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  • 451.
    Buendia, Ruben
    et al.
    Högskolan i Borås, Institutionen Ingenjörshögskolan.
    Gil-Pita, Roberto
    Seoane, Fernando
    Högskolan i Borås, Institutionen Ingenjörshögskolan.
    Cole Parameter Estimation from the Modulus of the Electrical Bioimpeadance for Assessment of Body Composition. A Full Spectroscopy Approach2011Inngår i: Journal of Electrical Bioimpedance, ISSN 1891-5469, E-ISSN 1891-5469, Vol. 2, s. 72-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Activities around applications of Electrical Bioimpedance Spectroscopy (EBIS) have proliferated in the past decade significantly. Most of these activities have been focused in the analysis of the EBIS measurements, which eventually might enable novel applications. In Body Composition Assessment (BCA), the most common analysis approach currently used in EBIS is based on the Cole function, which most often requires curve fitting. One of the most implemented approaches for obtaining the Cole parameters is performed in the impedance plane through the geometrical properties that the Cole function exhibit in such domain as depressed semi-circle. To fit the measured impedance data to a semi-circle in the impedance plane, obtaining the Cole parameters in an indirect and sequential manner has several drawbacks. Applying a Non-Linear Least Square (NLLS) iterative fitting on the spectroscopy measurement, obtains the Cole parameters considering the frequency information contained in the measurement. In this work, from experimental total right side EBIS measurements, the BCA parameters have been obtained to assess the amount and distribution of whole body fluids. The values for the BCA parameters have been obtained using values for the Cole parameters estimated with both approaches: circular fitting on the impedance plane and NLLS impedance-only fitting. The comparison of the values obtained for the BCA parameters with both methods confirms that the NLLS impedance-only is an effective alternative as Cole parameter estimation method in BCA from EBIS measurements. Using the modulus of the Cole function as the model for the fitting would eliminate the need for performing phase detection in the acquisition process, simplifying the hardware specifications of the measurement instrumentation when implementing a bioimpedance spectrometer.

  • 452. Buendia, Ruben
    et al.
    Seoane, Fernando
    Högskolan i Borås, Institutionen Ingenjörshögskolan.
    Gil-Pita, Roberto
    A Novel Approach for Removing the Hook Effect Artefact from Electrical Bioimpedance Spectroscopy Measurements2009Inngår i: Journal of Physics: Conference Series, Institute of Physics Publishing Ltd. , 2009Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Very often in Electrical Bioimpedance (EBI) spectroscopy measurements the presence of stray capacitances creates a measurement artefact commonly known as Hook Effect. Such an artefact creates a hook-alike deviation of the EBI data noticeable when representing the measurement on the impedance plane. Such Hook Effect is noticeable at high frequencies but it also causes a data deviation at lower measurement frequencies. In order to perform any accurate analysis of the EBI spectroscopy data, the influence of the Hook Effect must be removed. An established method to compensate the hook effect is the well known Td compensation, which consist on multiplying the obtained spectrum, Zmeas() by a complex exponential in the form of exp[jTd]. Such a method cannot correct entirely the Hook Effect since the hook-alike deviation occurs a broad frequency range in both magnitude and phase of the measured impedance, and by using a real value for Td. First, a real value only modifies the phase of the measured impedance and second, it can only correct the Hook Effect at a single frequency. In addition, the process to select a value for Td by an iterative process with the aim to obtain the best Cole fitting lacks solid scientific grounds. In this work the Td compensation method is revisited and a modified approach for correcting the Hook Effect that includes a novel method for selecting the correcting values is proposed. The initial validation results confirm that the proposed method entirely corrects the Hook Effect at all frequencies.

  • 453.
    Buendia, Ruben
    et al.
    Högskolan i Borås, Institutionen Ingenjörshögskolan.
    Seoane Martinéz, Fernando
    Högskolan i Borås, Institutionen Ingenjörshögskolan.
    Harris, M.
    Caffarel, J.
    Gil, R.
    Hook Effect Correction & Resistance-based Cole Fitting Prior Cole Model-based Analysis: Experimental Validation2010Konferansepaper (Fagfellevurdert)
  • 454. Buentke, E
    et al.
    Nordström, Anders
    Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Lin, H
    Björklund, AC
    Laane, E
    Harada, M
    Lu, L
    Tegnebratt, T
    Stone-Elander, S
    Heyman, M
    Söderhäll, S
    Porwit, A
    Östenson, CG
    Shoshan, M
    Tamm, K Pokrovskaja
    Grandér, D
    Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells2011Inngår i: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 1, nr e31, s. 9-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.

  • 455.
    Buetti-Dinh, Antoine
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    S100A4 and its role in metastasis – computational integration of data on biological networks2015Annet (Annet vitenskapelig)
  • 456.
    Bugaytsova, Jeanna A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Björnham, Oscar
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Swedish Defence Research Agency, 906 21 Umeå, Sweden.
    Chernov, Yevgen A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gideonsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Henriksson, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mendez, Melissa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sjöström, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mahdavi, Jafar
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. School of Life Sciences, CBS, University of Nottingham, NG7 2RD Nottingham, UK.
    Shevtsova, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ilver, Dag
    Moonens, Kristof
    Quintana-Hayashi, Macarena P.
    Moskalenko, Roman
    Aisenbrey, Christopher
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bylund, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Schmidt, Alexej
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Åberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Brännström, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Koeniger, Verena
    Vikström, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Rakhimova, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hofer, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ögren, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Liu, Hui
    Goldman, Matthew D.
    Whitmire, Jeannette M.
    Åden, Jörgen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Younson, Justine
    Kelly, Charles G.
    Gilman, Robert H.
    Chowdhury, Abhijit
    Mukhopadhyay, Asish K.
    Nair, G. Balakrish
    Papadakos, Konstantinos S.
    Martinez-Gonzalez, Beatriz
    Sgouras, Dionyssios N.
    Engstrand, Lars
    Unemo, Magnus
    Danielsson, Dan
    Suerbaum, Sebastian
    Oscarson, Stefan
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gröbner, Gerhard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Holgersson, Jan
    Esberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Strömberg, Nicklas
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Landström, Maréne
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Eldridge, Angela M.
    Chromy, Brett A.
    Hansen, Lori M.
    Solnick, Jay V.
    Linden, Sara K.
    Haas, Rainer
    Dubois, Andre
    Merrell, D. Scott
    Schedin, Staffan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Remaut, Han
    Arnqvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Berg, Douglas E.
    Boren, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence2017Inngår i: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, nr 3, s. 376-389Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

  • 457.
    Buizza, Giulia
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem. Politecnico di Milano, CartCasLab, Department of Electronics Information and Bioengineering, piazza Leonardo Da Vinci 42, Milan 20133, Italy.
    Toma-Dasu, I.
    Lazzeroni, M.
    Paganelli, C.
    Riboldi, M.
    Chang, Yongjun
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem.
    Smedby, Örjan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Wang, Chunliang
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Early tumor response prediction for lung cancer patients using novel longitudinal pattern features from sequential PET/CT image scans2018Inngår i: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 54, s. 21-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: A new set of quantitative features that capture intensity changes in PET/CT images over time and space is proposed for assessing the tumor response early during chemoradiotherapy. The hypothesis whether the new features, combined with machine learning, improve outcome prediction is tested. Methods: The proposed method is based on dividing the tumor volume into successive zones depending on the distance to the tumor border. Mean intensity changes are computed within each zone, for CT and PET scans separately, and used as image features for tumor response assessment. Doing so, tumors are described by accounting for temporal and spatial changes at the same time. Using linear support vector machines, the new features were tested on 30 non-small cell lung cancer patients who underwent sequential or concurrent chemoradiotherapy. Prediction of 2-years overall survival was based on two PET-CT scans, acquired before the start and during the first 3 weeks of treatment. The predictive power of the newly proposed longitudinal pattern features was compared to that of previously proposed radiomics features and radiobiological parameters. Results: The highest areas under the receiver operating characteristic curves were 0.98 and 0.93 for patients treated with sequential and concurrent chemoradiotherapy, respectively. Results showed an overall comparable performance with respect to radiomics features and radiobiological parameters. Conclusions: A novel set of quantitative image features, based on underlying tumor physiology, was computed from PET/CT scans and successfully employed to distinguish between early responders and non-responders to chemoradiotherapy. 

  • 458.
    Bunlang, Sawai
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper.
    Effekt av ftalaterna DiNP och MiNP på morfologi och celltillväxt i SH-SY5Y humana neuroblastom celler2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 459.
    Burek, M.
    et al.
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Maddika, Subbareddy
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada .
    Burek, C. J.
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Daniel, P. T.
    Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany.
    Schulze-Osthoff, Klaus
    nstitute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany .
    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, .
    Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1dependent2006Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 25, nr 15, s. 2213-2222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in transformed but not in normal cells, thus making it a promising candidate as a novel anticancer therapeutic. The mechanism of apoptin-induced apoptosis is largely unknown. Here, we report that contrary to previous assumptions, Bcl-2 and Bcl-x(L) inhibit apoptin-induced cell death in several tumor cell lines. In contrast, deficiency of Bax conferred resistance, whereas Bax expression sensitized cells to apoptin-induced death. Cell death induction by apoptin was associated with cytochrome c release from mitochondria as well as with caspase-3 and -7 activation. Benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad spectrum caspase inhibitor, was highly protective against apoptin-induced cell death. Apoptosis induced by apoptin required Apaf-1, as immortalized Apaf-1-deficient fibroblasts as well as tumor cells devoid of Apaf-1 were strongly protected. Thus, our data indicate that apoptin-induced apoptosis is not only Bcl-2- and caspase dependent, but also engages an Apaf-1 apoptosome-mediated mitochondrial death pathway.

  • 460.
    Burla, Bo
    et al.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore.
    Arita, Makoto
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan; Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, Japan.
    Arita, Masanori
    National Institute of Genetics, Shizuoka, Japan and RIKEN Center for Sustainable Resource Science, Yokohama, Japan.
    Bendt, Anne K.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore.
    Cazenave-Gassiot, Amaury
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Dennis, Edward A.
    Departments of Pharmacology and Chemistry and Biochemistry, School of Medicine, University of California at San Diego, La Jolla, CA, USA.
    Ekroos, Kim
    Lipidomics Consulting Ltd., Esbo, Finland.
    Han, Xianlin
    Barshop Institute for Longevity and Aging Studies and Department of Medicine-Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
    Ikeda, Kazutaka
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
    Liebisch, Gerhard
    Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
    Lin, Michelle K.
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Loh, Tze Ping
    Department of Laboratory Medicine, National University Hospital, Singapore.
    Meikle, Peter J.
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
    Orešič, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. Turku Centre for Biotechnology, University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland.
    Quehenberger, Oswald
    Departments of Pharmacology and Medicine, School of Medicine, University of California at San Diego, La Jolla, CA, USA.
    Shevchenko, Andrej
    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
    Torta, Federico
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Wakelam, Michael J. O.
    Babraham Institute, Cambridge, United Kingdom.
    Wheelock, Craig E.
    Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Wenk, Markus R.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore; Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines2018Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 59, nr 10, s. 2001-2017Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

  • 461.
    Burvall Engman, Amanda
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Förändring av temperaturtrösklar vid kvantitativ sensorisk testning: Med avseende på stimuleringshastighet och interstimulusintervall2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 462.
    Burén, Victoria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Riskbedömning gällande humant papilloma virus (HPV) kontamination: Undersökning av den analysprocess från provtagning, cytologisk utstryk på glas till amplifiering av DNA som bidrar till diagnos av cervixcancer2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 463. Busch, S
    et al.
    Kirsebom, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Notbohm, H
    Hartmann, R K
    Differential role of the intermolecular base-pairs G292-C(75) and G293-C(74) in the reaction catalyzed by Escherichia coli RNase P RNA.2000Inngår i: J Mol Biol, ISSN 0022-2836, Vol. 299, nr 4, s. 941-51Artikkel i tidsskrift (Fagfellevurdert)
  • 464.
    Byhlén, Liselott
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Enterobacteriaceae och amoxicillin-klavulansyra: Effekt av bestämt förhållande respektive bestämd koncentration av klavulansyra på MIC-värden och zon/MIC-korrelation2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Förekomsten av bakterier med olika typer av resistensmekanismer ökar globalt. De varianter som på engelska benämns ”Extended spectrum β-lactamases” (ESBL) är en heterogen grupp β- laktamaser som genom hydrolys inaktiverar β-laktamantibiotika och därigenom ger resistens mot bland annat β -laktamantibiotika som penicilliner och cefalosporiner. Resistensbestämning på kliniska laboratorier utförs huvudsakligen med lappdiffusion eller Minimum Inhibiting Concentration (MIC)-bestämning med gradienttester. Infektioner orsakade av ESBL-producerande organismer kan behandlas med β-laktamantibiotika kombinerat med en β-laktamasinhibitor. I Europa rekommenderas resistensbestämning med bestämd koncentration β-laktamasinhibitor, men produkter på marknaden saknas.

    Syftet med projektet var att utvärdera olika typer av gradienttester med amoxicillin- klavulansyra från två leverantörer (Etest och MIC Test Strip, MTS) och undersöka hur klavulansyra påverkar resistensbestämningen, samt att se hur resultat från lappdiffusion korrelerar med resultat från ovan nämnda tester.

    Lappdiffusion och MIC- bestämning med gradienttester med antingen bestämt förhållande av amoxicillin-klavulansyra (2:1) (Etest och MTS) eller bestämd koncentration klavulansyra (2mg/L) (MTS) utfördes med Escherichia coli (både med ESBL-positiva och ESBL-negativa stammar) samt med Proteus mirabilis. ESBL-detektion med cefpodoxim och cefpodoxim-klavulansyra utfördes parallellt.

    För P. mirabilis korrelerade lappdiffusionsresultat mycket bra med resultat från samtliga gradienttester. För E. coli korrelerade lappdiffusionsresultat mycket bra med MIC-värden vid användning av Etest 2:1 medan MTS 2:1 gav högre MIC-värden än referensdistributionen och resulterade i sämre korrelation. MIC-bestämning med MTS 2 mg/L resulterade i högre MIC-värden.

    Den nuvarande zonbrytpunkten behöver justeras för att korrelera med tolkningen från amoxicillin-klavulansyra med bestämd koncentration av klavulansyra 2 mg/L, framförallt för ESBL- producerande E. coli.

  • 465.
    Bylund, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Lokal validering av GLI 2012: En retrospektiv studie om referensvärden för spirometri vid klinisk fysiologi i Umeå2016Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 466.
    Byrnes, Andrea
    et al.
    Dept Genetics and dept Biostatistics, University of North Carolina.
    Jacks, Andreas
    Dept Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Dahlman-Wright, Karin
    Dept Biosciences and Nutrition, Karolinska Institutet.
    Evengård, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wright, Fred A
    Dept Biostatistics, University of North Carolina.
    Pedersen, Nancy L
    Dept Medical Epidemiology and Biostatistis, Karolinska Institutet.
    Sullivan, Patrick F
    Dept Genetics, Univ of North Carolina, Dept Medical Epid and Biostat, Karol Institutet.
    Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker2009Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 6, s. e5805-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes.

    METHODS: Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays.

    FINDINGS: There were no significant differences in gene expression for any transcript.

    CONCLUSIONS: Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.

  • 467.
    Bystry, Vojtech
    et al.
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Agathangelidis, Andreas
    IRCCS San Raffaele Sci Inst, Div Mol Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bikos, Vasilis
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hadzidimitriou, Anastasia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy2015Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, nr 23, s. 3844-3846Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motivation: An ever-increasing body of evidence supports the importance of B cell receptor immunoglobulin (BcR IG) sequence restriction, alias stereotypy, in chronic lymphocytic leukemia (CLL). This phenomenon accounts for similar to 30% of studied cases, one in eight of which belong to major subsets, and extends beyond restricted sequence patterns to shared biologic and clinical characteristics and, generally, outcome. Thus, the robust assignment of new cases to major CLL subsets is a critical, and yet unmet, requirement. Results: We introduce a novel application, ARResT/AssignSubsets, which enables the robust assignment of BcR IG sequences from CLL patients to major stereotyped subsets. ARResT/AssignSubsets uniquely combines expert immunogenetic sequence annotation from IMGT/V-QUEST with curation to safeguard quality, statistical modeling of sequence features from more than 7500 CLL patients, and results from multiple perspectives to allow for both objective and subjective assessment. We validated our approach on the learning set, and evaluated its real-world applicability on a new representative dataset comprising 459 sequences from a single institution.

  • 468.
    Byström, Klara
    Örebro universitet, Institutionen för hälsovetenskaper.
    Uttryck av virus-lika partiklar specifika för Yellow fever virus, Tick-born encephalitis och Langat virus i cellkultur2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 469.
    Byström, Roberth
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    SOD1´s Law: An Investigation of ALS Provoking Properties in SOD12009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Proteins are the most important molecules in the cell since they take care of most of the biological functions which resemble life. To ensure that everything is working properly the cell has a rigorous control system to monitor the proper function of its proteins and sends old or dysfunctional proteins for degradation. Unfortunately, this system sometimes fails and the once so vital proteins start to misbehave or to accumulate and in the worst case scenario these undesired processes cause the death of their host. One example is Amyotrophic Lateral Sclerosis (ALS); a progressive and always fatal neurodegenerative disorder that is proposed to derive from accumulation of aberrant proteins. Over 140 mutations in the human gene encoding the cytosolic homodimeric enzyme Cu/Zn-Superoxide Dismutase (SOD1) are linked to ALS. The key event in SOD1 associated ALS seems to be the pathological formation of toxic protein aggregates as a result of initially unfolded or partly structured SOD1-mutants.

    Here, we have compared the folding behaviour of a set of ALS associated SOD1 mutants. Based on our findings we propose that SOD1 mediated ALS can be triggered by a decrease in protein stability but also by mutations which reduce the net charge of the protein. Both findings are in good agreement with the hypothesis for protein aggregation.

    SOD1 has also been found to be able to interact with mitochondrial membranes and SOD1 inclusions have been detected in the inter-membrane space of mitochondria originating from the spinal cord. The obvious question then arose; does the misfolding and aggregation of SOD1 involve erroneous interactions with membranes?

    Here, we could show that there is an electrostatically driven interaction between the reduced apo SOD1 protein including ALS associated SOD1-mutants and charged lipid membrane surfaces. This association process changes the secondary structures of these mutants in a way quite different from the situation found in membrane free aqueous environment. However, the result show that mutants interact with charged lipid vesicles to lesser extent than wildtype SOD1. This opposes the correlation between decreased SOD1 stability and disease progression. We therefore suggest that the observed interaction is not a primary cause in the ALS mechanism.

  • 470.
    Byström, Roberth
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Aisenbrey, Christopher
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Oliveberg, Mikael
    Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
    Gröbner, Gerhard
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Electrostatic interactions between negatively charged phospolipid membranes and SOD1 protein: Effect of charge changing fALS mutationsManuskript (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is closely connected to single site mutations of the Cu/Zn superoxide dismutase (SOD1) protein, whose pathological conversion into misfolded aggregates is a hallmark of ALS. To explore the impact of protein net charge changing ALS relevant SOD1 mutations on their ability to interact with neuronal membranes and the consequences for their folding behaviour, we studied by circular dichroism the conformational changes of the SOD1pWT, SOD1N86D and SOD1N86K species in their apo-state in the presence of increasing amounts of negatively charged lipid bilayers.. The results clearly indicate an electrostatically driven association process, where the association event induces a pronounced increase in the helical character of the pWT and the N86D species, characterized by long patient survival times. To the opposite, the charge reducing N86K mutation shows more pronounced β-like features in the presence of membranes in comparison to the other two species; an observation which most likely reflects its reduced stability in its apo-state in combination with a very fast ALS progression.

  • 471.
    Byström, Roberth
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Andersen, Peter Munch
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurologi.
    Gröbner, Gerhard
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
    Oliveberg, Mikael
    Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
    Identification of property outliers among ALS-associated SOD1 mutations: Common effect on surface hydrogen bondsManuskript (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    In good accord with the protein-aggregation hypothesis for neurodegenerative diseaseALS-associated SOD1 mutations are found to reduce structural stability or netrepulsive charge. Moreover there are weak indications that the ALS diseaseprogression is correlated with the degree of mutational impact on the SOD1 structure.A bottleneck for obtaining more conclusive information about these structure-diseaserelationships, however, is the large intrinsic variability in patient survival times andinsufficient disease statistics for the majority of ALS-provoking mutations. As analternative test of the structure-disease relationship we focus here on the SOD1 amutation that appears to be outliers in the data set. The results identify several ALSprovokingmutations whose only effect on apo SOD1 is the elimination orintroduction of a single charge, i.e., D76V/Y, D101N and N139D/K. Thethermodynamic stability and folding behaviour of these mutants are indistinguishablefrom the wildtype control, showing that structurally benign replacements of individualsurface charges are sufficient to trigger ALS. Moreover, D101N is a clear outlier inthe plot of stability loss vs. patient survival time by having too rapid diseaseprogression. Common to the identified mutations is that they truncate conserved saltlinksand/or H-bond networks in the functional loops IV or VII. The results show thatthe local impact of ALS-associated mutations on the SOD1 molecule can sometimesoverrun their global effects on stability and net repulsive charge, and point at theanalysis of property outliers as an efficient strategy for mapping out new ALSprovokingfeatures.

  • 472.
    Byström, Sanna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Affinity assays for profiling disease-associated proteins in human plasma2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Affinity-based proteomics offers opportunities for the discovery and validation of disease-associated proteins in human body fluids. This thesis describes the use of antibody-based immunoassays for multiplexed analysis of proteins in human plasma, serum and cerebrospinal fluid (CSF). This high-throughput method was applied with the objective to identify proteins associated to clinical variables. The main work in this thesis was conducted within the diseases of multiple sclerosis and malignant melanoma, as well as mammographic density, a risk factor for breast cancer.

    The suspension bead array (SBA) technology has been the main method for the work presented in this thesis (Paper I-IV). SBA assays and other affinity proteomic technologies were introduced for protein profiling of sample material obtained from clinical collaborators and biobanks. Perspectives on the validation of antibody selectivity by means of e.g. immuno-capture mass spectrometry are also provided.

    Paper I describes the development and application of a protocol for multiplexed pro- tein profiling of CSF. The analysis of 340 CSF samples from patients with multiple sclerosis and other neurological disease revealed proteins with potential association to disease progression (GAP43) and inflammation (SERPINA3). Paper II continued on this work with an extended investigation of more than 1,000 clinical samples and included both plasma and CSF collected from the same patients. Comparison of disease subtypes and controls revealed five plasma proteins of potential diagnostic relevance, such as IRF8 and GAP43. The previously reported associations for GAP43 and SERPINA3 in CSF was confirmed. Subsequent immunohistochemical analysis of post-mortem brain tissue revealed differential protein expression in disease affected areas. In Paper III, 150 serum samples from patients with cutaneous malignant melanoma were analyzed. Protein profiles from antibody bead arrays suggested three proteins (RGN, MTHFD1L, STX7) of differential abundance between patients with no disease recurrence and low tumor thickness (T-stage 1 and 2) compared to patients with high tumor thickness (T-stage 3 and 4) and disease recurrence. We observed MTHFD1L expression in tissue of a majority of patients, while expression of STX7 in melanoma tissue had been reported previously. Paper IV describes the analysis of protein in plasma in relation to mammographic breast density (MD), one of the strongest risk factors for the development of breast cancers. More than 1,300 women without prior history of breast cancer were screened. Linear associations to MD in two independent sample sets were found for 11 proteins, which are expressed in the breast and involved in tissue homeostasis, DNA repair, cancer development and/or progression in MD.

    In conclusion, this thesis describes the use of multiplexed antibody bead arrays for protein profiling of serum, plasma and CSF, and it shortlists disease associated proteins for further validation studies. 

  • 473.
    Byström, Sanna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Eklund, Martin
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Eriksson, Mikael
    Czene, Kamila
    Hall, Per
    Schwenk, Jochen. M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Gabrielson, Marike
    Affinity proteomic profiling of plasma for proteins associated to mammographic breast densityManuskript (preprint) (Annet vitenskapelig)
  • 474.
    Byström, Sanna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Edqvist, Per-Henrik
    Nyaiesh, Etienne-Nicholas
    Drobin, Kimi
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Uhlén, Matthias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Bergqvist, Michael
    Pontén, Fredrik
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Affinity proteomics exploration of melanoma identifies proteins in serum with associations to T-stage and recurrenceManuskript (preprint) (Annet vitenskapelig)
  • 475.
    Bzdula, Jessica
    Linköpings universitet, Hälsouniversitetet.
    Den preanalytiska fasen – Hur viktigt är det att blanda serumrören?2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund: Cirka 2/3 av alla preanalytiska fel uppkommer i den preanalytiska fasen, där blandning av provrör direkt efter provtagningen är en av faktorerna. Studiens syfte var att jämföra analysresultaten för glukos, laktatdehydrogenas samt kalium i serum från blandade rör med oblandade rör. Studiens syfte var även att undersöka hållbarheten på dessa tre analyter i rumstemperatur (25 °C) under sju dagar.

    Metod: 100 blandade och 100 oblandade serumrör med gel, från 100 patienter, analyserades på Architect ci2800. Analysresultaten jämfördes statistiskt med parat t-test. Alla serumrör förvarades i rumstemperatur under sju dagar och de tre analyterna analyserades dagligen. Analysresultaten jämfördes statistiskt med ANOVA.

    Resultat: Studien visade ingen statistiskt signifikant skillnad (p > 0,05) för glukos samt kalium mellan de oblandade och blandade rören. Laktatdehydrogenas uppvisar en statistiskt signifikant skillnad (p < 0,05) mellan de oblandade och blandade rören. Skillnaderna i hållbarheten mellan dag 1, dag 2 och dag 7 för glukos, laktatdehydrogenas och kalium visade sig vara statistiskt signifikanta (p < 0,05).

    Slutsats: Studien indikerar att det inte är nödvändigt att blanda serumrören direkt efter provtagningen men det är viktigt att blanda andra typer av rör, exempelvis citratrör, därför är det bra att skapa sig en rutin då man blandar alla rör. Glukos är den mest stabila analyten i rumstemperatur i sju dagar medan kalium är den minst stabila.

  • 476. Bárcena-Uribarri, Iván
    et al.
    Thein, Marcus
    Barbot, Mariam
    Sans-Serramitjana, Eulalia
    Bonde, Mari
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Mentele, Reinhard
    Lottspeich, Friedrich
    Bergström, Sven
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Benz, Roland
    Study of the protein complex, pore diameter, and pore-forming activity of the Borrelia burgdorferi P13 porin2014Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, nr 27, s. 18614-18624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    P13 is one of the major outer membrane proteins of Borrelia burgdorferi. Previous studies described P13 as a porin. In the present study some structure and function aspects of P13 were studied. P13 showed according to lipid bilayer studies a channel-forming activity of 0.6 nanosiemens in 1 M KCl. Single channel and selectivity measurements demonstrated that P13 had no preference for either cations or anions and showed no voltage-gating up to +/-100 mV. Blue native polyacrylamide gel electrophoresis was used to isolate and characterize the P13 protein complex in its native state. The complex had a high molecular mass of about 300 kDa and was only composed of P13 monomers. The channel size was investigated using non-electrolytes revealing an apparent diameter of about 1.4 nm with a 400-Da molecular mass cut-off. Multichannel titrations with different substrates reinforced the idea that P13 forms a general diffusion channel. The identity of P13 within the complex was confirmed by second dimension SDS-PAGE, Western blotting, mass spectrometry, and the use of a p13 deletion mutant strain. The results suggested that P13 is the protein responsible for the 0.6-nanosiemens pore-forming activity in the outer membrane of B. burgdorferi.

  • 477. Bäck, Anne Tuiskunen
    et al.
    Lundkvist, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Dengue viruses: an overview.2013Inngår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dengue viruses (DENVs) cause the most common arthropod-borne viral disease in man with 50-100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF) is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  • 478.
    Bäcklund, Fredrik G.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Pallbo, Jon
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Solin, Niclas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Controlling Amyloid Fibril Formation by Partial Stirring2016Inngår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 105, nr 5, s. 249-259Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many proteins undergoes self-assembly into fibrillar structures known as amyloid fibrils. During the self-assembly process related structures, known as spherulites, can be formed. Herein we report a facile method where the balance between amyloid fibrils and spherulites can be controlled by stirring of the reaction mixture during the initial stages of the self-assembly process. Moreover, we report how this methodology can be used to prepare non-covalently functionalized amyloid fibrils. By stirring the reaction mixture continuously or for a limited time during the lag phase the fibril length, and hence the propensity to form liquid crystalline phases, can be influenced. This phenomena is utilized by preparing films consisting of aligned protein fibrils incorporating the laser dye Nile red. The resulting films display polarized Nile red fluorescence.

  • 479.
    Bäcklund, Fredrik G.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Solin, Niclas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Tuning the aqueous self-assembly process of insulin by a hydrophobic additive2015Inngår i: RSC ADVANCES, ISSN 2046-2069, Vol. 5, nr 112, s. 92254-92262Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biomolecular self-assembly is an efficient way of preparing soft-matter based materials. Herein we report a novel method, based on the use of insoluble additives in aqueous media, for influencing the self-assembly process. Due to their low solubility, the use of hydrophobic additives in aqueous media is problematic; however, by mixing the additive with the biomolecule in the solid state, prior to solvation, this problem can be circumvented. In the investigated self-assembly system, where bovine insulin self-assembles into spherical structures, the inclusion of the hydrophobic material α-sexithiophene (6T) results in significant changes in the self-assembly process. Under our reaction conditions, in the case of materials prepared from insulin-only the growth of spherulites typically stops at a diameter of 150μm. However, by adding 2 weight % of hydrophobic material, spherulite growth continues up to diameters in the mm-range. The spherulites incorporate 6T and are thus fluorescent. The method reported herein should be of interest to all scientists working in the field of self-assembly as the flexible materials preparation, based simply on co-grinding of commercially available materials, adds another option to influence the structure and properties of products formed by  self-assembly reactions.

  • 480.
    Bäcklund, Fredrik Gustaf
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Ajjan, Fátima Nadia
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Solin, Niclas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Convection Induced Air-Water Interface Assembly of Amyloid FibrilsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    We report that hydrophobically modified amyloid fibrils form macroscopic films at the air-water interface. The hydrophobically modified fibrils are prepared in a two step process. First bovine insulin is ground with a hydrophobic compound. The resulting material is dissolved in acidic water and heated to induce assembly into fibrils incorporating the hydrophobic compounds. Upon dilution followed by asymmetric heating, resulting in convection flow, the fibrills form highly ordered films with thicknesses from 80 nm and up. The thickness of the film can be controlled by the fibril concentration and/or reaction time. The films contain anisotropic domains spanning several square centimeters. In addition, the films contains ordered assemblies of dyes that display emission of polarized light.

  • 481.
    Bäcklund, Madeleine
    Örebro universitet, Hälsoakademin.
    Molekylärgenetisk typning av Propionibacterium acnes isolerade från prostata, perineum och panna hos patienter med prostatacancer2011Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 482.
    Bäcklund, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Frankel, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Vrinnevi Hospital, Norrköping, Sweden.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Trunk sway in idiopathic normal pressure hydrocephalus: quantitative assessment in clinical practice2017Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, s. 62-70, artikkel-id 54Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).

    Methods: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group.

    Results: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p < 0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p < 0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p < 0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture.

    Conclusions: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up. 

  • 483.
    Bäckman, Hans G
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Pessoa, João
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Eneqvist, Therese
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Glaser, Elzbieta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Binding of divalent cations is essential for the activity of the organellar peptidasome in Arabidopsis thaliana, AtPreP.2009Inngår i: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 583, nr 17, s. 2727-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dual-targeted mitochondrial and chloroplastic zinc metallooligopeptidase from Arabidopsis, AtPreP, functions as a peptidasome that degrades targeting peptides and other small unstructured peptides. In addition to Zn located in the catalytic site, AtPreP also contains two Mg-binding sites. We have investigated the role of Mg-binding using AtPreP variants, in which one or both sites were rendered unable to bind Mg(2+). Our results show that metal binding besides that of the active site is crucial for AtPreP proteolysis, particularly the inner site appears essential for normal proteolytic function. This is also supported by its evolutionary conservation among all plant species of PreP.

  • 484.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Linköping, Sweden.
    Lind, Anne-Li
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Thulin, Måns
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gerdle, Björn
    Linköping University, Linköping, Sweden.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    High Levels of Cerebrospinal Fluid Chemokines Point to the Presence of Neuroinflammation in Peripheral Neuropathic Pain: A Cross-Sectional Study of Two Cohorts of Patients Compared to Healthy ControlsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called “gliotransmitters”, a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile for neuropathic pain patients. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation.  

    CSF samples were collected from two cohorts of patients with neuropathic pain (n=11 and n=16, respectively) and healthy controls (n=11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek® Multiplex Inflammation I, Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares – discriminant analysis, were used for statistical analyses.

    CSF levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared to healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in fibromyalgia patients. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Since it has been suggested that prevalent co-morbidities to chronic pain (e.g., depression, anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation is a common mediator.

  • 485.
    Bäckström, Annie
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jämförelse mellan två nedkylningsmetoder av helblodsenheter för vidare framställning av trombocytkoncentrat avsedda för transfusion2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Trombocytopeni behandlas primärt med trombocyttransfusion. Trombocytkoncentraten kan erhållas genom poolning av lättcellskikt framställda ur helblodsenheter från flera blodgivare. Helblodsenheterna kyls vanligen ner på en CompoCool®-platta för att snabbt komma ner till rumstemperatur och kan då prepareras redan efter 2 h. Detta brukar vara logistiskt fördelaktigt och gynnar erytrocyterna som framställs ur samma helblodsenheter. Det går även att låta helblodsenheterna kylas ner i rumstemperatur vilket å andra sidan sägs ge ett högre trombocytutbyte då studier visat att trombocyter är känsliga för kyla. Syftet med examensarbetet var att framställa och jämföra kvaliteten på trombocytkoncentrat där helblodsenheten hade kylts ner på CompoCool®-platta respektive kylts ner i rumstemperatur. Hypotesen var att trombocytutbytet skulle bli högre vid nedkylning av helblodsenheten i rumstemperatur än vid nedkylning på CompoCool®-platta. Framställningen av trombocytkoncentraten gjordes genom poolning av 5 st lättcellskikt och en påse trombocytsuspensionsmedium efterföljt av centrifugering och separation i en automatisk blodkomponents separator. Kvalitén utvärderades med avseende på trombocytkoncentration, leukocytkoncentration, swirling samt bakterieodling. Samtliga resultat för kvalitetskontrollerna låg inom de rekommenderade gränsvärdena. Det beräknade t-testet för trombocytkoncentrationen var högre än det kritiska t-värdet vilket innebar att det var en signifikant skillnad mellan de olika nedkylningsmetoderna. Genom användning av de erhållna resultaten kunde hypotesen bekräftas och slutsatsen dras att trombocytutbytet är signifikant högre då helblodsenheten kyls ner i rumstemperatur jämfört med CompoCool®-platta. 

  • 486.
    Bäckström, Michelle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    IgE-förekomst i lymfoida och endokrina organ: jämförelse mellan NOD-och B6-möss2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 487.
    Börjesson, Emma
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Analys av 25-hydroxyvitamin D i primärvården2015Independent thesis Basic level (degree of Bachelor), 180 hpOppgave
    Abstract [en]

    Background: The interest of vitamin D has increased in the last years. That is because there is so many possible positive effects of vitamin D and also because many individuals has vitamin D deficiency. Modern man spends much time indoors which leads to lower levels of vitamin D. People who have emigrated from a sunny climate to a Nordic climate often gets a deficiency due to a more pigmented skin which requires a larger amount of UVB to get an adequate synthesis of vitamin D.

    Aim: The aim with this study is to compare and evaluate how similar the instrument mini VIDAS measures 25(OH)D total against the current existing method cobas e 602. A discussion about if 25(OH)D total has a place in primary health care is included in the study.

    Method: The comparison was based on 39 samples. The samples was analyzed on cobas e 602 and mini VIDAS. A precision test was performed. External controls from DEQAS was also included in the study. The results have been presented with simple linear regression analysis, mean value, SD and CV.

    Results: The comparison between cobas e 602 and mini VIDAS gave a coefficient of determination of 81,34 %. mini VIDAS was closest to the external controls target values.

    Conclusion: There is no obvious conclusions about if mini VIDAS fulfills the requirement to be introduced to primary health care. The coefficient of determination of 81,34 % should be at least 95 %. However is mini VIDAS closer to the external controls target values then cobas e 602. There is factors that implies that 25(OH)D total has a place in primary health care with regards to demand, use and because many individuals has vitamin D deficiency. The instrument is also user-friendly to a primary health care laboratory.

  • 488.
    Bülow, Katrin
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Jämförelse av selektivitet för Clostridium difficile mellan två olika odlingsmedier2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 489.
    Caban, Kelvin
    et al.
    Columbia Univ, Dept Chem, 3000 Broadway,MC3126, New York, NY 10027 USA..
    Pavlov, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Ehrenberg, Måns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Gonzalez, Ruben L., Jr.
    Columbia Univ, Dept Chem, 3000 Broadway,MC3126, New York, NY 10027 USA..
    A conformational switch in initiation factor 2 controls the fidelity of translation initiation in bacteria2017Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikkel-id 1475Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Initiation factor (IF) 2 controls the fidelity of translation initiation by selectively increasing the rate of 50S ribosomal subunit joining to 30S initiation complexes (ICs) that carry an N-formyl-methionyl-tRNA (fMet-tRNA(fMet)). Previous studies suggest that rapid 50S subunit joining involves a GTP- and fMet-tRNA(fMet)-dependent "activation" of IF2, but a lack of data on the structure and conformational dynamics of 30S IC-bound IF2 has precluded a mechanistic understanding of this process. Here, using an IF2-tRNA single-molecule fluorescence resonance energy transfer signal, we directly observe the conformational switch that is associated with IF2 activation within 30S ICs that lack IF3. Based on these results, we propose a model of IF2 activation that reveals how GTP, fMet-tRNA(fMet), and specific structural elements of IF2 drive and regulate this conformational switch. Notably, we find that domain III of IF2 plays a pivotal, allosteric, role in IF2 activation, suggesting that this domain can be targeted for the development of novel antibiotics.

  • 490.
    Cable, N.
    et al.
    Department of Epidemiology and Public Health, University College London, London, UK.
    Hiyoshi, Ayako
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Kondo, N.
    Department of Health and Social Behavior, School of Public Health, University of Tokyo, Tokyo, Japan.
    Aida, J.
    Division of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan.
    Sjöqvist, Hugo
    Kondo, K.
    Center for Preventive Medical Science, Chiba University, Chiba, Japan.
    Identifying Frail-Related Biomarkers among Community-Dwelling Older Adults in Japan: A Research Example from the Japanese Gerontological Evaluation Study2018Inngår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikkel-id 5362948Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We examined correlating clinical biomarkers for the physical aspect of frailty among community-dwelling older adults in Japan, using Japanese Gerontological Evaluation Study (JAGES). We used information from the JAGES participants (N = 3,128) who also participated in the community health screening in 2010. We grouped participants' response to the Study of Osteoporotic Fracture (SOF) Frailty Index into robust (=0), intermediate frail (=1), and frail (=2+) ones to indicate physical aspect of frailty. Independent of sex and age, results from multinomial logistic regression showed above normal albumin and below normal HDL and haemoglobin levels were positively associated with intermediate frail (RRR = 1.99, 95% CI = 1.22-3.23; RRR = 1.36, 95% CI = 1.33-1.39; RRR = 1.36, 95% CI = 1.23-1.51, resp.) and frail cases (RRR = 2.27, 95% CI = 1.91-2.70; RRR = 1.59, 95% CI = 1.51-1.68; RRR = 1.40, 95% CI = 1.28-1.52, resp.). Limited to women, above normal Hb1Ac level was similarly associated with intermediate frail and frail cases (RRR = 1.18, 95% CI = 1.02, 1.38; RRR = 2.56, 95% CI = 2.23-2.95, resp.). Use of relevant clinical biomarkers can help in assessment of older adults' physical aspect of frailty.

  • 491.
    Caesar, Jenny
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan.
    Segmentation of the Brain from MR Images2005Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    KTH, Division of Neuronic Engineering, have a finite element model of the head. However, this model does not contain detailed modeling of the brain. This thesis project consists of finding a method to extract brain tissues from T1-weighted MR images of the head. The method should be automatic to be suitable for patient individual modeling.

    A summary of the most common segmentation methods is presented and one of the methods is implemented. The implemented method is based on the assumption that the probability density function (pdf) of an MR image can be described by parametric models. The intensity distribution of each tissue class is modeled as a Gaussian distribution. Thus, the total pdf is a sum of Gaussians. However, the voxel values are also influenced by intensity inhomogeneities, which affect the pdf. The implemented method is based on the expectation-maximization algorithm and it corrects for intensity inhomogeneities. The result from the algorithm is a classification of the voxels. The brain is extracted from the classified voxels using morphological operations.

  • 492.
    Cai, Bing
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ceramic Materials for Administration of Potent Drugs2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis aimed to investigate and document the potential of applying ceramics in two specific drug delivery applications: tamper-resistant opioid formulations and transdermal enhancement protrusions.

    Geopolymers were developed into the matrix for a tamper-resistant formulation, aiming to protect drug substances from non-medical abuse. The synthesis conditions and excipients composition of the geopolymer-based formulation were modified in this work to facilitate a stable and extended drug delivery. Results showed that 37ºC 100% humidity for 48 hours were applicable conditions to obtain geopolymer with suitable mechanical strength and porosity. Moreover, it was found that the integration of poly(methyl acrylate) into the geopolymer-based formulation could reduce the drug release at low pH and, meanwhile, maintain the mechanical strength. Therefore, the geopolymer-based drug formulations concluded from these studies were applied in oral and transdermal delivery systems. Evidence of the tamper-resistance of geopolymer-based oral and transdermal formulations was documented and compared to the corresponding commercial opioid formulations. The results provided experimental support for the positive effects of geopolymers as drug carriers for the tamper-resistance of oral and transdermal delivery systems.

    Self-setting bioceramics, calcium phosphate and calcium sulfate were fabricated into transdermal enhancement protrusions in this work for the first time. Results showed that, under mild conditions, both bioceramics could form pyramid-shaped needles in the micron size. The drug release from these needles could be controlled by the bulk surface area, porosity and degradation of the bioceramics. An in vitro insertion test showed that the bioceramic microneedles had enough mechanical strength to insert into skin. Further optimization on the geometry of needles and the substrate material was also performed. The higher aspect-ratio needles with a flexible and self-swellable substrate could release most of the drug content within 4 hours and could penetrate through the stratum corneum by manual insertion. This study explored the potential application of bioceramics in transdermal enhancement protrusions and showed promising indication of their future developments.

  • 493.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Aluminum release from geopolymer-based opioid formulation2014Konferansepaper (Fagfellevurdert)
  • 494.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Evaluation of the effect of polymer content on drug release and mechanical strength of a geopolymer ER formulation for opioid drugs2014Konferansepaper (Fagfellevurdert)
  • 495.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Söderkvist, Karin
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    A new screening in-vitro method to study drug release in early development of transdermal drug delivery systems2012Inngår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 23, nr Suppl. 5, s. 22-Artikkel i tidsskrift (Fagfellevurdert)
  • 496.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Xia, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Development and evaluation of self-setting bioceramic microneedles2014Konferansepaper (Fagfellevurdert)
  • 497.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Xia, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bioceramic microneedles with flexible and self-swelling substrate2015Inngår i: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 94, s. 404-410Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery.

  • 498.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Xia, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bioceramic microneedles with flexible and self-swelling substrateArtikkel i tidsskrift (Annet vitenskapelig)
  • 499.
    Cai, Demin
    et al.
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Wang, Junjian
    Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA..
    Jia, Yimin
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Liu, Haoyu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Yuan, Mengjie
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Dong, Haibo
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Zhao, Ruqian
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms2016Inngår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1861, nr 1, s. 41-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal methyl-donor nutrient on neonatal expression of hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated with down-regulated hepatic expression of lipogenic genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine to s-adenosyl homocysteine ratio was elevated in the liver of betaine-exposed piglets, which was accompanied by DNA hypermethylation on FAS and SCD gene promoters and more enriched repression histone mark H31K27me3 on SCD gene promoter. Furthermore, glucocorticoid receptor (GR) binding to SCD gene promoter was diminished along with reduced serum cortisol and liver GR protein content in betaine-exposed piglets. GR-mediated SCD gene regulation was confirmed in HepG2 cells in vitro. Dexamethasone (Dex) drastically increased the luciferase activity of porcine SCD promoter, while the deletion of GR response element on SCD promoter significantly attenuated Dex-mediated SCD transactivation. In addition, miR-let-7e, miR-1285 and miR-124a, which respectively target porcine SCD, ACC and GR, were significantly up-regulated in the liver of betaine-exposed piglets, being in accordance with decreased protein content of these three genes. Taken together, our results suggest that maternal dietary betaine supplementation during gestation attenuates hepatic lipogenesis in neonatal piglets via epigenetic and GR-mediated mechanisms.

  • 500.
    Cai, Demin
    et al.
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Yuan, Mengjie
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Jia, Yimin
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Liu, Haoyu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hu, Yun
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Zhao, Ruqian
    Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
    Maternal gestational betaine supplementation-mediated suppression of hepatic cyclin D2 and presenilin1 gene in newborn piglets is associated with epigenetic regulation of the STAT3-dependent pathway2015Inngår i: Journal of Nutritional Biochemistry, ISSN 0955-2863, E-ISSN 1873-4847, Vol. 26, nr 12, s. 1622-1631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Betaine, which donates methyl groups through methionine metabolism for DNA and protein methylation, is critical for epigenetic gene regulation, especially during fetal development. Here we fed gestational sows with control or betaine supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal betaine on hepatic cell proliferation in neonatal piglets. Neonatal piglets born to betaine-supplemented sows demonstrated a reduction of cell number and DNA content in the liver, which was associated with significantly down-regulated hepatic expression of cell cycle regulatory genes, cyclin D2 (CCND2) and presenilin1 (PSEN1). Moreover, STAT3 binding to the promoter of CCND2 and PSEN1 was also lower in betaine-exposed piglets, accompanied by strong reduction of STAT3 mRNA and protein expression, along with its phosphorylation at Tyr705 and Ser727 residues. Also, prenatal betaine exposure significantly attenuated upstream kinases of STAT3 signaling pathway (phospho-ERK1/2, phospho-SRC and phospho-JAK2) in the livers of neonates. Furthermore, the repressed STAT3 expression in the liver of betaine-exposed piglets was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter, together with significantly up-regulated expression of H3K27me3 and enhancer of zeste homolog 2 (EZH2) proteins, as well as miR-124a, which targets STAT3. Taken together, our results suggest that maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 and PSEN1 genes via a STAT3-dependent pathway. These neonatal changes in cell cycle and proliferation regulation may lead to lower liver weight and hepatic DNA content at weaning.

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