| 1. |
- Frostfeldt, Gunnar, et al.
(författare)
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Low molecular weight heparin (Dalteparin) as adjuvant treatment to thrombolysis in acute myocardial infarction-a pilot study : BIOchemical markers in acute coronary syndromes (BIOMACS II)
- 1999
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Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 33:3, s. 627-633
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.
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| 2. |
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| 3. |
- Frostfeldt, Gunnar, et al.
(författare)
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Possible reasons for the prognostic value of troponin-T on admission in patients with ST-elevation myocardial infarction
- 2001
-
Ingår i: Coronary Artery Disease. - 0954-6928 .- 1473-5830. ; 12:3, s. 227-237
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with acute myocardial infarction and ST-segment elevation, increased troponin-T (TnT) on admission implies an increased mortality. OBJECTIVE: To elucidate the underlying mechanisms of the prognostic value of TnT. METHODS AND RESULTS: One hundred and one patients were included and all received thrombolytic treatment. The patients were compared according to TnT level on admission (cut-off 0.1 microg/l). Elevation of TnT was associated with long-term mortality and also with longer delay, more episodes of chest pain during the last 24 h and fewer noninvasive signs of reperfusion at 90 min. In the group with elevated TnT, the coronary angiography at 24 h showed a strong trend towards lower patency in the infarct-related artery. TnT was also associated with increased infarct size if a higher cut-off level (0.43 microg/l) was used. In univariate analysis, elevated TnT, longer delay, repeated chest pain, Q-waves on admission and reduced left ventricular (LV) function were significantly associated with long-term mortality. In multivariate models, only reduced LV function and less than TIMI (thrombolysis in myocardial infarction) grade 3 flow turned out to be significant independent risk factors. CONCLUSIONS: The prognostic value of TnT level on admission regarding long-term mortality was confirmed and seems mainly to be explained by its association with longer delay and recent myocardial damage, but its association with reduced effect of thrombolytic treatment, larger infarct size and impaired LV function might also be of importance.
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| 4. |
- Hedström, Brita, et al.
(författare)
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Visby Innerstad : En användningsplan
- 1973
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Rapport (populärvet., debatt m.m.)abstract
- Sedan lång tid föreligger i stort sett enighet om att bevara innerstadens bebyggelse och att anpassa eventuella nytillskott till det redan bestående. Med den inställningen har förändringsprocessen både dämpats och mildrats men ändå inte bragts att avstanna. Förändringar sker ständigt om det också huvudsakligen i smått: de många synbart så anspråkslösa byggnadsåtgärderna adderar efterhand ihop sig till något större och mer genomgripande. Långsamt, nästan omärkligt, ändrar innerstaden sitt ansikte.Ändå är det inte själva husen som förändrats mest utan användningen av dem. Ur funktionell synpunkt har 1950 - och 60-talen har varit något av en omstörtning i innerstadens historia: den har förlorat nästan hälften av de boende, en stor del av detaljhandeln och praktiskt taget helt sin gamla roll som skolcentrum. I gengäld har ytterstaden vuxit ut till ett sammanhängande kilometerbrett bälte. Till stor del av denna funktionella förändring en följd av beslutet att bevara innerstadens bebyggelse. Vad som inte fått plats inom den gamla ramen har etablerats utandör den.Föreliggande arbete vill ge en översiktlig bild av förändringsförloppen, sedda i ett långt tidsperspektiv men med tonvikt på dagsläget. Bebyggelsen tas upp till utförlig granskning men också användningen av den. Det är just samspelet mellan husen och de funtkioner, de fyller, som kan sägas utgöra bokens huvudtema. I de flesta fall är detta sammanhang hus-användning alldeles konfliktfritt och föranleder därför inte heller någon diskussion. Vad som behandlas är de relativt få problematiska fallen, hus som borde rustas upp för att fylla sin uppgift, hus som är olämpligt nyttjade eller inte använda alls. En serie sådana fall tas upp till systematisk genomgång; samtidigt berörs också de trafik - och miljömässiga konsekvenserna. Bokens syfte är alltså klart: den ger ett underlag av fakta för arbetet med att jämka samman byggnader och användningsformer. I den meningen kan skriften kallas en anvädningsplan för Visby innanför murarna.Arkitekturskolanas arbete har bedrivitis parallellt med den kommunala Innerstadskommitténs verksamhet. Något organiserat samarbete har inte förekommit med de informella kontakterna har varit både täta och goda. Att likheterna mellan Innerstadskommittén och Arkitekturskolans slutsatser blivit så pass stora, kan tillskrivas en gemensam helhetssyn.En av Arkitekturskolans elever, arkitekt Lars-Ingvar Larsson, har tidigare självständigt genomfört en undersökning av förändringar i innerstaden 1945-70- Denna studie publicerats separat och bör uppfattas som ett komplement till den hör föreliggande.Förutom de i innehållsförteckningen nämnda har ytterligare några aktivt medverkat i arbetet. Studiet av trafikfrågorna i innerstaden, i hamnen och öster om ringmuren leddes av Åke Claesson, I fältstudier och diskussioner medverkande Göran Månsson.Arkitekturskolan har fått god hjälp av ett antal initierade personer i Visby. Särskild tacksamhet är vi skyldiga byggnadsnämnden ordförande Henning Jacobson, kommunalrådet C B Stenström, stadsarkitekten Måns Hagbergm f. länsbostadsdorektören Åke Malmberg och landsantikvarien Gunnar Svahnström. I boken publiceringskostnaderna har ekonomiskt bidrag lämnats av Gotlands kommun och Riksantikvarieämbetet.Boken har redigerats av Sture Balgård och Ann Mari Westerlind med hjälp av Henrik O Andersson, Bo Ek, Göran Lindahl, Fredrik von Platen, John Sjöström Gunnar Westerlind och Hans Wetterfors.Skeppsholmen, Stockholm, sommaren 1973.Arkitekturskolans lärare och elever.
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| 5. |
- Morfeldt, E, et al.
(författare)
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Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein : implications for antigenic variation.
- 2001
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 167:7, s. 3870-7
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Tidskriftsartikel (refereegranskat)abstract
- Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the approximately 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HVRs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.
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| 6. |
- van Sorge, Nina M., et al.
(författare)
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Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
- 2021
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Ingår i: EMBO Journal. - : Wiley-VCH Verlagsgesellschaft. - 0261-4189 .- 1460-2075. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
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| 7. |
- André, Ingemar, et al.
(författare)
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Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP
- 2006
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:14, s. 4559-4568
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an similar to 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of similar to 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.
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| 8. |
- Areschoug, Thomas, et al.
(författare)
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A Proline-Rich Region with a Highly Periodic Sequence in Streptococcal beta Protein Adopts the Polyproline II Structure and Is Exposed on the Bacterial Surface.
- 2002
-
Ingår i: Journal of Bacteriology. - 0021-9193. ; 184:22, s. 6376-6383
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Tidskriftsartikel (refereegranskat)abstract
- Proline-rich regions have been identified in many surface proteins of pathogenic streptococci and staphylococci. These regions have been suggested to be located in cell wall-spanning domains and/or to be required for surface expression of the protein. Because little is known about these regions, which are found in extensively studied and biologically important surface proteins, we characterized the proline-rich region in one such protein, the beta protein of group B streptococci. The proline-rich region in beta, designated the XPZ region, has a proline at every third position, and the sequence is highly periodic in other respects. Immunochemical analysis showed that the XPZ region was not associated with the cell wall but was exposed on the bacterial surface. Moreover, characterization of a beta mutant lacking the XPZ region demonstrated that this region was not required for surface expression of the beta protein. Comparison of the XPZ region in different beta proteins showed that it varied in size but always retained the typical sequence periodicity. Circular dichroism spectroscopy indicated that the XPZ region had the structure of a polyproline II helix, an extended and solvent-exposed structure with exactly three residues per turn. Because of the three-residue sequence periodicity in the XPZ region, it is expected to be amphipathic and to have distinct nonpolar and polar surfaces. This study identified a proline-rich structure with unique properties that is exposed on the surface of an important human pathogen.
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| 9. |
- Areschoug, Thomas, et al.
(författare)
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Host-pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development.
- 2004
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 22 Suppl 1:Suppl 1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes (group A streptococcus) causes a variety of diseases, including acute pharyngitis, impetigo, rheumatic fever and the streptococcal toxic shock syndrome. Moreover, S. pyogenes was responsible for the classical example of a nosocomial infection, the epidemics of puerperal fever (childbed fever) that caused the death of numerous women in earlier centuries. The most extensively studied virulence factor of S. pyogenes is the surface M protein, which inhibits phagocytosis and shows antigenic variation. Recent data indicate that many M proteins confer phagocytosis resistance because the variable N-terminal region has non-overlapping sites that specifically bind two components of the human immune system, the complement inhibitor C4b-binding protein (C4BP) and IgA-Fc. Concerning puerperal fever, molecular and epidemiological analysis suggests that the S. pyogenes surface protein R28 may have played a pathogenetic role in these epidemics. This article summarizes the properties of M protein and the R28 protein and considers a potential problem encountered in connection with the use of animal models for vaccine development.
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| 10. |
- Areschoug, Thomas, et al.
(författare)
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Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.
- 2002
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:15, s. 12642-12648
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Tidskriftsartikel (refereegranskat)abstract
- The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein, but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate and non-overlapping regions in beta. Heparin, a known ligand for FH, specifically inhibited the binding between beta and FH, suggesting that FH has overlapping binding sites for beta and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that beta-expressing GBS may use bound FH to evade complement attack. The finding that beta protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.
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| 11. |
- Bengtsson, Gunnar, et al.
(författare)
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A design scheme for incomplete state or output feedback with applications to boiler and power system control
- 1974
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Ingår i: Automatica. - : Elsevier BV. - 0005-1098. ; 10:1, s. 15-30
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Tidskriftsartikel (refereegranskat)abstract
- The problem of designing a linear feedback when all state variables are not available is discussed. The design scheme is based on computation of a complete state feedback and a reduction to a specified structure. The reduction is made by approximation of the eigenspace corresponding to a set of dominant eigenvalues. The method consists of successive choices of weightings on this space. The method is applied to the control of a boiler and a three-machine power system. In the power system case the complete state feedback can be replaced by local output feedback without significant decrease in performance.The examples indicate that the proposed method is a realistic design method for multivariable systems.
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| 12. |
- Berggård, Karin, et al.
(författare)
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Bordetella pertussis binds to human C4b-binding protein (C4BP) at a site similar to that used by the natural ligand C4b
- 2001
-
Ingår i: European Journal of Immunology. - 1521-4141. ; 31:9, s. 2771-2780
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Tidskriftsartikel (refereegranskat)abstract
- Human complement regulators are important targets for pathogenic microorganisms. In one such interaction, Bordetella pertussis binds human C4b-binding protein (C4BP), a high-molecular-weight plasma protein that acts as inhibitor of the classical pathway of complement activation. At least two different B. pertussis surface components, one of which is the virulence factor filamentous hemagglutinin (FHA), contribute to the binding. We used a set of C4BP mutants and monoclonal antibodies to characterize the region in C4BP that binds B. pertussis and analyzed the salt sensitivity of the interaction. These studies indicated that positively charged residues at the interface between complement control protein modules 1-2 in the C4BP alpha-chain are important for binding, and that the site in C4BP that binds B. pertussis is very similar, but not identical, to the C4b-binding site. Bacteria-bound C4BP retained its complement regulatory function and B. pertussis selectively bound C4BP in human plasma, indicating that binding occurs also in vivo. Together, these findings indicate that B. pertussis exploits a site in C4BP, resembling that used by the natural ligand C4b.
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| 13. |
- Bergman Bruhn, Åsa, et al.
(författare)
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Motivational factors for occupational safety and health improvements : A mixed-method study within the Swedish equine sector
- 2023
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Ingår i: Safety Science. - : Elsevier. - 0925-7535 .- 1879-1042. ; 159
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning systematic occupational safety and health management is beneficial for both individuals and organizations, and employee motivation seems to be crucial for positive outcomes. Occupational safety and health issues are a major concern for the Swedish equine sector since the work environment in horse stables is known to be characterized by low mechanization, high physical workloads, and high injury risks. The purpose of this study was to gain an increased understanding of how systematic occupational safety and health management is performed and which factors that influence motivation for occupational safety and health improvements in the Swedish equine sector. An explanatory sequential mixed-methods study, based on quantitative data from questionnaires and qualitative data from semi-structured interviews, was conducted. Various statistical analyses were performed to obtain quantitative data and an abductive applied thematic analysis was applied for the qualitative data. The results indicate that both intrinsic motivators, i.e. attitudes, values, and influence, as well as contextual factors such as motivational management, occupational culture, and workplace resources, influence compliance in systematic occupational safety and health management and participation in occupational safety and health improvements, which in turn affect workplace outcomes regarding safety and health. The positive relationship found between an implemented and functioning systematic occupational safety and health management and employee motivation for occupational safety and health improvements indicate the importance of employee involvement and participation. Understanding the motivational factors for occupational safety and health improvements from an employee perspective is an important step to creating healthy and sustainable workplaces.
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| 14. |
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| 15. |
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| 16. |
- Bernsel, Andreas, et al.
(författare)
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Prediction of membrane-protein topology from first principles
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:20, s. 7177-7181
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Tidskriftsartikel (refereegranskat)abstract
- The current best membrane-protein topology-prediction methods are typically based on sequence statistics and contain hundreds of parameters that are optimized on known topologies of membrane proteins. However, because the insertion of transmembrane helices into the membrane is the outcome of molecular interactions among protein, lipids and water, it should be possible to predict topology by methods based directly on physical data, as proposed >20 years ago by Kyte and Doolittle. Here, we present two simple topology-prediction methods using a recently published experimental scale of position-specific amino acid contributions to the free energy of membrane insertion that perform on a par with the current best statistics-based topology predictors. This result suggests that prediction of membrane-protein topology and structure directly from first principles is an attainable goal, given the recently improved understanding of peptide recognition by the translocon.
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| 17. |
- Bilén, Anna-Karin, et al.
(författare)
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Miljökvalitetsmålen 2016 : Årlig uppföljning av miljökvalitetsmålen
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Blekinge bedöms inte något miljökvalitetsmål vara möjligt att nå till år 2020. För att kunna lämna över ett hållbart samhälle till nästa generation krävs förebyggande arbete, ef?????????????????r. Ambitionerna måste öka och miljöfrågorna prioriteras högre på den politiska agendan.De mål som rör biologisk mångfald och bevarande av kulturmiljö följer enneutral eller negativ trend. I odlingslandskapet leder färre lantbrukare ochbrist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och????????????????????????????????????????,främst möte insekter.För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar.Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen.Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Lokala och regionala åtgärder såsom arbete för en giftfri förskola och minskade utsläpp av mikroplaster är steg i rätt riktning.Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Det pågår insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
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| 18. |
- Blom, Anna M., et al.
(författare)
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A novel interaction between type IV pili of Neisseria gonorrhoeae and the human complement regulator C4B-binding protein
- 2001
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 166:11, s. 6764-6770
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Tidskriftsartikel (refereegranskat)abstract
- C4b-binding protein (C4BP) is an important plasma inhibitor of the classical pathway of complement activation. Several bacterial pathogens bind C4BP, which may contribute to their virulence. In the present report we demonstrate that isolated type IV pili from Neisseria gonorrhoeae bind human C4BP in a dose-dependent and saturable manner. C4BP consists of seven identical alpha-chains and one beta-chain linked together with disulfide bridges. We found that pili bind to the alpha-chain of C4BP, which is composed of eight homologous complement control protein (CCP) domains. From the results of an inhibition assay with C4b and a competition assay in which we tested mutants of C4BP lacking individual CCPs, we concluded that the binding area for pili is localized to CCP1 and CCP2 of the alpha-chain. The binding between pili and C4BP was abolished at 0.25 M NaCl, implying that it is based mostly on ionic interactions, similarly to what have been observed for C4b-C4BP binding. Furthermore, the N-terminal part of PilC, a structural component of pili, appeared to be responsible for binding of C4BP. Membrane cofactor protein, previously shown to be a receptor for pathogenic N. gonorrhoeae on the surface of epithelial cells, competed with C4BP for binding to pili only at high concentrations, suggesting that different parts of pili are involved in these two interactions. Accordingly, high concentrations of C4BP were required to inhibit binding of N. gonorrhoeae to Chang conjunctiva cells, and no inhibition of binding was observed with cervical epithelial cells.
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| 19. |
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| 20. |
- Brandén, Gunnar
(författare)
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Understanding Intergenerational Mobility : Inequality, Student Aid and Nature-Nurture Interactions
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay I: A body of evidence has emerged in the literature on intergenerational mobility documenting that unequal countries experience less social mobility: a relationship known as the Great Gatsby Curve. In this paper I estimate the Great Gatsby Curve within Sweden across 125 commuting zones and 20 cohorts, exploiting both cross-sectional and longitudinal variation. I find that children who were exposed to higher levels of inequality during childhood experienced less social mobility as adults, thereby confirming the existence of a Great Gatsby Curve in Sweden. I also present new evidence on the underlying mechanisms of the Great Gatsby Curve. By decomposing intergenerational mobility into separate transmission channels, I find that the Great Gatsby Curve is exclusively driven by the mediating effect that children's educational attainment and development of cognitive and non-cognitive skills has on the persistence of income across generations. Hence, the results suggest that adverse effects of inequality on mobility can be alleviated by policies that target children's educational attainment and development of cognitive and non-cognitive skills.
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| 21. |
- Carlin, Aaron F., et al.
(författare)
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Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
- 2009
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 206:8, s. 1691-1699
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Tidskriftsartikel (refereegranskat)abstract
- Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS. protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.
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| 22. |
- Carlsson, Fredric, et al.
(författare)
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Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.
- 2003
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 198:7, s. 1057-1068
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Tidskriftsartikel (refereegranskat)abstract
- The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.
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| 23. |
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| 24. |
- Carlsson, Fredric, et al.
(författare)
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Signal sequence directs localized secretion of bacterial surface proteins.
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 442:7105, s. 943-946
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Tidskriftsartikel (refereegranskat)abstract
- All living cells require specific mechanisms that target proteins to the cell surface. In eukaryotes, the first part of this process involves recognition in the endoplasmic reticulum of amino-terminal signal sequences and translocation through Sec translocons, whereas subsequent targeting to different surface locations is promoted by internal sorting signals(1). In bacteria, N-terminal signal sequences promote translocation across the cytoplasmic membrane, which surrounds the entire cell, but some proteins are nevertheless secreted in one part of the cell by poorly understood mechanisms(2,3). Here we analyse localized secretion in the Gram-positive pathogen Streptococcus pyogenes, and show that the signal sequences of two surface proteins, M protein and protein F ( PrtF), direct secretion to different subcellular regions. The signal sequence of M protein promotes secretion at the division septum, whereas that of PrtF preferentially promotes secretion at the old pole. Our work therefore shows that a signal sequence may contain information that directs the secretion of a protein to one subcellular region, in addition to its classical role in promoting secretion. This finding identifies a new level of complexity in protein translocation and emphasizes the potential of bacterial systems for the analysis of fundamental cell-biological problems(4).
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| 25. |
- Catton, Erin A., et al.
(författare)
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Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
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