Cross-talk between T-Ag presence and pRb family and p53/p73 signaling in mouse and human medulloblastoma.

The formation and progression of mudulloblastoma (MB) is poorly understood. However, somatic inactivation of pRb/p105, in combination with a somatic or a germ-line TP53 inactivation, leads to MB in a mouse model. Presently, there is no specific evidence of pathway/s alterations for the other two members of the retinoblastoma family, pRb2/p130 and/or p107 in MB. JC virus (JCV) is a human polyomavirus. Although there is no firm evidence that this virus plays a causal role in human neoplasia, it has been clearly proven that JCV is highly oncogenic when injected into the brain of experimental animals. The mechanism of JCV-induced tumorigenesis is not entirely clear. However, several studies relate the oncogenic properties of JCV mainly to its early protein large T-antigen (T-Ag), which is able to bind and inactivate both TP53 and Rb family proteins. Here, we compared the protein expression profiles of p53, p73, pRb family proteins, and PCNA, as main regulators of cell proliferation and death, in different cell lines of mouse primitive neuroectodermal tumors (PNET), either T-Ag-positive or -negative, and in human MB cell lines. Our goal was to determine if changes in the relative expression of these regulators could trigger molecular perturbations underlying MB pathogenesis in mouse and human cells. Our results support that the presence of JCV T-Ag may interfere with the expression of pRb family proteins, specific p73 isoforms, and p53. In turn, this "perturbation" may trigger a network of signals strictly connected with survival and apoptosis.

The impacts of COVID-19 pandemic on public transit demand in the United States.

The COVID-19 pandemic and related restrictions led to major transit demand decline for many public transit systems in the United States. This paper is a systematic analysis of the dynamics and dimensions of this unprecedented decline. Using transit demand data derived from a widely used transit navigation app, we fit logistic functions to model the decline in daily demand and derive key parameters: base value, the apparent minimal level of demand and cliff and base points, representing the initial date when transit demand decline began and the final date when the decline rate attenuated. Regression analyses reveal that communities with higher proportions of essential workers, vulnerable populations (African American, Hispanic, Female, and people over 45 years old), and more coronavirus Google searches tend to maintain higher levels of minimal demand during COVID-19. Approximately half of the agencies experienced their decline before the local spread of COVID-19 likely began; most of these are in the US Midwest. Almost no transit systems finished their decline periods before local community spread. We also compare hourly demand profiles for each system before and during COVID-19 using ordinary Procrustes distance analysis. The results show substantial departures from typical weekday hourly demand profiles. Our results provide insights into public transit as an essential service during a pandemic.