Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice

Fabry disease is a lysosomal storage disorder caused by a deficiency of a-galactosidase A (a-gal A) activity that results in progressive globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background a-gal A activity. Next, we transplanted normal human CD34(+) cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-a-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma a-gal A activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb(3) reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.Fil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yoshimitsu, Makoto. Kagoshima University; Japón. University Health Network; CanadáFil: Mizue, Nobuo. University Health Network; CanadáFil: Au, Bryan C. Y.. University Health Network; CanadáFil: Wang, James C. M.. University Health Network; CanadáFil: Fan, Xin. University Health Network; CanadáFil: Takenaka, Toshihiro. Kagoshima University; JapónFil: Medin, Jeffrey A. University Health Network; Canadá. University of Toronto; Canad

Geology of Byobu Rock and Gobanme Rock, Prince Olav Coast, East Antarctica

We report here the geology of Byobu Rock and Gobanme Rock outcrops hitherto unmapped in the Prince Olav Coast, East Antarctica. Both these outcrops expose high-grade metamorphic and igneous rocks. The metamorphic rock units comprise mainly of gneisses migmatized to variable extent and amphibolites, whereas igneous rocks comprise of granites and pegmatites. Preliminary structural data obtained from the outcrops identified the regional, steep to moderately dipping foliation trend in the WNW-ESE at Byobu Rock, whereas they trend in the NW-SE direction at Gobanme Rock. Two generations of folding were identified, an earlier tight isoclinal intrafolial folds and a late regional open fold. The three deformational events identified are comparable and consistent with those reported in the neighboring outcrops in the Prince Olav Coast. Metamorphic P-T conditions estimated based on various geothermobarometries indicate that the rocks have experienced granulite grade conditions during peak metamorphism (770-880°C and 6-9kbar). The finding of orthopyroxene at Byobu Rock in this study extends the orthopyroxene-in isograd in the progressive metamorphic zone in the Lutzow-Holm Complex further eastward beyond Tenmondai Rock. Inclusions of kyanite within garnet in metapelitic rocks suggest a clockwise P-T path, consistent with the P-T paths suggested for the Lutzow-Holm Complex. Preliminary bulk rock geochemical investigations indicate that granitic rocks and quartzo-feldspathic gneiss mostly belong to volcanic arc granite suite, though their origin remains indistinct. Electron microprobe dating of monazites from representative rocks gave Pan-African ages (557±33Ma), consistent with the regional metamorphic ages reported earlier. Thus, based on the similarities on structural, petrological, geochemical and geochronological data, the Byobu Rock and Gobanme Rock are considered to be integral part of the Pan-African Lutzow-Holm Complex with analogous geological history

Calc-silicate rocks and marbles from Lutzow-Holm Complex,East Antarctica, with special reference to the mineralogy and geochemical characteristics of calc-silicate mega-boudins from Rundvagshetta

We report here the mode of occurrence of calc-silicate rocks and marbles from the Lutzow-Holm Complex, East Antarctica, and a worked example from Rundvagshetta. Calc-silicate boudins were observed in Cape Hinode, Akarui Point, Byobu Rock, Skarvsnes, Skallevikshalsen and Rundvagshetta, whereas they were reported earlier from Sinnan Rock, Cape Ryugu, Akebono Rock, Cape Hinode, Niban Rock, Kasumi Rock, Daruma Rock, Cape Omega, Langhovde, Ytrehovdeholmen and Skarvsnes. They vary in size from decimeters to few meters and are commonly enclosed within pelitic or psammitic gneisses. In addition, extensive layers of marbles and calc-silicate rocks are distributed in Skallevikshalsen. The calc-silicate mega-boudins within the layered pyroxene-gneiss from Rundvagshetta, up to 5m long and 2m thick, comprises of coarse to medium grained assemblage of scapolite+anorthite+garnet+clinopyroxene+calcite+quartz+titanite±wollastonite. Co-existing scapolite and plagioclase suggest a "minimum" estimate of peak metamorphic temperature of ～830°C . Peak metamorphic mineral assemblages equilibrated at moderate to high X_(CO2) conditions (0.3-0.7) and temperatures between 850 and 1000°C , consistent with the ultrahigh temperature metamorphic conditions reported in the region. Multistage garnet corona formation preserved in the calc-silicate assemblage suggests a local increase in hydrous fluid activity during retrogression. Preliminary bulk rock geochemistry of different mineralogical zones in the boudin shows chemical potential gradients in some major elements, especially SiO_2, Al_2O_3 and CaO, possibly controlled by the compositional variations in the protolith. Altogether, these results suggest that calc-silicate rocks preserve information on the metamorphic evolution and help us in deducing the geodynamic evolution of high-grade terrains

Geochemistry of mafic metamorphic rocks in the Lutzow-Holm Complex, East Antarctica: Implications for tectonic evolution

Mafic metamorphic rocks are widely distributed through the Lutzow-Holm Complex (LHC) of East Antarctica, as layers between or enclaves within metasedimentary and metaigneous lithologies. It has been inferred that the peak metamorphic grade of the LHC progressively increases in a southwestern direction from amphibolite-facies to granulite-facies conditions, with mineral assemblages in the mafic metamorphic rocks changing from hornblende (magnesiohornblende)±biotite+plagioclase to orthopyroxene+clinopyroxene±hornblende (pargasite, magnesiohasting-site and tschermakite)±biotite±garnet+plagioclase. Field relationships suggest that amphibolite-grade mafic metamorphic rocks derive from mafic magma intruded into metasedimentary units, whereas granulite-facies mafic metamorphic rocks are a mixture of detrital blocks and mafic sill or intrusions. Major and trace element compositions of mafic metamorphic rocks are similar to those of igneous rocks of tholeiite affinity, and can be divided into volcanic-arc basalt (VAB)-type or mid-ocean ridge basalt (MORB)-type compositions. On a regional scale, VAB-type lithologies are predominant in amphibolite-facies areas, and MORB-type lithologies predominate in granulite-facies areas. On the basis of HFSE concentrations and Nb/Y ratios, MORB-type lithologies have T-type and E-type MORB compositions with oceanic plateau basalt and back-arc basin basalt affinities, and are occasionally found in the field intercalated with metasedimentary layers, characteristic of magmatism and sedimentation cycles in a marginal sea basin setting. Such field relationships provide information on the tectonic environment of protolith formation in the LHC. Various crustal components have been amalgamated into a relatively narrow mobile belt, which was subjected to high-grade metamorphism during the final closure of oceanic basins as a result of continent-continent collision

Granulites from Cape Hinode in the amphibolite-facies eastern part of Prince Olav Coast, East Antarctica: New evidence for allochthonous block in the Lutzow-Holm Complex

High-grade metamorphic rocks occurring along the Prince Harald, Soya, and Prince Olav Coasts make up the Latest Proterozoic-Early Paleozoic Lutzow-Holm Complex, which is the youngest orogenic belt in the East Antarctic Shield. A systematic increase in metamorphic grade from east to west, ranging from upper amphibolite facies on the eastern Prince Olav Coast to upper granulite facies at the head of Lutzow-Holm Bay, has been well-established in the complex. However, granulites are newly found to occur as blocks sitting within meta-tonalites at Cape Hinode located on the amphibolite-facies eastern Prince Olav Coast. In addition, it is newly revealed that kyanite occurs rather commonly in meta-tonalites which contain hornblende with or without clinopyroxene. The modes of occurrence in the field, petrographical features, and major element bulk rock compositions of the granulites and related rocks are given in some detail in this study. These, along with the previously presented geochronological, geochemical and petrographical data, would indicate that the rocks in the Cape Hinode area as a whole make up a Mesoproterozoic allochthonous block in the Latest Proterozoic-Early Paleozoic Lutzow-Holm Complex

A Thermo‐ and mechanoresponsive cyano‐substituted oligo(p‐phenylene vinylene) derivative with five emissive states

Multiresponsive materials that display predefined photoluminescence color changes upon exposure to different stimuli are attractive candidates for advanced sensing schemes. Herein, we report a cyano-substituted oligo(p-phenylene vinylene) (cyano-OPV) derivative that forms five different solvent-free solid-state molecular assemblies, luminescence properties of which change upon thermal and mechanical stimulation. Single-crystal X-ray structural analysis suggested that tolyl groups introduced at the termini of solubilizing side-chains of the cyano-OPV play a pivotal role in its solid-state arrangement. Viewed more broadly, this report shows that the introduction of competing intermolecular interactions into excimer-forming chromophores is a promising design strategy for multicolored thermo- and mechanoresponsive luminescent materials

Kinetic Study on Palm Oil Waste Decomposition

No abstract available

P-wave tomography of the mantle beneath the South Pacific Superswell revealed by joint ocean floor and islands broadband seismic experiments

International audienceThree-dimensional P-wave velocity structure of the mantle beneath the South Pacific Superswell is determined through passive broadband seismic experiments on the ocean floor and islands between 2003 and 2005. We collected approximately 1500 relative times of long-period teleseismic P-waves by using a waveform cross-correlation. We analyzed this data set with relative time tomography to depths of 2000 km. The resultant structure shows lateral heterogeneity of approximately +/- 2%, in which a distinct low velocity region is found beneath the center of the Superswell at a depth of 1600 km. At 1200km depth, an elongated low velocity region is found beneath the Society to Pitcairn hotspots. At 800 km depth, two linear low velocity regions are located beneath Tuamotu and Austral islands. Isolated low velocity regions are identified beneath the Society, Marquesas, and Macdonald hotspots at 400 km depth. Our new tomographic images reveal that the large low velocity region rooted in the deep lower mantle is split into two sheets at 1200 km depth and these terminate at approximately 800 km depth. This feature appears to be consistent with the characteristics of a thermo-chemical pile or dome

Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

Introduction: This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury