Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.

Macrophages sense pathogens and orchestrate specific immune responses. Stimulus specificity is thought to be achieved through combinatorial and dynamical coding by signaling pathways. While NFκB dynamics are known to encode stimulus information, dynamical coding in other signaling pathways and their combinatorial coordination remain unclear. Here, we established live-cell microscopy to investigate how NFκB and p38 dynamics interface in stimulated macrophages. Information theory and machine learning revealed that p38 dynamics distinguish cytokine TNF from pathogen-associated molecular patterns and high doses from low, but contributed little to information-rich NFκB dynamics when both pathways are considered. This suggests that immune response genes benefit from decoding immune signaling dynamics or combinatorics, but not both. We found that the heterogeneity of the two pathways is surprisingly uncorrelated. Mathematical modeling revealed potential sources of uncorrelated heterogeneity in the branched pathway network topology and predicted it to drive gene expression variability. Indeed, genes dependent on both p38 and NFκB showed high scRNAseq variability and bimodality. These results identify combinatorial signaling as a mechanism to restrict NFκB-AND-p38-responsive inflammatory cytokine expression to few cells.

Effect of W Addition on Fe-P-C-B Soft-Magnetic Amorphous Alloy.

In this work, the thermal behavior, soft magnetic properties, and structure of Fe86-xP11C2B1Wx (x = 0, 0.1, 0.2, 0.4, 0.6, 0.8, 1, 2, and 4) amorphous alloys were researched by several experimental methods and ab initio molecular dynamics. The addition of W improved the thermal stability of the alloy system when the first onset crystallization temperature (Tx1) increased from 655 K to 711 K, significantly reduced the coercivity Hc, and decreased the saturation magnetization Bs. The Fe85.6P11C2B1W0.4 alloy showed optimal soft magnetic performance, with low Hc of 1.4 A/m and relatively good Bs of 1.52 T. The simulation results suggested that W atoms increased the distance of the neighboring Fe-Fe pair, reduced the coordination number, narrowed the gap between the spin-up and spin-down electrons of each atom, and decreased the average magnetic moment of the Fe atoms. This work demonstrates a micro-alloying strategy to greatly reduce Hc while maintaining high Bs.