Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.

α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown. Here, we show that mice lacking α-DGN exhibit significantly higher viral titers in the lungs after Influenza A virus (IAV) infection (strain A/Puerto Rico/8/1934 H1N1), suggesting an inability to control virus load. Consistent with this, overexpression of α-DGN before infection or intranasal treatment with recombinant α-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant α-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for α-DGN in IAV proliferation.

Morphology and chemical behavior of model CsOx/Cu2O/Cu(111) nanocatalysts for methanol synthesis: Reaction with CO2 and H2.

Cs is a promoter of Cu-based catalysts for the synthesis of alcohols from CO2 hydrogenation. Scanning tunneling microscopy and ambient-pressure x-ray photoelectron spectroscopy were used to study the morphology and chemical properties of surfaces generated by the deposition of cesium on Cu2O/Cu(111) and Cu(111) substrates. CsOx nanostructures were formed after Cs metal was deposited on Cu2O/Cu(111) at 300 K. The formed CsOx protrude over the surface of copper oxide by 2-4 Å, with the dimension at the base of the nanostructures being in the range of 1-3 nm. Heating to elevated temperature induced significant changes in the size and dispersion of the CsOx nanostructures, and there was a clear reconstruction of the copper oxide substrate, which then exhibited long range order with a hexagonally packed structure. The as-deposited and annealed surfaces of CsOx/Cu2O/Cu(111) were more reactive toward CO2 than plain Cu2O/Cu(111) or clean Cu(111). However, none of them were stable in the presence of H2, which fully reduced the copper oxide at 400-450 K. In CsOx/Cu(111), the CsOx nanoclusters were dispersed all over the metallic copper in no particular order. The CsOx species had an average width of 2 nm and ∼1 Å height. The CsOx/Cu(111) systems exhibited the highest activity for the binding and dissociation of CO2, suggesting that the CsOx-copper interface plays a key role in alcohol synthesis.

Collagen VI deficiency reduces muscle pathology, but does not improve muscle function, in the γ-sarcoglycan-null mouse.

Muscular dystrophy is characterized by progressive skeletal muscle weakness and dystrophic muscle exhibits degeneration and regeneration of muscle cells, inflammation and fibrosis. Skeletal muscle fibrosis is an excessive deposition of components of the extracellular matrix including an accumulation of Collagen VI. We hypothesized that a reduction of Collagen VI in a muscular dystrophy model that presents with fibrosis would result in reduced muscle pathology and improved muscle function. To test this hypothesis, we crossed γ-sarcoglycan-null mice, a model of limb-girdle muscular dystrophy type 2C, with a Col6a2-deficient mouse model. We found that the resulting γ-sarcoglycan-null/Col6a2Δex5 mice indeed exhibit reduced muscle pathology compared with γ-sarcoglycan-null mice. Specifically, fewer muscle fibers are degenerating, fiber size varies less, Evans blue dye uptake is reduced and serum creatine kinase levels are lower. Surprisingly, in spite of this reduction in muscle pathology, muscle function is not significantly improved. In fact, grip strength and maximum isometric tetanic force are even lower in γ-sarcoglycan-null/Col6a2Δex5 mice than in γ-sarcoglycan-null mice. In conclusion, our results reveal that Collagen VI-mediated fibrosis contributes to skeletal muscle pathology in γ-sarcoglycan-null mice. Importantly, however, our data also demonstrate that a reduction in skeletal muscle pathology does not necessarily lead to an improvement of skeletal muscle function, and this should be considered in future translational studies.

Imaging the ordering of a weakly adsorbed two-dimensional condensate: ambient-pressure microscopy and spectroscopy of CO2 molecules on rutile TiO2(110).

Disorder-Order transitions in a weakly adsorbed two-dimensional film have been identified for the first time using ambient-pressure scanning tunneling microscopy (AP-STM) and X-ray photoelectron spectroscopy (AP-XPS). As of late, great effort has been devoted to the capture, activation and conversion of carbon dioxide (CO2), a ubiquitous greenhouse gas and by-product of many chemical processes. The high stability and non-polar nature of CO2 leads to weak bonding with well-defined surfaces of metals and oxides. CO2 adsorbs molecularly on the rutile TiO2(110) surface with a low adsorption energy of ∼10 kcal mol-1. In spite of this weak binding, images of AP-STM show that a substantial amount of CO2 can reside on a TiO2(110) surface at room temperature forming two-dimensionally ordered films. We have employed microscopic imaging under in situ conditions, soft X-ray spectroscopy and theory to decipher the unique ordering behavior seen for CO2 on TiO2(110).

Hydrogenation of CO2 on ZnO/Cu(100) and ZnO/Cu(111) Catalysts: Role of Copper Structure and Metal-Oxide Interface in Methanol Synthesis.

The results of kinetic tests and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) show the important role played by a ZnO-copper interface in the generation of CO and the synthesis of methanol from CO2 hydrogenation. The deposition of nanoparticles of ZnO on Cu(100) and Cu(111), θoxi < 0.3 monolayer, produces highly active catalysts. The catalytic activity of these systems increases in the sequence: Cu(111) < Cu(100) < ZnO/Cu(111) < ZnO/Cu(100). The structure of the copper substrate influences the catalytic performance of a ZnO-copper interface. Furthermore, size and metal-oxide interactions affect the chemical and catalytic properties of the oxide making the supported nanoparticles different from bulk ZnO. The formation of a ZnO-copper interface favors the binding and conversion of CO2 into a formate intermediate that is stable on the catalyst surface up to temperatures above 500 K. Alloys of Zn with Cu(111) and Cu(100) were not stable at the elevated temperatures (500-600 K) used for the CO2 hydrogenation reaction. Reaction with CO2 oxidized the zinc, enhancing its stability over the copper substrates.