Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn−/− mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn−/− mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn−/− mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn−/− mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn−/− mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn−/− mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes

Geology, petrography and geochemistry of the A-type granites from the Morro Redondo Complex (PR-SC), southern Brazil, Graciosa Province

The Morro Redondo Complex is one of the most important occurrences of the Graciosa A-type Province, southern Brazil. It consists of the Papanduva and Quiriri granitic plutons and a contemporaneous bimodal volcanic association. The Papanduva Pluton includes massive and deformed peralkaline alkali-feldspar granites with Na-Ca and Na-amphiboles and clinopyroxenes. The deformed types are the most evolved rocks in the province and carry rare ‘agpaitic’ minerals, some being described for the first time in granites from Brazil. The larger Quiriri Pluton comprises massive, slightly peraluminous, biotite syeno- and monzogranites with rare Ca-amphibole. Biotite compositions are relatively homogeneous, whereas sodic amphiboles and clinopyroxenes show increasing Na and Fe3+ evolving paths. The Morro Redondo granites are ferroan, with high SiO2, alkalis and HFSE contents; the peralkaline types registering the highest fe#. LILE and HFSE abundances increase with the agpaitic index and the most evolved are HHP granites, with radiogenic heat production up to 5.7 µWm–3. Geothermobarometric estimates indicate emplacement under low pressures (∼100 MPa), at temperatures up to 850-800 °C, and relatively reduced (QFM) and oxidized (+1 REPLACE_LT ΔQFM REPLACE_LT +3) environments for the Papanduva and Quiriri Plutons, respectively. In both cases, melts evolved to relatively high oxidation states upon crystallization progress

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion