826 research outputs found

    3D co-cultures of osteoblasts and endothelial cells in DegraPol foam: Histological and high field MRI analyses of pre-engineered capillary networks in bone grafts

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    Tissue engineering of bone grafts was addressed in a critical size model on the chick chorioallantoic membrane model (CAM assay), using DegraPol(R) (DP) foam as scaffold material. The scaffolds were seeded with cultures of human osteoblasts (OB) and human en notdo notthelial cells (EC), respectively, or with a co-culture of the two cell types (control: no cells). In vitro samples (7 days cultivation) and ex vivo CAM samples at incubation day 15 (ID 15) were analyzed by high field magnetic resonance imaging (MRI) and histology. The co-culture system performed best with respect to perfusion, as assessed by contrast-enhanced MRI using Gd-DTPA. The scaffold seeded by the co-culture supported an increased vascular ingrowth, which was confirmed by histological analysis. DP foam is a suitable scaffold for bone tissue engineering and the MRI technique allows for non-destructive and quantitative assessment of perfusion capability during early stages of bone forming constructs

    Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase

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    This work was supported by the Medical Research Council and the Scottish Funding Council.Influenza virus sialidase has an essential role in the virus’ life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the ‘150-loop’, providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.Publisher PDFPeer reviewe

    Heterogeneous ice nucleation on dust particles sourced from nine deserts worldwide - Part 1: Immersion freezing

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    Desert dust is one of the most abundant ice nucleating particle types in the atmosphere. Traditionally, clay minerals were assumed to determine the ice nucleation ability of desert dust and constituted the focus of ice nucleation studies over several decades. Recently some feldspar species were identified to be ice active at much higher temperatures than clay minerals, redirecting studies to investigate the contribution of feldspar to ice nucleation on desert dust. However, so far no study has shown the atmospheric relevance of this mineral phase. For this study four dust samples were collected after airborne transport in the troposphere from the Sahara to different locations (Crete, the Peloponnese, Canary Islands, and the Sinai Peninsula). Additionally, 11 dust samples were collected from the surface from nine of the biggest deserts worldwide. The samples were used to study the ice nucleation behavior specific to different desert dusts. Furthermore, we investigated how representative surface-collected dust is for the atmosphere by comparing to the ice nucleation activity of the airborne samples. We used the IMCA-ZINC setup to form droplets on single aerosol particles which were subsequently exposed to temperatures between 233 and 250 K. Dust particles were collected in parallel on filters for offline cold-stage ice nucleation experiments at 253–263 K. To help the interpretation of the ice nucleation experiments the mineralogical composition of the dusts was investigated. We find that a higher ice nucleation activity in a given sample at 253 K can be attributed to the K-feldspar content present in this sample, whereas at temperatures between 238 and 245 K it is attributed to the sum of feldspar and quartz content present. A high clay content, in contrast, is associated with lower ice nucleation activity. This confirms the importance of feldspar above 250 K and the role of quartz and feldspars determining the ice nucleation activities at lower temperatures as found by earlier studies for monomineral dusts. The airborne samples show on average a lower ice nucleation activity than the surface-collected ones. Furthermore, we find that under certain conditions milling can lead to a decrease in the ice nucleation ability of polymineral samples due to the different hardness and cleavage of individual mineral phases causing an increase of minerals with low ice nucleation ability in the atmospherically relevant size fraction. Comparison of our data set to an existing desert dust parameterization confirms its applicability for climate models. Our results suggest that for an improved prediction of the ice nucleation ability of desert dust in the atmosphere, the modeling of emission and atmospheric transport of the feldspar and quartz mineral phases would be key, while other minerals are only of minor importance

    Interaction of Na+ Ion With the Solvated Gramicidin A Transmembrane Channel

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    A 6-12-1 atom-atom pair potential for the interaction of a Na+ion with gramicidin A (GA) has been derived from ab initio SCF calculations on the intermolecular interaction energies between one Na+ion and GA molecular fragments. This potential has been used to obtain iso-energy maps, which in turn provide an energy profile of the Na+ion in the GA channel. We have applied this potential in Monte Carlo simulations in order to obtain i) the number of water molecules which can be placed inside the GA channel and ii) the hydration structures of the GA channel in the presence of one Na+ion
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