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  • 1
    Article
    Article
    Battling the bureaucracy hydra (2016)
    Details
    Language: English
    In: Science (New York, N.Y.), 29 January 2016, Vol.351(6272), pp.530
    Description: “How hard can it be to write a contract?” I asked myself. After all, I had already overcome some long odds. Seven weeks earlier—just days before I was to fly to Brussels for the second evaluation phase of a European Research Council (ERC) Starting Grant application—the Icelandic volcano
    Keywords: Sciences (General) ; Biology;
    ISSN: 00368075
    E-ISSN: 1095-9203
    DOI: 10.1126/science.351.6272.530
    URL: View this record in MEDLINE/PubMed
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  • 2
    Article
    Article
    A riboswitch-regulated antisense RNA in Listeria monocytogenes (2013)
    Details
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 06 August 2013, Vol.110(32), pp.13132-7
    Description: Riboswitches are ligand-binding elements located in 5' untranslated regions of messenger RNAs, which regulate expression of downstream genes. In Listeria monocytogenes, a vitamin B12-binding (B12) riboswitch was identified, not upstream of a gene but downstream, and antisense to the adjacent gene, pocR, suggesting it might regulate pocR in a nonclassical manner. In Salmonella enterica, PocR is a transcription factor that is activated by 1,2-propanediol, and subsequently activates expression of the pdu genes. The pdu genes mediate propanediol catabolism and are implicated in pathogenesis. As enzymes involved in propanediol catabolism require B12 as a cofactor, we hypothesized that the Listeria B12 riboswitch might be involved in pocR regulation. Here we demonstrate that the B12 riboswitch is transcribed as part of a noncoding antisense RNA, herein named AspocR. In the presence of B12, the riboswitch induces transcriptional termination, causing aspocR to be transcribed as a short transcript. In contrast, in the absence of B12, aspocR is transcribed as a long antisense RNA, which inhibits pocR expression. Regulation by AspocR ensures that pocR, and consequently the pdu genes, are maximally expressed only when both propanediol and B12 are present. Strikingly, AspocR can inhibit pocR expression in trans, suggesting it acts through a direct interaction with pocR mRNA. Together, this study demonstrates how pocR and the pdu genes can be regulated by B12 in bacteria and extends the classical definition of riboswitches from elements governing solely the expression of mRNAs to a wider role in controlling transcription of noncoding RNAs.
    Keywords: Asrna ; Cobalamin ; Infection ; Bacterial Proteins -- Genetics ; Listeria Monocytogenes -- Genetics ; RNA, Antisense -- Genetics ; Riboswitch -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
    DOI: 10.1073/pnas.1304795110
    URL: View this record in MEDLINE/PubMed
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  • 3
    Article
    Article
    A riboswitch-regulated antisense RNA in Listeria monocytogenes (2013)
    Details
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 6 August 2013, Vol.110(32), pp.13132-13137
    Description: Riboswitches are ligand-binding elements located in 5' untranslated regions of messenger RNAs, which regulate expression of downstream genes. In Listeria monocytogenes, a vitamin B₁₂-binding (B₁₂) riboswitch was identified, not upstream of a gene but downstream, and antisense to the adjacent gene, pocR, suggesting it might regulate pocR in a nonclassical manner. In Salmonella entérica, PocR is a transcription factor that is activated by 1,2-propanediol, and subsequently activates expression of the pdu genes. The pdu genes mediate propanediol catabolism and are implicated in pathogenesis. As enzymes involved in propanediol catabolism require B₁₂ as a cofactor, we hypothesized that the Listeria B₁₂ riboswitch might be involved in pocR regulation. Here we demonstrate that the B₁₂ riboswitch is transcribed as part of a noncoding antisense RNA, herein named AspocR. In the presence of B₁₂, the riboswitch induces transcriptional termination, causing aspocR to be transcribed as a short transcript. In contrast, in the absence of B₁₂, aspocR is transcribed as a long antisense RNA, which inhibits pocR expression. Regulation by AspocR ensures that pocR, and consequently the pdu genes, are maximally expressed only when both propanediol and B₁₂ are present. Strikingly, AspocR can inhibit pocR expression in trans, suggesting it acts through a direct interaction with pocR mRNA. Together, this study demonstrates how pocR and the pdu genes can be regulated by B₁₂ in bacteria and extends the classical definition of riboswitches from elements governing solely the expression of mRNAs to a wider role in controlling transcription of noncoding RNAs.
    Keywords: Physical sciences -- Chemistry -- Chemical compounds ; Biological sciences -- Biology -- Genetics ; Physical sciences -- Chemistry -- Chemical compounds ; Biological sciences -- Biology -- Microbiology ; Physical sciences -- Chemistry -- Chemical compounds ; Biological sciences -- Biology -- Genetics ; Biological sciences -- Biology -- Genetics ; Biological sciences -- Biology -- Microbiology ; Biological sciences -- Biology -- Genetics ; Biological sciences -- Biology -- Microbiology
    ISSN: 00278424
    ISSN: 01689525
    E-ISSN: 13624555
    DOI: 10.1016/j.tig.2015.01.005
    URL: View this record in JSTOR
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  • 4
    Article
    Article
    A Listeria monocytogenes RNA helicase essential for growth and ribosomal maturation at low temperatures uses its C terminus for appropriate interaction with the ribosome (2012)
    Details
    Language: English
    In: Journal of bacteriology, August 2012, Vol.194(16), pp.4377-85
    Description: Listeria monocytogenes, a Gram-positive food-borne human pathogen, is able to grow at temperatures close to 0°C and is thus of great concern for the food industry. In this work, we investigated the physiological role of one DExD-box RNA helicase in Listeria monocytogenes. The RNA helicase Lmo1722 was required for optimal growth at low temperatures, whereas it was dispensable at 37°C. A Δlmo1722 strain was less motile due to downregulation of the major subunit of the flagellum, FlaA, caused by decreased flaA expression. By ribosomal fractionation experiments, it was observed that Lmo1722 was mainly associated with the 50S subunit of the ribosome. Absence of Lmo1722 decreased the fraction of 50S ribosomal subunits and mature 70S ribosomes and affected the processing of the 23S precursor rRNA. The ribosomal profile could be restored to wild-type levels in a Δlmo1722 strain expressing Lmo1722. Interestingly, the C-terminal part of Lmo1722 was redundant for low-temperature growth, motility, 23S rRNA processing, and appropriate ribosomal maturation. However, Lmo1722 lacking the C terminus showed a reduced affinity for the 50S and 70S fractions, suggesting that the C terminus is important for proper guidance of Lmo1722 to the 50S subunit. Taken together, our results show that the Listeria RNA helicase Lmo1722 is essential for growth at low temperatures, motility, and rRNA processing and is important for ribosomal maturation, being associated mainly with the 50S subunit of the ribosome.
    Keywords: Protein Interaction Mapping ; RNA Processing, Post-Transcriptional ; Listeria Monocytogenes -- Enzymology ; RNA Helicases -- Metabolism ; RNA, Ribosomal, 23s -- Metabolism
    ISSN: 00219193
    E-ISSN: 1098-5530
    DOI: 10.1128/JB.00348-12
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  • 5
    Article
    Article
    Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes (2016)
    Details
    Language: English
    In: Journal of bacteriology, 01 December 2016, Vol.198(23), pp.3233-3243
    Description: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen Listeria monocytogenes We found that the L. monocytogenes protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF.
    Keywords: Anti-Bacterial Agents -- Metabolism ; Listeria Monocytogenes -- Metabolism ; Riboflavin -- Analogs & Derivatives
    ISSN: 00219193
    E-ISSN: 1098-5530
    DOI: 10.1128/JB.00388-16
    URL: View this record in MEDLINE/PubMed
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  • 6
    Article
    Article
    Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria (2016)
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    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 2016, Vol.113(51), pp.14733-14738
    Description: Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a...
    Keywords: Natural Sciences ; Chemical Sciences ; Organic Chemistry ; Naturvetenskap ; Kemi ; Organisk Kemi ; Medical And Health Sciences ; Basic Medicine ; Medical Genetics ; Medicin Och Hälsovetenskap ; Medicinska Och Farmaceutiska Grundvetenskaper ; Medicinsk Genetik ; Listeria ; Prfa ; Activation ; Glutathione ; Virulence
    ISSN: 0027-8424
    E-ISSN: 10916490
    DOI: 10.1073/pnas.1614028114
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  • 7
    Article
    Article
    Antibacterial and antivirulence effect of 6-N-hydroxylaminopurine in Listeria monocytogenes (2017)
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    Language: English
    In: Nucleic Acids Research, 2017, Vol. 45(4), pp. 1914-1924
    Description: The emerging development of antibiotic resistant bacteria calls for novel types of antibacterial agents. In this work we examined the putative antibacterial effect of purine analogs in Listeria monocytogenes. We show that, among several tested purine analogs, only 6-N-hydroxylaminopurine (6-N-HAP) reduces the viability of the Gram-positive pathogenListeria monocy-togenes. As in Bacillus subtilis, 6-N-HAP terminates expression at guanine riboswitches in L. monocyto-genes hence preventing expression of their downstream genes. However, we show that the bacteriocidal effect of the compound was unlinked to the terminated expression at the guanine riboswitches. When further examining the antimicrobial effect, we observed that 6-N-HAP acts as a potent mutagen in L. monocytogenes, by increasing the mutation rate and inducing the SOS-response. Also, addition of 6N-HAP decreased virulence gene expression by reducing both the levels and activity of the virulence regulator PrfA.
    Keywords: Medical And Health Sciences ; Basic Medicine ; Microbiology In The Medical Area ; Medicin Och Hälsovetenskap ; Medicinska Och Farmaceutiska Grundvetenskaper ; Mikrobiologi Inom Det Medicinska Området
    ISSN: 0305-1048
    E-ISSN: 13624962
    DOI: 10.1093/nar/gkw1308
    URL: View this record in Uppsala University Library
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  • 8
    Article
    Article
    Cycles of light and dark co‐ordinate reversible colony differentiation in L isteria monocytogenes (2013)
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    In: Molecular Microbiology, February 2013, Vol.87(4), pp.909-924
    Description: Recently, several light receptors have been identified in non‐phototrophic bacteria, but their physiological roles still remain rather elusive. Here we show that colonies of the saprophytic bacterium undergo synchronized multicellular behaviour on agar plates, in response to oscillating light/dark conditions, giving rise to alternating ring formation (opaque and translucent rings). On agar plates, bacteria from opaque rings survive increased levels of reactive oxygen species (), as well as repeated cycles of light and dark, better than bacteria from translucent rings. The ring formation is strictly dependent on a blue‐light receptor, , acting through the stress‐sigma factor, σ. A transposon screening identified 48 mutants unable to form rings at alternating light conditions, with several of them showing a decreased σ activity/level. However, some of the tested mutants displayed a varied σ activity depending on which of the two stress conditions tested (light or exposure). Intriguingly, the transcriptional regulator and the virulence factor were shown to be required for ring formation by a mechanism involving activation of σ. All in all, this suggests a distinct pathway for that converge into a common signalling pathway for σ activation. Our results show that night and day cycles co‐ordinate a reversible differentiation of a colony at room temperature, by a process synchronized by a blue‐light receptor and σ.
    Keywords: Listeria;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
    DOI: 10.1111/mmi.12140
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  • 9
    Article
    Article
    Samhällskunskap i den nya ämneslärarutbildningen: Samhällskunskapens innehåll och ämnesdidaktik vid 14 lärosäten i Sverige mellan 2009-2015 (2017)
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    Language: Swedish
    In: Nordidactica, 2017(2017:4), pp.1-27
    Description: Abstract: Syftet med artikeln är att analysera samhällskunskapsämnets innehåll i ämnes­lärarutbildningen vid lärosäten i Sverige. Avsikten är att analysera hur man vid olika lärosäten utformat ämnesinnehåll och ämnesdidaktisk integrering i kursplaner. Studien besvarar fyra frågor; I vilken omfattning...
    Keywords: Social Sciences ; Educational Sciences ; Didactics ; Samhällsvetenskap ; Utbildningsvetenskap ; Didaktik ; Samhällskunskap ; Ämnesdidaktik ; Ämnesteori ; Vetenskaplig Metodologi ; Normativ Teori ; Samhällskunskap ; Samhällskunskap
    ISSN: 2000-9879
    Source: SwePub (National Library of Sweden)
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  • 10
    Article
    Article
    Samhällskunskap i den nya ämneslärarutbildningen: Samhällskunskapens innehåll och ämnesdidaktik vid 14 lärosäten i Sverige mellan 2009-2015 (2017)
    Details
    Language: Swedish
    In: Nordidactica: Journal of Humanities and Social Science Education, 2017, Issue 2017:4, pp. 1-27
    Description: Abstract: Syftet med artikeln är att analysera samhällskunskapsämnets innehåll i ämnes­lärarutbildningen vid lärosäten i Sverige. Avsikten är att analysera hur man vid olika lärosäten utformat ämnesinnehåll och ämnesdidaktisk integrering i kursplaner. Studien besvarar fyra frågor; I vilken omfattning det förekommer lärandemål i samhällskunskap om (1) faktuell kunskapsöverföring, vetenskaplig metodologi, granskande undersökningar; (2) normativt innehåll; (3) ämnesdiscipliner respektive flervetenskapliga tematiseringar samt (4) ämnesdidaktik. Kursplaner i samhällskunskap från 14 lärosäten har analyserats vid två tillfällen, 2009 och 2015, dvs. före och efter den senaste lärarutbildningsreformen i Sverige. Resultaten visar att det totala antalet lärandemål i samhällskunskapskurserna ökat med 21 % och att detta i hög grad betingas av att statsmakten lagt in fler lärandemål i examensförordningen jämfört med tidigare. Analysen visar (1) att inslagen av ämnesdidaktisk integrering ökat i kursplanerna, (2) att andelen flervetenskapliga tematiseringar minskat, (3) att mängden ämnesteoretiska lärandemål varit oförändrade men fått fler inslag av normativt färgade problemställningar samt (4) att inslagen av vetenskaplig metodologi varit oförändrade. Analysen av kursplanerna indikerar behov av ytterligare analys och ämnesdidaktisk forskning om samhällskunskapsämnet möjligheter gällande bl.a. tvärvetenskaplig integrering, vetenskaplig metodologi samt betydelsen av normativa ansatser.
    Keywords: Samhällskunskap ; Ämnesdidaktik ; Ämnesteori ; Vetenskaplig Metodologi ; Normativ Teori ; Social Sciences ; Educational Sciences ; Didactics ; Samhällsvetenskap ; Utbildningsvetenskap ; Didaktik ; Samhällskunskap ; Samhällskunskap
    ISSN: 2000-9879
    Source: Uppsala University Library
    URL: View this record in Uppsala University Library
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