The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding

Myostatin is a member of the transforming growth factor-β (TGF-β) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-β class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. Overall, we have identified several characteristics unique to myostatin that will be paramount to the rational design of myostatin inhibitors that could be used in the treatment of muscle-wasting disorders

Experimental study of strain rate effects on normal weight concrete after exposure to elevated temperature

© 2016, RILEM. The effects of strain rate ranging from 10-4 to 300 s-1 on normal weight concrete after exposure to elevated temperature up to 1000 °C were experimentally investigated using a servo-hydraulic testing machine and a split Hopkinson pressure bar. The casted cylinder concrete specimens were firstly heated in a microwave oven, and then cooled down to the ambient temperature with control. Experimental results proved that the normal weight concrete after high temperature exposure still showed significant strain rate dependency. The dynamic increase factor(DIF) for compressive strength decreased with the exposed elevated temperature from 600 to 800 °C, and increased from 800 to 1000 °C. The DIF of concrete after exposure to elevated temperature is smaller than that at the ambient temperature according to CEB code. The larger the compressive strength is, the smaller the DIF of normal weight concrete after high temperature exposure will be. In addition, further comparison showed that the DIF after high temperature exposure is larger than that exactly at the same high temperature. An empirical model of DIF for normal weight concrete after elevated temperature exposure was proposed based on the experimental data. It obviously benefits the assessment of blast resistant capacity of post-fired concrete structures, as well as referred retrofitting techniques