The cellular responses to steroids are mediated by 2 general mechanisms: genomic and rapid/nongenomic effects. Identification of the mechanisms underlying aldosterone (ALDO)'s rapid vs their genomic actions is difficult to study, and these mechanisms are not clearly understood. Recent data suggest that striatin is a mediator of nongenomic effects of estrogen. We explored the hypothesis that striatin is an intermediary of the rapid/nongenomic effects of ALDO and that striatin serves as a novel link between the actions of the mineralocorticoid and estrogen receptors. In human and mouse endothelial cells, ALDO promoted an increase in phosphorylated extracellular signal-regulated protein kinases 1/2 (pERK) that peaked at 15 minutes. In addition, we found that striatin is a critical intermediary in this process, because reducing striatin levels with small interfering RNA (siRNA) technology prevented the rise in pERK levels. In contrast, reducing striatin did not significantly affect 2 well-characterized genomic responses to ALDO. Down-regulation of striatin with siRNA produced similar effects on estrogen's actions, reducing nongenomic, but not some genomic, actions. ALDO, but not estrogen, increased striatin levels. When endothelial cells were pretreated with ALDO, the rapid/nongenomic response to estrogen on phosphorylated endothelial nitric oxide synthase (peNOS) was enhanced and accelerated significantly. Importantly, pretreatment with estrogen did not enhance ALDO's nongenomic response on pERK. In conclusion, our results indicate that striatin is a novel mediator for both ALDO's and estrogen's rapid and nongenomic mechanisms of action on pERK and phosphorylated eNOS, respectively, thereby suggesting a unique level of interactions between the mineralocorticoid receptor and the estrogen receptor in the cardiovascular system.

No abstract

Physical Unclonable Functions (PUFs) are used for securing electronic designs across the implementation spectrum ranging from lightweight FPGA to server-class ASIC designs. However, current PUF implementations are vulnerable to model-building attacks; they often incur significant design overheads and are challenging to configure based on application-specific requirements. These factors limit their application, primarily in the case of the system on chip (SoC) designs used in diverse applications. In this work, we propose MeL-PUF -Memory-in-Logic PUF, a low-overhead, distributed, and synthesizable PUF that takes advantage of existing logic gates in a design and transforms them to create cross-coupled inverters (i.e. memory cells) controlled by a PUF control signal. The power-up states of these memory cells are used as the source of entropy in the proposed PUF architecture. These on-demand memory cells can be distributed across the combinational logic of various intellectual property (IP) blocks in a system on chip (SoC) design. They can also be synthesized with a standard logic synthesis tool to meet the area/power/performance constraints of a design. By aggregating the power-up states from multiple such memory cells, we can create a PUF signature or digital fingerprint of varying size. We evaluate the MeL-PUF signature quality with both circuit-level simulations as well as with measurements in FPGA devices. We show that MeL-PUF provides high-quality signatures in terms of uniqueness, randomness, and robustness, without incurring large overheads. We also suggest additional optimizations that can be leveraged to improve the performance of MeL-PUF .