Innate Intracellular Antiviral Responses Restrict the Amplification of Defective Virus Genomes of Parainfluenza Virus 5.

During the replication of parainfluenza virus 5 (PIV5), copyback defective virus genomes (DVGs) are erroneously produced and are packaged into "infectious" virus particles. Copyback DVGs are the primary inducers of innate intracellular responses, including the interferon (IFN) response. While DVGs can interfere with the replication of nondefective (ND) virus genomes and activate the IFN-induction cascade before ND PIV5 can block the production of IFN, we demonstrate that the converse is also true, i.e., high levels of ND virus can block the ability of DVGs to activate the IFN-induction cascade. By following the replication and amplification of DVGs in A549 cells that are deficient in a variety of innate intracellular antiviral responses, we show that DVGs induce an uncharacterized IFN-independent innate response(s) that limits their replication. High-throughput sequencing was used to characterize the molecular structure of copyback DVGs. While there appears to be no sequence-specific break or rejoining points for the generation of copyback DVGs, our findings suggest there are region, size, and/or structural preferences selected for during for their amplification.IMPORTANCE Copyback defective virus genomes (DVGs) are powerful inducers of innate immune responses both in vitro and in vivo They impact the outcome of natural infections, may help drive virus-host coevolution, and promote virus persistence. Due to their potent interfering and immunostimulatory properties, DVGs may also be used therapeutically as antivirals and vaccine adjuvants. However, little is known of the host cell restrictions which limit their amplification. We show here that the generation of copyback DVGs readily occurs during parainfluenza virus 5 (PIV5) replication, but that their subsequent amplification is restricted by the induction of innate intracellular responses. Molecular characterization of PIV5 copyback DVGs suggests that while there are no genome sequence-specific breaks or rejoin points for the generation of copyback DVGs, genome region, size, and structural preferences are selected for during their evolution and amplification

An X-Ray Study of the Supernova Remnant G290.1-0.8

G290.1-0.8 (MSH 11-61A) is a supernova remnant (SNR) whose X-ray morphology is centrally bright. However, unlike the class of X-ray composite SNRs whose centers are dominated by nonthermal emission, presumably driven by a central pulsar, we show that the X-ray emission from G290.1-0.8 is thermal in nature, placing the remnant in an emerging class which includes such remnants as W44, W28, 3C391, and others. The evolutionary sequence which leads to such X-ray properties is not well understood. Here we investigate two scenarios for such emission: evolution in a cloudy interstellar medium, and early-stage evolution of a remnant into the radiative phase, including the effects of thermal conduction. We construct models for these scenarios in an attempt to reproduce the observed center-filled X-ray properties of G290.1-0.8, and we derive the associated age, energy, and ambient density conditions implied by the models. We find that for reasonable values of the explosion energy, the remnant age is of order (1 - 2) x 10^{4} yr. This places a fairly strong constraint on any association between G290.1-0.8 and PSR J1105-610, which would require an anomalously large velocity for the pulsar.Comment: 7 pages, 7 figures, ApJ, accepte

New Evidence for Efficient Collisionless Heating of Electrons at the Reverse Shock of a Young Supernova Remnant

Although collisionless shocks are ubiquitous in astrophysics, certain key aspects of them are not well understood. In particular, the process known as collisionless electron heating, whereby electrons are rapidly energized at the shock front, is one of the main open issues in shock physics. Here we present the first clear evidence for efficient collisionless electron heating at the reverse shock of Tycho's supernova remnant (SNR), revealed by Fe-K diagnostics using high-quality X-ray data obtained by the Suzaku satellite. We detect K-beta (3p->1s) fluorescence emission from low-ionization Fe ejecta excited by energetic thermal electrons at the reverse shock front, which peaks at a smaller radius than Fe K-alpha (2p->1s) emission dominated by a relatively highly-ionized component. Comparison with our hydrodynamical simulations implies instantaneous electron heating to a temperature 1000 times higher than expected from Coulomb collisions alone. The unique environment of the reverse shock, which is propagating with a high Mach number into rarefied ejecta with a low magnetic field strength, puts strong constraints on the physical mechanism responsible for this heating, and favors a cross-shock potential created by charge deflection at the shock front. Our sensitive observation also reveals that the reverse shock radius of this SNR is about 10% smaller than the previous measurement using the Fe K-alpha morphology from the Chandra observations. Since strong Fe K-beta fluorescence is expected only from low-ionization plasma where Fe ions still have many 3p electrons, this feature is key to diagnosing the plasma state and distribution of the immediate postshock ejecta in a young SNR.Comment: 7 pages, 9 figures, resubmitted to ApJ with minor changes following the referee repor

Gravity, p-branes and a spacetime counterpart of the Higgs effect

We point out that the worldvolume coordinate functions $\hat{x}^\mu(\xi)$ of a $p$-brane, treated as an independent object interacting with dynamical gravity, are Goldstone fields for spacetime diffeomorphisms gauge symmetry. The presence of this gauge invariance is exhibited by its associated Noether identity, which expresses that the source equations follow from the gravitational equations. We discuss the spacetime counterpart of the Higgs effect and show that a $p$-brane does not carry any local degrees of freedom, extending early known general relativity features. Our considerations are also relevant for brane world scenarios.Comment: 5 pages, RevTeX. v2 (30-IV-03) with additional text and reference

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

HABITAT COMPLEXITY INFLUENCES CASCADING EFFECTS OF MULTIPLE PREDATORS

Although multiple predator effects and trophic cascades have both been demonstrated in a wide variety of ecosystems, ecologists have yet to incorporate these studies into an experimental framework that also manipulates a common and likely important factor, spatial heterogeneity. We manipulated habitat complexity, the presence of two top predators (toadfish and blue crabs), and one intermediate predator (mud crabs) to determine whether habitat complexity influences the strength of multiple predator interactions across multiple trophic levels in experimental oyster reef communities. In the absence of toadfish, blue crabs caused significant mud crab mortality. Despite also directly consuming mud crabs, toadfish indirectly benefited this intermediate predator by decreasing blue crab consumption of mud crabs. Toadfish suppression of mud crab foraging activity, and thus decreased mud crab encounters with blue crabs, is likely responsible for this counterintuitive result. Contrary to previous investigations which suggest that more complex habitats reduce interference interactions among predators, reef complexity strengthened emergent multiple predator effects (MPEs) on mud crabs. The degree to which these MPEs cascaded down to benefit juvenile oysters (basal prey) depended on both habitat complexity and nonconsumptive effects derived from predator-predator interactions. Habitat complexity reduced the foraging efficiency of each crab species individually but released crab interference interactions when together, so that the two crabs collectively consumed more oysters on complex reefs. Regardless of reef complexity, toadfish consistently decreased consumption of oysters by both crab species individually and when together. Therefore, interactions between predator identity and habitat complexity structure trophic cascades on oyster reefs. Furthermore, these cascading effects of multiple predators were largely mediated by nonconsumptive effects in this system

Predators, environment and host characteristics influence the probability of infection by an invasive castrating parasite

Not all hosts, communities or environments are equally hospitable for parasites. Direct and indirect interactions between parasites and their predators, competitors and the environment can influence variability in host exposure, susceptibility and subsequent infection, and these influences may vary across spatial scales. To determine the relative influences of abiotic, biotic and host characteristics on probability of infection across both local and estuary scales, we surveyed the oyster reef-dwelling mud crab Eurypanopeus depressus and its parasite Loxothylacus panopaei, an invasive castrating rhizocephalan, in a hierarchical design across >900 km of the southeastern USA. We quantified the density of hosts, predators of the parasite and host, the host's oyster reef habitat, and environmental variables that might affect the parasite either directly or indirectly on oyster reefs within 10 estuaries throughout this biogeographic range. Our analyses revealed that both between and within estuary-scale variation and host characteristics influenced L. panopaei prevalence. Several additional biotic and abiotic factors were positive predictors of infection, including predator abundance and the depth of water inundation over reefs at high tide. We demonstrate that in addition to host characteristics, biotic and abiotic community-level variables both serve as large-scale indicators of parasite dynamics

Genetic by environmental variation but no local adaptation in oysters ( Crassostrea virginica )

Functional trait variation within and across populations can strongly influence population, community, and ecosystem processes, but the relative contributions of genetic vs. environmental factors to this variation are often not clear, potentially complicating conservation and restoration efforts. For example, local adaptation, a particular type of genetic by environmental (G*E) interaction in which the fitness of a population in its own habitat is greater than in other habitats, is often invoked in management practices, even in the absence of supporting evidence. Despite increasing attention to the potential for G*E interactions, few studies have tested multiple populations and environments simultaneously, limiting our understanding of the spatial consistency in patterns of adaptive genetic variation. In addition, few studies explicitly differentiate adaptation in response to predation from other biological and environmental factors. We conducted a reciprocal transplant experiment of first-generation eastern oyster (Crassostrea virginica) juveniles from six populations across three field sites spanning 1000 km in the southeastern Atlantic Bight in both the presence and absence of predation to test for G*E variation in this economically valuable and ecologically important species. We documented significant G*E variation in survival and growth, yet there was no evidence for local adaptation. Condition varied across oyster cohorts: Offspring of northern populations had better condition than offspring from the center of our region. Oyster populations in the southeastern Atlantic Bight differ in juvenile survival, growth, and condition, yet offspring from local broodstock do not have higher survival or growth than those from farther away. In the absence of population-specific performance information, oyster restoration and aquaculture may benefit from incorporating multiple populations into their practices

Chandra ACIS Survey of M33 (ChASeM33): A First Look

We present an overview of the Chandra ACIS Survey of M33 (ChASeM33): A Deep Survey of the Nearest Face-on Spiral Galaxy. The 1.4 Ms survey covers the galaxy out to R \approx 18\arcmin (\approx 4 kpc). These data provide the most intensive, high spatial resolution assessment of the X-ray source populations available for the confused inner regions of M33. Mosaic images of the ChASeM33 observations show several hundred individual X-ray sources as well as soft diffuse emission from the hot interstellar medium. Bright, extended emission surrounds the nucleus and is also seen from the giant \hii regions NGC 604 and IC 131. Fainter extended emission and numerous individual sources appear to trace the inner spiral structure. The initial source catalog, arising from $\sim$~2/3 of the expected survey data, includes 394 sources significant at the $3\sigma$ confidence level or greater, down to a limiting luminosity (absorbed) of $\sim$1.6\ergs{35} (0.35 -- 8.0 keV). The hardness ratios of the sources separate those with soft, thermal spectra such as supernova remnants from those with hard, non-thermal spectra such as X-ray binaries and background active galactic nuclei. Emission extended beyond the Chandra point spread function is evident in 23 of the 394 sources. Cross-correlation of the ChASeM33 sources against previous catalogs of X-ray sources in M33 results in matches for the vast majority of the brighter sources and shows 28 ChASeM33 sources within 10\arcsec of supernova remnants identified by prior optical and radio searches. This brings the total number of such associations to 31 out of 100 known supernova remnants in M33.Comment: accepted for publication ApJS, full resolution images and complete tables available at http://hea-www.harvard.edu/vlp_m33_public

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity