98 research outputs found

    Adonis on Conflicts, Wars and Crises in the Middle East: Poetical Answers and Political Readings of the Past

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    I sin bok VĂ„ld och islam (svensk översĂ€ttning 2016) har den syriske poeten Adonis gett sin bild av varför situationen ser ut som den gör i Mellanöstern. Enligt Adonis utgör den islamiska traditionen och ett allt för starkt fasthĂ„llande vid traditionen ett problem som förhindrar förnyelse och nytĂ€nkande. Även om Adonis ger sin bild av situationen Ă€r det uppenbart att hans analys saknar viktiga nyanser. IstĂ€llet för att peka pĂ„ interna variationer och motsĂ€ttningar kring hur exempelvis bĂ„de religionen islam har tolkats och förstĂ„tt och hur muslimer har debatterat vad som kan avses med tradition sĂ„ mĂ„lar Adonis, speciellt i VĂ„ld och islam,  en negativ bild dĂ€r variation, motsĂ€ttningar och konflikter nedtonas. Dessa lĂ€sningar av historien Ă€r dock inget nya för Adonis och han har vid flera tillfĂ€llen framhĂ„llit dessa teman i sin poesi och essĂ€er

    Equilibrium-fluctuation-analysis of single liposome binding events reveals how cholesterol and Ca2+ modulate glycosphingolipid trans-interactions

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    Carbohydrate-carbohydrate interactions (CCIs) are of central importance for several biological processes. However, the ultra-weak nature of CCIs generates difficulties in studying this interaction, thus only little is known about CCIs. Here we present a highly sensitive equilibrium-fluctuation-analysis of single liposome binding events to supported lipid bilayers (SLBs) based on total internal reflection fluorescence (TIRF) microscopy that allows us to determine apparent kinetic rate constants of CCIs. The liposomes and SLBs both contained natural Le(x) glycosphingolipids (Gal beta 4( Fuc alpha 3) GlcNAc beta 3Gal beta 4Glc beta 1Cer), which were employed to mimic cell-cell contacts. The kinetic parameters of the self-interaction between Le(x)-containing liposomes and SLBs were measured and found to be modulated by bivalent cations. Even more interestingly, upon addition of cholesterol, the strength of the CCIs increases, suggesting that this interaction is strongly influenced by a cholesterol-dependent presentation and/or spatial organization of glycosphingolipids in cell membranes

    A virus biosensor with single virus-particle sensitivity based on fluorescent vesicle labels and equilibrium fluctuation analysis

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    Biosensors allowing for the rapid and sensitive detection of viral pathogens in environmental or clinical samples are urgently needed to prevent disease outbreaks and spreading. We present a bioanalytical assay for the detection of whole viral particles with single virus sensitivity. Specifically, we focus on the detection of human norovirus, a highly infectious virus causing gastroenteritis. In our assay configuration, virus-like particles are captured onto a supported lipid bilayer containing a virus-specific glycolipid and detected after recognition by a glycolipid-containing fluorescent vesicle. Read-out is performed after illumination of the vesicle labels by total internal reflection fluorescence microscopy. This allows for visualization of individual vesicles and for recording of their binding kinetics under equilibrium conditions (equilibrium fluctuation analysis), as demonstrated previously. In this work we extend the concept and demonstrate that this simple assay setup can be used as a bioanalytical assay for the detection of virus particles at a limit of detection of 16 fM. Furthermore, we demonstrate how the analysis of the single vesicle-virus-like particle interaction dynamics can contribute to increase the accuracy and sensitivity of the assay by discriminating specific from non-specific binding events. This method is suggested to be generally applicable, provided that these events display different interaction kinetics

    The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection.

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    In November 2004, 116 individuals in an elderly nursing home in El Grao de CastellĂłn, Spain were symptomatically infected with genogroup II.4 (GII.4) norovirus. The global attack rate was 54.2%. Genotyping of 34 symptomatic individuals regarding the FUT2 gene revealed that one patient was, surprisingly, a non-secretor, hence indicating secretor-independent infection. Lewis genotyping revealed that Lewis-positive and negative individuals were susceptible to symptomatic norovirus infection indicating that Lewis status did not predict susceptibility. Saliva based ELISA assays were used to determine binding of the outbreak virus to saliva samples. Saliva from a secretor-negative individual bound the authentic outbreak GII.4 Valencia/2004/Es virus, but did not in contrast to secretor-positive saliva bind VLP of other strains including the GII.4 Dijon strain. Amino acid comparison of antigenic A and B sites located on the external loops of the P2 domain revealed distinct differences between the Valencia/2004/Es and Dijon strains. All three aa in each antigenic site as well as 10/11 recently identified evolutionary hot spots, were unique in the Valencia/2004/Es strain compared to the Dijon strain. To the best of our knowledge, this is the first example of symptomatic GII.4 norovirus infection of a Le(a+b-) individual homozygous for the G428A nonsense mutation in FUT2. Taken together, our study provides new insights into the host genetic susceptibility to norovirus infections and evolution of the globally dominating GII.4 viruses.Original Publication: Beatrice Carlsson, Elin Kindberg, Javier Buesa, Gustaf E Rydell, Marta Fos LidĂłn, Rebeca Montava, Reem Abu Mallouh, Ammi Grahn, JesĂșs RodrĂ­guez-DĂ­az, Juan Bellido, Alberto Arnedo, Göran Larson and Lennart Svensson, The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection., 2009, PLoS ONE, (4), 5, e5593. http://dx.doi.org/10.1371/journal.pone.0005593 Licensed under Creative Common

    Arrival-angle anomalies across the USArray Transportable Array

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    We construct composite maps of surface-wave arrival-angle anomalies using clustered earthquakes and an array method for measuring wave-front geometry. This results in observations of arrival angles covering the entire footprint of the USArray Transportable Array during 2006–2010. Bands of arrival-angle deviations in the propagation direction indicate the presence of heterogeneous velocity structure both inside and outside of the array. We compare the observed patterns to arrival angles predicted using two global tomographic models, the mantle model S362ANI and the surface-wave-dispersion model GDM52. We use both ray-theory-based prediction methods and measurements on synthetic data calculated using a spectral-element method. Both models and all prediction methods produce similar mean arrival angles and long-wavelength patterns of anomalies which are similar to the observations. Predicted short-wavelength features generally do not agree with the observations. The spectral-element method produces some complexity that is not obtained using the ray-theory-based methods; this predicted complexity is similar in character to the observed patterns, but does not match them

    Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype–Dependent Manner

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    Background. The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo–blood group antigens (HBGAs) in an RV genotype–dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy

    b3galt6 Knock-out zebrafish recapitulate ÎČ3GalT6-deficiency disorders in human and reveal a trisaccharide proteoglycan linkage region

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    Proteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediated b3galt6 knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human beta 3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study, therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention

    The Mid-infrared Instrument for JWST and Its In-flight Performance

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    The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 ÎŒm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∌ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI
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