IGF-II is regulated by microRNA-125b in skeletal myogenesis

miR-125b is identified as a myogenic miRNA that regulates skeletal muscle differentiation by targeting IGF-II under the control of mTOR signaling

The Role of Phe82 and Phe351 in Auxin-Induced Substrate Perception by TIR1 Ubiquitin Ligase: A Novel Insight from Molecular Dynamics Simulations

It is well known that Auxin plays a key role in controlling many aspects of plant growth and development. Crystal structures of Transport inhibitor response 1 (TIR1), a true receptor of auxin, were very recently determined for TIR1 alone and in complexes with auxin and different synthetic analogues and an Auxin/Indole-3-Acetic Acid (Aux/IAA) substrate peptide. However, the dynamic conformational changes of the key residues of TIR1 that take place during the auxin and substrate perception by TIR1 and the detailed mechanism of these changes are still unclear. In the present study, various computational techniques were integrated to uncover the detailed molecular mechanism of the auxin and Aux/IAA perception process; these simulations included molecular dynamics (MD) simulations on complexes and the free enzyme, the molecular mechanics Poisson Boltzmann surface area (MM-PBSA) calculations, normal mode analysis, and hydrogen bond energy (HBE) calculations. The computational simulation results provided a reasonable explanation for the structure-activity relationships of auxin and its synthetic analogues in view of energy. In addition, a more detailed model for auxin and Aux/IAA perception was also proposed, indicating that Phe82 and Phe351 played a pivotal role in Aux/IAA perception. Upon auxin binding, Phe82 underwent conformational changes to accommodate the subsequent binding of Aux/IAA. As a result, auxin enhances the TIR1-Aux/IAA interactions by acting as a “molecular glue”. Besides, Phe351 acts as a “fastener” to further improve the substrate binding. The structural and mechanistic insights obtained from the present study will provide valuable clues for the future design of promising auxin analogues

Elevated miR-499 Levels Blunt the Cardiac Stress Response

The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response

Bone morphogenetic proteins in tissue engineering: the road from laboratory to the clinic: part I (basic concepts)

Discovered in 1965, bone morphogenetic proteins (BMPs) are a group of cytokines from the transforming growth factor-β (TGFβ) superfamily with significant roles in bone and cartilage formation. BMPs are used as powerful osteoinductive components of diverse tissue-engineering products for the healing of bone. Several BMPs with different physiological roles have been identified in humans. The purpose of this review is to cover the biological function of the main members of BMP family, the latest research on BMPs signalling pathways and advances in the production of recombinant BMPs for tissue engineering purposes

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed