Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD)

© 2017 The Author(s). We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD. We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects. Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages. Multiplex ELISA measured BAL cytokines. Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles. We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups. However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects. BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs. The mouse-model of COPD showed similar increase in mRNA for M2 markers. Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance. There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD

Correlators of Vertex Operators for Circular Strings with Winding Numbers in AdS5xS5

We compute semiclassically the two-point correlator of the marginal vertex operators describing the rigid circular spinning string state with one large spin and one windining number in AdS_5 and three large spins and three winding numbers in S^5. The marginality condition and the conformal invariant expression for the two-point correlator obtained by using an appropriate vertex operator are shown to be associated with the diagonal and off-diagonal Virasoro constraints respectively. We evaluate semiclassically the three-point correlator of two heavy circular string vertex operators and one zero-momentum dilaton vertex operator and discuss its relation with the derivative of the dimension of the heavy circular string state with respect to the string tension.Comment: 16 pages, LaTeX, no figure

Fermions and Type IIB Supergravity On Squashed Sasaki-Einstein Manifolds

We discuss the dimensional reduction of fermionic modes in a recently found class of consistent truncations of type IIB supergravity compactified on squashed five-dimensional Sasaki-Einstein manifolds. We derive the lower dimensional equations of motion and effective action, and comment on the supersymmetry of the resulting theory, which is consistent with N=4 gauged supergravity in $d=5$, coupled to two vector multiplets. We compute fermion masses by linearizing around two $AdS_{5}$ vacua of the theory: one that breaks N=4 down to N=2 spontaneously, and a second one which preserves no supersymmetries. The truncations under consideration are noteworthy in that they retain massive modes which are charged under a U(1) subgroup of the $R$-symmetry, a feature that makes them interesting for applications to condensed matter phenomena via gauge/gravity duality. In this light, as an application of our general results we exhibit the coupling of the fermions to the type IIB holographic superconductor, and find a consistent further truncation of the fermion sector that retains a single spin-1/2 mode.Comment: 43 pages, 2 figures, PDFLaTeX; v2: added references, typos corrected, minor change

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Holographic zero sound at finite temperature in the Sakai-Sugimoto model

In this paper, we study the fate of the holographic zero sound mode at finite temperature and non-zero baryon density in the deconfined phase of the Sakai-Sugimoto model of holographic QCD. We establish the existence of such a mode for a wide range of temperatures and investigate the dispersion relation, quasi-normal modes, and spectral functions of the collective excitations in four different regimes, namely, the collisionless quantum, collisionless thermal, and two distinct hydrodynamic regimes. For sufficiently high temperatures, the zero sound completely disappears, and the low energy physics is dominated by an emergent diffusive mode. We compare our findings to Landau-Fermi liquid theory and to other holographic models.Comment: 1+24 pages, 19 figures, PDFTeX, v2: some comments and references added, v3: some clarifications relating to the different regimes added, matches version accepted for publication in JHEP, v4: corrected typo in eq. (3.18