Functional Study Of Smyd2 Glutathionylation In Cardiomyocytes

Reactive oxygen species (ROS) are important signaling molecules that contribute to the etiology of multiple muscle-related diseases, including cardiomyopathy and heart failure. There is emerging evidence that cellular stress can lead to destabilization of sarcomeres, the contractile unit of muscle. However, it is not completely understood how cellular stress or ROS induce structural destabilization of sarcomeres or myofibrils. Protein glutathionylation is one of the major protein cysteine oxidative modifications that play an important role in redox signaling and oxidative stress. In this report, we used a clickable glutathione approach in a cardiomyocyte cell line, and found that SET and MYND Domain Containing 2 (SMYD2), lysine methyltransferase, can be selectively glutathionylated at Cys13. Functional studies showed that SMYD2 Cys13 glutathionylation serve as a key molecular event that leads to a loss of myofibril integrity and degradation of sarcomeric proteins mediated by matrix metalloprotease 2 (MMP-2) and calpain 1. Biochemical analysis demonstrated that SMYD2 glutathionylated at Cys13 loses its interaction with Hsp90 and N2A, a domain of titin that is important for stress-sensing. Upon dissociation from SMYD2, N2A or titin was susceptible to degradation by MMP-2, suggesting a protective role of SMYD2 in sarcomere stability. Taken together, our results identify SMYD2 glutathionylation as a novel molecular mechanism by which ROS contribute to sarcomere destabilization and potentially muscle dysfunction

The Effect of Mediation on Mediators: How Neuroscience Shows Mediation Techniques Can Be Utilized to Improve Emotional Well-Being, Empathy, and Emotional Intelligence

Published in cooperation with the American Bar Association Section of Dispute Resolutio

Benchmark methodologies for the optimized physical synthesis of RISC-V microprocessors

As technology continues to advance and chip sizes shrink, the complexity and design time required for integrated circuits have significantly increased. To address these challenges, Electronic Design Automation (EDA) tools have been introduced to streamline the design flow. These tools offer various methodologies and options to optimize power, performance, and chip area. However, selecting the most suitable methods from these options can be challenging, as they may lead to trade-offs among power, performance, and area. While architectural and Register Transfer Level (RTL) optimizations have been extensively studied in existing literature, the impact of optimization methods available in EDA tools on performance has not been thoroughly researched. This thesis aims to optimize a semiconductor processor through EDA tools within the physical synthesis domain to achieve increased performance while maintaining a balance between power efficiency and area utilization. By leveraging floorplanning tools and carefully selecting technology libraries and optimization options, the CV32E40P open-source processor is subjected to various floorplans to analyze their impact on chip performance. The employed techniques, including multibit components prefer option, multiplexer tree prefer option, identification and exclusion of problematic cells, and placement blockages, lead to significant improvements in cell density, congestion mitigation, and timing. The optimized synthesis results demonstrate a 71\% enhancement in chip design performance without a substantial increase in area, showcasing the effectiveness of these techniques in improving large-scale integrated circuits' performance, efficiency, and manufacturability. By exploring and implementing the available options in EDA tools, this study demonstrates how the processor's performance can be significantly improved while maintaining a balanced and efficient chip design. The findings contribute valuable insights to the field of electronic design automation, offering guidance to designers in selecting suitable methodologies for optimizing processors and other integrated circuits

Dynamic Control of Soft Robotic Arm: An Experimental Study

In this paper, a reinforced soft robot prototype with a custom-designed actuator-space string encoder are created to investigate dynamic soft robotic trajectory tracking. The soft robot prototype embedded with the proposed adaptive passivity control and efficient dynamic model make the challenging trajectory tracking tasks possible. We focus on the exploration of tracking accuracy as well as the full potential of the proposed control strategy by performing experimental validations at different operation scenarios: various tracking speed and external disturbance. In all experimental scenarios, the proposed adaptive passivity control outperforms the conventional PD feedback linearization control. The experimental analysis details the advantage and shortcoming of the proposed approach, and points out the next steps for future soft robot dynamic control.Comment: 7 pages, 12 figure