In Situ Synchrotron HEXRD Study on the Deformation Mechanism of a Nickel-Based Superalloy during Medium-Temperature Compression

The γ′ phase has an important influence on the deformation mechanism of solid-solution strengthening nickel-based superalloys. The microfracture behavior of the alloy depends on the mechanism of stress and strain partitioning between the γ and γ′ phase under load. In this study, the in situ synchrotron radiation high-energy X-ray diffraction technique was used to observe the deformation process of the FGH96 nickel-based superalloy with a γ′ volume fraction of about 40% at 650 °C and 750 °C. The results show that the (111) reflection had the greatest stiffness and showed plastic deformation first; while the (200) reflection bore a larger load. The γ phase yielded first and began to deform plastically; then the load was transferred to the γ′ phase. At 650 °C, the plastic deformation of the γ′ phase was relatively higher; while at 750 °C, the γ′ particle basically maintained elastic deformation with a tiny amount of plastic deformation

A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction

Synaptic transmission requires intricate coordination of the components involved in processing of incoming signals, formation and stabilization of synaptic machinery, neurotransmission and in all related signaling pathways. Changes to any of these components cause synaptic imbalance and disruption of neuronal circuitry. Extensive studies at the neuromuscular junction (NMJ) have greatly aided in the current understanding of synapses and served to elucidate the underlying physiology as well as associated adaptive and homeostatic processes. The heparan sulfate proteoglycan agrin is a vital component of the NMJ, mediating synaptic formation and maintenance in both brain and muscle, but very little is known about direct control of its expression. Here, we investigated the relationship between agrin and transcription factor early growth response-1 (Egr-1), as Egr-1 regulates the expression of many genes involved in synaptic homeostasis and plasticity. Using chromatin immunoprecipitation (ChIP), cell culture with cell lines derived from brain and muscle, and animal models, we show that Egr-1 binds to the AGRN gene locus and suppresses its expression. When compared with wild type (WT), mice deficient in Egr-1 (Egr-1−/−) display a marked increase in AGRN mRNA and agrin full-length and cleavage fragment protein levels, including the 22 kDa, C-terminal fragment in brain and muscle tissue homogenate. Because agrin is a crucial component of the NMJ, we explored possible physiological implications of the Egr-1-agrin relationship. In the diaphragm, Egr-1−/− mice display increased NMJ motor endplate density, individual area and area of innervation. In addition to increased density, soleus NMJs also display an increase in fragmented and faint endplates in Egr-1−/− vs. WT mice. Moreover, the soleus NMJ electrophysiology of Egr-1−/− mice revealed increased quantal content and motor testing showed decreased movement and limb muscle strength compared with WT. This study provides evidence for the potential involvement of a novel Egr-1-agrin pathway in synaptic homeostatic and compensatory mechanisms at the NMJ. Synaptic homeostasis is greatly affected by the process of aging. These and other data suggest that changes in Egr-1 expression may directly or indirectly promote age-related pathologies