Showing papers by "James P. Butler published in 2019"

The unjamming transition is distinct from the epithelial-to-mesenchymal transition

Abstract: Every organ surface and body cavity is lined by a confluent collective of epithelial cells. In homeostatic circumstances the epithelial collective remains effectively solid-like and sedentary. But during morphogenesis, remodeling or repair, as well as during malignant invasion or metastasis, the epithelial collective becomes fluid-like and migratory. This conversion from sedentary to migratory behavior has traditionally been understood as a manifestation of the epithelial-to-mesenchymal transition (EMT) or the partial EMT (pEMT). However, in certain contexts this conversion has been attributed to the recently discovered unjamming transition (UJT), in which epithelial cells move collectively and cooperatively. UJT and pEMT share certain aspects of collective cellular migration, but the extent to which these processes are distinct, overlapping or perhaps even identical has remained undefined. Using the confluent layer of well-differentiated primary human bronchial epithelial (HBE) cells, here we triggered UJT by exposing the sedentary layer to mechanical compression that mimics the mechanical environment of asthmatic bronchoconstricion. Cells thereafter migrated cooperatively, aligned into packs locally, and elongated systematically. Nevertheless, cell-cell junctions, apico-basal polarity, and barrier function remained intact in response, and mesenchymal markers remained unapparent. As such, pEMT was not evident. When we triggered pEMT and associated cellular migration by exposing the sedentary layer to TGF-β1, metrics of UJT versus pEMT diverged. To account for these striking physical observations a new mathematical model attributes the effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Together, these findings establish that UJT is sufficient to account for vigorous epithelial layer migration even in the absence of pEMT. Distinct gateways to cellular migration therefore become apparent - UJT as it might apply to migration of epithelial sheets, and EMT/pEMT as it might apply to migration of mesenchymal cells on a solitary or collective basis, activated during development, remodeling, repair or tumor invasion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, living tissue is therefore seen to comprise an active engineering material whose modules for plasticity, self-repair and regeneration, are far richer than had been previously appreciated.

The tumor suppressor p53 can promote collective cellular migration

Abstract: Loss of function of the tumor suppressor p53 is known to increase the rate of migration of cells transiting the narrow pores of the traditional Boyden chamber assay. Here by contrast we investigate how p53 impacts the rate of cellular migration within a 2D confluent cell layer and a 3D collagen-embedded multicellular spheroid. We use two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. In the confluent 2-D cell layer, for both EJ and HCT cells the migratory speeds and effective diffusion coefficients for the p53 null cells were significantly smaller than in p53-expressing cells. Compared to p53 expressers, p53-null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In the 3D multicellular spheroid, loss of p53 consistently reduced collective cellular migration into surrounding collagen matrix. As regards the role of p53 in cellular migration, extrapolation from the Boyden chamber assay to other cellular microenvironments is seen to be fraught even in terms of the sign of the effect. Together, these paradoxical results show that the effects of p53 on cellular migration are context-dependent.

A Modular Deep Learning Pipeline for Galaxy-Scale Strong Gravitational Lens Detection and Modeling

Abstract: Upcoming large astronomical surveys are expected to capture an unprecedented number of strong gravitational lensing systems in the Universe Deep learning is emerging as a promising practical tool in detection and quantification of these galaxy-scale image distortions However, absence of large quantities of representative data from current astronomical surveys requires development of robust forward modeling of synthetic lensing images Using a realistic and unbiased sample of the strong lenses created by using state-of-the-art extragalactic catalogs, we train a modular deep learning pipeline for uncertainty-quantified detection and modeling with intermediate image processing components for denoising and deblending the lensing systems We demonstrate a higher degree of interpretability and controlled systematics due to domain-specific task modules that are trained with different stages of synthetic image generation For lens detection and modeling, we obtain semantically meaningful latent spaces that separate classes and provide uncertainty estimates that explain the misclassified images and provide uncertainty bounds on the lens parameters In addition, we obtain an improved performance---lens detection (classification) improved from 82% with the baseline to 94%, while the lens modeling (regression) accuracy improved by 25% over the baseline model

Antipsychotic drug use and favourable natures of emotional functions in patients with dementia

Abstract: AIM To characterise the effects of antipsychotics on brain functions of patients with behavioural psychological symptoms of dementia (BPSD). METHODS Studies were performed during 6 weeks of intervention with either a nonantipsychotic drug (group A, n = 38) or an antipsychotic drug (group B, n = 10). RESULTS Neuropsychiatric Inventory scores were significantly decreased in both groups. Scores on the Mini-Mental State Examination did not change with intervention. By contrast, favourable natures of emotional functions, scored using the Delightful Emotional Index of 10 items, were significantly lower in the antipsychotic drug treatment group B relative to scores in the nonantipsychotic drug treatment group A. CONCLUSIONS Antipsychotics reduce favourite emotions as well as BPSD, and this should be considered in prescribing medications for patients with dementia.

Revisiting atelectasis in lung units with low ventilation/perfusion ratios.

Abstract: Breathing high concentrations of oxygen increases the likelihood of atelectasis because of oxygen absorption, which is thought to be inevitable in regions with relatively low ventilation/perfusion ...