CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2

The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1−/− mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1−/− peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam2CSK4 and to HSV-1. CD200R1−/− macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1−/− mice and CD200R1−/− fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence

CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2

The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1−/− mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1−/− peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam2CSK4 and to HSV-1. CD200R1−/− macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1−/− mice and CD200R1−/− fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence

Statistical estimates of absenteeism attributable to seasonal and pandemic influenza from the Canadian Labour Force Survey

<p>Abstract</p> <p>Background</p> <p>As many respiratory viruses are responsible for influenza like symptoms, accurate measures of the disease burden are not available and estimates are generally based on statistical methods. The objective of this study was to estimate absenteeism rates and hours lost due to seasonal influenza and compare these estimates with estimates of absenteeism attributable to the two H1N1 pandemic waves that occurred in 2009.</p> <p>Methods</p> <p>Key absenteeism variables were extracted from Statistics Canada's monthly labour force survey (LFS). Absenteeism and the proportion of hours lost due to own illness or disability were modelled as a function of trend, seasonality and proxy variables for influenza activity from 1998 to 2009.</p> <p>Results</p> <p>Hours lost due to the H1N1/09 pandemic strain were elevated compared to seasonal influenza, accounting for a loss of 0.2% of potential hours worked annually. In comparison, an estimated 0.08% of hours worked annually were lost due to seasonal influenza illnesses. Absenteeism rates due to influenza were estimated at 12% per year for seasonal influenza over the 1997/98 to 2008/09 seasons, and 13% for the two H1N1/09 pandemic waves. Employees who took time off due to a seasonal influenza infection took an average of 14 hours off. For the pandemic strain, the average absence was 25 hours.</p> <p>Conclusions</p> <p>This study confirms that absenteeism due to seasonal influenza has typically ranged from 5% to 20%, with higher rates associated with multiple circulating strains. Absenteeism rates for the 2009 pandemic were similar to those occurring for seasonal influenza. Employees took more time off due to the pandemic strain than was typical for seasonal influenza.</p

Structural basis for potency differences between GDF8 and GDF11.

BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor β (TGFβ) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Resolution of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 crystal structures reveals unique properties of both ligands, specifically in the type I receptor binding site. Lastly, substitution of GDF11 residues into GDF8 confers enhanced activity to GDF8. CONCLUSIONS: These studies identify distinctive structural features of GDF11 that enhance its potency, relative to GDF8; however, the biological consequences of these differences remain to be determined

The Vehicle, Spring 2013

Vol. 54, Issue 1 Table of Contents About Face!: A Confederacy of ClichesKaren Neuberg page 8 HopeJames Coxpage 9 IN or OUTTaryn DeVriespage 12 The Imagination of a ChildMaxwell Collinspage 16 How Free to be a TreeLeann Kirchnerpage 18 CrowsValentina Canopage 19 Old West PhotosFred Pollackpage 20 Lava LampFred Pollackpage 21 Mort MotGerry Mark Nortonpage 23 If ILaura Adrianpage 24 Finding my MonkeyDavid Lewitzkypage 25 Slow DragDavid Lewitzkypage 26 Political ScienceElizabeth Marlowpage 27 ...Were Punctuated By...Elizabeth Marlowpage 28 St. E Pt 1Elizabeth Marlowpage 29 The Steamboat CaptainElizabeth Marlowpage 30 Pretty EyesRyan Sheapage 31 The World is RoundRyan Sheapage 32 End SongsJason Graffpage 33 The Sensitive Youth Grows UpRichard King Perkins IIpage 41 Colors and LightKyle Owenspage 42 RE-TARDKarlyn Thayerpage 44 Where Is Waldo?Riley Parishpage 57 Beneath Shifting SoundsHolly Daypage 58 Talking Shop with Mike Kardospage 60 Winnie Davis Neely Award winner: Paper CutsGregory Robert Petersonpage 68 Paper-Mache PoetryGregory Robert Petersonpage 69 James K. Johnson Award winners: ValveChristopher Robinsonpage 72 Dear MotherEliot Thompsonpage 76 Why Are There Bars on the WindowsEliot Thompsonpage 77 To Be a ScholarEliot Thompsonpage 79 OccidentalEliot Thompsonpage 80 Falling is for the ClumsyEliot Thompsonpage 81 Scary MonstersC. David Banyaipage 83 I Called My Grandmother DollyRashelle Spearpage 90 Tender FleshH R Greenpage 92 Faking ItShelby Koehnepage 95 Contributor\u27s notespage 101https://thekeep.eiu.edu/vehicle/1095/thumbnail.jp

The Vehicle, Spring 2013

Vol. 54, Issue 1 Table of Contents About Face!: A Confederacy of ClichesKaren Neuberg page 8 HopeJames Coxpage 9 IN or OUTTaryn DeVriespage 12 The Imagination of a ChildMaxwell Collinspage 16 How Free to be a TreeLeann Kirchnerpage 18 CrowsValentina Canopage 19 Old West PhotosFred Pollackpage 20 Lava LampFred Pollackpage 21 Mort MotGerry Mark Nortonpage 23 If ILaura Adrianpage 24 Finding my MonkeyDavid Lewitzkypage 25 Slow DragDavid Lewitzkypage 26 Political ScienceElizabeth Marlowpage 27 ...Were Punctuated By...Elizabeth Marlowpage 28 St. E Pt 1Elizabeth Marlowpage 29 The Steamboat CaptainElizabeth Marlowpage 30 Pretty EyesRyan Sheapage 31 The World is RoundRyan Sheapage 32 End SongsJason Graffpage 33 The Sensitive Youth Grows UpRichard King Perkins IIpage 41 Colors and LightKyle Owenspage 42 RE-TARDKarlyn Thayerpage 44 Where Is Waldo?Riley Parishpage 57 Beneath Shifting SoundsHolly Daypage 58 Talking Shop with Mike Kardospage 60 Winnie Davis Neely Award winner: Paper CutsGregory Robert Petersonpage 68 Paper-Mache PoetryGregory Robert Petersonpage 69 James K. Johnson Award winners: ValveChristopher Robinsonpage 72 Dear MotherEliot Thompsonpage 76 Why Are There Bars on the WindowsEliot Thompsonpage 77 To Be a ScholarEliot Thompsonpage 79 OccidentalEliot Thompsonpage 80 Falling is for the ClumsyEliot Thompsonpage 81 Scary MonstersC. David Banyaipage 83 I Called My Grandmother DollyRashelle Spearpage 90 Tender FleshH R Greenpage 92 Faking ItShelby Koehnepage 95 Contributor\u27s notespage 101https://thekeep.eiu.edu/vehicle/1095/thumbnail.jp

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

“Extreme" porn? The implications of a label

Despite its prevalence, the term ‘extreme’ has received little critical attention. ‘Extremity’ is routinely employed in ways that imply its meanings are self-evident. However, the adjective itself offers no such clarity. This article focuses on one particular use of the term – ‘extreme porn’ – in order to illustrate a broader set of concerns about the pitfalls of labelling. The label ‘extreme’ is typically employed as a substitute for engaging with the term’s supposed referents (here, pornographic content). In its contemporary usage, ‘extreme’ primarily refers to a set of context-dependent judgements rather than absolute standards or any specific properties the ‘extreme’ item is alleged to have. Concurrently then, the label ‘extreme’ carries a host of implicit values, and the presumption that the term’s meanings are ‘obvious’ obfuscates those values. In the case of ‘extreme porn’, this obfuscation is significant because it has facilitated the cultural and legal suppression of pornography

A pair production telescope for medium-energy gamma-ray polarimetry

We describe the science motivation and development of a pair production telescope for medium-energy (∼5–200 MeV) gamma-ray polarimetry. Our instrument concept, the Advanced Energetic Pair Telescope (AdEPT), takes advantage of the Three-Dimensional Track Imager, a low-density gaseous time projection chamber, to achieve angular resolution within a factor of two of the pair production kinematics limit (∼0.6° at 70 MeV), continuum sensitivity comparable with the Fermi-LAT front detector (<3 × 10−6 MeV cm−2 s−1 at 70 MeV), and minimum detectable polarization less than 10% for a 10 mCrab source in 106 s.submittedVersionFil: Hunter, Stanley D. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Bloser, Peter F. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Depaola, Gerardo Osvaldo. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Dion, Michael P. Department of Energy. Office of Science. Pacific Northwest National Laboratory; Estados Unidos de América.Fil: DeNolfo, Georgia A. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Hanu, Andrei. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Iparraguirre, Lorenzo Marcos. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Legere, Jason. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Longo, Francesco. Università Degli Studi de Trieste. Dipartimento di fisica; Italia.Fil: McConnell, Mark L. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Nowicki, Suzanne F. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Nowicki, Suzanne F. University of Maryland, Baltimore County. Department of Physics; Estados Unidos de América.Fil: Ryan, James M. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Son, Seunghee. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Son, Seunghee. University of Maryland, Baltimore County. Department of Physics; Estados Unidos de América.Fil: Stecker, Floyd W. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Física de Partículas y Campo

A Tabletop X-Ray Tomography Instrument for Nanometer-Scale Imaging: Integration of a Scanning Electron Microscope with a Transition-Edge Sensor Spectrometer

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but is difficult to implement due to competing requirements on X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. Compact X-ray nanotomography tools operated in standard analysis laboratories exist, but are limited by X-ray optics and destructive sample preparation techniques. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while changing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot in a metal target, while the TES spectrometer isolates target photons with high signal-to-noise. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enable nanoscale, element-specific X-ray imaging in a compact footprint. The proof-of-concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in a Cu-SiO2 integrated circuit, and a path towards finer resolution and enhanced imaging capabilities is discussed.Comment: The following article has been submitted to Physical Review Applie