A New Method for Optimizing Sepsis Therapy by Nivolumab and Meropenem Combination: Importance of Early Intervention and CTL Reinvigoration Rate as a Response Marker.

Recently, there has been a growing interest in applying immune checkpoint blockers (ICBs), so far used to treat cancer, to patients with bacterial sepsis. We aimed to develop a method for predicting the personal benefit of potential treatments for sepsis, and to apply it to therapy by meropenem, an antibiotic drug, and nivolumab, a programmed cell death-1 (PD-1) pathway inhibitor. We defined an optimization problem as a concise framework of treatment aims and formulated a fitness function for grading sepsis treatments according to their success in accomplishing the pre-defined aims.

Molecular Mechanism of AMPA Receptor Modulation by TARP/Stargazin.

AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation.