticular, the choice of adjuvant, approximately five times more antibody can be produced per yearby a chicken than by a rabbit. Considering the cost of purchase and maintenance, rabbit antibodiesare ten times more expensive to produce. Serum antibody response in young and old chickens werecompared and no significant difference was found. The avidity of the egg yolk antibodies was foundto be similar to rabbit serum antibodies, but the qualitative properties of the immunoglobulinsdiffer. Different immunochemical and immunoelectrophoretic assays (different ELISAs, liquidphase immunosorbent assay, rocket-immunoelectrophoresis, fused-rocket-immunoelectrophoresis,line-immunoelectrophoresis, crossed-immunoelectro-phoresis, crossed-tandem-immunoelectro-phoresis, crossed-affino-immunoelectrophoresis, charge-shift-crossed-immunoelectrophoresis) weredeveloped for measuring antibody response, and analysing specificity and binding properties. TheIgG levels in developing oozytes (6 - 37 mm) were similar, and there was a significant linearcorrelation between antibody response in serum and corresponding egg yolk. From an animalwelfare point of view there are improvements associated with producing egg yolk antibodies insteadof rabbit serum antibodies.

  • 374.
    Bolshakova, A.V.
    et al.
    Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
    Petukhova, O.A.
    Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
    Pinaev, G.P.
    Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
    Magnusson, Karl-Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Comparative analysis of subcellular fractionation methods for revealing a-actinin 1 and a-actinin 4 in A431 cells2009Inngår i: Cell and Tissue Biology, ISSN 1990-519X, Vol. 3, nr 2, s. 188-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    a-Actinin 1 and a-actinin 4 are actin-binding proteins with shared structural functions that are responsible for the regulation of several processes in the cell. Based on previous data on the different distribution of these proteins in the nucleus and cytoplasm, we have studied in detail the presence of a-actinin 1 and a-actinin 4 in subcellular fractions in the A431 cells spread on fibronectin. The detection of a-actinins in some particular fractions has been shown to depend on the method of lysis, as well as whether the preliminary low-temperature freezing of cells was used. The application of various fractionation methods has allowed us to conclude that a-actinin 4 is present in all cytoplasmic and nuclear subfractions, whereas, in addition to in the cytoplasm, a-actinin 1 can also be revealed in the nuclear envelope fraction.

  • 375.
    Boman, Michaela
    Örebro universitet, Institutionen för hälsovetenskaper.
    En jämförelsestudie av två andningstekniker vid dynamisk spirometri2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 376.
    Bondza, Sina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Stenberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Andersson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Björkeund, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Conjugation Effects on Antibody-Drug Conjugates: Evaluation of Interaction Kinetics in Real Time on Living Cells2014Inngår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 11, nr 11, s. 4154-4163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibody-drug conjugates (ADC) have shown promising effects in cancer therapy by combining the target specificity of an antibody with the toxicity of a chemotherapeutic drug. As the number of therapeutic antibodies is significantly larger than those used as ADCs, there is unused potential for more effective therapies. However, the conjugation of an additional molecule to an antibody may affect the interaction with its target, altering association rate, dissociation rate, or both. Any changes of the binding kinetics can have subsequent effects on the efficacy of the ADCs, thus the kinetics are important to monitor during ADC development and production. This paper describes a method for the analysis of conjugation effects on antibody binding to its antigen, using the instrument LigandTracer and a fluorescent monovalent anti-IgG binder denoted FIBA, which did not affect the interaction. All measurements were done in real time using living cells which naturally expressed the antigens. With this method the binding profiles of different conjugations of the therapeutic anti-EGFR antibody cetuximab and the anti-CD44v6 antibody fragment AbD15171 were evaluated and compared. Even comparatively small modifications of cetuximab altered the interaction with the epidermal growth factor receptor (EGFR). In contrast, no impact on the AbD15171-CD44v6 interaction was observed upon conjugation. This illustrates the importance to study the binding profile for each ADC combination, as it is difficult to draw any general conclusion about conjugation effects. The modification of interaction kinetics through conjugation opens up new possibilities when optimizing an antibody or an ADC, since the conjugations can be used to create a binding profile more apt for a specific clinical need.

  • 377. Bontempi, EJ
    et al.
    Garcia, GA
    Buschiazzo, A
    Henriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Pravia, CA
    Ruiz, AM
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Pszenny, V
    The tyrosine aminotransferase from Trypanosoma rangeli: sequence andgenomic characterization2000Inngår i: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 189, nr 2, s. 253-257Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The complete sequence and genomic characterization of the tyrosine aminotransferase (TAT) gene from Trypanosoma rangeli is reported. The gene was found to be organized in a tandem multicopy gene array. A homologous mRNA species (2.5 kb) was identified in the epimastigote form of the parasite. From the deduced amino acid sequence, the gene encodes a protein of 420 amino acids with a predicted molecular mass of 46.4 kDa and a theoretical pI of 6.23. A high sequence identity was found with the Trypanosoma cruzi, human and rat enzymes. All the essential residues for TAT enzymatic activity are conserved, as well as a pyridoxal-phosphate attachment site typical of class-I aminotransferases. The recombinant enzyme was recognized by a monoclonal antibody against the T. cruzi enzyme. Additionally, the recombinant protein showed enzymatic activity when incubated with L-tyrosine and 2-oxoglutaric acid as substrates.

  • 378.
    Booy, Evan P.
    et al.
    Manitoba Institute of Cell Biology, and Department of Biochemistry and Medical Genetics, Univ. Manitoba, Winnipeg, Canada.
    Johar, Dina
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Maddika, Srilekha
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Pirzada, Hasan
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada.
    Sahib, Mickey M.
    Department of Oral Biology, University of Manitoba, Winnipeg, Canada .
    Gehrke, Iris
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada.
    Loewen, Shauna
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Louis, Sherif F.
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada.
    Kadkhoda, Kamran
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Mowat, Michael
    Manitoba Institute of Cell Biology,CancerCare Manitoba, University of Manitoba, ON6010-675 McDermot Ave., Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Monoclonal and bispecific antibodies as novel therapeutics2006Inngår i: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 54, nr 2, s. 85-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the "humanization of antibodies" or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies "armed" with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.

  • 379. Bora, Kangkana
    et al.
    Chowdhury, Manish
    KTH, Skolan för teknik och hälsa (STH).
    Mahanta, Lipi B.
    Kundu, Malay Kumar
    Das, Anup Kumar
    Automated classification of Pap smear images to detect cervical dysplasia2017Inngår i: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 138, s. 31-47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and objectives: The present study proposes an intelligent system for automatic categorization of Pap smear images to detect cervical dysplasia, which has been an open problem ongoing for last five decades. Methods: The classification technique is based on shape, texture and color features. It classifies the cervical dysplasia into two-level (normal and abnormal) and three-level (Negative for Intraepithelial Lesion or Malignancy, Low-grade Squamous Intraepithelial Lesion and High-grade Squamous Intraepithelial Lesion) classes reflecting the established Bethesda system of classification used for diagnosis of cancerous or precancerous lesion of cervix. The system is evaluated on two generated databases obtained from two diagnostic centers, one containing 1610 single cervical cells and the other 1320 complete smear level images. The main objective of this database generation is to categorize the images according to the Bethesda system of classification both of which require lots of training and expertise. The system is also trained and tested on the benchmark Herlev University database which is publicly available. In this contribution a new segmentation technique has also been proposed for extracting shape features. Ripplet Type I transform, Histogram first order statistics and Gray Level Co-occurrence Matrix have been used for color and texture features respectively. To improve classification results, ensemble method is used, which integrates the decision of three classifiers. Assessments are performed using 5 fold cross validation. Results: Extended experiments reveal that the proposed system can successfully classify Pap smear images performing significantly better when compared with other existing methods. Conclusion: This type of automated cancer classifier will be of particular help in early detection of cancer.

  • 380.
    Borg, Mathias
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Study of the insulin-like peptide 3 in human platelets2009Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    The insulin-like 3 peptide is autocrine/paracrine insulin-related hormone with a size of approximately 6kDa [1]. It mediates through a leucine richG-coupled receptor named LGR8. INSL3 is mainly expressed in human Leydig cells and is directly responsible for migration of the testis during the pre-natal period in maledevelopment. [2]

    INSL3 mRNA has recently been verified in human platelets whereas no mRNA has been detected for LGR8 (by Sanofi-Aventis GmbH in Frankfurt,Germany), indicating that INSL3 might be released through paracrine functions at sites of platelet adhesion and aggregation upon a vascular injury.Furthermore, has activated platelets been shown to translate essential proteins upon activation, in a term called “signal-dependent protein synthesis”.The B-Cell lymphoma-3 protein (BCL-3) is an example of such a protein [3], and there is a possibility that INSL3 might be also.

    In this thesis we wanted to detect the relaxin- like peptide 3 hormone (INSL3). (Its function, location and the timeframe of its release, when/if it issecreated in stimulated platelets).The source of platelet-derived INSL3 can be found with Western blotting and Enzyme immunoassay.

    Detection of the insulin-like 3 peptide in human platelets turned out to be a difficult challenge due to the small amount of INSL3 secretion uponplatelet activation; hence the total amount of INSL3 produced might be below detection limit.

  • 381.
    Borg, Olivia
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för biologi och miljö (BOM).
    Diversity of Avian Coronaviruses in Mallards Anas platyrhynchos, Ottenby, Sweden2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Coronavirus are single-stranded plus-strand RNA viruses that cause several respiratory and neurological diseases in a wide range of animals and humans. There are 4 main groups of Coronaviruses: alpha, beta, gamma and deltacoronavirus, where gamma and deltacoronaviruses have been found in wild birds. This study evaluated the epidemiology and phylogeny of coronavirus in Swedish waterfowl in order to increase the existing knowledge of these viruses in nature. The RNA-dependent RNA polymerase gene of 36 different samples from Mallards collected from Ottenby Bird Observatory, Sweden (56°12’58”N 16°24’40”E) in 2011 were sequenced. These sequences were characterized and compared to other gammacoronaviruses using a phylogenetic approach. Analysis revealed that there is diversity of sequences from the samples as there was evidence of at least 4 groups of RNA-dependent RNA-polymerase sequences. A difference of sequences over time was also detected which might suggest virus turnover due to host herd immunity. However, the results doesn´t demonstrate a clear pattern of reinfection with the same or different RNA-dependent RNA sequences within individuals over time. This study has contributed 1/3 of all gammacoronavirus sequences, and demonstrates the need in finding a method to complete genome sequence these viruses. Comparative genomic studies are important to determine the diversity of virus gene lineages and viral phenotypes, and also to be able to understand the relations behind interclass jumping, which is important to predict and avoid pandemics that coronavirus might cause.

  • 382.
    Borga, Magnus
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan.
    Friman, Ola
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet.
    Knutsson, Hans
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan.
    Blind Source Separation of Functional MRI Data2002Konferansepaper (Annet vitenskapelig)
  • 383.
    Borglund, Elin
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper.
    Patogenreducering av trombocytkoncentrat från aferes: Verifiering av INTERCEPT Blood Systems för införande på Transfusionsmedicin i Falun.2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 384.
    Borgstedt, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Överföring av Yersinia pseudotuberculosis effektorproteinet YopE till HeLa-celler, mer än en mekanism?2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 385.
    Borsa, Baris A
    et al.
    Istanbul Kemerburgaz University, School of Medicine, Istanbul 34217, Turkey.
    Tuna, Bilge G
    Yeditepe University, School of Medicine, Department of Biophysics, Istanbul Turkey.
    Hernandez, Frank J
    SOMAprobes S.L., Science and Technology Park of Gipuzkoa, San Sebastian 20009, Spain.
    Hernandez, Luiza I
    SOMAprobes S.L., Science and Technology Park of Gipuzkoa, San Sebastian 20009, Spain.
    Bayramoglu, Gulay
    Biochemical Processing and Biomaterial Research Laboratory, Gazi University, 06500 Ankara, Turkey; Department of Chemistry, Faculty of Sciences, Gazi University, 06500 Ankara, Turkey.
    Arica, M Yakup
    Biochemical Processing and Biomaterial Research Laboratory, Gazi University, 06500 Ankara, Turkey.
    Ozalp, V Cengiz
    Istanbul Kemerburgaz University, School of Medicine, Istanbul 34217, Turkey.
    Staphylococcus aureus detection in blood samples by silica nanoparticle-oligonucleotides conjugates.2016Inngår i: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 86, s. 27-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A fast, specific and sensitive homogeneous assay for Staphylococcus aureus detection was developed by measuring the activity of secreted nuclease from the bacteria via a modified DNA oligonucleotide. As biosensor format, an effective system, Nanokeepers as previously reported, were used for triggered release of confined fluorophores, and hence specific detection of S. aureus on nuclease activity was obtained. The interference from blood components for fluorescent quantification was eliminated by a pre-purification by aptamer-functionalized silica magnetic nanoparticles. The reported assay system was exclusively formed by nucleic acid oligos and magnetic or mesoporous silica nanoparticles, that can be used on blood samples in a stepwise manner. The assay was successfully used as a sensing platform for the specific detection of S. aureus cells as low as 682 CFU in whole blood.

  • 386. Borzacchiello, A
    et al.
    Mayol, L
    Ambrosio, L
    Gärskog, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Dahlqvist, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Rheological characterization of vocal folds after injection augmentation in a preliminary animal study2004Inngår i: Journal of bioactive and compatible polymers (Print), ISSN 0883-9115, E-ISSN 1530-8030, Vol. 19, nr 4, s. 331-341Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The investigation of vocal folds viscoelastic properties in an animal model (rabbit) after injection of various augmentation substances, 6 months after injection, is reported. The injected materials were: hyaluronan-based materials (Hylan B gel and Deflux(R)), cross-linked collagen (Zyplast(R)) and polytetrafluoroethylene (Teflon(R)). Rheological properties of the augmentation substances were also evaluated. The results from these animal experiments indicate that the viscoelastic properties of the vocal folds injected with Deflux(R), Zyplast(R) and Hylan B gel are similar to the healthy vocal folds (non-injected samples) used as control, thus demonstrating that these materials are good candidates for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.

  • 387.
    Borén, Therese
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Study of proteins related to the thyroid in the endometrium of women with unexplained infertilityTherese Borén2014Independent thesis Basic level (university diploma), 10 poäng / 15 hpOppgave
    Abstract [en]

    Infertility is a global health issue that can have many causes. It is, however, not always known why some couples cannot conceive even though there are no apparent reason in either the man or the woman. The woman can have normal menstrual cycles and the man can have normal semen.The purpose of this study was to investigate the presence and distribution of thyroid related proteins in endometrial biopsies. Eight biopsies was taken from women with unexplained infertility and 35 biopsies from healthy fertile woman. These were divided into smaller groups based on menstrual cycle day and analysed with immunohistochemistry for the detection of the thyroid related proteins MCT8 and DIO2.There were no significant differences between the groups and therefore are more studies required in the subject to be able to find factors that may help solving some cases of unexplainedinfertility.

  • 388. Bose, Indranil
    et al.
    Ohlander, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kutter, Christoph
    Russom, Aman
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    DNA Analysis on integrated all foil based microdevicesManuskript (preprint) (Annet vitenskapelig)
  • 389.
    Boström, Emelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Validering av kolonn för analys av alkoholer och glykoler med gaskromatografi: Jämförelse av två kolonner samt fortsatt validering för klinisk tillämpning2018Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 390.
    Boström, Markus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Utvärdering av 16S rRNA PCR vid mikrobiologisk diagnostik av misstänkt ortopedisk implantat infektioner2016Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 391.
    Bou-Francis, Antony
    et al.
    School of Mechanical Engineering, University of Leeds, UK.
    Lopez, Alejandro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Persson, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Hall, Richard M.
    School of Mechanical Engineering, University of Leeds, UK.
    Kapur, Nikil
    School of Mechanical Engineering, University of Leeds, UK.
    Assessing cement injection behaviour in cancellous bone: An in vitro study using flow models2014Inngår i: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 29, nr 4, s. 582-594Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding the cement injection behaviour during vertebroplasty and accurately predicting the cement placement within the vertebral body is extremely challenging. As there is no standardized methodology, we propose a novel method using reproducible and pathologically representative flow models to study the influence of cement properties on injection behaviour. The models, confined between an upper glass window and a lower aluminium plate, were filled with bone marrow substitute and then injected (4, 6 and 8min after cement mixing) with commercially available bone cements (SimplexP, Opacity+, OsteopalV and Parallax) at a constant flow rate (3mL/min). A load cell was used to measure the force applied on the syringe plunger and calculate the peak pressure. A camera was used to monitor the cement flow during injection and calculate the following parameters when the cement had reached the boundary of the models: the time to reach the boundary, the filled area and the roundness. The peak pressure was comparable to that reported during clinical vertebroplasty and showed a similar increase with injection time. The study highlighted the influence of cement formulations and model structure on the injection behaviour and showed that cements with similar composition/particle size had similar flow behaviour, while the introduction of defects reduced the time to reach the boundary, the filled area and the roundness. The proposed method provides a novel tool for quick, robust differentiation between various cement formulations through the visualization and quantitative analysis of the cement spreading at various time intervals.

  • 392.
    Bouro Wallgren, Sofia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Tolerance to virus infections could explain increased winter colony survival observed in Varroa destructor-resistant honey bees2018Independent thesis Advanced level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Honey bee colonies all over Europe and North America have been declining dramatically for over three decades and is continuing to do so which is causing significant threats to economy, agriculture and ecosystems. The main reason behind the declining colonies is an ectoparasitic mite known as Varroa destructor and viruses vectored by the mite. In previous studies, it has been suggested that a unique mite-resistant subpopulation of honey bees (Apis mellifera) in Gotland, Sweden have developed adaptive tolerance to these viruses as they have managed to survive high mite infestation through natural selection without any mite control treatment. This indicates that there might be a correlation between resistance to Varroa destructor and virus tolerance. This project examined if a correlation between virus resistance and/or virus tolerance can be observed in Varroa-resistant honey bees from unique subpopulations in Europe covering Sweden, Norway, France and Netherlands. Results showed that no correlation could be established based on the findings in this project. However, significant differences in winter colony survival numbers between mite-resistant and mite-susceptible honey bees suggest that tolerance mechanisms could be present in these subpopulations. Further studies are required to verify this hypothesis.

  • 393. Boutajangout, Allal
    et al.
    Lindberg, Hanna
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Awwad, Abdulaziz
    Paul, Arun
    Wahlberg, Elisabet
    Gudmundsdotter, Hanna
    Härd, Torleif
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Wisniewski, Thomas
    Affibody-mediated Reduction of Amyloid Burden and Improvement of Cognitive Decline in an Animal Model of Alzheimer’s diseaseManuskript (preprint) (Annet vitenskapelig)
  • 394. Bouzenzana, Jamel
    et al.
    Pelosi, Ludovic
    Briolay, Anne
    Briolay, Jerome
    Bulone, Vincent
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap.
    Identification of the first Oomycete annexin as a (1 -> 3)-beta-D-glucan synthase activator2006Inngår i: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 62, nr 2, s. 552-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    (1 -> 3)-beta-D-Glucans are major components of the cell walls of Oomycetes and as such they play an essential role in the morphogenesis and growth of these microorganisms. Despite the biological importance of (1 -> 3)-beta-D-glucans, their mechanisms of biosynthesis are poorly understood. Previous studies on (1 -> 3)-beta-D-glucan synthases from Saprolegnia monoica have shown that three protein bands of an apparent molecular weight of 34, 48 and 50 kDa co-purify with enzyme activity. However, none of the corresponding proteins have been identified. Here we have identified, purified, sequenced and characterized a protein from the 34 kDa band and clearly shown that it has all the biochemical properties of proteins from the annexin family. In addition, we have unequivocally demonstrated that the purified protein is an activator of (1 -> 3)-beta-D-glucan synthase. This represents a new type of function for proteins belonging to the annexin family. Two other proteins from the 48 and 50 kDa bands were identified as ATP synthase subunits, which most likely arise from contaminations by mitochondria during membrane preparation. The results, which are discussed in relation with the possible regulation mechanisms of (1 -> 3)-beta-D-glucan synthases, represent a first step towards a better understanding of cell wall polysaccharide biosynthesis in Oomycetes.

  • 395.
    Braian, Clara
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Svensson, Mattias
    Karolinska Institute, Sweden.
    Brighenti, Susanna
    Karolinska Institute, Sweden.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Parasa, Venkata R.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection2015Inngår i: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, nr 104, s. 1-9, artikkel-id e53084Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

  • 396.
    Braml, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lactoferricin Mediated Infection of Adenovirus 52019Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
  • 397.
    Brander, Gustaf
    et al.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rydell, Mina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul S.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study2018Inngår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, nr 5, s. 1189-1197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

  • 398.
    Brandt, Ludwig
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Pfefferle, Aline
    Goodridge, Jodie
    Malmberg, Karl-Johan
    Önfelt, Björn
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Cytotoxicity and killing kinetics of KIR educated NK cells2017Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, nr 4, s. 301-301Artikkel i tidsskrift (Annet vitenskapelig)
  • 399.
    Brandt, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Genexpressionsförändringar i fettväv hos individer med typ 2-diabetes efter intervention med paleolitisk kost i kombination med eller utan fysisk aktivitet2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 400.
    Branneby, Cecilia
    KTH, Skolan för bioteknologi (BIO), Biokemi.
    Exploiting enzyme promiscuity for rational design2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Enzymes are today well recognized in various industrial applications, being an important component in detergents, and catalysts in the production of agrochemicals, foods, pharmaceuticals, and fine chemicals. Their large use is mainly due to their high selectivity and environmental advantage, compared to traditional catalysts. Tools and techniques in molecular biology offer the possibility to screen the natural sources and engineer new enzyme activities which further increases their usefulness as catalysts, in a broader area.

    Although enzymes show high substrate and reaction selectivity many enzymes are today known to catalyze other reactions than their natural ones. This is called enzyme promiscuity. It has been suggested that enzyme promiscuity is Nature’s way to create diversity. Small changes in the protein sequence can give the enzyme new reaction specificity.

    In this thesis I will present how rational design, based on molecular modeling, can be used to explore enzyme promiscuity and to change the enzyme reaction specificity. The first part of this work describes how Candida antarctica lipase B (CALB), by a single point mutation, was mutated to give increased activity for aldol additions, Michael additions and epoxidations. The activities of these reactions were predicted by quantum chemical calculations, which suggested that a single-point mutant of CALB would catalyze these reactions. Hence, the active site of CALB, which consists of a catalytic triad (Ser, His, Asp) and an oxyanion hole, was targeted by site-directed mutagenesis and the nucleophilic serine was mutated for either glycine or alanine. Enzymes were expressed in Pichia pastoris and analyzed for activity of the different reactions. In the case of the aldol additions the best mutant showed a four-fold initial rate over the wild type enzyme, for hexanal. Also Michael additions and epoxidations were successfully catalyzed by this mutant.

    In the last part of this thesis, rational design of alanine racemase from Geobacillus stearothermophilus was performed in order to alter the enzyme specificity. Active protein was expressed in Escherichia coli and analyzed. The explored reaction was the conversion of alanine to pyruvate and 2-butanone to 2-butylamine. One of the mutants showed increased activity for transamination, compared to the wild type.

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