The inflammation that accompanies acute injury has dual functions: bactericidal action and repair. Bactericidal functions protect damaged tissue from infection, and repair functions are initiated to aid in the recovery of damaged tissue. Brain injury is somewhat different from injuries in other tissues in two respects. First, many cases of brain injury are not accompanied by infection: there is no chance of pathogens to enter in ischemia or even in traumatic injury if the skull is intact. Second, neurons are rarely regenerated once damaged. This raises the question of whether bactericidal inflammation really occurs in the injured brain; if so, how is this type of inflammation controlled? Many brain inflammation studies have been conducted using cultured microglia (brain macrophages). Even where animal models have been used, the behavior of microglia and neurons has typically been analyzed at or after the time of neuronal death, a time window that excludes the inflammatory response, which begins immediately after the injury. Therefore, to understand the patterns and roles of brain inflammation in the injured brain, it is necessary to analyze the behavior of all cell types in the injured brain immediately after the onset of injury. Based on our experience with both in vitro and in vivo experimental models of brain inflammation, we concluded that not only microglia, but also astrocytes, blood inflammatory cells, and even neurons participate and/or regulate brain inflammation in the injured brain. Furthermore, brain inflammation played by these cells protects neurons and repairs damaged microenvironment but not induces neuronal damage.

Highlights d The structure of b-arrestin 2 bound to CXCR7 phosphopeptide (C7pp) was solved d The C7pp-bound b-arrestin 2 shows small inter-domain rotation d The three C7pp phosphates bind with the positively charged residues on b-arrestin 2 d The phosphate-binding pocket around Arg148 recognizes the first phosphate of C7pp

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Rising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways.

Background: 8-Halogenated guanine is a promutagenic lesion that promotes insertion of guanine opposite the lesion during DNA replication. Results: 8-Bromoguanine forms Hoogsteen base pairing with G and Watson-Crick base pairing with C in the active site of pol␤. Conclusion: 8-Bromoguanine is well accommodated in the nascent base pair binding pocket of pol␤. Significance: Our structural studies provide insights into potential G to C mutations.