Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1

During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity

Dark Matter in split extended supersymmetry

We consider the split extended (N=2) supersymmetry scenario recently proposed by Antoniadis et al. [hep-ph/0507192] as a realistic low energy framework arising from intersecting brane models. While all scalar superpartners and charged gauginos are naturally at a heavy scale, the model low energy spectrum contains a Higgsino-like chargino and a neutralino sector made out of two Higgsino and two Bino states. We show that the lightest neutralino is a viable dark matter candidate, finding regions in the parameter space where its thermal relic abundance matches the latest determination of the density of matter in the Universe by WMAP. We also discuss dark matter detection strategies within this model: we point out that current data on cosmic-ray antimatter already place significant constraints on the model, while direct detection is the most promising technique for the future. Analogies and differences with respect to the standard split SUSY scenario based on the MSSM are illustrated.Comment: 14 pages, references added, typos corrected, matches with the published versio

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

Lipidomic Analysis of Arabidopsis T-DNA Insertion Lines Leads to Identification and Characterization of C-Terminal Alterations in FATTY ACID DESATURASE 6

Article states that mass-spectrometry-based screening of lipid extracts of wounded and unwounded leaves from a collection of 364 Arabidopsis thaliana T-DNA insertion lines produced lipid profiles that were scored on the number and significance of their differences from the leaf lipid profiles of wild-type plants. The analysis identified Salk_109175C, which displayed alterations in leaf chloroplast glycerolipid composition, including a decreased ratio between two monogalactosyldiacylglycerol (MGDG) molecular species, MGDG(18:3/16:3) and MGDG(18:3/18:3)

Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens

Investigating Protostellar Accretion-Driven Outflows Across the Mass Spectrum: JWST NIRSpec IFU 3-5~μ\mum Spectral Mapping of Five Young Protostars

Investigating Protostellar Accretion (IPA) is a Cycle 1 JWST program using the NIRSpec+MIRI IFUs to obtain 2.9--28 $\mu$m spectral cubes of five young protostars with luminosities of 0.2 to 10,000 L$_{\odot}$ in their primary accretion phase. This paper introduces the NIRSpec 2.9--5.3 $\mu$m data of the inner 840-9000 au with spatial resolutions from 28-300 au. The spectra show rising continuum emission, deep ice absorption, emission from H$_{2}$, H~I, and [Fe~II], and the CO fundamental series in emission and absorption. Maps of the continuum emission show scattered light cavities for all five protostars. In the cavities, collimated jets are detected in [Fe~II] for the four $< 320$~L$_{\odot}$ protostars, two of which are additionally traced in Br-$\alpha$. Knots of [Fe~II] emission are detected toward the most luminous protostar, and knots of [FeII] emission with dynamical times of $< 30$~yrs are found in the jets of the others. While only one jet is traced in H$_2$, knots of H$_2$ and CO are detected in the jets of four protostars. H$_2$ is seen extending through the cavities showing they are filled by warm molecular gas. Bright H$_2$ emission is seen along the walls of a single cavity, while in three cavities, narrow shells of H$_2$ emission are found, one of which has an [Fe~II] knot at its apex. These data show cavities containing collimated jets traced in atomic/ionic gas surrounded by warm molecular gas in a wide-angle wind and/or gas accelerated by bow shocks in the jets.Comment: 30 pages, 11 figure