620 research outputs found

    Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702

    Get PDF
    The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while others had a pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo.published_or_final_versio

    Gene expression patterns during adaptation of a helminth parasite to different environmental niches

    Get PDF
    Using a genomic microarray, gene expression at three different developmental stages of the schistosome parasite were analyzed, resulting in the identification of 1154 developmentally enriched transcripts

    Most vital segment barriers

    Get PDF
    We study continuous analogues of "vitality" for discrete network flows/paths, and consider problems related to placing segment barriers that have highest impact on a flow/path in a polygonal domain. This extends the graph-theoretic notion of "most vital arcs" for flows/paths to geometric environments. We give hardness results and efficient algorithms for various versions of the problem, (almost) completely separating hard and polynomially-solvable cases

    Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

    Get PDF
    Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction
    corecore