spconfShiny: An R Shiny application for calculating the spatial scale of smoothing splines for point data.

Epidemiological analyses of environmental exposures often benefit from including spatial splines in models to account for confounding by spatial location. Understanding how the number of splines relates to physical spatial differences is not always intuitive and can be context-dependent. To address this, we developed a R Shiny application, spconfShiny, that provides a user-friendly platform to calculate an effective bandwidth metric that quantifies the relationship between spatial splines and the range of implied spatial smoothing.

DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.

CDC7 kinase is crucial for DNA replication initiation and is involved in fork processing and replication stress response. Human CDC7 requires the binding of either DBF4 or DRF1 for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly.

CDC7 inhibition drives an inflammatory response and a p53-dependent senescent-like state in breast epithelial cells.

Drugs that block DNA replication prevent cell proliferation, which may result in anticancer activity. The latter is dependent on the drug's mode of action as well as on cell type-dependent responses to treatment. The inhibition of Cell division cycle 7-related protein kinase (CDC7), a key regulator of DNA replication, decreases the efficiency of origin firing and hampers the restarting of paused replication forks.

Egress of resident memory T cells from tissue with neoadjuvant immunotherapy: Implications for systemic anti-tumor immunity.

Introduction: Resident memory T (T) cells are embedded in peripheral tissue and capable of acting as sentinels that can respond quickly to repeat pathogen exposure as part of an endogenous anti-microbial immune response. Recent evidence suggests that chronic antigen exposure and other microenvironment cues may promote the development of T cells within solid tumors as well, and that this T phenotype can sequester tumor-specific T cells into tumors and out of circulation resulting in limited systemic antitumor immunity. Here, we perform a review of the published English literature and describe tissue-specific mediators of T cell differentiation in states of infection and malignancy with special focus on the role of TGF-β and how targeting TGF-β signaling could be used as a therapeutical approach to promote tumor systemic immunity.