Comparison of Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic humoral immunity.

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two-dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT.

Cognitive Flexibility in Mice: Effects of Puberty and Role of NMDA Receptor Subunits.

Cognitive flexibility refers to the ability to adapt flexibly to changing circumstances. In laboratory mice, we investigated whether cognitive flexibility is higher in pubertal mice than in adult mice, and whether this difference is related to the expression of distinct NMDA receptor subunits. Using the attentional set shifting task as a measure of cognitive flexibility, we found that cognitive flexibility was increased during puberty.

Dysregulation of cell polarity proteins synergize with oncogenes or the microenvironment to induce invasive behavior in epithelial cells.

Changes in expression and localization of proteins that regulate cell and tissue polarity are frequently observed in carcinoma. However, the mechanisms by which changes in cell polarity proteins regulate carcinoma progression are not well understood. Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior.

DNA damage signals through differentially modified E2F1 molecules to induce apoptosis.

E2F transcription can lead to cell proliferation or apoptosis, indicating that E2Fs control opposing functions. In a similar manner, DNA double-strand breaks can signal to induce cell cycle arrest or apoptosis. Specifically, pRB is activated following DNA damage, allowing it to bind to E2Fs and block transcription at cell cycle promoters; however, E2F1 is simultaneously activated, leading to transcription at proapoptotic promoters.

pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption.

Disruption of pRB-E2F interactions by E1A is a key event in the adenoviral life cycle that drives expression of early viral transcription and induces cell cycle progression. This function of E1A is complicated by E2F1, an E2F family member that controls multiple processes besides proliferation, including apoptosis and DNA repair. Recently, a second interaction site in pRB that only contacts E2F1 has been discovered, allowing pRB to control proliferation separately from other E2F1-dependent activities.

Characterization of an E2F1-specific binding domain in pRB and its implications for apoptotic regulation.

The retinoblastoma protein (pRB) has the dual capability to negatively regulate both E2F-induced cell cycle entry and E2F1-induced apoptosis. In this report, we characterize a unique pRB-E2F1 interaction. Using mutagenesis to disrupt E2F1 binding, we find that the ability of pRB to regulate E2F1-induced apoptosis is diminished when this interaction is lost.

The retinoblastoma protein regulates pericentric heterochromatin.

The retinoblastoma protein (pRb) has been proposed to regulate cell cycle progression in part through its ability to interact with enzymes that modify histone tails and create a repressed chromatin structure. We created a mutation in the murine Rb1 gene that disrupted pRb's ability to interact with these enzymes to determine if it affected cell cycle control. Here, we show that loss of this interaction slows progression through mitosis and causes aneuploidy.