CDC Poliomyelitis surveillance report number 242, October 13, 1961

Summary -- 1. Current Poliomyelitis Morbidity Trends -- 2. Reports -- 3. 1961 Poliomyelitis Cases Reported to PSU -- 4. Routine Poliomyelitis Surveillance-1961

Single-cell microglial transcriptomics during demyelination defines a microglial state required for lytic carcass clearance

Abstract Background Microglia regulate the response to injury and disease in the brain and spinal cord. In white matter diseases microglia may cause demyelination. However, how microglia respond and regulate demyelination is not fully understood. Methods To understand how microglia respond during demyelination, we fed mice cuprizone—a potent demyelinating agent—and assessed the dynamics of genetically fate-mapped microglia. We then used single-cell RNA sequencing to identify and track the microglial subpopulations that arise during demyelination. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cuprizone-induced cell death and used the viability dye acridine orange to monitor apoptotic and lytic cell morphologies after microglial ablation. Lastly, we treated serum-free primary microglial cultures to model distinct aspects of cuprizone-induced demyelination and assessed the response. Results The cuprizone diet generated a robust microglial response by week 4 of the diet. Single-cell RNA sequencing at this time point revealed the presence of several cuprizone-associated microglia (CAM) clusters. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. Using acridine orange to monitor apoptotic and lytic cell death after microglial ablation, we found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination. Conclusions Microglia serve multiple roles during demyelination, yet their transcriptomic state resembles other neurodegenerative conditions. The phagocytosis of cellular debris is likely a universal cause for a common neurodegenerative microglial state

Registered Replication Report

Finkel, Rusbult, Kumashiro, and Hannon (2002, Study 1) demonstrated a causal link between subjective commitment to a relationship and how people responded to hypothetical betrayals of that relationship. Participants primed to think about their commitment to their partner (high commitment) reacted to the betrayals with reduced exit and neglect responses relative to those primed to think about their independence from their partner (low commitment). The priming manipulation did not affect constructive voice and loyalty responses. Although other studies have demonstrated a correlation between subjective commitment and responses to betrayal, this study provides the only experimental evidence that inducing changes to subjective commitment can causally affect forgiveness responses. This Registered Replication Report (RRR) meta-analytically combines the results of 16 new direct replications of the original study, all of which followed a standardized, vetted, and preregistered protocol. The results showed little effect of the priming manipulation on the forgiveness outcome measures, but it also did not observe an effect of priming on subjective commitment, so the manipulation did not work as it had in the original study. We discuss possible explanations for the discrepancy between the findings from this RRR and the original study

Registered Replication Report: Study 1 From Finkel, Rusbult, Kumashiro, & Hannon (2002)

Finkel, Rusbult, Kumashiro, and Hannon (2002, Study 1) demonstrated a causal link between subjective commitment to a relationship and how people responded to hypothetical betrayals of that relationship. Participants primed to think about their commitment to their partner (high commitment) reacted to the betrayals with reduced exit and neglect responses relative to those primed to think about their independence from their partner (low commitment). The priming manipulation did not affect constructive voice and loyalty responses. Although other studies have demonstrated a correlation between subjective commitment and responses to betrayal, this study provides the only experimental evidence that inducing changes to subjective commitment can causally affect forgiveness responses. This Registered Replication Report (RRR) meta-analytically combines the results of 16 new direct replications of the original study, all of which followed a standardized, vetted, and preregistered protocol. The results showed little effect of the priming manipulation on the forgiveness outcome measures, but it also did not observe an effect of priming on subjective commitment, so the manipulation did not work as it had in the original study. We discuss possible explanations for the discrepancy between the findings from this RRR and the original study