HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages

HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes function to improve viral fitness by altering host pathways in ways that enable transmission to occur without interference from the immune response. We previously described changes in transcriptomes from HIV-1 infected and from IFN-stimulated macrophages and noted that transcription of IFN-regulated genes and genes related to cell cycle processes were upregulated during HIV-1 infection. In the present study, we sought to define the roles of individual viral accessory genes in upregulation of IFN-regulated and cell cycle-related genes using RNA sequencing. We observed that Vif induces a set of genes involved in mitotic processes and that these genes are potently downregulated upon stimulation with type-I and -II IFNs. Vpr also upregulated cell cycle-related genes and was largely responsible for inducing an attenuated IFN response. We note that the induced IFN response most closely resembled a type-III IFN response. Vpu and Nef-regulated smaller sets of genes whose transcriptomic signatures upon infection related to cytokine and chemokine processes. This work provides more insight regarding processes that are manipulated by HIV-1 accessory proteins at the transcriptional level.This research was partially funded by the National Institutes of Health, grants AI143567-02 (V.P. and M.C.) and AI122377-05 (V.P.) and by startup funds from the Department of Pathology, University of Utah School of Medicine (T.M.H.).S

Correction to: Bilingualism is associated with a delayed onset of dementia but not with a lower risk of developing it: A systematic review with meta-analyses

The original version of this article unfortunately contained the following mistakes. 1. In the Results section under the paragraph Disease Severity, the sentence “The PIs ranged between -0.47 and 0.57 MMSE points” should read -0.49 and 0.59 MMSE points. 2. In Figs. 3, 5, and 7, the labels “favour bilinguals” and “favours monolinguals” should be inverted. Therefore, it should be “favours monolinguals” and “favours bilinguals”. Please see below for the correct figures. © 2020, The Author(s)

Exact Scattering in the SU(n) Supersymmetric Principal Chiral Model

The complete spectrum of states in the supersymmetric principal chiral model based on SU(n) is conjectured, and an exact factorizable S-matrix is proposed to describe scattering amongst these states. The SU(n)_L*SU(n)_R symmetry of the lagrangian is manifest in the S-matrix construction. The supersymmetries, on the other hand, are incorporated in the guise of spin-1/2 charges acting on a set of RSOS kinks associated with su(n) at level n. To test the proposed S-matrix, calculations of the change in the ground-state energy in the presence of a coupling to a background charge are carried out. The results derived from the lagrangian using perturbation theory and from the S-matrix using the TBA are found to be in complete agreement for a variety of background charges which pick out, in turn, the highest weight states in each of the fundamental representations of SU(n). In particular, these methods rule out the possibility of additional CDD factors in the S-matrix. Comparison of the expressions found for the free-energy also yields an exact result for the mass-gap in these models: m/Lambda_{MS-bar}=(n/pi)sin(pi/n).Comment: 24 pages, plain tex with macro include

Effects of local meteorology and aerosols on ozone and nitrogen dioxide retrievals from OMI and pandora spectrometers in Maryland, USA during DISCOVER-AQ 2011

An analysis is presented for both ground- and satellite-based retrievals of total column ozone and nitrogen dioxide levels from the Washington, D.C., and Baltimore, Maryland, metropolitan area during the NASA-sponsored July 2011 campaign of Deriving Information on Surface COnditions from Column and VERtically Resolved Observations Relevant to Air Quality (DISCOVER-AQ). Satellite retrievals of total column ozone and nitrogen dioxide from the Ozone Monitoring Instrument (OMI) on the Aura satellite are used, while Pandora spectrometers provide total column ozone and nitrogen dioxide amounts from the ground. We found that OMI and Pandora agree well (residuals within ±25 % for nitrogen dioxide, and ±4.5 % for ozone) for a majority of coincident observations during July 2011. Comparisons with surface nitrogen dioxide from a Teledyne API 200 EU NOx Analyzer showed nitrogen dioxide diurnal variability that was consistent with measurements by Pandora. However, the wide OMI field of view, clouds, and aerosols affected retrievals on certain days, resulting in differences between Pandora and OMI of up to ±65 % for total column nitrogen dioxide, and ±23 % for total column ozone. As expected, significant cloud cover (cloud fraction \u3e0.2) was the most important parameter affecting comparisons of ozone retrievals; however, small, passing cumulus clouds that do not coincide with a high (\u3e0.2) cloud fraction, or low aerosol layers which cause significant backscatter near the ground affected the comparisons of total column nitrogen dioxide retrievals. Our results will impact post-processing satellite retrieval algorithms and quality control procedures

A Comparative Study of Single and Dual Perfusion During End-ischemic Subnormothermic Liver Machine Preservation

Background: It remains controversial if arterial perfusion in addition to portal vein perfusion during machine preservation improves liver graft quality. Comparative studies using both techniques are lacking. We studied the impact of using single or dual machine perfusion of donation after circulatory death rat livers. In addition, we analyzed the effect of pulsatile versus continuous arterial flow. Methods: Donation after circulatory death rat livers (n = 18) were preserved by 6 hours cold storage, followed by 1 hour subnormothermic machine perfusion (20 degrees C, pressure of 40/5 mm Hg) and 2 hours ex vivo warm reperfusion (37 degrees C, pressure of 80/11 mm Hg, 9% whole blood). Machine preservation was either through single portal vein perfusion (SP), dual pulsatile (DPP), or dual continuous perfusion (DCP) of the portal vein and hepatic artery. Hydrodynamics, liver function tests, histopathology, and expression of endothelial specific genes were assessed during 2 hours warm reperfusion. Results: At the end of reperfusion, arterial flow in DPP livers tended to be higher compared to DCP and SP grafts. However, this difference was not significant nor was better flow associated with better outcome. No differences in bile production or alanine aminotransferase levels were observed. SP livers had significantly lower lactate compared to DCP, but not DPP livers. Levels of Caspase-3 and tumor necrosis factor-alpha were similar between the groups. Expression of endothelial genes Kruppel-like-factor 2 and endothelial nitric oxide synthase tended to be higher in dual perfused livers, but no histological evidence of better preservation of the biliary endothelium or vasculature of the hepatic artery was observed. Conclusions: This study shows comparable outcomes after using a dual or single perfusion approach during end-ischemic subnormothermic liver machine preservation

Basigin mediation of Plasmodium falciparum red blood cell invasion does not require its transmembrane domain or interaction with monocarboxylate transporter 1

Plasmodium falciparum invasion of the red blood cell is reliant upon the essential interaction of PfRh5 with the host receptor protein basigin. Basigin exists as part of one or more multiprotein complexes, most notably through interaction with the monocarboxylate transporter MCT1. However, the potential requirement for basigin association with MCT1 and the wider role of basigin host membrane context and lateral protein associations during merozoite invasion has not been established. Using genetically manipulated in vitro derived reticulocytes, we demonstrate the ability to uncouple basigin ectodomain presentation from its transmembrane domain-mediated interactions, including with MCT1. Merozoite invasion of reticulocytes is unaffected by disruption of basigin-MCT1 interaction and by removal or replacement of the basigin transmembrane helix. Therefore, presentation of the basigin ectodomain at the red blood cell surface, independent of its native association with MCT1 or other interactions mediated by the transmembrane domain, is sufficient to facilitate merozoite invasion

SSGSS: The Spitzer-SDSS-GALEX Spectroscopic Survey

The Spitzer-SDSS-GALEX Spectroscopic Survey (SSGSS) provides a new sample of 101 star-forming galaxies at z < 0.2 with unprecedented multi-wavelength coverage. New mid- to far-infrared spectroscopy from the Spitzer Space Telescope is added to a rich suite of previous imaging and spectroscopy, including ROSAT, Galaxy Evolution Explorer, Sloan Digital Sky Survey, Two Micron All Sky Survey, and Spitzer/SWIRE. Sample selection ensures an even coverage of the full range of normal galaxy properties, spanning two orders of magnitude in stellar mass, color, and dust attenuation. In this paper we present the SSGSS data set, describe the science drivers, and detail the sample selection, observations, data reduction, and quality assessment. Also in this paper, we compare the shape of the thermal continuum and the degree of silicate absorption of these typical, star-forming galaxies to those of starburst galaxies. We investigate the link between star formation rate, infrared luminosity, and total polycyclic aromatic hydrocarbon luminosity, with a view to calibrating the latter for spectral energy distribution models in photometric samples and at high redshift. Last, we take advantage of the 5-40 micron spectroscopic and far-infrared photometric coverage of this sample to perform detailed fitting of the Draine et al. dust models, and investigate the link between dust mass and star formation history and active galactic nucleus properties.Comment: 60 pages, 20 figure

Mid-Infrared Spectral Measures of Star-Formation and AGN Activity in Normal Galaxies

We investigate the use of MIR PAH bands, continuum and emission lines as probes of star-formation and AGN activity in a sample of 100 'normal' and local (z~0.1) emission-line galaxies. The MIR spectra were obtained with the Spitzer Space Telescope Infrared Spectrograph (IRS) as part of the Spitzer-SDSS-GALEX Spectroscopic Survey (SSGSS) which includes multi-wavelength photometry from the UV to the FIR and optical spectroscopy. The continuum and features were extracted using PAHFIT (Smith et al. 2007), a decomposition code which we find to yield PAH equivalent widths up to ~30 times larger than the commonly used spline methods. Despite the lack of extreme objects in our sample (such as strong AGNs, low metallicity galaxies or ULIRGs), we find significant variations in PAH, continuum and emission line properties and systematic trends between these MIR properties and optically derived physical properties such as age, metallicity and radiation field hardness. We revisit the diagnostic diagram relating PAH equivalent widths and [Ne II]12.8micrometers/[O IV]25.9micrometers line ratios and find it to be in much better agreement with the standard optical star-formation/AGN classification than when spline decompositions are used, while also potentially revealing obscured AGNs. The luminosity of individual PAH components, of the continuum, and with poorer statistics, of the neon emission lines and molecular hydrogen lines, are found to be tightly correlated to the total IR luminosity, making individual MIR components good gauges of the total dust emission in SF galaxies. Like the total IR luminosity, these individual components can be used to estimate dust attenuation in the UV and in Halpha lines based on energy balance arguments. We also propose average scaling relations between these components and dust corrected, Halpha derived star-formation rates.Comment: Accepted for publication in Ap

A single-pot template reaction towards a manganese-based T1 contrast agent

Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL Me, and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b=21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (K a=4.2×10 3 M −1). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent