Chandra High Energy Transmission Grating Spectrum of AE Aquarii

(Abridged) The results of a Chandra X-ray Observatory High-Energy Transmission Grating (HETG) observation of the nova-like cataclysmic binary AE Aqr are described. First, the X-ray spectrum is that of an optically thin multi-temperature thermal plasma; the X-ray emission lines are broad, with widths that increase with the line energy, from sigma~1 eV for O VIII to sigma~5.5 eV for Si XIV; the X-ray spectrum is reasonably well fit by a plasma model with a Gaussian emission measure distribution that peaks at log T(K)=7.16, has a width sigma=0.48, an Fe abundance equal to 0.44 times solar, and other metal (primarily Ne, Mg, and Si) abundances equal to 0.76 times solar; and for a distance d=100 pc, the total emission measure EM=8.0E53 cm^-3 and the 0.5-10 keV luminosity L_X=1.1E31 erg/s. Second, based on the f/(i+r) flux ratios of the forbidden (f), intercombination (i), and recombination (r) lines of the He alpha triplets of N VI, O VII, and Ne IX measured by Itoh et al. in the XMM-Newton Reflection Grating Spectrometer spectrum and those of O VII, Ne IX, Mg XI, and Si XIII in the Chandra HETG spectrum, either the electron density of the plasma increases with temperature by over three orders of magnitude, from n_e~6E10 cm^-3 for N VI to n_e~1E14 cm^-3 for SI XIII, and/or the plasma is significantly affected by photoexcitation. Third, the radial velocity of the X-ray emission lines varies on the white dwarf spin phase, with two oscillations per spin cycle and an amplitude K~160 km/s. These results appear to be inconsistent with the recent models of Itoh et al., Ikhsanov, and Venter & Meintjes of an extended, low-density source of X-rays in AE Aqr, but instead support earlier models in which the dominant source of X-rays is of high density and/or in close proximity to the white dwarf.Comment: 13 pages including 1 table and 11 encapsulated postscript figure (3 in color); uses emulateapj.cls and apjfonts.sty; accepted on 2009 October 1 for publication in The Astrophysical Journa

Nuclear resonance tomography with a toroid cavity detector

A toroid cavity detection system for determining the spectral properties and distance from a fixed point for a sample using Nuclear Magnetic Resonance. The detection system consists of a toroid with a central conductor oriented along the main axis of the toroidal cylinder and perpendicular to a static uniform magnetic field oriented along the main axis of the toroid. An rf signal is inputted to the central conductor to produce a magnetic field perpendicular to the central axis of the toroid and whose field strength varies as the inverse of the radius of the toroid. The toroid cavity detection system can be used to encapsulate a sample, or the detection system can be perforated to allow a sample to flow into the detection device or to place the samples in specified sample tubes. The central conductor can also be coated to determine the spectral property of the coating and the coating thickness. The sample is then subjected to the respective magnetic fields and the responses measured to determine the desired properties

Quantitative non-canonical amino acid tagging based proteomics identifies distinct patterns of protein synthesis rapidly induced by hypertrophic agents in cardiomyocytes, revealing new aspects of metabolic remodeling

Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. Pathological myocardial growth is a risk factor for cardiac failure to which faster protein synthesis is a major driving element. We aimed to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are due to alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other non-dividing primary cells. To address this, an optimized QuaNCAT LC/MS method was used to selectively quantify newly synthesized proteins in such cells. The study showed both classical (phenylephrine; PE) and more recent (insulin) pathological cardiac hypertrophic agents increased the synthesis of proteins involved in glycolysis, the Krebs cycle / beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was upregulated by signaling through mTORC1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was upregulated in rat hearts following TAC. This isoform possesses specific regulatory properties that may be involved in metabolic remodeling and as a novel candidate biomarker. Levels of translation factor eEF1 also increased during TAC, likely contributing to faster cell mass accumulation. Interestingly, PKM2 and eEF1 were not up-regulated in pregnancy or exercise induced CH, suggesting them as pathological CH specific markers. The study methods may be of utility to the examination of protein synthesis in primary cells

Theranostic Copolymers Neutralize Reactive Oxygen Species and Lipid Peroxidation Products for the Combined Treatment of Traumatic Brain Injury

Traumatic brain injury (TBI) results in the generation of reactive oxygen species (ROS) and lipid peroxidation product (LPOx), including acrolein and 4-hydroxynonenal (4HNE). The presence of these biochemical derangements results in neurodegeneration during the secondary phase of the injury. The ability to rapidly neutralize multiple species could significantly improve outcomes for TBI patients. However, the difficulty in creating therapies that target multiple biochemical derangements simultaneously has greatly limited therapeutic efficacy. Therefore, our goal was to design a material that could rapidly bind and neutralize both ROS and LPOx following TBI. To do this, a series of thiol-functionalized biocompatible copolymers based on lipoic acid methacrylate and polyethylene glycol monomethyl ether methacrylate (FW ∼950 Da) (O950) were prepared. A polymerizable gadolinium-DOTA methacrylate monomer (Gd-MA) was also synthesized starting from cyclen to facilitate direct magnetic resonance imaging and in vivo tracking of accumulation. These neuroprotective copolymers (NPCs) were shown to rapidly and effectively neutralize both ROS and LPOx. Horseradish peroxidase absorbance assays showed that the NPCs efficiently neutralized H2O2, while R-phycoerythrin protection assays demonstrated their ability to protect the fluorescent protein from oxidative damage. 1H NMR studies indicated that the thiol-functional NPCs rapidly form covalent bonds with acrolein, efficiently removing it from solution. In vitro cell studies with SH-SY5Y-differentiated neurons showed that NPCs provide unique protection against toxic concentrations of both H2O2and acrolein. NPCs rapidly accumulate and are retained in the injured brain in controlled cortical impact mice and reduce post-traumatic oxidative stress. Therefore, these materials show promise for improved target engagement of multiple biochemical derangements in hopes of improving TBI therapeutic outcomes

The Three Dimensional Structure of EUV Accretion Regions in AM Herculis Stars: Modeling of EUV Photometric and Spectroscopic Observations

We have developed a model of the high-energy accretion region for magnetic cataclysmic variables and applied it to {\it Extreme Ultraviolet Explorer} observations of 10 AM Herculis type systems. The major features of the EUV light curves are well described by the model. The light curves exhibit a large variety of features such as eclipses of the accretion region by the secondary star and the accretion stream, and dips caused by material very close to the accretion region. While all the observed features of the light curves are highly dependent on viewing geometry, none of the light curves are consistent with a flat, circular accretion spot whose lightcurve would vary solely from projection effects. The accretion region immediately above the WD surface is a source of EUV radiation caused by either a vertical extent to the accretion spot, or Compton scattering off electrons in the accretion column, or, very likely, both. Our model yields spot sizes averaging 0.06 R$_{WD}$, or $f \sim 1 \times 10^{-3}$ the WD surface area, and average spot heights of 0.023 R$_{WD}$. Spectra extracted during broad dip phases are softer than spectra during the out-of-dip phases. This spectral ratio measurement leads to the conclusion that Compton scattering, some absorption by a warm absorber, geometric effects, an asymmetric temperature structure in the accretion region and an asymmetric density structure of the accretion columnare all important components needed to fully explain the data. Spectra extracted at phases where the accretion spot is hidden behind the limb of the WD, but with the accretion column immediately above the spot still visible, show no evidence of emission features characteristic of a hot plasma.Comment: 30 Pages, 11 Figure

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head &amp; neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-? signaling. Similar to TGF-?1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes

Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming

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Genetic variation of St. Louis encephalitis virus

St. Louis encephalitis virus (SLEV) has been regularly isolated throughout the Americas since 1933. Previous phylogenetic studies involving 62 isolates have defined seven major lineages (I–VII), further divided into 14 clades. In this study, 28 strains isolated in Texas in 1991 and 2001–2003, and three older, previously unsequenced strains from Jamaica and California were sequenced over the envelope protein gene. The inclusion of these new sequences, and others published since 2001, has allowed better delineation of the previously published SLEV lineages, in particular the clades of lineage II. Phylogenetic analysis of 106 isolates identified 13 clades. All 1991 and 2001–2003 isolates from Nueces, Jefferson and Harris Counties (Texas Gulf Coast) group in clade IIB with other isolates from these counties isolated during the 1980s and 1990s. This lack of evidence for introduction of novel strains into the Texas Gulf Coast over a long period of time is consistent with overwintering of SLEV in this region. Two El Paso isolates, both from 2002, group in clade VA with recent Californian isolates from 1998–2001 and some South American strains with a broad temporal range. Overall, these data are consistent with multiple introductions of SLEV from South America into North America, and provide support for the hypothesis that in most situations, SLEV circulates within a locality, with occasional incursions from other areas. Finally, SLEV has much lower nucleotide (10.1 %) and amino acid variation (2.8 %) than other members of the Japanese encephalitis virus complex (maximum variation 24.6 % nucleotide and 11.8 % amino acid)