A Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signaling

Rodney P. Kincaid, James M. Burke, Jennifer C. Cox, Christopher S. Sullivan, The University of Texas at Austin, Molecular Genetics and Microbiology, Austin, Texas, United States of AmericaEthel-Michele de Villiers, Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Heidelberg, GermanyTorque teno viruses (TTVs) are a group of viruses with small, circular DNA genomes. Members of this family are thought to ubiquitously infect humans, although causal disease associations are currently lacking. At present, there is no understanding of how infection with this diverse group of viruses is so prevalent. Using a combined computational and synthetic approach, we predict and identify miRNA-coding regions in diverse human TTVs and provide evidence for TTV miRNA production in vivo. The TTV miRNAs are transcribed by RNA polymerase II, processed by Drosha and Dicer, and are active in RISC. A TTV mutant defective for miRNA production replicates as well as wild type virus genome; demonstrating that the TTV miRNA is dispensable for genome replication in a cell culture model. We demonstrate that a recombinant TTV genome is capable of expressing an exogenous miRNA, indicating the potential utility of TTV as a small RNA vector. Gene expression profiling of host cells identifies N-myc (and STAT) interactor (NMI) as a target of a TTV miRNA. NMI transcripts are directly regulated through a binding site in the 3′UTR. SiRNA knockdown of NMI contributes to a decreased response to interferon signaling. Consistent with this, we show that a TTV miRNA mediates a decreased response to IFN and increased cellular proliferation in the presence of IFN. Thus, we add Annelloviridae to the growing list of virus families that encode miRNAs, and suggest that miRNA-mediated immune evasion can contribute to the pervasiveness associated with some of these viruses.This work was supported by grants RO1AI077746 from the National Institutes of Health, RP110098 from the Cancer Prevention and Research Institute of Texas, a Burroughs Wellcome Investigators in Pathogenesis Award to CSS, a UT Austin Powers Graduate Fellowship to RPK, a UT Austin Institute for Cellular and Molecular Biology fellowship, and the DKFZ for EMdV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Molecular BiosciencesMicrobiologyEmail: [email protected]

Electron scattering from pyrazine: Elastic differential and integral cross sections

We report on new measurements for elastic electron scattering from pyrazine. Absolute differential cross sections (DCSs) at seven discrete energies in the range 3-50 eV, and over the scattered electron angular range 10°-129°, were determined using a crossed electron-molecular beam spectrometer in conjunction with the well-established relative flow technique. Integral elastic cross sections were subsequently derived from those DCS data at each energy. Where possible comparison between the present results and those from sophisticated Schwinger multichannel and R-matrix computations is made, with generally quite good quantitative accord being found. Finally, in order to better study some of the rich resonance structure predicted by theory, results from elastic electron excitation functions are presented.Partial financial support from the Australian Research Council through its Centres of Excellence program is acknowledged

Defining Success: The Politics of Evaluation in Alcohol and Drug Abuse Treatment Programs

Alcohol and drug abuse treatment programs must respond to several important stakeholders or beneficiaries of services who have an investment in how success is defined. Utilizing data from recent statewide studies of treatment outcomes of alcohol and drug abuse services, this paper concludes that a strict adherence to an abstinence-only model of success, rigidly adopted by many in the treatment industry is counterproductive. Multiple measures of success are essential to fully understand and assess a changing model of intervention in the chemical dependency field

A positron trap and beam apparatus for atomic and molecular scattering experiments

An instrument has been designed and constructed to provide new insights into fundamental, low energy positron scattering processes. The design is based on the Surko trap system and produces a pulsed positron beam with an energy resolution of as good as 54 meV. The design and operation of the apparatus is explained, while the first experimental results from this apparatus have been demonstrated in recent publications.The authors would like to acknowledge the Australian Research Council for funding support, through the Centre of Excellence program, as well as the LIEF and Discovery funding programs

Therapeutic Administration of the Direct Thrombin Inhibitor Argatroban Reduces Hepatic Inflammation in Mice with Established Fatty Liver Disease

Thrombin generation is increased in patients with nonalcoholic fatty liver disease (NAFLD) and in mouse models of diet-induced obesity. Deficiency in the thrombin receptor protease activated receptor-1 reduces hepatic inflammation and steatosis in mice fed a Western diet. However, it is currently unclear whether thrombin inhibitors can modify the pathogenesis of established NAFLD. We tested the hypothesis that thrombin inhibition could reverse hepatic steatosis and inflammation in mice with established diet-induced NAFLD. Low-density lipoprotein receptor–deficient LDLr−/− mice were fed a control diet or a Western diet for 19 weeks. Mice were given the direct thrombin inhibitor argatroban ∼15 mg/kg/day or its vehicle via a miniosmotic pump for the final 4 weeks of the study. Argatroban administration significantly reduced hepatic proinflammatory cytokine expression and reduced macrophage and neutrophil accumulation in livers of mice fed a Western diet. Argatroban did not significantly impact hepatic steatosis, as indicated by histopathology, Oil Red O staining, and hepatic triglyceride levels. Argatroban reduced serum triglyceride and cholesterol levels in mice fed a Western diet. Argatroban reduced both α-smooth muscle actin expression and Type 1 collagen mRNA levels in livers of mice fed a Western diet, indicating reduced activation of hepatic stellate cells. This study indicates that therapeutic intervention with a thrombin inhibitor attenuates hepatic inflammation and several profibrogenic changes in mice fed a Western diet

Nano-porosity in GaSb induced by swift heavy ion irradiation

Nano-porous structures form in GaSb after ion irradiation with 185 MeV Au ions. The porous layer formation is governed by the dominant electronic energy loss at this energy regime. The porous layer morphology differs significantly from that previously reported for low-energy, ion-irradiated GaSb. Prior to the onset of porosity, positron annihilation lifetime spectroscopy indicates the formation of small vacancy clusters in single ion impacts, while transmission electron microscopy reveals fragmentation of the GaSb into nanocrystallites embedded in an amorphous matrix. Following this fragmentation process, macroscopic porosity forms, presumably within the amorphous phase.The authors thank the Australian Research Council for support and the staff at the ANU Heavy Ion Accelerator Facility for their continued technical assistance. R.C.E. acknowledges the support from the Office of Basic Energy Sciences of the U.S. DOE (Grant No. DE-FG02-97ER45656)

The H alpha Galaxy Survey VI. Star-forming companions of nearby field galaxies

We present a search for star-forming satellite galaxies that are close enough to their parent galaxies to be considered analogues of the Magellanic Clouds. Our search technique relied on the detection of the satellites in continuum-subtracted narrow-band H alpha imaging of the central galaxies, which removes most of the background and foreground line-of-sight companions, thus giving a high probability that we are detecting true satellites. The search was performed for 119 central galaxies at distances between 20 and 40 Mpc, although spatial incompleteness means that we have effectively searched 53 full satellite-containing volumes. We find only 9 probable star-forming satellites, around 9 different central galaxies, and 2 possible satellites. After incompleteness correction, this is equivalent to 0.17/0.21 satellites per central galaxy. The Small Magellanic Cloud is just below the median values of both star formation rate and R-band luminosity of the 9 probable satellites. The Large Magellanic Cloud, however, has a higher R-band luminosity than any of the 9 and is only exceeded in star formation rate by the one satellite that appears to be undergoing a tidally-induced starburst. Thus the Milky Way appears to be quite unusual, both in having two star-forming satellite galaxies and in the high luminosity of the Large Magellanic Cloud.Comment: 13 pages, accepted for publication in A&