The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.

The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKβ, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response

Supernova Remnants in the Magellanic Clouds. IV. X-Ray Emission from the Largest SNR in the LMC

We present the first X-ray detection of SNR 0450-70.9 the largest known supernova remnant (SNR) in the Large Magellanic Cloud. To study the physical conditions of this SNR, we have obtained XMM-Newton X-ray observations, optical images and high-dispersion spectra, and radio continuum maps. Optical images of SNR 0450-70.9 show a large, irregular elliptical shell with bright filaments along the eastern and western rims and within the shell interior. The interior filaments have higher [S II]/Halpha ratios and form an apparent inner shell morphology. The X-ray emission region is smaller than the full extent of the optical shell, with the brightest X-ray emission found within the small interior shell and on the western rim of the large shell. The expansion velocity of the small shell is ~220 km/s, while the large shell is ~120 km/s. The radio image shows central brightening and a fairly flat radio spectral index over the SNR. However, no point X-ray or radio source corresponding to a pulsar is detected and the X-ray emission is predominantly thermal. Therefore, these phenomena can be most reasonably explained in terms of the advanced age of the large SNR. Using hydrodynamic models combined with a nonequilibrium ionization model for thermal X-ray emission, we derived a lower limit on the SNR age of about 45,000 yr, well into the later stages of SNR evolution. Despite this, the temperature and density derived from spectral fits to the X-ray emission indicate that the remnant is still overpressured, and thus that the development is largely driven by hot gas in the SNR interior.Comment: Accepted for publication in The Astrophysical Journa

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Elemental Abundances in the Possible Type Ia Supernova Remnant G344.7-0.1

Recent studies on the Galactic supernova remnant (SNR) G344.7-0.1 have commonly claimed its origin to be a core-collapse supernova (SN) explosion, based on its highly asymmetric morphology and/or proximity to a star forming region. In this paper, however, we present an X-ray spectroscopic study of this SNR using Suzaku, which is supportive of a Type Ia origin. Strong K-shell emission from lowly ionized Fe has clearly been detected, and its origin is determined, for the first time, to be the Fe-rich SN ejecta. The abundance pattern is highly consistent with that expected for a somewhat-evolved Type Ia SNR. It is suggested, therefore, that the X-ray point-like source CXOU J170357.8-414302 located at the SNR's geometrical center is not associated with the SNR but is likely to be a foreground object. Our result further indicates that G344.7-0.1 is the first possible Type Ia SNR categorized as a member of the so-called "mixed-morphology" class. In addition, we have detected emission from He-like Al at ~1.6 keV, the first clear detection of this element in the spectrum of an extended X-ray source. The possible enhancement of the Al/Mg abundance ratio from the solar value suggests that the ambient interstellar medium has a relatively high metallicity (not less than 10% of the solar value), if this SNR has indeed a Type Ia origin. We also report marginal detection of Cr and Mn, although the measured fluxes have large statistical and systematic uncertainties.Comment: ApJ in pres

From Anderson to anomalous localization in cold atomic gases with effective spin-orbit coupling

We study the dynamics of a one-dimensional spin-orbit coupled Schrodinger particle with two internal components moving in a random potential. We show that this model can be implemented by the interaction of cold atoms with external lasers and additional Zeeman and Stark shifts. By direct numerical simulations a crossover from an exponential Anderson-type localization to an anomalous power-law behavior of the intensity correlation is found when the spin-orbit coupling becomes large. The power-law behavior is connected to a Dyson singularity in the density of states emerging at zero energy when the system approaches the quasi-relativistic limit of the random mass Dirac model. We discuss conditions under which the crossover is observable in an experiment with ultracold atoms and construct explicitly the zero-energy state, thus proving its existence under proper conditions.Comment: 4 pages and 4 figure

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Effect of disorder on quantum phase transitions in anisotropic XY spin chains in a transverse field

We present some exact results for the effect of disorder on the critical properties of an anisotropic XY spin chain in a transverse field. The continuum limit of the corresponding fermion model is taken and in various cases results in a Dirac equation with a random mass. Exact analytic techniques can then be used to evaluate the density of states and the localization length. In the presence of disorder the ferromagnetic-paramagnetic or Ising transition of the model is in the same universality class as the random transverse field Ising model solved by Fisher using a real space renormalization group decimation technique (RSRGDT). If there is only randomness in the anisotropy of the magnetic exchange then the anisotropy transition (from a ferromagnet in the $x$ direction to a ferromagnet in the $y$ direction) is also in this universality class. However, if there is randomness in the isotropic part of the exchange or in the transverse field then in a non-zero transverse field the anisotropy transition is destroyed by the disorder. We show that in the Griffiths' phase near the Ising transition that the ground state energy has an essential singularity. The results obtained for the dynamical critical exponent, the typical correlation length, and the temperature dependence of the specific heat near the Ising transition agree with the results of the RSRGDT and numerical work.Comment: 22 pages, RevTeX + epsf, 4 figure

The Nab Experiment: A Precision Measurement of Unpolarized Neutron Beta Decay

Neutron beta decay is one of the most fundamental processes in nuclear physics and provides sensitive means to uncover the details of the weak interaction. Neutron beta decay can evaluate the ratio of axial-vector to vector coupling constants in the standard model, $\lambda = g_A / g_V$, through multiple decay correlations. The Nab experiment will carry out measurements of the electron-neutrino correlation parameter $a$ with a precision of $\delta a / a = 10^{-3}$ and the Fierz interference term $b$ to $\delta b = 3\times10^{-3}$ in unpolarized free neutron beta decay. These results, along with a more precise measurement of the neutron lifetime, aim to deliver an independent determination of the ratio $\lambda$ with a precision of $\delta \lambda / \lambda = 0.03\%$ that will allow an evaluation of $V_{ud}$ and sensitively test CKM unitarity, independent of nuclear models. Nab utilizes a novel, long asymmetric spectrometer that guides the decay electron and proton to two large area silicon detectors in order to precisely determine the electron energy and an estimation of the proton momentum from the proton time of flight. The Nab spectrometer is being commissioned at the Fundamental Neutron Physics Beamline at the Spallation Neutron Source at Oak Ridge National Lab. We present an overview of the Nab experiment and recent updates on the spectrometer, analysis, and systematic effects.Comment: Presented at PPNS201

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types