39 research outputs found
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
Subtelomere organization in the genome of the microsporidian Encephalitozoon cuniculi: patterns of repeated sequences and physicochemical signatures
Asymptotic Solution of a Singularly Perturbed Linear-Quadratic Problem in Critical Case with Cheap Control
Asymptotic Approximations to the Solution of the Singularly Perturbed Linear-Quadratic Optimal Control Problem with Terminal Path Constraints
Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties
A statistical model to calculate inclusive hadronic cross sections
Hadronic cross sections are important ingredients in many of the ongoing research methods in high energy nuclear physics, and it is always important to measure and/or calculate the probabilities of different types of reactions. In heavy-ion transport simulations at a few GeV energies, these hadronic cross sections are essential and so far mostly the exclusive processes are used, however, if one interested in total production rates the inclusive cross sections are also necessary to know. In this paper, we introduce a statistical-based method, which is able to give good estimates to exclusive and inclusive cross sections as well in the energy range of a few GeV. The method and its estimates for not well-known cross sections, will be used in a Boltzmann-Uehling-Uhlenbeck (BUU) type off-shell transport code to explain charmonium and bottomonium mass shifts in heavy-ion collisions