83 research outputs found
Reconstructing phylogenetic level-1 networks from nondense binet and trinet sets
Binets and trinets are phylogenetic networks with two and three leaves, respectively. Here we consider the problem of deciding if there exists a binary level-1 phylogenetic network displaying a given set T of binary binets or trinets over a taxon set X, and constructing such a network whenever it exists. We show that this is NP-hard for trinets but polynomial-time solvable for binets. Moreover, we show that the problem is still polynomial-time solvable for inputs consisting of binets and trinets as long as the cycles in the trinets have size three. Finally, we present an O(3^{|X|} poly(|X|)) time algorithm for general sets of binets and trinets. The latter two algorithms generalise to instances containing level-1 networks with arbitrarily many leaves, and thus provide some of the first supernetwork algorithms for computing networks from a set of rooted 1 phylogenetic networks
Comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation
Limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased K(m) for 3'-sialylactose or 6'-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04(NA-H275Y) and RG-CA04 x Brisbane(NA-H275Y) viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCal(HA,NA), RG-NewCal(HA,NA-H275Y), RG-Brisbane(HA,NA-H275Y), and RG-NewCal(HA) x Brisbane(NA-H275Y) viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naive ferret model.published_or_final_versio
Comparable fitness and transmissibility between Oseltamivir-Resistant Pandemic 2009 and seasonal H1N1 Influenza Viruses with the H275Y Neuraminidase Mutation
Conference Theme: Translating Health Research into Policy and Practice for Health of the PopulationPoster Presentations - Emerging / Infectious Diseases: no. P65-Ab0010INTRODUCTION: Neuraminidase (NA) inhibitors are one of the limited options for the control of influenza. The H275Y NA mutation, which confers resistance to oseltamivir carboxylate, was initially considered to be of little clinical consequence due to limited detection of this mutation in field isolates prior to 2007-2008, when a globally spreading H275Y variant emerged. Oseltamivir-resistant A(H1N1)pdm09 viruses with the H275Y NA mutation has been reported since 2009 but have not replaced the …published_or_final_versio
Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the Pandemic H1N1 Influenza virus in ferrets
Conference Theme: Translating Health Research into Policy and Practice for Health of the PopulationPoster Presentations: Emerging / Infectious Diseases: no. P66-Ab0011published_or_final_versio
Timing and minimal access surgery for sciatica: a summary of two randomized trials
Scientific Assessment and Innovation in Neurosurgical Treatment Strategie
Big Domains Are Novel Ca2+-Binding Modules: Evidences from Big Domains of Leptospira Immunoglobulin-Like (Lig) Proteins
binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. with dissociation constants of 2–4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. binding
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