Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.

Non-melanoma skin cancer segmentation for histopathology dataset.

Densely labelled segmentation data for digital pathology images is costly to produce but is invaluable to training effective machine learning models. We make available 290 hand-annotated histopathology tissue sections of the 3 most common skin cancers; basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC). These non-melanoma skin cancers constitute over 90% of all skin cancer diagnoses and hence this dataset gives an opportunity to the scientific community to benchmark analytic methodologies on a significant portion of the dermatopathology workflow.

LLAMA: a robust and scalable machine learning pipeline for analysis of large scale 4D microscopy data: analysis of cell ruffles and filopodia.

Background: With recent advances in microscopy, recordings of cell behaviour can result in terabyte-size datasets. The lattice light sheet microscope (LLSM) images cells at high speed and high 3D resolution, accumulating data at 100 frames/second over hours, presenting a major challenge for interrogating these datasets. The surfaces of vertebrate cells can rapidly deform to create projections that interact with the microenvironment.

Interpretable deep learning systems for multi-class segmentation and classification of non-melanoma skin cancer.

We apply for the first-time interpretable deep learning methods simultaneously to the most common skin cancers (basal cell carcinoma, squamous cell carcinoma and intraepidermal carcinoma) in a histological setting. As these three cancer types constitute more than 90% of diagnoses, we demonstrate that the majority of dermatopathology work is amenable to automatic machine analysis. A major feature of this work is characterising the tissue by classifying it into 12 meaningful dermatological classes, including hair follicles, sweat glands as well as identifying the well-defined stratified layers of the skin.

Branching morphogenesis in the developing kidney is not impacted by nephron formation or integration.

Branching morphogenesis of the ureteric bud is integral to kidney development; establishing the collecting ducts of the adult organ and driving organ expansion via peripheral interactions with nephron progenitor cells. A recent study suggested that termination of tip branching within the developing kidney involved stochastic exhaustion in response to nephron formation, with such a termination event representing a unifying developmental process evident in many organs. To examine this possibility, we have profiled the impact of nephron formation and maturation on elaboration of the ureteric bud during mouse kidney development.

Branching morphogenesis in the developing kidney is governed by rules that pattern the ureteric tree.

Metanephric kidney development is orchestrated by the iterative branching morphogenesis of the ureteric bud. We describe an underlying patterning associated with the ramification of this structure and show that this pattern is conserved between developing kidneys, in different parts of the organ and across developmental time. This regularity is associated with a highly reproducible branching asymmetry that is consistent with locally operative growth mechanisms.

Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells.

Human pluripotent stem cells, after directed differentiation , can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis.

Analysed cap mesenchyme track data from live imaging of mouse kidney development.

This article provides detailed information on manually tracked cap mesenchyme cells from timelapse imaging of multiple ex vivo embryonic mouse kidneys. Cells were imaged for up to 18 h at 15 or 20 min intervals, and multiple cell divisions were tracked. Positional data is supplemented with a range of information including the relative location of the closest ureteric tip and a correction for drift due to bulk movement and tip growth.

Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip.

Morphogenesis of the mammalian kidney requires reciprocal interactions between two cellular domains at the periphery of the developing organ: the tips of the epithelial ureteric tree and adjacent regions of cap mesenchyme. While the presence of the cap mesenchyme is essential for ureteric branching, how it is specifically maintained at the tips is unclear. Using ex vivo timelapse imaging we show that cells of the cap mesenchyme are highly motile.

Cortical F-actin stabilization generates apical-lateral patterns of junctional contractility that integrate cells into epithelia.

E-cadherin cell-cell junctions couple the contractile cortices of epithelial cells together, generating tension within junctions that influences tissue organization. Although junctional tension is commonly studied at the apical zonula adherens, we now report that E-cadherin adhesions induce the contractile actomyosin cortex throughout the apical-lateral axis of junctions. However, cells establish distinct regions of contractile activity even within individual contacts, producing high tension at the zonula adherens but substantially lower tension elsewhere.

Independent contrasts and PGLS regression estimators are equivalent.

We prove that the slope parameter of the ordinary least squares regression of phylogenetically independent contrasts (PICs) conducted through the origin is identical to the slope parameter of the method of generalized least squares (GLSs) regression under a Brownian motion model of evolution. This equivalence has several implications: 1. Understanding the structure of the linear model for GLS regression provides insight into when and why phylogeny is important in comparative studies.