| 1. |
- Andersson, Anders, et al.
(författare)
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Effects of Tobacco Smoke on IL-16 in CD8+ Cells from Human Airways and Blood: a Key Role for Oxygen Free Radicals?
- 2011
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Ingår i: AJP - Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504. ; 300:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in CD8(+) and CD4(+)cells as well as the CD4(+) chemo-attractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood, while at the same time increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro; in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased whereas other markers of key cellular functions (membrane integrity, apoptosis and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects whereas a protein synthesis inhibitor, a beta-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.
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| 4. |
- Jauhiainen, Alexandra, 1981, et al.
(författare)
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Distinct cytoplasmic and nuclear functions of the stress induced protein DDIT3/CHOP/GADD153
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- DDIT3, also known as GADD153 or CHOP, encodes a basic leucine zipper transcription factor of the dimer forming C/EBP family. DDIT3 is known as a key regulator of cellular stress response, but its target genes and functions are not well characterized. Here, we applied a genome wide microarray based expression analysis to identify DDIT3 target genes and functions. By analyzing cells carrying tamoxifen inducible DDIT3 expression constructs we show distinct gene expression profiles for cells with cytoplasmic and nuclear localized DDIT3. Of 175 target genes identified only 3 were regulated by DDIT3 in both cellular localizations. More than two thirds of the genes were downregulated, supporting a role for DDIT3 as a dominant negative factor that could act by either cytoplasmic or nuclear sequestration of dimer forming transcription factor partners. Functional annotation of target genes showed cell migration, proliferation and apoptosis/survival as the most affected categories. Cytoplasmic DDIT3 affected more migration associated genes, while nuclear DDIT3 regulated more cell cycle controlling genes. Cell culture experiments confirmed that cytoplasmic DDIT3 inhibited migration, while nuclear DDIT3 caused a G1 cell cycle arrest. Promoters of target genes showed no common sequence motifs, reflecting that DDIT3 forms heterodimers with several alternative transcription factors that bind to different motifs. We conclude that expression of cytoplasmic DDIT3 regulated 94 genes. Nuclear translocation of DDIT3 regulated 81 additional genes linked to functions already affected by cytoplasmic DDIT3. Characterization of DDIT3 regulated functions helps understanding its role in stress response and involvement in cancer and degenerative disorders.
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| 5. |
- Almgren, Maria, et al.
(författare)
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Länge leve skolan! En text om utbildning, estetik och skolutveckling
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna skrift har arbetats fram av en grupp studenter på Lärande och samhälle som fortsättning och utveckling av examinationsuppgift på en terminslång kurs, där de hade att iscensätta ett dokumentärfilmsprojekt på högstadiet. Projektet ägde rum inom ramen för huvudämnet Kultur, medier, estetik (KME) - skapat genom en sammanslagning av estetiska ämnen med medie- och kulturstudier 2001 – som ända från starten har tillskrivit det estetiska en särskild förmåga att vända upp och ner på invanda synsätt och kritiserat skolan för att inte lämna tillräckligt utrymme åt denna radikala potential. Den som är det minsta intresserad av skol- och kulturarbete kan inte undgå att dras in i det nät av glödande engagemang, intrikata spörsmål och brottstycken av teoretiska diskussioner som dessa sju studenter väver. Man kommer mycket nära de problem de brottas med utan att någonsin hitta några definitiva svar. Viljan att göra nytt tillsammans med eleverna och med utgångspunkt i deras horisont är obändig. Men så är det ramarna för arbetet... De sju befinner sig i ett interregnum, i en korseld av krav från lärarutbildarna, lärarna på skolan och eleverna, som påminner dem: "Ni är inte våra lärare. Ni kommer hit några timmar i veckan från någon annanstans". Ingenting visar sig vara enkelt. Varför gläds inte eleverna åt att få göra något som kan få betydelse för dem "på riktigt"? Vad är egentligen skillnaden mellan dokumentär- och fiktionsfilm? Hur bedömer man elevernas prestationer i ett så pass öppet projekt? Finns det över huvud taget rum i dagens skola för en pedagogik som vill vara på en gång passionerad, polyfon, prövande och provokativ? Alla dessa är ord som väl kännetecknar skriftens första del, ett grafiskt kaos av utlagda spår som läsaren kan välja bland att följa. Här får man en "cut-up-bild" av de tankevärldar som studenterna försöker orientera sig mot och inom. Den läsare som finner estetiken för provocerande kan alltid börja med andra delen i stället, som analytiskt redogör för de olika filmprojekten. Del tre, slutligen, diskuterar förutsättningarna för de förhållningssätt som utvecklats inom KME att göra sig gällande inom ramen för den nya läroplanen Lgr 11.
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| 6. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 7. |
- Andersson, Emma K., et al.
(författare)
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Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones
- 2013
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Ingår i: Chemistry and Biology. - : Elsevier. - 1074-5521 .- 1879-1301. ; 20:10, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by "chemical chaperones."
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| 8. |
- Andersson, Evalena, et al.
(författare)
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Structure of bacteriophage T4 endonuclease II mutant E118A, a tetrameric GIY-YIG enzyme
- 2010
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 397:4, s. 1003-1016
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Tidskriftsartikel (refereegranskat)abstract
- Coliphage T4 endonuclease II (EndoII), encoded by gene denA, is a small (16Da, 136aa) enzyme belonging to the GIY-YIG family of endonucleases, which lacks a C-terminal domain corresponding to that providing most of the binding energy in the structurally characterized GIY-YIG endonucleases, I-TevI and UvrC. In vivo, it is involved in degradation of host DNA, permitting scavenging of host-derived nucleotides for phage DNA synthesis. EndoII primarily catalyzes single-stranded nicking of DNA; 5- to 10-fold less frequently double-stranded breaks are produced. The Glu118Ala mutant of EndoII was crystallized in space group P21 with four monomers in the asymmetric unit. The fold of the EndoII monomer is similar to that of the catalytic domains of UvrC and I-TevI. In contrast to these enzymes, EndoII forms a striking X-shaped tetrameric structure composed as a dimer of dimers, with a protruding hairpin domain not present in UvrC or I-TevI providing most of the dimerization and tetramerization interfaces. A bound phosphate ion in one of the four active sites of EndoII likely mimics the scissile phosphate in a true substrate complex. In silico docking experiments showed that a protruding loop containing a nuclease-associated modular domain 3 element is likely to be involved in substrate binding, as well as residues forming a separate nucleic acid binding surface adjacent to the active site. The positioning of these sites within the EndoII primary dimer suggests that the substrate would bind to a primary EndoII dimer diagonally over the active sites, requiring significant distortion of the enzyme or the substrate DNA, or both, for simultaneous nicking of both DNA strands. The scarcity of potential nucleic acid binding residues between the active sites indicates that EndoII may bind its substrate inefficiently across the two sites in the dimer, offering a plausible explanation for the catalytic preponderance of single-strand nicks. Mutations analyzed in earlier functional studies are discussed in their structural context.
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| 9. |
- Andersson Joona, Pernilla, 1977-, et al.
(författare)
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Being Employed by a Co-national: A Cul-de-sac or a Short Cut to the Main Road of the Labour Market?
- 2012
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Ingår i: Journal of International Migration and Integration. - : Springer Science+Business Media B.V.. - 1488-3473 .- 1874-6365. ; 13:1, s. 99-120
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Tidskriftsartikel (refereegranskat)abstract
- This paper analyses the impact of working in an ethnic economy on subsequent labour market performance for newly arrived immigrants. Is it a short cut to the labour market or does it lock immigrants into low income jobs? Working in an ethnic economy is defined as being employed by a self-employed co-national. The comparison group is a matched sample of newly arrived immigrants who were without employment during the same period. Swedish panel data for the period 1998–2005 are used, and the sample is restricted to male immigrants, 20–55 years of age. Using propensity score matching, we find that immigrants who were employed by self-employed co-nationals are more likely to be employed in the near future, but that the types of employment they have are associated with lower incomes. Many continue to be employed by self-employed co-nationals or become self-employed themselves.
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