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Summary: Neurofibromatosis type 1 (NF1) is a dominant genetic disorder manifesting, in part, as cognitive defects. Previous study indicated that neurofibromin (NF1 protein) interacts with valosin-containing protein (VCP)/P97 to control dendritic spine formation, but the mechanism is unknown. Here, using Nf1+/– mice and transgenic mice overexpressing wild-type Vcp/p97, we demonstrate that neurofibromin acts with VCP to control endoplasmic reticulum (ER) formation and consequent protein synthesis and regulates dendritic spine formation, thereby modulating contextual fear memory and social interaction. To validate the role of protein synthesis, we perform leucine supplementation in vitro and in vivo. Our results suggest that leucine can effectively enter the brain and increase protein synthesis and dendritic spine density of Nf1+/– neurons. Contextual memory and social behavior of Nf1+/– mice are also restored by leucine supplementation. Our study suggests that the “ER-protein synthesis” pathway downstream of neurofibromin and VCP is a critical regulator of dendritic spinogenesis and brain function.

The effects of La content on the microstructure and properties of 0.15nanoSiCp/Zn-36.5Al-2.5Cu-0.8 Mg composites were studied. Results show that La not only effectively eliminated the shrinkage defects during the solidification process, but also refined the as-cast microstructure and promoted the dispersion of nano-reinforced particles. The improvement in mechanical properties of the composites gradually slowed down with the addition of La, but the wear resistance significantly increased with the increased La content. Thermal mismatch strengthening mechanism was identified in nano-SiCp on Zn-36.5Al-2.5Cu-0.8 Mg matrix induced by La addition. In addition, the rare earth compounds formed by excessive La were easy to aggregate on the grain or grain boundary, which resulted in brittle fracture. [ABSTRACT FROM AUTHOR]

Summary: Impaired interhemispheric connectivity is commonly found in various psychiatric disorders, although how interhemispheric connectivity regulates brain function remains elusive. Here, we use the mouse amygdala, a brain region that is critical for social interaction and fear memory, as a model to demonstrate that contralateral connectivity intensifies the synaptic response of basolateral amygdalae (BLA) and regulates amygdala-dependent behaviors. Retrograde tracing and c-FOS expression indicate that contralateral afferents widely innervate BLA non-randomly and that some BLA neurons innervate both contralateral BLA and the ipsilateral central amygdala (CeA). Our optogenetic and electrophysiological studies further suggest that contralateral BLA input results in the synaptic facilitation of BLA neurons, thereby intensifying the responses to cortical and thalamic stimulations. Finally, pharmacological inhibition and chemogenetic disconnection demonstrate that BLA contralateral facilitation is required for social interaction and memory. Our study suggests that interhemispheric connectivity potentiates the synaptic dynamics of BLA neurons and is critical for the full activation and functionality of amygdalae. : Huang et al. show that contralateral innervation between two basolateral amygdalae (BLA) in the two brain hemispheres evokes the synaptic activity of BLA and intensifies the BLA response to ipsilateral afferents, including cortical and thalamic inputs. BLA contralateral connectivity is required for amygdala-dependent behaviors, including social interaction and memory. Keywords: amygdala, anterior commissure, associative memory, contralateral innervation, social interaction, synaptic facilitation

Breakage, Helmholtz free energy, and nonlinearity are involved in many fundamental phenomena of complex systems across natural sciences. However, a mathematical equation that can express the entire life cycle of complex natural objects (such as rock-like quasi-brittle materials) is lacking. We expand the material body system to an isolated compound thermodynamic system to establish an innovative theoretical model induced by coupling nonlinear separation of Helmholtz free energy and breakage evolution that can be used to express the extreme entire life model of rock under unequal amplitude loading and unloading cycle. We gain crucial insights into the life essence of limestone, which is termed "Negative Dissipation." This study first shows that the change in the mechanical properties of quasi-brittle materials caused by the timely evolution of breakage can be represented by the nonlinear separation of Helmholtz free energy and negative dissipation. An analytical solution to the nonlinear separation variables of Helmholtz free energy is provided by combining the method of solving nonlinear partial differential equations in mathematics and thermodynamic law. An analytical solution of Helmholtz free energy considering nonlinearity and breakage is proposed, and an equation that can reflect the constitutive mechanics law of the entire life cycle of rock in the theoretical model is presented. Theoretical results are consistent with the experimental data obtained from limestone samples with different prefabricated cracks. This original study provides a theoretical foundation for the life model of complex natural objects for nonlinear breakage and an early warning investigation of rocks under various unprecedented conditions. This study first found that the change in the mechanical properties of complex natural objects caused by the timely evolution of breakage can be represented by the nonlinear separation of Helmholtz free energy. We establish an innovative theoretical model induced by coupling nonlinear separation of Helmholtz free energy and breakage evolution. The innovative theory includes three parts: (1) an analytical solution to the nonlinear separation variables of Helmholtz free energy, (2) an analytical solution of Helmholtz free energy considering nonlinearity and breakage, and (3) an equation of the theoretical model that can reflect the constitutive mechanics' law of the entire life of quasi-brittle rocks is presented for the first time. This original research result provides the foundation for a more in-depth life cycle of quasi-brittle rocks to develop the theoretical basis for the nonlinear breakage and early warning research of materials under various unprecedented conditions. We report a route to material microstructure composition, which may open an alternative pathway to quasi-brittle materials, which may, in turn, open a door into the mysterious world of science. [ABSTRACT FROM AUTHOR]