132 research outputs found

    Students' ontological security and agency in science education - an example from reasoning about the use of gene technology

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    This paper reports on a study of how students' reasoning about socioscientific issues is framed by three dynamics: societal structures, agency and how trust and security issues are handled. Examples from gene technology were used as the forum for interviews with 13 Swedish highschool students (year 11, age 17–18). A grid based on modalities from the societal structures described by Giddens was used to structure the analysis. The results illustrate how the participating students used both modalities for 'Legitimation' and 'Domination' to justify positions that accept or reject new technology. The analysis also showed how norms and knowledge can be used to justify opposing positions in relation to building trust in science and technology, or in democratic decisions expected to favour personal norms. Here, students accepted or rejected the authority of experts based on perceptions of the knowledge base that the authority was seen to be anchored in. Difficulty in discerning between material risks (reduced safety) and immaterial risks (loss of norms) was also found. These outcomes are used to draw attention to the educational challenges associated with students' using knowledge claims (Domination) to support norms (Legitimation) and how this is related to the development of a sense of agency in terms of sharing norms with experts or with laymen.Web of Scienc

    Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.

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    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

    Media studies in higher education: a case study of the social construction and reception of pedagogic discourse.

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    This thesis develops a social semiotic analysis of pedagogic\ud communication in a media studies course which the author taught from\ud 1993 until 1997. The author taught the course as part of an undergraduate\ud honours degree about science, culture and communication in a university in\ud the UK. The analysis describes the structuring of pedagogic practice on the\ud level of the curriculum, and within the author's own "Communicating\ud Science" module. The analysis also describes student receptions of\ud pedagogic practice. The research reveals the extent to which pedagogic\ud communication served to sustain the order which the degree was designed\ud to contest: an order based on positivist conceptions of science, science\ud communication, and therein, media theory and practice. The thesis\ud concludes by proposing a theory of instruction which is designed to enable\ud students to acquire the rules of realisation for more critical forms of science\ud communication

    Extreme Sequence Divergence but Conserved Ligand-Binding Specificity in Streptococcus pyogenes M Protein

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    Many pathogenic microorganisms evade host immunity through extensive sequence variability in a protein region targeted by protective antibodies. In spite of the sequence variability, a variable region commonly retains an important ligand-binding function, reflected in the presence of a highly conserved sequence motif. Here, we analyze the limits of sequence divergence in a ligand-binding region by characterizing the hypervariable region (HVR) of Streptococcus pyogenes M protein. Our studies were focused on HVRs that bind the human complement regulator C4b-binding protein (C4BP), a ligand that confers phagocytosis resistance. A previous comparison of C4BP-binding HVRs identified residue identities that could be part of a binding motif, but the extended analysis reported here shows that no residue identities remain when additional C4BP-binding HVRs are included. Characterization of the HVR in the M22 protein indicated that two relatively conserved Leu residues are essential for C4BP binding, but these residues are probably core residues in a coiled-coil, implying that they do not directly contribute to binding. In contrast, substitution of either of two relatively conserved Glu residues, predicted to be solvent-exposed, had no effect on C4BP binding, although each of these changes had a major effect on the antigenic properties of the HVR. Together, these findings show that HVRs of M proteins have an extraordinary capacity for sequence divergence and antigenic variability while retaining a specific ligand-binding function

    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)

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    AbstractOBJECTIVESThis 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.BACKGROUNDLow-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.METHODSIn 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.RESULTSDalteparin 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).CONCLUSIONSWhen 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

    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.

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    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

    Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5

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    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 ÎČ 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 ÎČ 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

    Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

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    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-alpha and thus shortened treatment duration (P <0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P <0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an antiviral effect differently regulated across IL28B genotypes.Peer reviewe

    Late gadolinium uptake demonstrated with magnetic resonance in patients where automated PERFIT analysis of myocardial SPECT suggests irreversible perfusion defect

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    <p>Abstract</p> <p>Background</p> <p>Myocardial perfusion single photon emission computed tomography (MPS) is frequently used as the reference method for the determination of myocardial infarct size. PERFIT<sup>Ÿ </sup>is a software utilizing a three-dimensional gender specific, averaged heart model for the automatic evaluation of myocardial perfusion. The purpose of this study was to compare the perfusion defect size on MPS, assessed with PERFIT, with the hyperenhanced volume assessed by late gadolinium enhancement magnetic resonance imaging (LGE) and to relate their effect on the wall motion score index (WMSI) assessed with cine magnetic resonance imaging (cine-MRI) and echocardiography (echo).</p> <p>Methods</p> <p>LGE was performed in 40 patients where clinical MPS showed an irreversible uptake reduction suggesting a myocardial scar. Infarct volume, extent and major coronary supply were compared between MPS and LGE as well as the relationship between infarct size from both methods and WMSI.</p> <p>Results</p> <p>MPS showed a slightly larger infarct volume than LGE (MPS 29.6 ± 23.2 ml, LGE 22.1 ± 16.9 ml, p = 0.01), while no significant difference was found in infarct extent (MPS 11.7 ± 9.4%, LGE 13.0 ± 9.6%). The correlation coefficients between methods in respect to infarct size and infarct extent were 0.71 and 0.63 respectively. WMSI determined with cine-MRI correlated moderately with infarct volume and infarct extent (cine-MRI vs MPS volume r = 0.71, extent r = 0.71, cine-MRI vs LGE volume r = 0.62, extent r = 0.60). Similar results were achieved when wall motion was determined with echo. Both MPS and LGE showed the same major coronary supply to the infarct area in a majority of patients, Kappa = 0.84.</p> <p>Conclusion</p> <p>MPS and LGE agree moderately in the determination of infarct size in both absolute and relative terms, although infarct volume is slightly larger with MPS. The correlation between WMSI and infarct size is moderate.</p
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