Checkpoint adaptation in recombination-deficient cells drives aneuploidy and resistance to genotoxic agents.

Human cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ recombination-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge. We demonstrate that adaptation inhibition, either pharmacologically, or genetically, drastically reduces the occurrence of resistant cells. Additionally, the aneuploid phenotypes of the resistant cells can be specifically targeted to induce cytotoxicity. We provide evidence that TORC1 inhibition with rapamycin, in combination with DNA damaging agents, can prevent both checkpoint adaptation and the continued growth of aneuploid resistant cells.

Attention and Information Acquisition: Comparison of Mouse-Click with Eye-Movement Attention Tracking.

Attention is crucial as a fundamental prerequisite for perception. The measurement of attention in viewing and recognizing the images that surround us constitutes an important part of eye movement research, particularly in advertising-effectiveness research. Recording eye and gaze (i.e. eye and head) movements is considered the standard procedure for measuring attention. However, alternative measurement methods have been developed in recent years, one of which is mouse-click attention tracking (mcAT) by means of an on-line based procedure that measures gaze motion via a mouse-click (i.e. a hand and finger positioning maneuver) on a computer screen. Here we compared the validity of mcAT with eye movement attention tracking (emAT). We recorded data in a between subject design via emAT and mcAT and analyzed and compared 20 subjects for correlations. The test stimuli consisted of 64 images that were assigned to eight categories. Our main results demonstrated a highly significant correlation (p < 0.001) between mcAT and emAT data. We also found significant differences in correlations between different image categories. For simply structured pictures of humans or animals in particular, mcAT provided highly valid and more consistent results compared to emAT. We concluded that mcAT is a suitable method for measuring the attention we give to the images that surround us, such as photographs, graphics, art or digital and print advertisements.