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  • 1
    Publication Date: 2015-05-20
    Description: Single genes are often subject to alternative splicing, which generates alternative mature mRNAs. This phenomenon is widespread in animals, and observed in over 90% of human genes. Recent data suggest it may also be common in Apicomplexa. These parasites have small genomes, and economy of DNA is evolutionarily favoured in this phylum. We investigated the mechanism of alternative splicing in Toxoplasma gondii , and have identified and localized TgSR3, a homologue of ASF/SF2 (alternative-splicing factor/splicing factor 2, a serine-arginine–rich, or SR protein) to a subnuclear compartment. In addition, we conditionally overexpressed this protein, which was deleterious to growth. qRT-PCR was used to confirm perturbation of splicing in a known alternatively-spliced gene. We performed high-throughput RNA-seq to determine the extent of splicing modulated by this protein. Current RNA-seq algorithms are poorly suited to compact parasite genomes, and hence we complemented existing tools by writing a new program, GeneGuillotine, that addresses this deficiency by segregating overlapping reads into distinct genes. In order to identify the extent of alternative splicing, we released another program, JunctionJuror, that detects changes in intron junctions. Using this program, we identified about 2000 genes that were constitutively alternatively spliced in T. gondii . Overexpressing the splice regulator TgSR3 perturbed alternative splicing in over 1000 genes.
    Keywords: Transcriptome Mapping - Monitoring Gene Expression
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 1999-12-03
    Description: Chemokine receptors serve as portals of entry for certain intracellular pathogens, most notably human immunodeficiency virus (HIV). Myxoma virus is a member of the poxvirus family that induces a lethal systemic disease in rabbits, but no poxvirus receptor has ever been defined. Rodent fibroblasts (3T3) that cannot be infected with myxoma virus could be made fully permissive for myxoma virus infection by expression of any one of several human chemokine receptors, including CCR1, CCR5, and CXCR4. Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin. These findings suggest that poxviruses, like HIV, are able to use chemokine receptors to infect specific cell subtypes, notably migratory leukocytes, but that their mechanisms of receptor interactions are distinct.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lalani, A S -- Masters, J -- Zeng, W -- Barrett, J -- Pannu, R -- Everett, H -- Arendt, C W -- McFadden, G -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1968-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The John P. Robarts Research Institute and Department of Immunology, The University of Western Ontario, London, Ontario N6G 2V4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583963" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antibodies/immunology ; Benzoquinones ; Cell Line ; Cercopithecus aethiops ; Chemokine CCL5/pharmacology ; Gene Expression ; Humans ; Lactams, Macrocyclic ; Mice ; Myxoma virus/genetics/*metabolism ; Pertussis Toxin ; Quinones/pharmacology ; Receptors, CCR1 ; Receptors, CCR5/immunology/metabolism ; Receptors, CXCR4/metabolism ; Receptors, Chemokine/*metabolism ; Receptors, Virus/*metabolism ; Rifabutin/analogs & derivatives ; Signal Transduction ; Tumor Cells, Cultured ; Virulence Factors, Bordetella/pharmacology ; beta-Galactosidase/biosynthesis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McFadden, G -- New York, N.Y. -- Science. 1998 Jan 2;279(5347):40-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada N6G 2V4. mcfadden@rri.on.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9441409" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis ; Codon ; Genes, Viral ; Glutathione Peroxidase/genetics/*metabolism ; HeLa Cells ; Humans ; Hydrogen Peroxide/metabolism ; Keratinocytes/cytology/metabolism ; Molluscum contagiosum virus/enzymology/*genetics/*metabolism ; Oxidation-Reduction ; *Oxidative Stress ; Phagocytes/metabolism ; Proteins/genetics/*metabolism ; Reactive Oxygen Species/*metabolism ; Selenoproteins ; Viral Proteins/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-11-20
    Description: Many poxvirus-encoded virulence factors have been identified as proteins that are secreted from infected cells. The major secreted protein (37 kilodaltons) from cells infected with myxoma virus is encoded by the M-T7 open reading frame. This protein has significant sequence similarity to the human and mouse receptors for interferon-gamma (IFN-gamma). Furthermore, the myxoma M-T7 protein specifically binds rabbit IFN-gamma and inhibits the biological activity of extracellular IFN-gamma, one of the key regulatory cytokines in the host immune response against viral infections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Upton, C -- Mossman, K -- McFadden, G -- New York, N.Y. -- Science. 1992 Nov 20;258(5086):1369-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Alberta, Edmonton, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1455233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cells, Cultured ; Cloning, Molecular ; *Genes, Viral ; In Vitro Techniques ; Interferon-gamma/metabolism ; Molecular Sequence Data ; Myxoma virus/*genetics/pathogenicity ; Protein Binding ; Rabbits ; Receptors, Interferon/*genetics ; Restriction Mapping ; Sequence Alignment ; Sequence Homology, Amino Acid ; Viral Interference ; Viral Proteins/*genetics ; Viral Structural Proteins/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 2 (1990), S. 2147-2156 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The linear stability of circular Couette flow between concentric infinite cylinders is considered for the case when the inner cylinder is rotated at a constant angular velocity and the outer cylinder is driven sinusoidally in time with zero mean rotation. This configuration was studied experimentally by Walsh and Donnelly [Phys. Rev. Lett. 60, 700 (1988)]. The critical Reynolds numbers calculated from linear stability theory agree with the experimental values, except at large modulation amplitudes and small frequencies. The theoretical values are obtained using Floquet theory implemented in two distinct approaches: (1) a truncated Fourier series representation in time and (2) a fundamental solution matrix based on a Chebyshev-pseudospectral representation in space. For large-amplitude, low-frequency modulation, the linear eigenfunctions are temporally complex, consisting of a quiescent interval followed by rapid change in the perturbed flow velocities.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 2 (1990), S. 700-705 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The linear stability of circular Couette flow between concentric infinite cylinders is considered for the case that the stationary outer cylinder is a crystal–melt interface rather than a rigid surface. A radial temperature difference is maintained across the liquid gap, and equations for heat transport in the crystal and melt phases are included to extend the ordinary formulation of this problem. The stability of this two-phase system depends on the Prandtl number. For small Prandtl number the linear stability of the two-phase system is given by the classical results for a rigid-walled system. For increasing values of the Prandtl number, convective heat transport becomes significant and the system becomes increasingly less stable. Previous results in a narrow-gap approximation are extended to the case of a finite gap, and both axisymmetric and nonaxisymmetric disturbance modes are considered. The two-phase system becomes less stable as the finite gap tends to the narrow-gap limit. The two-phase system is more stable to nonaxisymmetric modes with azimuthal wavenumber n=1; the stability of these n=1 modes is sensitive to the latent heat of fusion.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Fluids 28 (1985), S. 2716-2722 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The effect of rigid vertical boundaries on the onset of convective instability is calculated for the salt finger regime of double-diffusive convection. The unperturbed state is a quiescent fluid with constant vertical gradients of temperature and solute, which are stabilizing and destabilizing, respectively. The horizontal boundaries are taken to be stress-free and perfectly conducting. The lateral boundaries are perfectly insulating for solute. Changing from thermally insulating to thermally conducting sidewalls results in a strong destabilization of the flow for large thermal Rayleigh numbers even in the limit that the separation between the sidewalls approaches infinity. Further, for thermally conducting sidewalls, a decrease in the separation of the sidewalls may destabilize the system.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 5 (1993), S. 1891-1903 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The linear stability of a modulated Taylor–Couette system when the inner cylindrical boundary consists of a crystalline solid-liquid interface is considered. Both experimentally and in numerical calculations it is found that the two-phase system is significantly less stable than the analogous rigid-walled system for materials with moderately large Prandtl numbers. A numerical treatment based on Floquet theory is described, which gives results that are in good agreement with preliminary experimental findings. In addition, this instability is further examined by carrying out a formal asymptotic expansion of the solution in the limit of large Prandtl number. In this limit the Floquet analysis is considerably simplified, and the linear stability of the modulated system can be determined to leading order through a conventional stability analysis, without recourse to Floquet theory. The resulting simplified problem is then studied for both the narrow gap geometry and for the case of a finite gap. It is surprising that the determination of the linear stability of the two-phase system is considerably simpler than that of the rigid-walled system, despite the complications introduced by the presence of the crystal-melt interface.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 3 (1991), S. 2847-2858 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The effect of vertical, sinusoidal, time-dependent gravitational acceleration on the onset of solutal convection during directional solidification is analyzed in the limit of large modulation frequency Ω. When the unmodulated state is unstable, the modulation amplitude required to stabilize the system is determined by the method of averaging, and is O(Ω). Comparison of the results from the averaged equations with numerical solutions of the full linear stability equations (based on Floquet theory) show that the difference is O(Ω1/2). When the unmodulated state is stable, resonant modes of instability occur at large modulation amplitude. These are analyzed using matched asymptotic expansions to elucidate the boundary-layer structure for both the Rayleigh–Bénard and directional solidification configurations. The leading-order term for the modulation amplitude is of O(Ω2); the first-order correction of O(Ω3/2) is calculated, and the results are compared with numerical solutions of the full linear stability equations. Based on these analyses, a thorough examination of the dependence of the stability criteria on the unmodulated Rayleigh number, Schmidt number, and distribution coefficient, is carried out.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Fluids 9 (1997), S. 1870-1879 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We present a diffuse-interface treatment of the internal gravity waves which have been observed experimentally by Berg et al. in xenon near its thermodynamic critical point. The results are compared with theoretical predictions by Berg et al. that were obtained using separate models above and below the critical temperature Tc. The diffuse-interface model applies both above and below Tc, and is formulated by using the density as an order parameter. The diffuse interface is represented as a transition zone of rapid but smooth density variation in the model, and density gradients appear in a capillary tensor, or Korteweg stress term, in the momentum equation. We obtain static density profiles, compute internal wave frequencies and compare with the experimental data and theoretical results of Berg et al. both above and below the critical temperature. The results reveal a singularity in the diffuse-interface model in the limit of incompressible perturbations.
    Type of Medium: Electronic Resource
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