Diabetes mellitus is the most common metabolic disorder worldwide and a major risk factor for cardiovascular disease. MicroRNAs are negative regulators of gene expression that have been implicated in ...many biological processes, including metabolism. Here we show that the Let-7 family of microRNAs regulates glucose metabolism in multiple organs. Global and pancreas-specific overexpression of Let-7 in mice resulted in impaired glucose tolerance and reduced glucose-induced pancreatic insulin secretion. Mice overexpressing Let-7 also had decreased fat mass and body weight, as well as reduced body size. Global knockdown of the Let-7 family with an antimiR was sufficient to prevent and treat impaired glucose tolerance in mice with diet-induced obesity, at least in part by improving insulin sensitivity in liver and muscle. AntimiR treatment of mice on a high-fat diet also resulted in increased lean and muscle mass, but not increased fat mass, and prevented ectopic fat deposition in the liver. These findings demonstrate that Let-7 regulates multiple aspects of glucose metabolism and suggest antimiR-induced Let-7 knockdown as a potential treatment for type 2 diabetes mellitus. Furthermore, our Cre-inducible Let-7-transgenic mice provide a unique model for studying tissue-specific aspects of body growth and type 2 diabetes.
Determining the oxygen fugacity of Earth's silicate mantle is of prime importance because it affects the speciation and mobility of volatile elements in the interior and has controlled the character ...of degassing species from the Earth since the planet's formation. Oxygen fugacities recorded by garnet-bearing peridotite xenoliths from Archaean lithosphere are of particular interest, because they provide constraints on the nature of volatile-bearing metasomatic fluids and melts active in the oldest mantle samples, including those in which diamonds are found. Here we report the results of experiments to test garnet oxythermobarometry equilibria under high-pressure conditions relevant to the deepest mantle xenoliths. We present a formulation for the most successful equilibrium and use it to determine an accurate picture of the oxygen fugacity through cratonic lithosphere. The oxygen fugacity of the deepest rocks is found to be at least one order of magnitude more oxidized than previously estimated. At depths where diamonds can form, the oxygen fugacity is not compatible with the stability of either carbonate- or methane-rich liquid but is instead compatible with a metasomatic liquid poor in carbonate and dominated by either water or silicate melt. The equilibrium also indicates that the relative oxygen fugacity of garnet-bearing rocks will increase with decreasing depth during adiabatic decompression. This implies that carbon in the asthenospheric mantle will be hosted as graphite or diamond but will be oxidized to produce carbonate melt through the reduction of Fe(3+) in silicate minerals during upwelling. The depth of carbonate melt formation will depend on the ratio of Fe(3+) to total iron in the bulk rock. This 'redox melting' relationship has important implications for the onset of geophysically detectable incipient melting and for the extraction of carbon dioxide from the mantle through decompressive melting.
The composition of Earth's atmosphere depends on the redox state of the mantle, which became more oxidizing at some stage after Earth's core started to form. Through high-pressure experiments, we ...found that Fe
in a deep magma ocean would disproportionate to Fe
plus metallic iron at high pressures. The separation of this metallic iron to the core raised the oxidation state of the upper mantle, changing the chemistry of degassing volatiles that formed the atmosphere to more oxidized species. Additionally, the resulting gradient in redox state of the magma ocean allowed dissolved CO
from the atmosphere to precipitate as diamond at depth. This explains Earth's carbon-rich interior and suggests that redox evolution during accretion was an important variable in determining the composition of the terrestrial atmosphere.
The chemical composition of Earth's lower mantle can be constrained by combining seismological observations with mineral physics elasticity measurements. However, the lack of laboratory data for ...Earth's most abundant mineral, (Mg,Fe,Al)(Al,Fe,Si)O3 bridgmanite (also known as silicate perovskite), has hampered any conclusive result. Here we report single-crystal elasticity data on (Al,Fe)-bearing bridgmanite (Mg0.9Fe0.1Si0.9Al0.1)O3 measured using high-pressure Brillouin spectroscopy and X-ray diffraction. Our measurements show that the elastic behaviour of (Al,Fe)-bearing bridgmanite is markedly different from the behaviour of the MgSiO3 endmember. We use our data to model seismic wave velocities in the top portion of the lower mantle, assuming a pyrolitic mantle composition and accounting for depth-dependent changes in iron partitioning between bridgmanite and ferropericlase. We find excellent agreement between our mineral physics predictions and the seismic Preliminary Reference Earth Model down to at least 1,200 kilometres depth, indicating chemical homogeneity of the upper and shallow lower mantle. A high Fe3+/Fe2+ ratio of about two in shallow-lower-mantle bridgmanite is required to match seismic data, implying the presence of metallic iron in an isochemical mantle. Our calculated velocities are in increasingly poor agreement with those of the lower mantle at depths greater than 1,200 kilometres, indicating either a change in bridgmanite cation ordering or a decrease in the ferric iron content of the lower mantle.
Pore scale modeling plays a key role in fluid flow through porous media and associated macroscale constitutive relationships. The polyhedral shape and effective local pore size within granular ...material microstructure are computed in this study by means of the Euclidean Distance Transform (EDT), a local maxima search (non-maximum suppression), and a segmentation process. Various synthetic packed particles are simulated and employed as comparative models during the computation of pore size distribution (PSD). Reconstructed un-sheared and sheared Ottawa 20-30 sand samples are used to compute PSD for non-trivial and non-spherical models.
Thermodynamic parameters have been calibrated for a geobarometer suitable for use on eclogitic mantle xenoliths. The barometer is based on the incorporation of tetrahedrally coordinated aluminum in ...clinopyroxene coexisting with garnet and has been calibrated using the results of piston cylinder and multi-anvil experiments performed between pressures of 3 and 7 GPa and temperatures from 1,200 to 1,550 °C. Starting materials were hydrous and anhydrous synthetic mixtures of basaltic bulk compositions that yielded homogeneous bimineralic garnet–clinopyroxene phase assemblages. The experimental data set was expanded by employing results from previous experimental studies conducted in eclogitic systems, which widened the range of applicable conditions and compositions. The calibration reproduces experimental pressures of bimineralic eclogite assemblages, in addition to SiO
2
-saturated and kyanite-bearing eclogites, to within 0.4 GPa at the 95 % confidence interval. The barometer was then used to examine equilibration pressures recorded by natural mantle eclogites from various xenolith locations covering a wide pressure, temperature, and compositional range.
In mid-February 2015, a large number of deaths were observed in the sole extant population of an endangered species of freshwater snapping turtle, Myuchelys georgesi, in a coastal river in New South ...Wales, Australia. Mortalities continued for approximately 7 weeks and affected mostly adult animals. More than 400 dead or dying animals were observed and population surveys conducted after the outbreak had ceased indicated that only a very small proportion of the population had survived, severely threatening the viability of the wild population. At necropsy, animals were in poor body condition, had bilateral swollen eyelids and some animals had tan foci on the skin of the ventral thighs. Histological examination revealed peri-orbital, splenic and nephric inflammation and necrosis. A virus was isolated in cell culture from a range of tissues. Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Its closest relatives are nidoviruses that have recently been described in pythons and lizards, usually in association with respiratory disease. In contrast, in the affected turtles, the most significant pathological changes were in the kidneys. Real time PCR assays developed to detect this virus demonstrated very high virus loads in affected tissues. In situ hybridisation studies confirmed the presence of viral nucleic acid in tissues in association with pathological changes. Collectively these data suggest that this virus is the likely cause of the mortalities that now threaten the survival of this species. Bellinger River Virus is the name proposed for this new virus.
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