Image-based deep learning reveals the responses of human motor neurons to stress and VCP-related ALS

OBJECTIVES: Although morphological attributes of cells and their substructures are recognized readouts of physiological or pathophysiological states, these have been relatively understudied in amyotrophic lateral sclerosis (ALS) research. MATERIALS AND METHODS: In this study, we integrate multichannel fluorescence high-content microscopy data with deep-learning imaging methods to reveal - directly from unsegmented images - novel neurite-associated morphological perturbations associated with (ALS-causing) VCP-mutant human motor neurons (MNs). RESULTS: Surprisingly, we reveal that previously unrecognized disease-relevant information is withheld in broadly used and often considered 'generic' biological markers of nuclei (DAPI) and neurons (β III-tubulin). Additionally, we identify changes within the information content of ALS-related RNA binding protein (RBP) immunofluorescence imaging that is captured in VCP-mutant MN cultures. Furthermore, by analysing MN cultures exposed to different extrinsic stressors, we show that heat stress recapitulates key aspects of ALS. CONCLUSIONS: Our study therefore reveals disease-relevant information contained in a range of both generic and more specific fluorescent markers, and establishes the use of image-based deep learning methods for rapid, automated and unbiased identification of biological hypotheses

Flexible Working in the UK and its Impact on Couples' Time Coordination

The ability to combine work with quality time together as a family is at the heart of the concept of work-life balance. Using previously unexploited data on couples work schedules we investigate the effect of flexible working on couples coordination of their daily work schedules in the UK. We consider three distinct dimensions of flexible working: flexibility of daily start and finish times (flexitime), flexibility of work times over the year (annualized hours), and generalized control of working hours. We show that having flexitime at work increases a couples amount of coordination of their daily work schedules by a half to one hour, which is double the margin of adjustment enjoyed by couples with no flexitime. The impact is driven by couples with children. In contrast to flexitime, the other two forms of flexible working do not seem to increase synchronous time. Our results suggest that having flexitime plays an important role in relaxing the work scheduling constraints faced by families with young children, and that effective flexible working time arrangements are those that increase the workers and not the employers flexibility