lnu.sePublications
Change search
Refine search result
1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Nilsson, Bo
    et al.
    Uppsala University.
    Hamad, Osama
    Uppsala University.
    Ahlström, Håkan
    Uppsala University.
    Kullberg, Joel
    Uppsala University.
    Johansson, Lars
    Uppsala University.
    Lindhagen, Lars
    Uppsala University.
    Haenni, Arvo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Lind, Lars
    Uppsala University.
    3 and 4 are strongly related to cardiovascular risk factors and to the metabolic syndrome2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 6, p. 587-596Article in journal (Refereed)
    Abstract [en]

    Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals. Methods In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed. Results C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating thatthe association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4 months. Conclusion A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that theadipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity.

  • 2.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    A Functional Monomer Is Not Enough: Principal Component Analysis of the Influence of Template Complexation in Pre-Polymerization Mixtures on Imprinted Polymer Recognition and Morphology2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 11, p. 20572-20584Article in journal (Refereed)
    Abstract [en]

    In this report, principal component analysis (PCA) has been used to explore the influence of template complexation in the pre-polymerization phase on template molecularly imprinted polymer (MIP) recognition and polymer morphology. A series of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)-crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate (MMA) as the functional monomer, and the stoichiometry between template, functional monomer and crosslinker was varied. The polymers were characterized using radioligand equilibrium binding experiments, gas sorption measurements, swelling studies and data extracted from molecular dynamics (MD) simulations of all-component pre-polymerization mixtures. The molar fraction of the functional monomer in the MAA-polymers contributed to describing both the binding, surface area and pore volume. Interestingly, weak positive correlations between the swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed. Polymers prepared with MMA as a functional monomer and a polymer prepared with only EGDMA were found to share the same characteristics, such as poor rebinding capacities, as well as similar surface area and pore volume, independent of the molar fraction MMA used in synthesis. The use of PCA for interpreting relationships between MD-derived descriptions of events in the pre-polymerization mixture, recognition properties and morphologies of the corresponding polymers illustrates the potential of PCA as a tool for better understanding these complex materials and for their rational design.

  • 3.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Söderberg, Pernilla
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    A Phage Display Screening Derived Peptide with Affinity for the Adeninyl Moiety2014In: Biosensors, ISSN 2079-6374, Vol. 4, no 2, p. 137-149Article in journal (Refereed)
    Abstract [en]

    Phage display screening of a surface-immobilized adenine derivative led to the identification of a heptameric peptide with selectivity for adenine as demonstrated through quartz crystal microbalance (QCM) studies. The peptide demonstrated a concentration dependent affinity for an adeninyl moiety decorated surface (KD of 968 ± 53.3 μM), which highlights the power of piezoelectric sensing in the study of weak interactions. 

  • 4.
    Zabriskie, Matthew S.
    et al.
    University of Utah, USA.
    Eide, Christopher A.
    Oregon Health & Science University, USA;Howard Hughes Medical Institute, USA.
    Tantravahi, Srinivas K.
    University of Utah, USA.
    Vellore, Nadeem A.
    University of Utah, USA.
    Estrada, Johanna
    University of Utah, USA.
    Nicolini, Franck E.
    Centre Hospitalier Lyon Sud, France.
    Khoury, Hanna J.
    Emory University, USA.
    Larson, Richard A.
    University of Chicago, USA.
    Konopleva, Marina
    University of Texas, USA.
    Cortes, Jorge E.
    University of Texas, USA.
    Kantarjian, Hagop
    University of Texas, USA.
    Jabbour, Elias J.
    University of Texas, USA.
    Kornblau, Steven M.
    University of Texas, USA.
    Lipton, Jeffrey H.
    University of Toronto, Canada.
    Rea, Delphine
    Hospital Saint-Louis, France.
    Stenke, Leif
    Karolinska Institutet.
    Barbany, Gisela
    Karolinska Institutet.
    Lange, Thoralf
    University of Leipzig, Germany.
    Hernandez-Boluda, Juan-Carlos
    Hospital Clı´nico Universitario, Spain.
    Ossenkoppele, Gert J.
    VU University Medical Center, Netherlands.
    Press, Richard D.
    Oregon Health & Science University, USA.
    Chuah, Charles
    Singapore General Hospital, Singapore.
    Goldberg, Stuart L.
    John Theurer Cancer Center at Hackensack University Medical Center, USA.
    Wetzler, Meir
    Roswell Park Cancer Institute, USA.
    Mahon, Francois-Xavier
    Centre Hospitalier Universitaire de Bordeaux, France.
    Etienne, Gabriel
    Institut Bergonie, France.
    Baccarani, Michele
    University of Bologna, Italy.
    Soverini, Simona
    University of Bologna, Italy.
    Rosti, Gianantonio
    University of Bologna, Italy.
    Rousselot, Philippe
    Université de Versailles, France.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Deininger, Marie
    University of Utah, USA.
    Reynolds, Kimberly R.
    University of Utah, USA.
    Heaton, William L.
    University of Utah, USA.
    Eiring, Anna M.
    University of Utah, USA.
    Pomicter, Anthony D.
    University of Utah, USA.
    Khorashad, Jamshid S.
    University of Utah, USA.
    Kelley, Todd W.
    University of Utah, USA.
    Baron, Riccardo
    University of Utah, USA.
    Druker, Brian J.
    Oregon Health & Science University Knight Cancer Institute, USA;Howard Hughes Medical Institute, USA.
    Deininger, Michael W.
    University of Utah, USA.
    O'Hare, Thomas
    University of Utah, USA.
    BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia2014In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 26, no 3, p. 428-442Article in journal (Refereed)
    Abstract [en]

    Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.

  • 5.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Aastrup, Teodor
    Attana AB, Stockholm.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Biotin selective polymer nano-films2014In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 12, article id 8Article in journal (Refereed)
    Abstract [en]

    Background: The interaction between biotin and avidin is utilized in a wide range of assay and diagnostic systems. A robust material capable of binding biotin should offer scope in the development of reusable assay materials and biosensor recognition elements. Results: Biotin-selective thin (3-5 nm) films have been fabricated on hexadecanethiol self assembled monolayer (SAM) coated Au/quartz resonators. The films were prepared based upon a molecular imprinting strategy where N, N'-methylenebisacrylamide and 2-acrylamido-2-methylpropanesulfonic acid were copolymerized and grafted to the SAM-coated surface in the presence of biotin methyl ester using photoinitiation with physisorbed benzophenone. The biotinyl moiety selectivity of the resonators efficiently differentiated biotinylated peptidic or carbohydrate structures from their native counterparts. Conclusions: Molecularly imprinted ultra thin films can be used for the selective recognition of biotinylated structures in a quartz crystal microbalance sensing platform. These films are stable for periods of at least a month. This strategy should prove of interest for use in other sensing and assay systems.

  • 6.
    Olsson, Viktoria
    et al.
    Kristianstad University.
    Nyberg, Maria
    Kristianstad University.
    Pajalic, Zada
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Kristianstad University.
    Örtman, Gerd
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Westergren, Albert
    Kristianstad University.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wendin, Karin
    Kristianstad University.
    Designing meals for elderly with eating difficulties: a cooperative approach.2014Conference paper (Other academic)
  • 7.
    Moll, Guido
    et al.
    Karolinska Institutet;Karolinska University Hospital Huddinge.
    Alm, Jessica J.
    Karolinska University Hospital Huddinge.
    Davies, Lindsay C.
    Cardiff University, UK.
    von Bahr, Lena
    Karolinska University Hospital Huddinge.
    Heldring, Nina
    Karolinska University Hospital Huddinge.
    Stenbeck-Funke, Lillemor
    Uppsala University.
    Hamad, Osama A.
    Uppsala University.
    Hinsch, Robin
    Karolinska University Hospital Huddinge.
    Ignatowicz, Lech
    Locke, Matthew
    Cardiff University, UK.
    Lönnies, Helena
    Karolinska Institutet;Karolinska University Hospital Huddinge.
    Lambris, John D.
    University of Pennsylvania School of Medicine, USA.
    Teramura, Yuji
    Uppsala University;The University of Tokyo, Japan.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet;Karolinska University Hospital Huddinge.
    Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties?2014In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 32, no 9, p. 2430-2442Article in journal (Refereed)
    Abstract [en]

    We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties. Freeze-thawed MSCs demonstrated reduced responsiveness to proinflammatory stimuli, an impaired production of anti-inflammatory mediators, increased triggering of the IBMIR, and a strong activation of the complement cascade compared to fresh cells. This resulted in twice the efficiency in lysis of thawed MSCs after 1 hour of serum exposure. We found a 50% and 80% reduction in viable cells with freshly detached as opposed to thawed in vitro cells, indicating a small benefit for fresh cells. In evaluation of clinical response, we report a trend that fresh cells, and cells of low passage, demonstrate improved clinical outcome. Patients treated with freshly harvested cells in low passage had a 100% response rate, twice the response rate of 50% observed in a comparable group of patients treated with freeze-thawed cells at higher passage. We conclude that cryobanked MSCs have reduced immunomodulatory and blood regulatory properties directly after thawing, resulting in faster complement-mediated elimination after blood exposure. These changes seem to be paired by differences in therapeutic efficacy in treatment of immune ailments after hematopoietic stem cell transplantation. Stem Cells 2014;32:2430–2442

  • 8.
    Sandholm, Kerstin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Henningsson, Anna J.
    Linköping University.
    Säve, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bergström, Sven
    Umeå University.
    Forsberg, Pia
    Linköping University.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ernerudh, Jan
    Linköping University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e108013-Article in journal (Refereed)
    Abstract [en]

    Aim: Here we investigated the role of complement activation in phagocytosis and the release of cytokines and chemokines in response to two clinical isolates: Borrelia afzelii K78, which is resistant to complement-mediated lysis, and Borrelia garinii LU59, which is complement-sensitive. Methods: Borrelia spirochetes were incubated in hirudin plasma, or hirudin-anticoagulated whole blood. Complement activation was measured as the generation of C3a and sC5b-9. Binding of the complement components C3, factor H, C4, and C4BP to the bacterial surfaces was analyzed. The importance of complement activation on phagocytosis, and on the release of cytokines and chemokines, was investigated using inhibitors acting at different levels of the complement cascade. Results: 1) Borrelia garinii LU59 induced significantly higher complement activation than did Borrelia afzelii K78. 2) Borrelia afzelii K78 recruited higher amounts of factor H resulting in significantly lower C3 binding. 3) Both Borrelia strains were efficiently phagocytized by granulocytes and monocytes, with substantial inhibition by complement blockade at the levels of C3 and C5. 4) The release of the pro-inflammatory cytokines and chemokines IL-1 beta, IL-6, TNF, CCL20, and CXCL8, together with the anti-inflammatory IL-10, were increased the most (by>10-fold after exposure to Borrelia). 5) Both strains induced a similar release of cytokines and chemokines, which in contrast to the phagocytosis, was almost totally unaffected by complement blockade. Conclusions: Our results show that complement activation plays an important role in the process of phagocytosis but not in the subsequent cytokine release in response to live Borrelia spirochetes.

  • 9.
    Tetko, Igor V.
    et al.
    German Research Center for Environmental Health, Germany.
    Schramm, Karl-Werner
    German Research Center for Environmental Health, Germany.
    Knepper, Thomas
    Fresenius University of Applied Sciences, Germany.
    Peijnenburg, Willie J. G. M.
    National Institute for Public Health and the Environment - RIVM, Netherlands;Leiden University, Netherlands.
    Hendriks, A. Jan
    Radboud University Nijmegen, Netherlands.
    Navas, Jose M.
    Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria INIA, Spain.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Öberg, Tomas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Todeschini, Roberto
    University of Milano-Bicocca, Italy.
    Schlosser, Eva
    German Research Center for Environmental Health, Germany.
    Brandmaier, Stefan
    German Research Center for Environmental Health, Germany.
    Experimental and theoretical studies in the EU FP7 Marie Curie Initial Training Network Project, Environmental ChemOinformatics (ECO)2014In: ATLA (Alternatives to Laboratory Animals), ISSN 0261-1929, Vol. 42, no 1, p. 7-11Article in journal (Other academic)
  • 10.
    Golker, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fundamental Studies on Molecularly Imprinted Materials2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis focuses on fundamental studies aimed at elucidating factors that influence molecularly imprinted polymer (MIP) formation and ligand recognition. To this end, a series of computational techniques, in particular chemometrics and molecular dynamics (MD) in conjunction with polymer synthesis and physical characterization studies have been employed.

     

    In Paper I, the multivariate analysis method principal component analysis (PCA) was used to investigate the role of incubation media on polymer-ligand recognition, and results highlighted the importance of several solvent parameters on recognition. In Paper II, all-component MD simulations were used to examine the role of polymerization mixture stoichiometry on MIP-template recognition. Correlations between nature and extent of template complexation and recognition were observed. The influence of the acidic functionality of the methacrylic acid used in these polymers on polymer-template recognition and morphology was examined in Paper III. PCA was then used in Paper IV to identify relationships between interactions in the pre-polymerization mixture, polymer functionality, recognition and morphology using the polymers described in Paper II and III.

  • 11.
    Suriyanarayanan, Subramanian
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nawaz, Hazrat
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ndizeye, Natacha
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Hierarchical Thin Film Architectures for Enhanced Sensor Performance: Liquid Crystal-Mediated Electrochemical Synthesis of Nanostructured Imprinted Polymer Films for the Selective Recognition of Bupivacaine2014In: Biosensors, ISSN 2079-6374, Vol. 4, no 2, p. 90-110Article in journal (Refereed)
    Abstract [en]

    Nanostructured bupivacaine-selective molecularly imprinted 3-aminophenylboronic acid-p-phenylenediamine co-polymer (MIP) films have been prepared on gold-coated quartz (Au/quartz) resonators by electrochemical synthesis under cyclic voltammetric conditions in a liquid crystalline (LC) medium (triton X-100/water). Films prepared in water and in the absence of template were used for control studies. Infrared spectroscopic studies demonstrated comparable chemical compositions for LC and control polymer films. SEM studies revealed that the topologies of the molecularly imprinted polymer films prepared in the LC medium (LC-MIP) exhibit discernible 40 nm thick nano-fiber structures, quite unlike the polymers prepared in the absence of the LC-phase. The sensitivity of the LC-MIP in a quartz crystal microbalance (QCM) sensor platform was 67.6 ± 4.9 Hz/mM under flow injection analysis (FIA) conditions, which was ≈250% higher than for the sensor prepared using the aqueous medium. Detection was possible at 100 nM (30 ng/mL), and discrimination of bupivacaine from closely related structural analogs was readily achieved as reflected in the corresponding stability constants of the MIP-analyte complexes. The facile fabrication and significant enhancement in sensor sensitivity together highlight the potential of this LC-based imprinting strategy for fabrication of polymeric materials with hierarchical architectures, in particular for use in surface-dependent application areas, e.g., biomaterials or sensing.

  • 12.
    Kumar, Jitender
    et al.
    Uppsala University.
    Lind, P. Monica
    Uppsala University.
    Salihovic, Samira
    Uppsala University.
    van Bavel, Bert
    Örebro University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Lind, Lars
    Uppsala University.
    Ingelsson, Erik
    Uppsala University.
    Influence of persistent organic pollutants on the complement system in a population-based human sample2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 71, p. 94-100Article in journal (Refereed)
    Abstract [en]

    Background: Persistent organic pollutants (POPS) are toxic compounds generated through various industrial activities and have adverse effects on human health. Studies performed in cell cultures and animals have revealed that POPs can alter immune-system functioning. The complement system is part of innate immune system that helps to clear pathogens from the body. We performed a large-scale population-based study to find out associations between summary measures of different POPs and different complement system markers. Methods: In this cross-sectional study, 16 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, octachloro-p-dibenzodioxin, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were analyzed for their association with levels of protein complement 3 (C3), 3a (C3a), 4 (C4) and C3a/C3 ratio. A total of 992 individuals (all aged 70 years, 50% females) were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. Regression analysis adjusting for a variety of confounders was performed to study the associations of different POP exposures (total toxic equivalency value or TEQ and sum of 16 PCBs) with protein complements. Results: The TEQ values were found to be positively associated with C3a (beta = 0.07, 95% CI = 0.017-0.131, p = 0.01) and C3a/C3 ratio (beta = 0.07, 95% Cl = 0.015-0.126, p = 0.01) taking possible confounders into account. The association observed was mainly driven by PCB-126. Conclusion: In this study involving 992 elderly individuals from the general population, we showed that POPs, mainly PCB-126, were associated with levels of complement system markers indicating that the association of these toxic compounds with downstream disease could be mediated by activation of immune system. (C) 2014 Elsevier Ltd. All rights reserved.

  • 13.
    Bustin, Stephen A.
    et al.
    Anglia Ruskin University, UK.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Iba, Michael
    Rutgers University, USA.
    International Journal of Molecular Science Best Paper Award 20142014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 1, p. 1683-1685Article in journal (Other academic)
  • 14.
    Klapper, Yvonne
    et al.
    Uppsala University.
    Hamad, Osama A.
    Uppsala University.
    Teramura, Yuji
    Uppsala University.
    Leneweit, Gero
    Assoc Promot Canc Therapy, Germany.
    Nienhaus, G. Ulrich
    Karlsruhe Inst Technol KIT, Germany.
    Ricklin, Daniel
    Univ Penn, USA.
    Lambris, John D.
    Univ Penn, USA.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 11, p. 3688-3696Article in journal (Refereed)
    Abstract [en]

    Liposomes are becoming increasingly important as drug delivery systems, to target a drug to specific cells and tissues and thereby protecting the recipient from toxic effects of the contained drug. Liposome preparations have been described to activate complement. In this study, we have investigated complement activation triggered by neutral dimyristoyl-phosphocholine (DMPC) liposomes in human plasma and whole-blood systems. Incubation in plasma led to the generation of complement activation products (C3a and sC5b-9). Unexpectedly, investigations of surface-bound C3 revealed contact activated, conformationally changed C3 molecules on the liposomes. These changes were characterized by Western blotting with C3 monoclonal antibodies, and by incubating liposomes with purified native C3 and factors I and H. Quartz crystal microbalance analysis confirmed binding of C3 to planar DMPC surfaces. In addition, we demonstrated that DMPC liposomes bound to or were phagocytized by granulocytes in a complement-dependent manner, as evidenced by the use of complement inhibitors. In summary, we have shown that C3 is activated both by convertase-dependent cleavage, preferentially in the fluid phase, by mechanisms which are not well elucidated, and also by contact activation into C3(H2O) on the DMPC surface. In particular, this contact activation has implications for the therapeutic regulation of complement activation during liposome treatment. (C) 2013 Elsevier Ltd. All rights reserved.

  • 15.
    Cleland, Dougal
    et al.
    The University of Newcastle, Australia.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    McCluskey, Adam
    The University of Newcastle, Australia.
    Molecular dynamics approaches to the design and synthesis of PCB targeting molecularly imprinted polymers: interference to monomer-template interactions in imprinting of 1,2,3-trichlorobenzene2014In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 12, no 5, p. 844-853Article in journal (Refereed)
    Abstract [en]

    The interactions between each component of the pre-polymerisation mixtures used in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5-pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four molecular dynamics simulations. These simulations revealed that the relative frequency of functional monomer template (FM T) interactions was consistent with results obtained by the synthesis and evaluation of the actual MIPs. The higher frequency of 1 interaction with tri-methylstyrene (TMS; 54.7%) than 1 interaction with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%) also correlated well with the observed differences in IF (3.7) of 2 MIPs imprinted using PFS as the FM than the IF (2,8) of 2 MIPs imprinted using TMS as the FM. The TMS-1 interaction dominated the molecular simulation due to high interaction energies, but the weaker TMS-2 resulted in low interaction maintenance, and thus lower IF values. Examination of the other pre-polymerisation mixture components revealed that the low levels of TMS-2 interaction was, in part, due to interference caused by the cross linker (CL) ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason was, however, attributed to MeOH interactions with TMS in both a hydrogen bond and perpendicular configuration. This positioned a MeOH directly above the it-orbital of all TMS for an average of 63.8% of MD2 creating significant interference to pi-pi stacking interactions between 2 and TMS. These findings are consistent with the deviation from the 'normal' molecularly imprinted polymer synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29 observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations correctly predicted the high level of interference from other MIP synthesis components. The effect on PFS-1 interaction by MeOH was significantly lower and thus this system was not adversely affected.

  • 16.
    Whitcombe, Michael J.
    et al.
    Univ Leicester, UK.
    Kirsch, Nicole
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Molecular imprinting science and technology: a survey of the literature for the years 2004-20112014In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 27, no 6, p. 297-401Article, review/survey (Refereed)
    Abstract [en]

    Herein, we present a survey of the literature covering the development of molecular imprinting science and technology over the years 2004-2011. In total, 3779 references to the original papers, reviews, edited volumes and monographs from this period are included, along with recently identified uncited materials from prior to 2004, which were omitted in the first instalment of this series covering the years 1930-2003. In the presentation of the assembled references, a section presenting reviews and monographs covering the area is followed by sections describing fundamental aspects of molecular imprinting including the development of novel polymer formats. Thereafter, literature describing efforts to apply these polymeric materials to a range of application areas is presented. Current trends and areas of rapid development are discussed. Copyright (c) 2014 John Wiley & Sons, Ltd.

  • 17.
    ten Siethoff, Lasse
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Lard, Mercy
    Lund university.
    Generosi, Johanna
    Lund university.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Lund university.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Molecular Motor Propelled Filaments Reveal Light-Guiding in Nanowire Arrays for Enhanced Biosensing2014In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 14, no 2, p. 737-742Article in journal (Refereed)
    Abstract [en]

    Semiconductor nanowire arrays offer significant potential for biosensing applications with optical read-out due to their high surface area and due to the unique optical properties of one-dimensional materials. A challenge for optical read-out of analyte-binding to the nanowires is the need to efficiently collect and detect light from a three-dimensional volume. Here we show that light from fluorophores attached along Several mu m long vertical Al2O3 coated gallium phosphide nanowires couples into the wires, is guided along them and emitted at the tip. This enables effective collection of light emitted by fluorescent analytes located at different focal planes along the nanowire. We unequivocally demonstrate the light-guiding effect using a novel method whereby the changes in emitted fluorescence intensity are observed when fluorescent cytoskeletal filaments are propelled by molecular motors along the wires. The findings are discussed in relation to nanobiosensor developments, other nanotechnological applications, and fundamental studies of motor function.

  • 18.
    Shoravi, Siamak
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    On the Influence of Crosslinker on Template Complexation in Molecularly Imprinted Polymers: A Computational Study of Prepolymerization Mixture Events with Correlations to Template-Polymer Recognition Behavior and NMR Spectroscopic Studies2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 6, p. 10622-10634Article in journal (Refereed)
    Abstract [en]

    Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contribution of crosslinker to determining the nature of molecularly imprinted polymer-template selectivity.

  • 19.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Rhodium-Catalyzed Oxidative Perfluoroalkenylation by Carbonyl Group Directed C-H Bond Activation2014In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 32, p. 7211-7219Article in journal (Refereed)
    Abstract [en]

    The selective activation of C-H bonds under mild Rh-III catalytic conditions has been developed for the perfluoroalkenylation of various cyclic and acyclic aromatic ketones. This protocol uses versatile reagents and mild conditions. It requires a very low catalyst loading and has exceptional functional group tolerance as well as provides products in good to excellent yields. An application of this approach was described for the preparation of perfluoroethyl acrylate derivatives of biologically active substances.

  • 20.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Rhodium(III)-catalysed aerobic synthesis of highly functionalized indoles from N-arylurea under mild conditions through C-H activation2014In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 50, no 95, p. 14964-14967Article in journal (Refereed)
    Abstract [en]

    A Rh(III) catalysed amino arylation of alkynes using copper as the terminal oxidant for regeneration of the catalytically active species under aerobic conditions is described. This novel C-H activation reaction was applied to the synthesis of a wide range of substituted indoles from N-arylureas.

  • 21.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Ctr Biomat Chem.
    Structural and computational insights into the versatility of cadmium binding to proteins2014In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 43, no 7, p. 2878-2887Article in journal (Refereed)
    Abstract [en]

    Cadmium is a highly toxic group XII metal, similar to zinc and mercury. Unlike zinc, which is one of the most common metal cofactors in biology, cadmium is highly toxic. Many Zn2+-binding proteins can bind Cd2+-ions without significantly affecting their structures. Here, the protein data bank is analysed with regard to protein-cadmium interactions, which shows that cadmium can bind to a variety of ion binding sites in proteins. Statistical analysis of Cd2+-side chain interactions is compared with a similar analysis of other ions. This analysis reveals that with regard to amino acid side-chain preference, Cd2+ is more similar to Mn2+ than to Zn2+ or Hg2+. Finally, the interaction energies of three native metal binding proteins are calculated where Cd2+ binds instead of Zn2+, Ca2+ or Cu2+. The interaction energies are decomposed into individual components whose contributions are discussed.

  • 22.
    Nilsson, Bo
    et al.
    Uppsala University.
    Teramura, Yuji
    Uppsala University;University of Tokyo.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    The role and regulation of complement activation as part of the thromboinflammation elicited in cell therapies2014In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 61, no 2, p. 185-190Article, review/survey (Refereed)
    Abstract [en]

    Cell therapies in which the cells come into direct contact with blood and other body fluids are emerging treatment procedures for patients with various diseases, such as diabetes mellitus, liver insufficiency, and graft-versus-host disease. However, despite recent progress, these procedures are associated with tissue loss caused by thromboinflammatory reactions. These deleterious reactions involve the activation of the complement and coagulation cascades and platelet and leukocyte activation, ultimately resulting in clot formation and damage to the implanted cells. In this concept review, we discuss the basic mechanisms underlying the thrombininflammatory process, with special reference to the engagement of complement and emerging strategies for the therapeutic regulation of these reactions that include the use of selective systemic inhibitors and various procedures to coat the surfaces of the cells. The coating procedures may also be applied to other treatment modalities in which similar mechanisms are involved, including whole organ transplantation, treatment with biomaterials in contact with blood, and extracorporeal procedures. (C) 2014 Published by Elsevier Ltd.

  • 23.
    Chavan, Swapnil
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ballabio, Davide
    University of Milano-Bicocca, Italy.
    Consonni, Viviana
    University of Milano-Bicocca, Italy.
    Todeschini, Roberto
    University of Milano-Bicocca, Italy.
    Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 10, p. 18162-18174Article in journal (Refereed)
    Abstract [en]

    A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  • 24.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University of Zürich, Switzerland.
    Caflisch, Amedeo
    University of Zürich, Switzerland.
    Wild type and mutants of the HET-s(218-289) prion show different flexibility at fibrillar ends: A simulation study2014In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 82, no 3, p. 399-404Article in journal (Refereed)
    Abstract [en]

    The C-terminal segment (residues 218–289) of the HET-s protein of the filamentous fungus Podosporina anserina is a prion-forming domain. The structural model of the HET-s(218–289) amyloid fibril based on solid-state nuclear magnetic resonance (NMR) restraints shows a β solenoid topology which is comprised of a β-sheet core and interconnecting loops. For the single-point mutants Phe286Ala and Trp287Ala, slower aggregation rates in vitro and loss of prionic infectivity have been reported recently. Here we have used molecular dynamics to compare the flexibility of the mutants and wild type. The simulations, initiated from a trimeric aggregate extracted from the NMR structural model, show structural stability on a 100-ns time scale for wild type and mutants. Analysis of the fluctuations along the simulations reveals that the mutants are less flexible than the wild type in the C-terminal segment at only one of the two external monomers. Analysis of interaction energy and buried accessible surface indicates that residue Phe286 in particular is stabilized in the Trp287Ala mutant. The simulation results provide an atomistic explanation of the suggestion (based on indirect experimental evidence) that flexibility at the protofibril end(s) is required for fibril elongation. Moreover, they provide further evidence that the growth of the HET-s amyloid fibril is directional.

1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf