Profiles and Dynamics of the Transcriptome of Microglial Cells Reveal their Inflammatory Status

The primary role of microglia in the maintenance of brain homeostasis is to respond to disturbances in the microenvironment. In this study, we cultured murine neonatal microglia and activated them with lipopolysaccharide (LPS) and benzoyl ATP (bzATP) to characterize changes in the transcriptome in response to various in vivo stimuli caused by pathogens, injury, or toxins. Activation by bzATP, an agonist of purinergic receptors, induces a transient wave of transcriptional changes. However, a long-lasting transcriptional profile affecting thousands of genes occurs only following a combination of bzATP and LPS. This profile is dominated by a coordinated induction of cytokines (e.g., IL1-alpha; and IL1-beta), chemokines, and their direct regulators. Many of these inflammatory-related genes are up-regulated by several orders of magnitude. We identified the TNF-alpha and NF-kB pathways as the principal hubs for signaling of interleukin and chemokine induction in this cell system. We propose that primary microglia under controlled activation paradigms can be used for testing reagents that could attenuate their activated state. Such a microglial system could serve as a model for changes occurring in the aging brain and neurodegenerative diseases.

Linking Time-Domain Vibration Behaviors to Spatial-Domain Propagating Waves in a Leaf-like Gradient-Index Phononic Crystal Lens

It is known that a propagating wave at a certain spatial point can be decomposed into plane waves propagating at different angles. In this work, by designing a gradient index phononic crystal lens (GRIN PCL) with transverse-continuous leaf-like unit cells, we theoretically and experimentally show that the spatial-domain propagating waves in finite periodic structures can be linked to their time-domain vibration behaviors. The full-field instantaneous focusing behaviors of Lamb waves in the proposed leaf-like GRIN PCL give an example of the wave-vibration linkage in finite periodic structures while allowing a certain complexity. The conclusion in this paper can help one skip iterative time-consuming finite element analysis (e.g., time-stepping solutions) to avoid possible numerical instabilities occurred in calculating transient wave field on practical finite metamaterials or phononic crystals having unit cells with complicated configurations.