High contrast Mach-Zehnder lithium atom interferometer in the Bragg regime

We have constructed an atom interferometer of the Mach-Zehnder type, operating with a supersonic beam of lithium. Atom diffraction uses Bragg diffraction on laser standing waves. With first order diffraction, our apparatus has given a large signal and a very good fringe contrast (74%), which we believe to be the highest ever observed with atom interferometers. This apparatus will be applied to high sensitivity measurementsComment: 6 pages, 3 figures, accepted by Appl. Phys.

The cytokine language of monocytes and macrophages in systemic sclerosis

Many important observations suggest monocyte/macrophage involvement in systemic sclerosis (SSc). A high concentration of immune mediators, such as IL-6, IL-10 and IL-13, the infiltration of mononuclear cells in affected organs and the production of autoantibodies suggest that immune system dysfunction drives SSc pathogenesis. The recently reported study by Higashi-Kuwata and colleagues, in light of other observations, provides further insight into activation of macrophages/monocytes in SSc patients, suggesting that these cells undergo distinct activation pathways. These results emphasize the need for more detailed analyses of the several markers now defined in SSc peripheral blood mononuclear cells and tissues to better define the cytokine language speaking to monocytes/macrophages in SSc that promote vascular injury and tissue fibrosis

An Accessory to the ‘Trinity’: SR-As Are Essential Pathogen Sensors of Extracellular dsRNA, Mediating Entry and Leading to Subsequent Type I IFN Responses

Extracellular RNA is becoming increasingly recognized as a signaling molecule. Virally derived double stranded (ds)RNA released into the extracellular space during virus induced cell lysis acts as a powerful inducer of classical type I interferon (IFN) responses; however, the receptor that mediates this response has not been identified. Class A scavenger receptors (SR-As) are likely candidates due to their cell surface expression and ability to bind nucleic acids. In this study, we investigated a possible role for SR-As in mediating type I IFN responses induced by extracellular dsRNA in fibroblasts, a predominant producer of IFNβ. Fibroblasts were found to express functional SR-As, even SR-A species thought to be macrophage specific. SR-A specific competitive ligands significantly blocked extracellular dsRNA binding, entry and subsequent interferon stimulated gene (ISG) induction. Candidate SR-As were systematically investigated using RNAi and the most dramatic inhibition in responses was observed when all candidate SR-As were knocked down in unison. Partial inhibition of dsRNA induced antiviral responses was observed in vivo in SR-AI/II-/- mice compared with WT controls. The role of SR-As in mediating extracellular dsRNA entry and subsequent induced antiviral responses was observed in both murine and human fibroblasts. SR-As appear to function as ‘carriers’, facilitating dsRNA entry and delivery to the established dsRNA sensing receptors, specifically TLR3, RIGI and MDA-5. Identifying SR-As as gatekeepers of the cell, mediating innate antiviral responses, represents a novel function for this receptor family and provides insight into how cells recognize danger signals associated with lytic virus infections. Furthermore, the implications of a cell surface receptor capable of recognizing extracellular RNA may exceed beyond viral immunity to mediating other important innate immune functions

MARCO, TLR2, and CD14 Are Required for Macrophage Cytokine Responses to Mycobacterial Trehalose Dimycolate and Mycobacterium tuberculosis

Virtually all of the elements of Mycobacterium tuberculosis (Mtb) pathogenesis, including pro-inflammatory cytokine production, granuloma formation, cachexia, and mortality, can be induced by its predominant cell wall glycolipid, trehalose 6,6′-dimycolate (TDM/cord factor). TDM mediates these potent inflammatory responses via interactions with macrophages both in vitro and in vivo in a myeloid differentiation factor 88 (MyD88)-dependent manner via phosphorylation of the mitogen activated protein kinases (MAPKs), implying involvement of toll-like receptors (TLRs). However, specific TLRs or binding receptors for TDM have yet to be identified. Herein, we demonstrate that the macrophage receptor with collagenous structure (MARCO), a class A scavenger receptor, is utilized preferentially to “tether” TDM to the macrophage and to activate the TLR2 signaling pathway. TDM-induced signaling, as measured by a nuclear factor-kappa B (NF-κB)-luciferase reporter assay, required MARCO in addition to TLR2 and CD14. MARCO was used preferentially over the highly homologous scavenger receptor class A (SRA), which required TLR2 and TLR4, as well as their respective accessory molecules, in order for a slight increase in NF-κB signaling to occur. Consistent with these observations, macrophages from MARCO−/− or MARCO−/−SRA−/− mice are defective in activation of extracellular signal-related kinase 1/2 (ERK1/2) and subsequent pro-inflammatory cytokine production in response to TDM. These results show that MARCO-expressing macrophages secrete pro-inflammatory cytokines in response to TDM by cooperation between MARCO and TLR2/CD14, whereas other macrophage subtypes (e.g. bone marrow–derived) may rely somewhat less effectively on SRA, TLR2/CD14, and TLR4/MD2. Macrophages from MARCO−/− mice also produce markedly lower levels of pro-inflammatory cytokines in response to infection with virulent Mtb. These observations identify the scavenger receptors as essential binding receptors for TDM, explain the differential response to TDM of various macrophage populations, which differ in their expression of the scavenger receptors, and identify MARCO as a novel component required for TLR signaling

Genome-Wide Screen for Mycobacterium tuberculosis Genes That Regulate Host Immunity

In spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb) establishes persistent infection in otherwise healthy individuals, making it one of the most widespread and deadly human pathogens. Mtb's prolonged survival may reflect production of microbial factors that prevent even more vigorous immunity (quantitative effect) or that divert the immune response to a non-sterilizing mode (qualitative effect). Disruption of Mtb genes has produced a list of several dozen candidate immunomodulatory factors. Here we used robotic fluorescence microscopy to screen 10,100 loss-of-function transposon mutants of Mtb for their impact on the expression of promoter-reporter constructs for 12 host immune response genes in a mouse macrophage cell line. The screen identified 364 candidate immunoregulatory genes. To illustrate the utility of the candidate list, we confirmed the impact of 35 Mtb mutant strains on expression of endogenous immune response genes in primary macrophages. Detailed analysis focused on a strain of Mtb in which a transposon disrupts Rv0431, a gene encoding a conserved protein of unknown function. This mutant elicited much more macrophage TNFα, IL-12p40 and IL-6 in vitro than wild type Mtb, and was attenuated in the mouse. The mutant list provides a platform for exploring the immunobiology of tuberculosis, for example, by combining immunoregulatory mutations in a candidate vaccine strain

Dynamics of laser-induced Cesium atom desorption from porous glass

The dynamics of short pulsed infrared laser-induced desorption of Cesium atoms from porous silica samples has been investigated. We find most probable kinetic energies of 69 ± 6 meV for desorption laser fluences between 60 and 190 mJ/cm2, significantly higher compared to those obtained for Cs desorption from plain glass, 40 ± 2 meV, but lower compared to those observed for Na and Rb desorption from polymeric surfaces, 200 meV. This is explained qualitatively by scattering of the desorbing atoms with the silica nanochannels, thus suggesting different pulsed laser photodesorption processes for atoms embedded in hard porous dielectrics as compared to polymeric thin films. © 2006 Elsevier B.V. All rights reserved

Dynamics of laser-induced Cesium atom desorption from porous glass

The dynamics of short pulsed infrared laser-induced desorption of Cesium atoms from porous silica samples has been investigated. We find most probable kinetic energies of 69 ± 6 meV for desorption laser fluences between 60 and 190 mJ/cm2, significantly higher compared to those obtained for Cs desorption from plain glass, 40 ± 2 meV, but lower compared to those observed for Na and Rb desorption from polymeric surfaces, 200 meV. This is explained qualitatively by scattering of the desorbing atoms with the silica nanochannels, thus suggesting different pulsed laser photodesorption processes for atoms embedded in hard porous dielectrics as compared to polymeric thin films. © 2006 Elsevier B.V. All rights reserved

Frequency measurement of the 2S-12D transitions in hydrogen and deuterium, new determination of the Rydberg constant

International audienc

Optical frequency measurement of the 2S-12D transitions in hydrogen and deuterium: Rydberg constant and lamb shift determinations

International audienc

Optical frequency measurement of the 2S-12D transitions in hydrogen and deuterium: Rydberg constant and lamb shift determinations

International audienc