Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs

Telomeres are guanine-rich sequences at the end of chromosomes which shorten during each replication event and trigger cell cycle arrest and/or controlled death (apoptosis) when reaching a threshold length. The enzyme telomerase replenishes the ends of telomeres and thus prolongs the life span of cells, but also causes cellular immortalisation in human cancer. G-quadruplex (G4) stabilising drugs are a potential anticancer treatment which work by changing the molecular structure of telomeres to inhibit the activity of telomerase. We investigate the dynamics of telomere length in different conformational states, namely t-loops, G-quadruplex structures and those being elongated by telomerase. By formulating deterministic differential equation models we study the effects of various levels of both telomerase and concentrations of a G4-stabilising drug on the distribution of telomere lengths, and analyse how these effects evolve over large numbers of cell generations. As well as calculating numerical solutions, we use quasicontinuum methods to approximate the behaviour of the system over time, and predict the shape of the telomere length distribution. We find those telomerase and G4-concentrations where telomere length maintenance is successfully regulated. Excessively high levels of telomerase lead to continuous telomere lengthening, whereas large concentrations of the drug lead to progressive telomere erosion. Furthermore, our models predict a positively skewed distribution of telomere lengths, that is, telomeres accumulate over lengths shorter than the mean telomere length at equilibrium. Our model results for telomere length distributions of telomerase-positive cells in drug-free assays are in good agreement with the limited amount of experimental data available

Education in Global Health Radiology

Radiologists and radiology professionals have noted the gaps in diagnostic and interventional imaging access worldwide as documented by the World Health Organization. Since global health focuses on issues that transcend national boundaries, emphasizes solutions that often require global cooperation, and is multidisciplinary, then the concept of radiology education in global health should consider this broader context of international partnership and collaboration. There are several models in place for education in the global health setting with emphasis on radiology. This chapter discusses faculty exchanges, scholarly collaboration, partnership, formal education, online education as a tool, integration of global health concepts into radiology curricula, and socially responsible collaboration. Regardless of the type of model used, educational goals and objectives should be based on initial assessment data and address the appropriate needs. Curricula should be established in partnership with all stakeholders and with consideration for ethical best practices, continuous evaluation and improvement of the program, and open communication among stakeholders