| 1. |
- Cole, Michelle J., et al.
(författare)
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Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data
- 2019
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.RESULTS: dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.
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| 2. |
- Danielsson, Angelika, 1981-, et al.
(författare)
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An ex vivo loop system models the toxicity and efficacy of PEGylated and unmodified adenovirus serotype 5 in whole human blood
- 2010
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Ingår i: Gene Therapy. - : Nature Publishing Group. - 0969-7128 .- 1476-5462. ; 17:6, s. 752-762
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Tidskriftsartikel (refereegranskat)abstract
- Polyethylene glycol coating (PEGylation) of adenovirus serotype 5 (Ad5) has been shown to effectively reduce immunogenicity and increase circulation time of intravenously administered virus in mouse models. Herein, we monitored clot formation, complement activation, cytokine release and blood cell association upon addition of uncoated or PEGylated Ad5 to human whole blood. We used a novel blood loop model where human blood from healthy donors was mixed with virus and incubated in heparin-coated PVC tubing while rotating at 37°C for up to 8 hours. Production of the complement components C3a and C5a and the cytokines IL-8, RANTES and MCP-1 was significantly lower with 20K-PEGylated Ad5 than with uncoated Ad5. PEGylation prevented clotting and reduced Ad5 binding to blood cells in blood with low ability to neutralize Ad5. The effect was particularly pronounced in monocytes, granulocytes, B-cells and T-cells, but could also be observed in erythrocytes and platelets. In conclusion, PEGylation of Ad5 can reduce the immune response mounted in human blood, although the protective effects are rather modest in contrast to published mouse data. Our findings underline the importance of developing reliable models and we propose the use of human whole blood models in pre-clinical screening of gene therapy vectors.
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| 3. |
- Danielsson, Angelika, 1981-, et al.
(författare)
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The HDAC Inhibitor FK228 Enhances Adenoviral Transgene Expression by a Transduction-Independent Mechanism but Does Not Increase Adenovirus Replication
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. e14700-
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Tidskriftsartikel (refereegranskat)abstract
- The histone deacetylase inhibitor FK228 has previously been shown to enhance adenoviral transgene expression when cells are pre-incubated with the drug. Upregulation of the coxsackie adenovirus receptor (CAR) has been proposed as the main mechanism. In the present study, we found that the highest increase in transgene expression was achieved when non-toxic concentrations of FK228 were added immediately after transduction demonstrating that the main effect by which FK228 enhances transgene expression is transduction independent. FK228 had positive effects both on Ad5 and Ad5/f35 vectors with a variety of transgenes and promoters, indicating that FK228 works mainly by increasing transgene expression at the transcriptional level. In some cases, the effects were dramatic, as demonstrated by an increase in CD40L expression by FK228 from 0.3% to 62% when the murine prostate cancer cell line TRAMP-C2, was transduced with Ad[CD40L]. One unexpected finding was that the transgene expression of an adenoviral vector with the prostate-specific PPT promoter decreased in the human prostate cancer cell line LNCaP when FK228 was administered. This is probably a consequence of phenotypic alteration of LNCaP towards a neuroendocrine phenotype after FK228 treatment. The observations in this study indicate that FK228 enhances adenoviral therapy by a transduction-independent mechanism. Furthermore, since histone deacetylase inhibitors may alter the phenotype of cells, it is important to keep in mind that the activity and specificity of tissue- and tumor-specific promoters may also be affected.
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| 4. |
- Fredriksson, Karolina, et al.
(författare)
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Klassrumsdialog i matematikundervisningen : matematiska samtal i helklass i grundskolan
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna systematiska översikt ger en bild av vad forskningen sammantaget säger om hur lärare kan leda samtal i helklass för att få elever att delta i gemensamma matematiska resonemang. Det handlar om diskussioner i vilka eleverna använder och analyserar matematiska begrepp och argumenterar matematiskt. Detta är förmågor som kursplanen i matematik anger att undervisningen ska ge eleverna förutsättningar att utveckla, och som forskning lyfter fram att elever i svensk skola behöver förstärka. Översikten rör också frågor om hur lärare kan möta och ta tillvara elevers olikheter i undervisningen, närmare bestämt hur lärare kan få med elever som inte är så benägna att delta i gemensamma resonemang, och hur elevers olika idéer kan bli en del av de matematiska samtalen och berika dem. Översikten utgår från följande frågeställning:Vad kännetecknar klassrumsdialoger som engagerar elever i matematiskaresonemang och som möter och tar tillvara elevers olikheter, och vad kännetecknarlärarens ledning av sådana dialoger?Översikten är en sammanställning av arton forskningsstudier som systematiskt har valts ut av forskare efter omfattande litteratursökningar i internationella forskningsdatabaser. Sökningarna resulterade i 10 528 studier.Studierna bygger på ingående observationer och analyser av dialoger i helklass mellan lärare och elever. Det är klassrumssituationer som lärare skulle kunna känna igen sig i. Analyserna sätter ord på det som sker och ger förståelse i form av olika begrepp och strukturer. Denna vetenskapligt grundade kunskap kan utgöra stöd för lärare när de planerar och leder klassrumsdialoger i matematikundervisningen.
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| 5. |
- Gutzat, Ruben, et al.
(författare)
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Arabidopsis shoot stem cells display dynamic transcription and DNA methylation patterns
- 2020
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Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:20
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Tidskriftsartikel (refereegranskat)abstract
- In plants, aerial organs originate continuously from stem cells in the center of the shoot apical meristem. Descendants of stem cells in the subepidermal layer are progenitors of germ cells, giving rise to male and female gametes. In these cells, mutations, including insertions of transposable elements or viruses, must be avoided to preserve genome integrity across generations. To investigate the molecular characteristics of stem cells inArabidopsis, we isolated their nuclei and analyzed stage-specific gene expression andDNAmethylation in plants of different ages. Stem cell expression signatures are largely defined by developmental stage but include a core set of stem cell-specific genes, among which are genes implicated in epigenetic silencing. Transiently increased expression of transposable elements in meristems prior to flower induction correlates with increasingCHGmethylation during development and decreasedCHHmethylation, before stem cells enter the reproductive lineage. These results suggest that epigenetic reprogramming may occur at an early stage in this lineage and could contribute to genome protection in stem cells during germline development.
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| 6. |
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| 7. |
- Jacobsson, Susanne, 1974-, et al.
(författare)
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WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014
- 2016
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Ingår i: Journal of Antimicrobial Chemotherapy. - Oxford, United Kingdom : Oxford University Press. - 0305-7453 .- 1460-2091. ; 71:11, s. 3109-3116
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms.Methods: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS.Results: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate.Conclusions: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.
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| 8. |
- Lundgren, A., et al.
(författare)
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Resonance-Mode Electrochemical Impedance Measurements of Silicon Dioxide Supported Lipid Bilayer Formation and Ion Channel Mediated Charge Transport
- 2011
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 83:20, s. 7800-7806
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Tidskriftsartikel (refereegranskat)abstract
- A single-chip electrochemical method based on impedance measurements in resonance mode has been employed to study lipid monolayer and bilayer formation on hydrophobic alkanethiolate and SiO(2) substrates, respectively. The processes were monitored by temporally resolving changes in interfacial capacitance and resistance, revealing information about the rate of formation, coverage, and defect density (quality) of the layers at saturation. The resonance-based impedance measurements were shown to reveal significant differences in the layer formation process of bilayers made from (i) positively charged lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (POEPC), (ii) neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on SiO(2), and (iii) monolayers made from POEPC on hydrophobic alkanethiolate substrates. The observed responses were represented with an equivalent circuit, suggesting that the differences primarily originate from the presence of a conductive aqueous layer between the lipid bilayers and the SiO(2). In addition, by adding the ion channel gramicidin D to bilayers supported on SiO(2), channel-mediated charge transport could be measured with high sensitivity (resolution around 1 pA).
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| 9. |
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| 10. |
- Maitland, Norman, et al.
(författare)
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Gene Transfer Vectors Targeted to Human Prostate Cancer : Do We Need Better Preclinical Testing Systems?
- 2010
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 21:7, s. 815-827
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Tidskriftsartikel (refereegranskat)abstract
- Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans.
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| 11. |
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