1,131 research outputs found
An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response.
Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space.
IMPORTANCE In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response
A search for heavy Kaluza-Klein electroweak gauge bosons at the LHC
The feasibility for the observation of a certain leptonic Kaluza-Klein (KK)
hard process in {\em pp} interactions at the LHC is presented. Within the
TeV extra dimensional theoretical framework with the focus on
the KK excitations of the Standard Model and gauge bosons, the
hard-process, , has
been used where is the initial state parton, the final state lepton and
is the KK excitation of the
boson. For this study the analytic form for the hard process cross
section has been independently calculated by the authors and has been
implemented using the {\sc Moses} framework. The Moses framework itself, that
has been written by the authors, was used as an external process within the
{\sc Pythia} Monte Carlo generator which provides the phase space generation
for the final state leptons and partons from the initial state hadrons, and the
simulation of initial and final state radiation and hadronization. A brief
discussion of the possibility for observing and identifying the unique
signature of the KK signal given the current LHC program is also presented.Comment: 16 pages 10 figures, MCnet number: MCnet/10/06, Accepted by JHE
Landscape of fear visible from space
By linking ecological theory with freely-available Google Earth satellite imagery, landscape-scale footprints of behavioural interactions between predators and prey can be observed remotely. A Google Earth image survey of the lagoon habitat at Heron Island within Australia's Great Barrier Reef revealed distinct halo patterns within algal beds surrounding patch reefs. Ground truth surveys confirmed that, as predicted, algal canopy height increases with distance from reef edges. A grazing assay subsequently demonstrated that herbivore grazing was responsible for this pattern. In conjunction with recent behavioural ecology studies, these findings demonstrate that herbivores' collective antipredator behavioural patterns can shape vegetation distributions on a scale clearly visible from space. By using sequential Google Earth images of specific locations over time, this technique could potentially allow rapid, inexpensive remote monitoring of cascading, indirect effects of predator removals (e.g., fishing; hunting) and/or recovery and reintroductions (e.g., marine or terrestrial reserves) nearly anywhere on earth
Constraints on Non-Newtonian Gravity from Recent Casimir Force Measurements
Corrections to Newton's gravitational law inspired by extra dimensional
physics and by the exchange of light and massless elementary particles between
the atoms of two macrobodies are considered. These corrections can be described
by the potentials of Yukawa-type and by the power-type potentials with
different powers. The strongest up to date constraints on the corrections to
Newton's gravitational law are reviewed following from the E\"{o}tvos- and
Cavendish-type experiments and from the measurements of the Casimir and van der
Waals force. We show that the recent measurements of the Casimir force gave the
possibility to strengthen the previously known constraints on the constants of
hypothetical interactions up to several thousand times in a wide interaction
range. Further strengthening is expected in near future that makes Casimir
force measurements a prospective test for the predictions of fundamental
physical theories.Comment: 20 pages, crckbked.cls is used, to be published in: Proceedings of
the 18th Course of the School on Cosmology and Gravitation: The Gravitational
Constant. Generalized Gravitational Theories and Experiments (30 April- 10
May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata,
20pp. (Kluwer, in print, 2003
Mangroves enhance the biomass of coral reef fish communities in the Caribbean
Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs
Detecting the orientation of magnetic fields in galaxy clusters
Clusters of galaxies, filled with hot magnetized plasma, are the largest
bound objects in existence and an important touchstone in understanding the
formation of structures in our Universe. In such clusters, thermal conduction
follows field lines, so magnetic fields strongly shape the cluster's thermal
history; that some have not since cooled and collapsed is a mystery. In a
seemingly unrelated puzzle, recent observations of Virgo cluster spiral
galaxies imply ridges of strong, coherent magnetic fields offset from their
centre. Here we demonstrate, using three-dimensional magnetohydrodynamical
simulations, that such ridges are easily explained by galaxies sweeping up
field lines as they orbit inside the cluster. This magnetic drape is then lit
up with cosmic rays from the galaxies' stars, generating coherent polarized
emission at the galaxies' leading edges. This immediately presents a technique
for probing local orientations and characteristic length scales of cluster
magnetic fields. The first application of this technique, mapping the field of
the Virgo cluster, gives a startling result: outside a central region, the
magnetic field is preferentially oriented radially as predicted by the
magnetothermal instability. Our results strongly suggest a mechanism for
maintaining some clusters in a 'non-cooling-core' state.Comment: 48 pages, 21 figures, revised version to match published article in
Nature Physics, high-resolution version available at
http://www.cita.utoronto.ca/~pfrommer/Publications/pfrommer-dursi.pd
LHC Predictions from a Tevatron Anomaly in the Top Quark Forward-Backward Asymmetry
We examine the implications of the recent CDF measurement of the top-quark
forward-backward asymmetry, focusing on a scenario with a new color octet
vector boson at 1-3 TeV. We study several models, as well as a general
effective field theory, and determine the parameter space which provides the
best simultaneous fit to the CDF asymmetry, the Tevatron top pair production
cross section, and the exclusion regions from LHC dijet resonance and contact
interaction searches. Flavor constraints on these models are more subtle and
less severe than the literature indicates. We find a large region of allowed
parameter space at high axigluon mass and a smaller region at low mass; we
match the latter to an SU(3)xSU(3)/SU(3) coset model with a heavy vector-like
fermion. Our scenario produces discoverable effects at the LHC with only 1-2
inverse femtobarns of luminosity at 7-8 TeV. Lastly, we point out that a
Tevatron measurement of the b-quark forward-backward asymmetry would be very
helpful in characterizing the physics underlying the top-quark asymmetry.Comment: 35 pages, 10 figures, 4 table
Phenomenology of event shapes at hadron colliders
We present results for matched distributions of a range of dijet event shapes
at hadron colliders, combining next-to-leading logarithmic (NLL) accuracy in
the resummation exponent, next-to-next-to leading logarithmic (NNLL) accuracy
in its expansion and next-to-leading order (NLO) accuracy in a pure alpha_s
expansion. This is the first time that such a matching has been carried out for
hadronic final-state observables at hadron colliders. We compare our results to
Monte Carlo predictions, with and without matching to multi-parton tree-level
fixed-order calculations. These studies suggest that hadron-collider event
shapes have significant scope for constraining both perturbative and
non-perturbative aspects of hadron-collider QCD. The differences between
various calculational methods also highlight the limits of relying on
simultaneous variations of renormalisation and factorisation scale in making
reliable estimates of uncertainties in QCD predictions. We also discuss the
sensitivity of event shapes to the topology of multi-jet events, which are
expected to appear in many New Physics scenarios.Comment: 70 pages, 25 figures, additional material available from
http://www.lpthe.jussieu.fr/~salam/pp-event-shapes
Composite GUTs: models and expectations at the LHC
We investigate grand unified theories (GUTs) in scenarios where electroweak
(EW) symmetry breaking is triggered by a light composite Higgs, arising as a
Nambu-Goldstone boson from a strongly interacting sector. The evolution of the
standard model (SM) gauge couplings can be predicted at leading order, if the
global symmetry of the composite sector is a simple group G that contains the
SM gauge group. It was noticed that, if the right-handed top quark is also
composite, precision gauge unification can be achieved. We build minimal
consistent models for a composite sector with these properties, thus
demonstrating how composite GUTs may represent an alternative to supersymmetric
GUTs. Taking into account the new contributions to the EW precision parameters,
we compute the Higgs effective potential and prove that it realizes
consistently EW symmetry breaking with little fine-tuning. The G group
structure and the requirement of proton stability determine the nature of the
light composite states accompanying the Higgs and the top quark: a coloured
triplet scalar and several vector-like fermions with exotic quantum numbers. We
analyse the signatures of these composite partners at hadron colliders:
distinctive final states contain multiple top and bottom quarks, either alone
or accompanied by a heavy stable charged particle, or by missing transverse
energy.Comment: 55 pages, 13 figures, final version to be published in JHE
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