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  • 151.
    Andersson, Claes
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Microsomal glutathione transferase: Species characteristics, catalysis and topology1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The membrane-bound detoxication enzyme microsomal glutathione transferase is localized predominantly in the liver of mammalian species, where it is present in high concentrations in the endoplasmic reticulum and the outer mitochondrial membrane. The enzyme conjugates a broad range of hydrophobic xenobiotics bearing reactive electrophilic centers to glutathione, which facilitates deactivation and excretion.

    The microsomal glutathione transferase activity is increased several-fold upon the addition of sulfhydryl reagents, as well as by partial proteolysis. This unique property could reflect a mechanism of regulation of the enzyme in vivo. The microsomal glutathione transferase was purified from mouse and human liver and found to be similar to the rat enzyme in its structural properties, its activity profile and its ability to be activated by sulfhydryl reagents. The human enzyme displayed glutathione peroxidase/transferase activity towards products of lipid peroxidation, indicative of a functional role in protection against lipid peroxidation.

    The histidine-specific reagent diethylpyrocarbonate (DEPC) rapidly inactivated the microsomal glutathione transferase and it was shown that 90 % of the activity was lost within the time period required for modification of the most reactive histidine. Inclusion of the substrate analogue S-hexylglutathione decreased the inactivation rate, indicating a functional importance for this histidine residue. Data is also presented which supports the involvement of arginine and lysine residue(s) in catalysis.

    A random sequential catalytic mechanism could be defined for the microsomal glutathione transferase by the use of alternate substrate diagnosis. Chemical catalysis appears to rely on the lowering of the pKa of the thiol in glutathione to approximately 6.4. Activation of the enzyme was found to increase the catalytic efficiency towards a much broader range of substrates than was previously realized. This can be considered as a well-suited defence mechanism against toxic insult by electrophiles, when glutathione levels are usually decreased.

    The thiol substrate specificity of microsomal glutathione transferase was investigated by the use of one glycyl- and eight y-glutamyl-modified glutathione analogues. The a-amino group of the glutamyl residue was demonstrated to be of preferential functional importance for the activity of the activated enzyme. The a-carboxyl of the glutamyl residue is obligatory for activity as demonstrated by the lack of activity with the descarboxy analogue 4-Abu-L-Cys-Gly. It was also noted that the activated microsomal glutathione transferase is more selective towards the thiol substrates than is the unactivated enzyme.

    By comparing the tryptic cleavage products from intact and permeabilized microsomes, it was shown that the lysine-4 of the enzyme is located at the luminal side of the endoplasmic reticulum, whereas lysine-41 faces the cytosol. A hydrophobic stretch (positions 11-35) is the likely membranespanning region and additional membrane association is indicated. The active site, as well as the site of activation (cysteine-49), were demonstrated to face the cytosol.

  • 152.
    Andersson, Dan I
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Nicoloff, Hervé
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hjort, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mechanisms and clinical relevance of bacterial heteroresistance2019Inngår i: Nature Reviews Microbiology, ISSN 1740-1526, E-ISSN 1740-1534, Vol. 17, nr 8, s. 479-496Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Antibiotic heteroresistance is a phenotype in which a bacterial isolate contains subpopulations of cells that show a substantial reduction in antibiotic susceptibility compared with the main population. Recent work indicates that heteroresistance is very common for several different bacterial species and antibiotic classes. The resistance phenotype is often unstable, and in the absence of antibiotic pressure it rapidly reverts to susceptibility. A common mechanistic explanation for the instability is the occurrence of genetically unstable tandem amplifications of genes that cause resistance. Due to their instability, low frequency and transient character, it is challenging to detect and study these subpopulations, which often leads to difficulties in unambiguously classifying bacteria as susceptible or resistant. Finally, in vitro experiments, mathematical modelling, animal infection models and clinical studies show that the resistant subpopulations can be enriched during antibiotic exposure, and increasing evidence suggests that heteroresistance can lead to treatment failure.

  • 153.
    Andersson, David C.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Martinez, N.
    Zeller, D.
    Rondahl, S. H.
    Koza, M. M.
    Frick, B.
    Ekstrom, F.
    Peters, J.
    Linusson, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Changes in dynamics of alpha-chymotrypsin due to covalent inhibitors investigated by elastic incoherent neutron scattering2017Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, nr 37, s. 25369-25379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An essential role of enzymes is to catalyze various chemical reactions in the human body and inhibition of the enzymatic activity by small molecules is the mechanism of action of many drugs or tool compounds used to study biological processes. Here, we investigate the effect on the dynamics of the serine protease alpha-chymotrypsin when in complex with two different covalently bound inhibitors using elastic incoherent neutron scattering. The results show that the inhibited enzyme displays enhanced dynamics compared to the free form. The difference was prominent at higher temperatures (240-310 K) and the type of motions that differ include both small amplitude motions, such as hydrogen atom rotations around a methyl group, and large amplitude motions, such as amino acid side chain movements. The measurements were analyzed with multivariate methods in addition to the standard univariate methods, allowing for a more in-depth analysis of the types of motions that differ between the two forms. The binding strength of an inhibitor is linked to the changes in dynamics occurring during the inhibitor-enzyme binding event and thus these results may aid in the deconvolution of this fundamental event and in the design of new inhibitors.

  • 154. Andersson, E.
    et al.
    Stenrup, Michael
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi (stängd 20110512).
    Eland, J.H.D.
    Hedin, L.
    Berglund, M.
    Karlsson, L.
    Larson, Åsa
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi (stängd 20110512).
    Ågren, Hans
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi (stängd 20110512).
    Rubensson, Jan Erik
    Feifel, Raimund
    Single-photon core-valence double ionization of molecular oxygen2008Inngår i: Physical Review A. Atomic, Molecular, and Optical Physics, ISSN 1050-2947, E-ISSN 1094-1622, Vol. 78, nr 2, s. 023409-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 155.
    Andersson, Hans O.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Fridborg, Kerstin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Löwgren, Seved
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Alterman, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Mühlman, Anna
    Björsne, Magnus
    Garg, Neeraj
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Kvarnström, Ingemar
    Schaal, Wesley
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Classon, Björn
    Karlén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Ahlsén, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Nillroth, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Vrang, Lotta
    Öberg, Bo
    Samuelsson, Bertil
    Hallberg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Unge, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors2003Inngår i: European Journal of Biochemistry, ISSN 0014-2956, E-ISSN 1432-1033, Vol. 270, nr 8, s. 1746-1758Artikkel i tidsskrift (Fagfellevurdert)
  • 156.
    Andersson, Helene
    et al.
    KTH, Tidigare Institutioner, Bioteknologi.
    van den Berg, A.
    Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities2004Inngår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 4, nr 2, s. 98-103Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

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

  • 157.
    Andersson, Helene
    et al.
    KTH, Tidigare Institutioner, Signaler, sensorer och system.
    van den Berg, A.
    Microtechnologies and nanotechnologies for single-cell analysis2004Inngår i: Current Opinion in Biotechnology, ISSN 0958-1669, E-ISSN 1879-0429, Vol. 15, nr 1, s. 44-49Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

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

  • 158.
    Andersson, Håkan S.
    Högskolan i Kalmar, Naturvetenskapliga institutionen. Lund University, Sweden.
    On the Nature and Origin of Recognition in Molecularly Imprinted Polymers.: Paths Towards Their Rational Design.1997Licentiatavhandling, monografi (Annet vitenskapelig)
  • 159.
    Andersson, Håkan S.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Towards the Rational Design of Molecularly Imprinted Polymers1999Doktoravhandling, med artikler (Annet vitenskapelig)
  • 160.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    Sundberg, Per
    University of Gothenburg.
    Rosengren, K. Johan
    University of Queensland.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?2016Inngår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82, nr Supplement 1, artikkel-id P549Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.

  • 161.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Uppsala university.
    Jacobsson, Erik
    Uppsala University.
    Laborde, Quentin
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Rosengren, K. Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides - a novel family of nemertean peptide neurotoxins2018Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    We recently discovered a novel family of neuroactive peptides in nemerteans, which we have named alpha-nemertides (1). One of these peptides, nemertide alpha-1, has been the subject of detailed studies with regard to structure and effects. The peptide exhibits exceptional potency against a number of arthropod species. Moreover, in vitro experiments suggest that alpha-1 acts primarily on voltage-gated sodium channels, and that this action is selective for arthropods by two orders of magnitude over vertebrate species. Using transcriptomic and proteomic approaches, we have identified 10 alpha-nemertides, but this number is likely to increase. These peptides alongside with a series of mutants are currently under evaluation by our group, with the goal to improve our understanding of structure-function relationships. In addition, we are considering potential practical uses of alpha-nemertides. In this talk, I will describe the current status of this research project.

    1. E. Jacobsson et al., Peptide ion channel toxins from the bootlace worm, the longest animal on Earth. Scientific reports 8, 4596 (2018).

  • 162.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Rosengren, K. Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Discovery of novel ion-channel active peptide toxins in a North Sea Ribbon Worm2016Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis [1]. In addition, their epidermis contains thick mucus of similar toxic constitution. One very potent toxin reported in ribbon worm mucus is tetrodotoxin (TTX). However, despite significant efforts, Strand et al. [2] were unable to detect any TTX, neither in the mucus of the ribbon worm Lineus longissimus, nor from Vibrio alginolyticus cultures isolated from and cultivated in the mucus. These observations challenged the notion of general presence of TTX in ribbon worm mucus, and prompted us to look for other toxins [3]. Using LC-MS analysis of mucus extracts, we identified three peptides present in significant amounts. The peptides were sequenced using a combination of MS/MS analysis and transcriptomics, and whereas one of them strongly resembles the only peptide toxin previously characterized from ribbon worms, Neurotoxin B-IV [4], the other two were found to represent a previously unknown class of peptide toxins. The most abundant of these was synthesized, and its 3D structure determined. Preliminary toxicity tests on shore crab (C. maenas) indicated toxicity (through paralysis) on par with that of TTX. Further analyses have indicated that its toxic effects are due to binding to voltage sensitive sodium channels.

     

    With L. longissimus as our primary target, we are now mapping the presence of peptide toxins in ribbon worms, with the objectives to establish routes for synthesis, and to characterize the biological activities and structures of these peptides. The number of peptides of this novel class is increasing, and synthesis and characterization is well underway. The striking potencies of these peptides make them potentially amenable as novel insecticidal or anthelmintic leads, pharmacological tools or in biotechnology applications.

     

    References

    1. Strand M, Sundberg P. Nationalnyckeln till Sveriges flora och fauna [DO-DP]. Stjärnmaskar-Slemmaskar: Sipuncula-Nemertea: Artdatabanken, SLU; 2010.

    2. Strand M, Hedstrom M, Seth H, McEvoy EG, Jacobsson E, Goransson U, Andersson HS, Sundberg P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive? Marine Drugs. 2016;14(4).

    3. Strand M, Andersson HS. Slemmaskens hemlighet. Forskning & Framsteg. 2016;(2):26-33.

    4. Blumenthal KM, Kem WR. Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. The Journal of Biological Chemistry. 1976;251(19):6025-9.

  • 163.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Rosengren, K. Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Mapping the diversity of nemertean peptide toxins2018Konferansepaper (Annet vitenskapelig)
  • 164.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Peigneur, Steve
    University of Leuven (KU Leuven), Belgium.
    Lebbe, Eline
    University of Leuven (KU Leuven), Belgium.
    Rosengren, K. Johan
    University of Queensland.
    Tytgat, Jan
    University of Leuven (KU Leuven), Belgium.
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides, a novel family of marine peptide neurotoxins from ribbon worms2017Konferansepaper (Annet vitenskapelig)
  • 165.
    Andersson, Inger
    et al.
    Department of Molecular Biology, Swedish University of Agricultural Sciences.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Structure and function of Rubisco2008Inngår i: Plant physiology and biochemistry (Paris), ISSN 0981-9428, E-ISSN 1873-2690, Vol. 46, nr 3, s. 275-291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the major enzyme assimilating CO2 into the biosphere. At the same time Rubisco is an extremely inefficient catalyst and its carboxylase activity is compromised by an opposing oxygenase activity involving atmospheric O2. The shortcomings of Rubisco have implications for crop yield, nitrogen and water usage, and for the global carbon cycle. Numerous high-resolution crystal structures of different forms of Rubisco are now available, including structures of mutant enzymes. This review uses the information provided in these structures in a structure-based sequence alignment and discusses Rubisco function in the context of structural variations at all levels – amino acid sequence, fold, tertiary and quaternary structure – with an evolutionary perspective and an emphasis on the structural features of the enzyme that may determine its function as a carboxylase.

  • 166.
    Andersson, Jan O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Eukaryotic gene transfer: adaptation and replacements2008Inngår i: Horizontal Gene Transfer in the Evolution of Pathogenesis / [ed] Michael Hensel, Herbert Schmidt, Cambridge: Cambridge University Press , 2008, s. 293-316Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 167.
    Andersson, Jan O
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Andersson, Siv GE
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Pseudogenes, junk DNA, and the dynamics of Rickettsia genomes2001Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 18, nr 5, s. 829-839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies of neutrally evolving sequences suggest that differences in eukaryotic genome sizes result from different rates of DNA loss. However, very few pseudogenes have been identified in microbial species, and the processes whereby genes and genomes deteriorate in bacteria remain largely unresolved. The typhus-causing agent, Rickettsia prowazekii, is exceptional in that as much as 24% of its 1.1-Mb genome consists of noncoding DNA and pseudogenes. To test the hypothesis that the noncoding DNA in the R. prowazekii genome represents degraded remnants of ancestral genes, we systematically examined all of the identified pseudogenes and their flanking sequences in three additional Rickettsia species. Consistent with the hypothesis, we observe sequence similarities between genes and pseudogenes in one species and intergenic DNA in another species. We show that the frequencies and average sizes of deletions are larger than insertions in neutrally evolving pseudogene sequences. Our results suggest that inactivated genetic material in the Rickettsia genomes deteriorates spontaneously due to a mutation bias for deletions and that the noncoding sequences represent DNA in the final stages of this degenerative process.

  • 168.
    Andersson, Jessica
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylärbiologi och funktionsgenomik.
    Activation, reaction mechanism and allosteric regulation of the anaerobic ribonucleotide reductase from bacteriophage T42000Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    Ribonucleotide reductase (RNR) catalyse the conversion of ribonucleotides to their corresponding deoxyribonucleotides in all organisms. The deoxyribonucleotides are the building blocks for DNA. Three different classes of RNR are found, class I, II and III. The class I RNRs operate under aerobic conditions, the class III RNRs operate under anaerobic conditions and the class II RNRs are indifferent to oxygen. All classes of RNR catalyse the reaction using a free radical mechanism. The free radical is generated to initiate the reaction mechanism but the generation differs between the classes.

    I have worked with the anaerobic class III RNR from bacteriophage T4 and the work presented in this thesis involves several different aspects of the enzyme. The class III RNR from phage T4 can be used as a model for other class III RNRs.

    From isotope labelling experiments, we show that a stable glycyl radical forms in the phage T4 class III RNR. I used site-directed mutagenesis to locate the glycyl radical to Gly580 in the NrdD protein of the T4 class III RNR. The glycyl radical is absolutely required for enzymatic activity.

    Also using protein engineering, I show for the first time, the importance of cysteines in radical generation and the reaction mechanism of the class III RNRs. Four cysteines in the C-terminal of T4 NrdD are responsible for the last step in the generation of the glycyl radical at Gly580. Two cysteines in the active site of T4 NrdD, Cys79 and Cys290 are required for the reaction mechanism of the enzyme. A third residue within the active site, Asn311 is most likely also important for catalytic activity. A reaction mechanism that is different from the class I and II RNRs has been proposed.

    The first crystal structure of a class III RNR, the class III RNR from phage T4 is presented. Structural relationships with the known class I RNR structure is discussed as well as similarities with another glycyl-radical enzyme.

    Finally, the allosteric regulation of the class III RNR from phage T4 was characterized. Almost all RNRs are allosterically regulated to keep the deoxynucleotide pools balanced in the cell. Similarities to other RNRs as well as a unique feature of the class III RNR from phage T4 is discussed.

  • 169.
    Andersson, Johan
    Växjö universitet, Fakulteten för matematik/naturvetenskap/teknik, Institutionen för teknik och design.
    Hantering av bränsleflis: Enkätundersökning och bedömning av kvalitetsaspekter2008Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Med globalt ökat klimathot och ett ökat användande av biologiskt nedbrytbara material för att bland annat driva vår motorpark och värma våra hus kommer även ett krav på ökat produktion av utsläppsreducerande (koldioxid CO2) material så som biobränsle.

    För att kunna reducera utsläppen krävs inte bara att vi ökar produktionen av biologiskt nedbrytbart ämnen utan att dessa material har de egenskaperna som de förbränningssystem de används till optimalt kräver.

    Ett av de biologiskt nedbrytbara materialen är biobränsle, framställt av skogsavfall (grot). Dess hantering ifrån avverkningstillfället tills in- transport till förbränningen har varit kärnan i detta arbete. De två grundfrågorna som har varit själva motorn i arbetet har kretsat kring;

    o Vem äger vad i olika hanteringssteg?

    o Vem vet vad i olika hanteringssteg?

    Syftet med denna undersökning var att bland annat försöka få reda på svaren på frågorna ovan men även att väcka ett ökat intresse och förståelse kring hanteringen av biobränslet från avverkningstillfället fram till in- transport till en terminal alternativt direkt in till panncentralen.

    Undersökningen gjordes genom en enkätundersökning på Internet. Enkäten skickades ut till berörda parter i Sverige per e-post och adressaterna kunde svara direkt i datorn och skicka tillbaka enkäten utan att skriva ut den. Svaren från Skåne i söder upp till Mälardalen i norr vilket gör att man kan säga att denna undersökning gäller för södra Sverige.

    Fulltekst (pdf)
    FULLTEXT01
  • 170.
    Andersson, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Prefibrillar oligomeric Transthyretin mutants - amyloid conformation, toxicity and association with Serum amyloid P component2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Amyloidoses represent a heterogeneous group of diseases characterized by abnormal protein metabolism leading to extracellular deposition of fibrillar, proteinaceous amyloid in various tissues and organs of the body. To date more than 20 different proteins have been linked to diseases with amyloid depositions, of which Alzheimer’s disease and the prion-associated diseases are the most well known. Despite the origin of protein in the amyloid, the fibrils share some common biochemical and biophysical properties such as a diameter of 8-13 nm, a β-pleated sheet secondary structure packed in an ordered crystal-like way, Congo red and thioflavin binding with characteristic spectroscopic patterns and decoration of the fibrils with Serum amyloid P component and glycoseaminoglycans.

    The plasma protein transthyretin (TTR) is associated with familial amyloidosis with polyneuropathy (FAP) and senile systemic amyloidosis (SSA). FAP is a lethal, autosomal inherited disorder caused by point mutations in the TTR-gene. More than 80 different mutations have been associated with amyloid formation and linked to FAP. The interpretation is that amino acid replacements at different sites of the polypeptide lead to reduced stability. Mutant TTR were constructed that have a strong tendency to self-aggregate under physiological conditions. The precipitates were shown to be amyloid by staining with thioflavin T and Congo red. As the mutants were sensitive to trypsin cleavage compared to plasma TTR, we suggest that the mutants represent amyloid precursors or that they may share structural properties with intermediates on a pathway leading to amyloid deposition. Monoclonal antibodies were generated that exclusively recognize the amyloidogenic folding of TTR providing direct biochemical evidence for a structural change in amyloidogenic intermediates. Two cryptic epitopes were mapped to a domain of TTR, where most mutations associated with amyloidosis occur and is proposed to be displaced at the initial phase of amyloid formation. Amyloidogenic intermediates of TTR were shown to induce a toxic, free radical dependent, response in cultured neuroblastoma cells. Morphological studies revealed a correlation between toxicity (apoptosis) and the presence of immature amyloid suggesting that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism.

    Serum amyloid P component (SAP) is a highly conserved plasma glycoprotein universally found associated with amyloid depositions independently of protein origin. SAP’s role in amyloid formation is contradictory since both inhibition and promotion of aggregation have been shown in the case of fibril formation from the Aβ peptide of Alzheimer’s disease. Amyloidogenic prefibrils of TTR were shown to bind SAP and no interference with aggregation was detected. SAP co-localize in patches with mutant TTR on the surface of neuroblastoma cells and prevent apoptosis induced by mutant TTR and Aβ peptide, while several other molecules known to decorate amyloid fibrils were without effect.

    Fulltekst (pdf)
    FULLTEXT01
  • 171.
    Andersson, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Holm Nielsen, Ellen
    Svehag, SvenErik
    Lundgren, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Only amyloidogenic inermediates of transthyretin induce apoptosis2002Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 294, nr 2, s. 309-314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism. 

  • 172.
    Andersson, Ken G.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Combinatorial Protein Engineering Of Affibody Molecules Using E. Coli Display And Rational Design Of Affibody-Based Tracers For Medical Imaging2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

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

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

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

     

    Fulltekst (pdf)
    20170831 Avhandling Kappa Ken Andersson
  • 173.
    Andersson, Ken G.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Persson, Jonas
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Autotransporter-mediated display of a naïve Affibody library on the outer membrane of E. coliManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

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

  • 174.
    Andersson, Ken G.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Sjöstrand, Nanna
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Coupled release and site-specific conjugation of Affibody molecules from the surface of E. coli using Sortase AManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

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

  • 175.
    Andersson, Malena
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi. Institutionen för biokemi och organisk kemi, Biokemi.
    Mannervik, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi. Institutionen för biokemi och organisk kemi, Biokemi.
    Exploring protein evolution by saturation mutagenesis of the GST M2-2 active site residue 2102005Inngår i: FEBS Journal, Vol. 272, s. 81 Suppl-Artikkel i tidsskrift (Annet vitenskapelig)
  • 176.
    Andersson, Marie
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Elucidation of the product synthesis of the sesquiterpene synthase Cop6 isolated from Coprinus cinereus2009Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Mushrooms are believed to have a great potential for production of bioactive metabolites e. g. terpenes, a group of interesting compounds with diverse chemical properties such as antitumour and antibacterial activity. Cop6 is a terpene cyclase isolated from the mushroom Coprinus cinereus that catalyzes the cyclization of farnesyl diphosphate (FPP) to mainly α-cuprenene. In this study gas chromatography combined with mass spectroscopy (GC-MS) is used to analyze the product profile of Cop6 mutants created by PCR based site directed mutagenesis. The goal is to produce trichodiene, the parent hydrocarbon in the biosynthesis of trichothecene antibiotics and mycotoxins. Valine instead of tyrosine in amino acid position 195 resulted in cyclisation of (E)-β-Farnesene and (3Z,6E)-α-Farnesene besides the products of the wild type enzyme. Another mutant with aspartic acid instead of asparagine in position 224 resulted in the synthesis of β-Bisabolene except for α-cuprenene and methionine in position 74 instead of isoleucine killed the activity of the cyclase. Furthermore, an attempt to saturation of position 98 was made, resulting in four mutants. Two of them essentially killed the activity of the cyclase whereas two had minor effect of the product profile compared to the wild type. 

    Fulltekst (pdf)
    FULLTEXT01
  • 177.
    Andersson, Marie
    Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
    Immunopathogenesis of relapsing fever borreliosis2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Relapsing fever (RF) is caused by different species of Borrelia transmitted by soft ticks or by the human body louse. Illness is characterized by reappearing peaks of high concentrations of spirochetes in blood, concordant with fever peaks separated by asymptomatic periods. Neuroborreliosis is one of the most severe manifestations of RF borreliosis. To understand the immune response during early RF, we analyzed immune cells in brain and kidney of mice infected with B. crocidurae during the acute infection. Our results indicate that brain defense is comprised primarily of innate immune cells. Despite the infiltration of innate immune cells, Borrelia was not completely eradicated. A failure of the host brain to clear the bacteria may give the pathogen a niche where it can persist. Using our mouse model, we revealed that Borrelia duttonii could persist in the mouse brain for up to 270 days, without being present in the circulation. The infection was silent with no change in host gene expression, and the spirochetes could re-enter the circulation after immunosuppression. We propose that the brain is used by the pathogen to evade host immunity and serves as a possible natural reservoir for B. duttonii, a spirochete that has rarely been found in any mammalian host other than man. Borrelia-induced complications during pregnancy have been reported, and are especially common in RF. In our established mouse model of gestational RF, we could show that the fetuses suffered from severe pathology and growth retardation, probably as a consequence of placental destruction. We could also show trans-placental transmission of the bacteria leading to neonatal RF. Surprisingly, pregnant dams had a lower bacterial load and less severe disease, showing that pregnancy has a protective effect during RF. We have used the gestational RF model to investigate host factors favoring disease resolution. Because the spleen is the primary organ responsible for trapping and removing blood-borne pathogens, we have compared temporal changes in spleen immune cell populations and cytokine/chemokine induction during the infection. Spleens of pregnant mice had earlier neutrophil infiltration, as well as faster and higher production of pro-inflammatory mediators. This rapid, robust response suggests a more effective host defense. Thus, an enhanced pro-inflammatory response during pregnancy imparts a distinct advantage in controlling the severity of relapsing fever infection.

    Fulltekst (pdf)
    FULLTEXT01
  • 178. Andersson, Marlene
    et al.
    Chen, Gefei
    Otikovs, Martins
    Landreh, Michael
    Nordling, Kerstin
    Kronqvist, Nina
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Jornvall, Hans
    Knight, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Struktur- och molekylärbiologi.
    Ridderstrale, Yvonne
    Holm, Lena
    Meng, Qing
    Jaudzems, Kristaps
    Chesler, Mitchell
    Johansson, Jan
    Rising, Anna
    Carbonic Anhydrase Generates CO2 and H+ That Drive Spider Silk Formation Via Opposite Effects on the Terminal Domains2014Inngår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 12, nr 8, s. e1001921-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spider silk fibers are produced from soluble proteins (spidroins) under ambient conditions in a complex but poorly understood process. Spidroins are highly repetitive in sequence but capped by nonrepetitive N- and C-terminal domains (NT and CT) that are suggested to regulate fiber conversion in similar manners. By using ion selective microelectrodes we found that the pH gradient in the silk gland is much broader than previously known. Surprisingly, the terminal domains respond in opposite ways when pH is decreased from 7 to 5: Urea denaturation and temperature stability assays show that NT dimers get significantly stabilized and then lock the spidroins into multimers, whereas CT on the other hand is destabilized and unfolds into ThT-positive beta-sheet amyloid fibrils, which can trigger fiber formation. There is a high carbon dioxide pressure (pCO(2)) in distal parts of the gland, and a CO2 analogue interacts with buried regions in CT as determined by nuclear magnetic resonance (NMR) spectroscopy. Activity staining of histological sections and inhibition experiments reveal that the pH gradient is created by carbonic anhydrase. Carbonic anhydrase activity emerges in the same region of the gland as the opposite effects on NT and CT stability occur. These synchronous events suggest a novel CO2 and proton-dependent lock and trigger mechanism of spider silk formation.

    Fulltekst (pdf)
    fulltext
  • 179.
    Andersson, Martin
    Stockholms universitet.
    Structural studies and design of Di-iron carboxylate proteins2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Di-iron carboxylate proteins perform a wide range of chemical reactions in the cell. These reactions often involve activation of dioxygen to generate highly oxidative species that can be used in catalysis. One member of the di-iron carboxylate family is the enzyme ribonucleotide reductase (RNR). This enzyme is essential for DNA synthesis since it is a key enzyme on the pathway for de-novo synthesis of deoxyribonucleotides, the building blocks of DNA. To perform its catalytic function RNR is dependent on a protein radical. In this thesis I have used x-ray crystallographic methods to investigate the mechanism of O2 activation and radical generation in the R2 subunit of RNR. These structural studies have lead to a proposal of a detailed mechanism, which could be common to most O2 activating di-iron carboxylate proteins. The alternative oxidase is a membrane protein that has been proposed to belong to the di-iron carboxylate family. This protein is a ubiquinol/oxygen oxidoreductase and can act as a terminal electron acceptor in the respiratory chain. I have used homology modelling to make a structural model of this enzyme, which provides new insights into its functions and its relationship to the other di-iron carboxylate proteins.

    Given the strong oxidative power of the di-iron carboxylate proteins they would be very useful as oxidants in various industrial applications. Another part of my project has been aimed towards the design of a di-iron carboxylate enzyme tailored for industrial and environmental applications using a small and stable di-iron carboxylate protein as a starting framework, namely the bacterioferritin protein. This work has lead to the synthesis of a gene library with many potential enzymatic activities.

  • 180.
    Andersson, Mattias K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Karlson, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    The extended cleavage specificity of the rodent β-chymases rMCP-1 and mMCP-4 reveal major fumctional similarities to the human mast cell chymase2008Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 45, nr 3, s. 766-775Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In rat and mouse the phylogenetic homologues of the human mast cell alpha-chymase (rMCP-5 and mMCP-5) have lost their chymase activity and instead become elastases. To investigate whether rodents hold enzymes with equivalent function as the primate alpha-chymases, we have determined the extended cleavage specificity of the major connective tissue mast cell beta-chymases in rat and mouse, rMCP-1 and mMCP-4. By using a phage display approach we determined the enzyme/substrate interaction in seven positions, both N- and C-terminal of the cleaved bond. The two proteases were found to display rather similar specificities. Both enzymes prefer Phe in position P1, and aliphatic amino acids are favoured N-terminal of the cleaved bond, i.e. Leu in P2 and Val in P3 and P4. Val and Leu are overrepresented also in positions P1' and P3'. The two enzymes differ clearly only in one position, the P2' residue, where mMCP-4 strongly prefers negatively charged amino acids while rMCP-1 favours Ser. Interestingly, Asp and Glu are often present in position P2' of known substrates for the human chymase. Overall, these two rodent beta-chymases have very similar amino acid preferences as the human chymase, particularly mMCP-4, which most likely have a very similar function as the human chymase. This finding indicates that rodent and primate connective tissue mast cells seem to have relatively similar proteolytic repertoires, although they express different sets of serine proteases.

  • 181.
    Andersson, Mattias K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi.
    Pemberton, Alan D.
    Miller, Hugh R. P.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi.
    Extended cleavage specificity of mMCP-1, the major mucosal mast cell protease in mouse - High specificity indicates high substrate selectivity2008Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 45, nr 9, s. 2548-2558Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mucosal mast cells are in the mouse predominantly found in the epithelium of the gastrointestinal tract. They express the beta-chymases mMCP-1 and mMCP-2. During nematode infections these intraepithelial mast cells increase in numbers and high amounts of mMCP-1 appear in the jejunal lumen and in the circulation. A targeted deletion of this enzyme leads to decreased ability to expel the intraepithelial nematode Trichinella spiralis. A suggested role for mMCP-1 is alteration of epithelial permeability by direct or indirect degradation of epithelial and endothelial targets, however, no such substrates have yet been identified. To enable a screening for natural substrates we performed a detailed analysis of the extended cleavage specificity of mMCP-1, using substrate phage display technology. In positions P1 and P1' distinct preferences for Phe and Ser, respectively, were observed. In position P2 a high selectivity for large hydrophobic amino acids Phe, Trp and Leu was detected, and in position P2' aliphatic amino acids Leu, Val and Ala was preferred. In positions P3 and P4, N-terminal of the cleaved bond, mMCP-1 showed specificity for aliphatic amino acids. The high selectivity in the P2, P1, P1' and P2' positions indicate that mMCP-1 has a relatively narrow set of in vivo substrates. The consensus sequence was used to screen the mouse protein database for potential substrates. A number of mouse extracellular or membrane proteins were identified and cell adhesion and connective tissue components were a dominating subfamily. This information, including the exact position of potential cleavage sites, can now be used in a more focused screening to identify which of these target molecules is/are responsible for the increased intestinal permeability observed in parasite infected mice.

  • 182.
    Andersson, Michael R.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Functional aspects of inorganic phosphate transport2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Inorganic phosphate is an essential nutrient for all organisms. It is required for many cellular components as nucleic acids and phospholipids, and as energy-carrying compounds such as ATP. Thus, a regulated uptake of this pivotal nutrient is of outermost importance. Depending of the availability of phosphate in the surroundings the yeast Saccharomyces cerevisiae make use of two different systems for transporting phosphate into the interior of the cell: a low-affinity system that is active during surplus phosphate conditions and a high-affinity system that is active when the availability becomes limited. This thesis focuses on the high-affinity system, which is comprised of the Pho84 and Pho89 transporters. Of the two transporters, Pho84 is the predominant one, responsible for almost all phosphate uptake during low phosphate conditions, and the contribution of Pho89 is of minor importance. Hence Pho84 is by far the most well characterized phosphate transporter. Even though much is known about phosphate transporters in yeast little in known about how phosphate is transported. The work in this thesis aims to broaden the knowledge about the transport mechanism by the means of site-directed mutagenesis and functional characterization. Also the similarity of Pho84 to glucose sensors and the potential role of conserved residues in phosphate signaling are investigated. By the use of a high-affinity system deletion strain (∆Pho84 ∆Pho89), we also managed to investigate the functional importance of well conserved residues in Pho89. In summary: the work presented in this thesis has contributed to increase the knowledge about transport mechanisms in phosphate transporters.

    Fulltekst (pdf)
    fulltext
  • 183.
    Andersson, Michael R.
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Samyn, Dieter R.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Persson, Bengt L.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Mutational analysis of conserved glutamic acids of Pho89, a Saccharomyces cerevisiae high-affinity inorganic phosphate:Na+ symporter2012Inngår i: Biologia (Bratislava), ISSN 0006-3088, E-ISSN 1336-9563, Vol. 67, nr 6, s. 1056-1061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Saccharomyces cerevisiae, the high-affinity phosphate transport system comprises the Pho84 and Pho89 permeases. The Pho89 permease catalyzes import of inorganic phosphate in a symport manner by utilizing Na+ ions as co-solute. We have addressed the functional importance of two glutamic acid residues at positions 55 and 491. Both residues are highly conserved amongst members of the inorganic phosphate transporter (PiT) family, which might be an indication of functional importance. Moreover, both residues have been shown to be of critical importance in the hPit2 transporter. We have created site-directed mutations of both E55 and E491 to lysine and glutamine. We observed that in all four cases there is a dramatic impact on the transport activity, and thus it seems that they indeed are of functional importance. Following these observations, we addressed the membrane topology of this protein by using several prediction programs. TOPCONS predicts a 7-5 transmembrane segment organization, which is the most concise topology as compared to the hPiT2 transporter. By understanding the functionality of these residues, we are able to correlate the Pho89 topology to that of the hPiT2, and can now further analyze residues which might play a role in the transport activity.

  • 184.
    Andersson, Niki
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Biology and biodiversity of tardigrades in the world and in Sweden: Current status and future visions2017Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Tardigrades are small water-dwelling invertebrates that can live almost anywhere in the world. Even though they are well-known our knowledge about them is still scarce. The aim of this study was therefore to explore our current knowledge about tardigrades by: (1) explore their global phylogeny and biogeography based on bioinformatics (2) screen for tardigrades in select locations of northern Sweden and compare with other Swedish locations, and (3) identify at least one tardigrade from northern Sweden and explore the published biomarkers for further identification. The bulk of this thesis was based on evaluation of the Silva database for analyzing SSU (small subunit) and LSU (large subunit) tardigrade sequences and create phylogenetic trees. Some initial lab work was performed using samples of moss and lichen from Piteå, Vindeln and Öland. Results show that only few countries have been explored with regard to tardigrades, and in Sweden more research have been performed in the south compared to the north. The phylogenetic trees give a rough overview of tardigrade relatedness but many of the sequences need to be improved and more sequence work from additional environments is needed. In the lab tardigrades were only found from the Piteå samples, and one of those was identified as Macrobiotus hufelandi, for which a new biomarker was created. Overall, tardigrade research need to continue and expand to other regions in order to understand how these organisms differ between different environments, and more work is needed to ensure higher quality of sequences added to databases.

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  • 185.
    Andersson, Robert
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik.
    Boutonnet, Magali
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik, Kemisk teknologi.
    Järås, Sven
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik.
    On-line gas chromatographic analysis of higher alcohol synthesis products from syngas2012Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1247, s. 134-145Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 186.
    Andersson, S.G.E.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi. MOLECULAR EVOLUTION.
    Karlberg, O.
    Canbäck, B.
    Kurland, C.G.
    On the origin of mitochondria: a genomics perspective.2003Inngår i: Phil. Trans. R. Soc. Lond., Vol. 358, s. 165-169Artikkel i tidsskrift (Fagfellevurdert)
  • 187.
    Andersson, Siv G. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Stress management strategies in single bacterial cells2016Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, nr 15, s. 3921-3923Artikkel i tidsskrift (Annet vitenskapelig)
  • 188.
    Andersson, Siv G.E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Deterioration of alpha-Proteobacterial human pathogen genomes2005Inngår i: Threat of Infection: Microbes of High Pathogenic Potential – Strategies for Detection, Control and Eradication, Internationales Symposium vom 25. bis 28. Juli 2004 in Würzburg / [ed] Jörg Hacker, Hans-Dieter Klenk, 2005, Vol. 92, nr 344, s. 81-86Konferansepaper (Annet vitenskapelig)
  • 189.
    Andersson Svahn, Helene
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). University of Twente, Netherlands .
    Van Den Berg, A.
    Single cells or large populations?2007Inngår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 7, nr 5, s. 544-546Artikkel i tidsskrift (Fagfellevurdert)
  • 190.
    Andersson, Sören
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    CHIMERIC MOMP ANTIGEN2015Patent (Annet (populærvitenskap, debatt, mm))
    Fulltekst (pdf)
    Patent
  • 191.
    Andersson, Sören
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Chimeric MOMP antigen2014Patent (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.

    Fulltekst (pdf)
    Patent
  • 192. Andersson, Ulrika
    et al.
    Leighton, Brendan
    Young, Martin E
    Blomstrand, Eva
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Newsholme, Eric A
    Inactivation of aconitase and oxoglutarate dehydrogenase in skeletal muscle in vitro by superoxide anions and/or nitric oxide.1998Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 249, nr 2, s. 512-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Strips of rat soleus muscle were incubated in media containing a superoxide generating system and/or the nitric oxide donor sodium nitroprusside (SNP) before the maximal catalytic activities of aconitase, citrate synthase, and oxoglutarate dehydrogenase were measured. The maximal activities of aconitase and oxoglutarate dehydrogenase were both decreased by 25-30% by superoxide anions; however, only the maximal activity of aconitase was decreased, by approximately 50%, by incubation of muscles with SNP. Furthermore, when both superoxide and NO were present in the medium, aconitase activity was decreased by 70%. The maximal activity of citrate synthase was not affected by any of the treatments. This is the first time that superoxide anions or NO has been shown to inactivate aconitase and oxoglutarate dehydrogenase in skeletal muscle. It is suggested that these effects may be responsible for some alterations in skeletal muscle metabolism, and these possibilities are discussed.

  • 193.
    Anderung, C
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiolgoi.
    Baubliene, J
    Daugnora, L
    Götherström, A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Mitochondrial DNA from medieval wisent remains indicates loss of genetic variation in the modern population.2006Inngår i: Molecular Ecology, Vol. 15, s. 2083-Artikkel i tidsskrift (Fagfellevurdert)
  • 194.
    Anderung, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Baubliene, Jurgita
    Daugnora, Linas
    Götherström, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Medieval remains from Lithuania indicate loss of a mitochondrial haplotype in Bison bonasus.2006Inngår i: Mol Ecol, ISSN 0962-1083, Vol. 15, nr 10, s. 3083-Artikkel i tidsskrift (Fagfellevurdert)
  • 195.
    Andrade, Luis E. C.
    et al.
    Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Rheumatol Div, Rua Botucatu 740, BR-04023062 Sao Paulo, SP, Brazil;Fleury Med & Hlth Labs, Immunol Div, Sao Paulo, Brazil.
    Klotz, Werner
    Med Univ Innsbruck, Dept Internal Med 2, Innsbruck, Austria.
    Herold, Manfred
    Med Univ Innsbruck, Dept Internal Med 2, Innsbruck, Austria.
    Conrad, Karsten
    Tech Univ Dresden, Inst Immunol, Dresden, Germany.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fritzler, Marvin J.
    Univ Calgary, Cumming Sch Med, Dept Med, Calgary, AB, Canada.
    von Mühlen, Carlos A.
    Brazilian Soc Autoimmun, Porto Alegre, RS, Brazil.
    Satoh, Minoru
    Univ Occupat & Environm Hlth, Dept Clin Nursing, Kitakyushu, Fukuoka, Japan.
    Damoiseaux, Jan
    Maastricht Univ, Med Ctr, Cent Diagnost Lab, Maastricht, Netherlands.
    Cruvinel, Wilson de Melo
    Univ Catolica Goias, Goiania, Go, Brazil.
    Chan, Edward K. L.
    Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA.
    International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I2018Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, nr 10, s. 1783-1788Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The indirect immunofluorescence assay (IFA) on HEp-2 cells is the reference method for autoantibody screening. The HEp-2 IFA pattern provides useful information on the possible autoantibodies in the sample. The International Consensus on Antinuclear Antibody Patterns (ICAP) initiative seeks to define and harmonize the nomenclature of HEp-2 IFA patterns. The most relevant and usual patterns have been assigned an alphanumeric code from anti-cell (AC)-1 to AC-28 and were organized into a classification algorithm (www.ANApatterns.org). The systemic sclerosis-associated autoantibodies to DNA topoisomerase I (Topo I) produce a peculiar composite 5-element HEp-2 IFA pattern (Topo I-like pattern) comprising the staining of the nucleus, metaphase chromatin plate, nucleolar organizing region, cytoplasm and nucleolus. In a recent assessment of the European Consensus Finding Study Group on autoantibodies, a well-defined anti-Topo I sample was blindly analyzed and classified according to ICAP AC patterns by 43 participant laboratories across Europe. There were wide variations among these laboratories in reporting nuclear, nucleolar and cytoplasmic patterns, indicating the inadequacy of the existing AC patterns to report the Topo I-like pattern. Several ICAP member laboratories independently demonstrated the overall consistency of the HEp-2 IFA Topo I-like pattern using HEp-2 slides from different manufacturers. The ICAP committee reviewed 24 candidate images and selected the four most representative images to be available on the ICAP website. The proper recognition of the AC-29 pattern should trigger suspicion of the presence of anti-Topo I antibodies, which may engender appropriate analyte-specific reflex tests to confirm the autoantibody specificity.

  • 196.
    Andre, Ingemar
    et al.
    Lund University.
    Bjelic, Sinisa
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Computational assessment of folding energy landscapes in heterodimeric coiled coils2018Inngår i: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 86, nr 7, s. 790-801Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs-into-holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes.

  • 197. Andres Valderrama, J
    et al.
    Shingler, Victoria
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Carmona, Manuel
    Diaz, Eduardo
    AccR is a master regulator involved in carbon catabolite repression of the anaerobic catabolism of aromatic compounds in Azoarcus sp CIB2014Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, nr 4, s. 1892-1904Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we characterized the first known transcriptional regulator that accounts for carbon catabolite repression (CCR) control of the anaerobic catabolism of aromatic compounds in bacteria. The AccR response regulator of Azoarcus sp. CIB controls succinate-responsive CCR of the central pathways for the anaerobic catabolism of aromatics by this strain. Phosphorylation of AccR to AccR-P triggers a monomer-to-dimer transition as well as the ability to bind to the target promoter and causes repression both in vivo and in vitro. Substitution of the Asp(60) phosphorylation target residue of the N-terminal receiver motif of AccR to a phosphomimic Glu residue generates a constitutively active derivative that behaves as a superrepressor of the target genes. AccR-P binds in vitro to a conserved inverted repeat (ATGCA-N-6-TGCAT) present at two different locations within the P-N promoter of the bzd genes for anaerobic benzoate degradation. Because the DNA binding-proficient C-terminal domain of AccR is monomeric, we propose an activation mechanism in which phosphorylation of Asp(60) of AccR alleviates interdomain repression mediated by the N-terminal domain. The presence of AccR-like proteins encoded in the genomes of other -proteobacteria of the Azoarcus/Thauera group further suggests that AccR constitutes a master regulator that controls anaerobic CCR in these bacteria.

  • 198.
    Andresen, Liis
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Holmqvist, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, Uppsala, Sweden.
    CLIP-Seq in Bacteria: Global Recognition Patterns of Bacterial RNA-Binding Proteins2018Inngår i: High-Density Sequencing Applications in Microbial Molecular Genetics / [ed] Carpousis, A J, ELSEVIER ACADEMIC PRESS INC , 2018, s. 127-145Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    RNA-protein interactions are at the heart of many central cellular processes, and RNA-binding proteins (RBPs) associate with virtually all RNA molecules in a cell. In bacteria, global RBPs, often in conjunction with small regulatory RNAs, affect physiology and virulence by controlling transcription, translation, and RNA decay. To understand how these regulatory proteins orchestrate global gene expression, detailed maps of their cellular RNA binding sites are required. To this end, cross-linking and immunoprecipitation followed by deep sequencing (CLIP-seq) has revolutionized RBP studies by providing knowledge about global recognition patterns of RBPs in both eukaryotic and bacterial cells. In this chapter, we provide a step-by-step protocol for global mapping of bona fide RBP binding sites using CLIP-seq in bacteria. This protocol has been successfully applied for charting the binding sites of Hfq, CsrA, and ProQ, three global regulatory RBPs in Salmonella enterica and Escherichia coli, and should be readily applicable to other RBPs and bacterial species.

  • 199.
    Andresen, Liis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 36549Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p) ppGpp (de la Fuente-Nunez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p) ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p) ppGpp synthesis moderately sensitizes-rather than protects-E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p) ppGpp.

    Fulltekst (pdf)
    fulltext
  • 200.
    Andrys, Rudolf
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi. Charles University Prague, Czech Republic .
    Zurita, Javier
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Zguna, Nadezda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Verschueren, Klaas
    De Borggraeve, Wim M.
    Ilag, Leopold L.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Improved detection of beta-N-methylamino-L-alanine using N-hydroxysuccinimide ester of N-butylnicotinic acid for the localization of BMAA in blue mussels (Mytilus edulis)2015Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 407, nr 13, s. 3743-3750Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    beta-N-Methylamino-l-alanine (BMAA) is an important non-protein amino acid linked to neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). Because it can be transferred and bioaccumulated higher up the food chain, it poses significant public health concerns; thus, improved detection methods are of prime importance for the identification and management of these toxins. Here, we report the successful use of N-hydroxysuccinimide ester of N-butylnicotinic acid (C-4-NA-NHS) for the efficient separation of BMAA from its isomers and higher sensitivity in detecting BMAA compared to the current method of choice using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization. Implementation of this efficient method allowed localization of BMAA in the non-visceral tissues of blue mussels, suggesting that more efficient depuration may be required to remove this toxin prior to consumption. This is a crucial method in establishing the absence or presence of the neurotoxic amino acid BMAA in food, environmental or biomedical samples.

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