527 research outputs found

    Accumulation of copy-back viral genomes during respiratory syncytial virus infection is preceded by diversification of the copy-back viral genome population followed by selection

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    RNA viruses generate nonstandard viral genomes during their replication, including viral genomes of the copy-back (cbVGs) type that cannot replicate in the absence of a standard virus. cbVGs play a crucial role in shaping virus infection outcomes due to their ability to interfere with virus replication and induce strong immune responses. However, despite their critical role during infection, the principles that drive the selection and evolution of cbVGs within a virus population are poorly understood. As cbVGs are dependent on the virus replication machinery to be generated and replicated, we hypothesized that host factors that affect virus replication exert selective pressure on cbVGs and drive their evolution within a virus population. To test this hypothesis, we used respiratory syncytial virus (RSV) as a model and took an experimental evolution approach by serially passaging RSV in immune-competent human lung adenocarcinoma A549 control and immune-deficient A549 Signal transducer and activator of transcription 1 (STAT1) KO cells, which allow higher levels of virus replication. As predicted, we observed that virus populations accumulated higher amounts of cbVGs in the more permissive A549 STAT1 KO cells over time; however, unexpectedly, the predominant cbVG species after passages in the two conditions were different. While A549 STAT1 KO cells accumulated relatively short cbVGs, A549 control cells mainly contained cbVGs of much longer predicted size, which have not been described previously. These long cbVGs were predominant at first in both cell line

    Two new triterpenoid saponins from the leaves of Bupleurum lancifolium (Apiaceae)

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    Chemical investigation of the leaves of Bupleurum lancifolium led to the isolation and identification of two triterpenoid saponins previously undescribed named 3-O-[α-L-rhamnopyranosyl (1 → 4)-β-D-glucopyranosyl] echinocystic acid 28-O-β-D-glucopyranosyl ester (1) and 3-O-[α-L-rhamnopyranosyl (1 → 4)-β-D-glucopyranosyl] oleanolic acid 28-O-β-D-glucopyranosyl ester (2) along with the two known compounds isorhamnetin 3-rutinoside (3) and rutin (4). Their structures were elucidated by different spectroscopic methods, including HRESIMS analysis as well as 1D and 2D NMR experiments

    Comment on "First Observation of Ground State Dineutron Decay: 16Be"

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    A recent measurement [Spyrou et al., PRL 108, 102501 (2012)] of the in-flight decay of 16Be into 14Be+n+n has been interpreted as the first case of dineutron emission. Here we point out that the inclusion of the n-n interaction neglected in the description of the direct three-body decay can generate strong enhancements at low n-n relative energy and angle, as observed, without any need to invoke dineutron decay.Comment: Final version, published in Physical Review Letter

    The frequency and duration of Salmonella-macrophage adhesion events determines infection efficiency.

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    Salmonella enterica causes a range of important diseases in humans and a in a variety of animal species. The ability of bacteria to adhere to, invade and survive within host cells plays an important role in the pathogenesis of Salmonella infections. In systemic salmonellosis, macrophages constitute a niche for the proliferation of bacteria within the host organism. Salmonella enterica serovar Typhimurium is flagellated and the frequency with which this bacterium collides with a cell is important for infection efficiency. We investigated how bacterial motility affects infection efficiency, using a combination of population-level macrophage infection experiments and direct imaging of single-cell infection events, comparing wild-type and motility mutants. Non-motile and aflagellate bacterial strains, in contrast to wild-type bacteria, collide less frequently with macrophages, are in contact with the cell for less time and infect less frequently. Run-biased Salmonella also collide less frequently with macrophages but maintain contact with macrophages for a longer period of time than wild-type strains and infect the cells more readily. Our results suggest that uptake of S. Typhimurium by macrophages is dependent upon the duration of contact time of the bacterium with the cell, in addition to the frequency with which the bacteria collide with the cell.SA was supported by an Oliver Gatty studentship, and this work was funded from EU-ITN Transpol (PC), BBSRC Research Development Fellowship BB/H021930/1 (JAW and CEB).This is the final version of the article. It first appeared from the Royal Society. via http://dx.doi.org/10.1098/rstb.2014.003

    OPA1 functions in mitochondria and dysfunctions in optic nerve

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    OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA), a blinding disease that affects specifically the retinal ganglion cells (RGCs), which function consists in connecting the neuro-retina to the brain. OPA1 encodes an intra-mitochondrial dynamin, involved in inner membrane structures and ubiquitously expressed, raising the critical question of the origin of the disease pathophysiology. Here, we review the fundamental knowledge on OPA1 functions and regulations, highlighting their involvements in mitochondrial respiration, membrane dynamic and apoptosis. In light of these functions, we then describe the remarkable RGC mitochondrial network physiology and analyse data collected from animal models expressing OPA1 mutations. If, to date RGC mitochondria does not present any peculiarity at the molecular level, they represent possible targets of numerous assaults, like light, pressure, oxidative stress and energetic impairment, which jeopardize their function and survival, as observed in OPA1 mouse models. Although fascinating fields of investigation are still to be addressed on OPA1 functions and on DOA pathophysiology, we have reached a conspicuous state of knowledge with pertinent cell and animal models, from which therapeutic trials can be initiated and deeply evaluated

    Structure of 13^{13}Be probed via secondary beam reactions

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    The low-lying level structure of the unbound neutron-rich nucleus 13^{13}Be has been investigated via breakup on a carbon target of secondary beams of 14,15^{14,15}B at 35 MeV/nucleon. The coincident detection of the beam velocity 12^{12}Be fragments and neutrons permitted the invariant mass of the 12^{12}Be+nn and 12^{12}Be+nn+nn systems to be reconstructed. In the case of the breakup of 15^{15}B, a very narrow structure at threshold was observed in the 12^{12}Be+nn channel. Contrary to earlier stable beam fragmentation studies which identified this as a strongly interacting ss-wave virtual state in 13^{13}Be, analysis here of the 12^{12}Be+nn+nn events demonstrated that this was an artifact resulting from the sequential-decay of the 14^{14}Be(2+^+) state. Single-proton removal from 14^{14}B was found to populate a broad low-lying structure some 0.70 MeV above the neutron-decay threshold in addition to a less prominent feature at around 2.4 MeV. Based on the selectivity of the reaction and a comparison with (0-3)ω\hbar\omega shell-model calculations, the low-lying structure is concluded to most probably arise from closely spaced Jπ^\pi=1/2+^+ and 5/2+^+ resonances (Er_r=0.40±\pm0.03 and 0.850.11+0.15^{+0.15}_{-0.11} MeV), whilst the broad higher-lying feature is a second 5/2+^+ level (Er_r=2.35±\pm0.14 MeV). Taken in conjunction with earlier studies, it would appear that the lowest 1/2+^+ and 1/2^- levels lie relatively close together below 1 MeV.Comment: 14 pages, 13 figures, 2 tables. Accepted for publication in Physical Review

    The beta-decay of 22Al

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    In an experiment performed at the LISE3 facility of GANIL, we studied the decay of 22Al produced by the fragmentation of a 36Ar primary beam. A beta-decay half-life of 91.1 +- 0.5 ms was measured. The beta-delayed one- and two-proton emission as well as beta-alpha and beta-delayed gamma decays were measured and allowed us to establish a partial decay scheme for this nucleus. New levels were determined in the daughter nucleus 22Mg. The comparison with model calculations strongly favours a spin-parity of 4+ for the ground state of 22Al
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