Understanding the limitations of radiation-induced cell cycle checkpoints

The DNA damage response pathways involve processes of double-strand break (DSB) repair and cell cycle checkpoint control to prevent or limit entry into S phase or mitosis in the presence of unrepaired damage. Checkpoints can function to permanently remove damaged cells from the actively proliferating population but can also halt the cell cycle temporarily to provide time for the repair of DSBs. Although efficient in their ability to limit genomic instability, checkpoints are not foolproof but carry inherent limitations. Recent work has demonstrated that the G1/S checkpoint is slowly activated and allows cells to enter S phase in the presence of unrepaired DSBs for about 4–6 h post irradiation. During this time, only a slowing but not abolition of S-phase entry is observed. The G2/M checkpoint, in contrast, is quickly activated but only responds to a level of 10–20 DSBs such that cells with a low number of DSBs do not initiate the checkpoint or terminate arrest before repair is complete. Here, we discuss the limitations of these checkpoints in the context of the current knowledge of the factors involved. We suggest that the time needed to fully activate G1/S arrest reflects the existence of a restriction point in G1-phase progression. This point has previously been defined as the point when mitogen starvation fails to prevent cells from entering S phase. However, cells that passed the restriction point can respond to DSBs, albeit with reduced efficiency

Understanding Individual Differences in Acquired Flavour Liking in Humans

The majority of human food likes and dislikes are learned, and there are multiple learning models which explain how flavour liking may be acquired. Two models based on flavour-based learning have attracted considerable attention as potential explanations for acquisition of flavour liking. The first model is based on associations between a novel flavour and an existing liked or disliked flavour (flavour-flavour learning: FFL) and the second based on associations between the flavour and an effect of ingestion (flavour-consequence learning: FCL). However, experimental studies of acquired flavour liking based on these models have had mixed outcomes, with as many studies unable to find changes in liking post-training as there are studies reporting positive findings. This brief review discusses the extent to which the apparent inconsistency in the literature may reflect individual differences in evaluation of the training flavour in FFL or the consequence in FCL. The conclusion is that an understanding of these individual differences can explain many apparent inconsistencies in the flavour-learning literature. These findings also suggest that differences in sensitivity to these types of learning may explain individual differences in sensitivity to hedonically-driven overeating