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.

An application of node and edge nonlinear hypergraph centrality to a protein complex hypernetwork.

The use of graph centrality measures applied to biological networks, such as protein interaction networks, underpins much research into identifying key players within biological processes. This approach however is restricted to dyadic interactions and it is well-known that in many instances interactions are polyadic. In this study we illustrate the merit of using hypergraph centrality applied to a hypernetwork as an alternative.

Renoprotective Effects of Mineralocorticoid Receptor Antagonists Against Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a growing epidemic worldwide and a leading cause of end-stage kidney disease. Mineralocorticoid receptor (MR) blockade using Finerenone is a recently approved therapeutic approach to slow down the progression of DKD in patients with type 2 diabetes in addition to other therapies such as angiotensin-II converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) analogs. This review elaborates on the pathophysiologic pathways activated by aldosterone (the human mineralocorticoid) in DKD, the pharmacology of three different generations of mineralocorticoid receptor antagonists (MRAs), specifically, spironolactone, eplerenone, and finerenone, and the mechanisms by which these MRAs elicit their protective effects on the kidney under diabetic settings.

Hypergraphs and centrality measures identifying key features in gene expression data.

Multidisciplinary approaches can significantly advance our understanding of complex systems. For instance, gene co-expression networks align prior knowledge of biological systems with studies in graph theory, emphasising pairwise gene to gene interactions. In this paper, we extend these ideas, promoting hypergraphs as an investigative tool for studying multi-way interactions in gene expression data.

Anti-CD3 monoclonal antibodies for the prevention and treatment of type 1 diabetes: A literature review.

Purpose: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells, resulting in a loss of insulin production. Patients with T1D carry a substantial disease burden as well as substantial short-term and long-term risks associated with inadequate glycemic control. Currently, treatment mainly consists of insulin, which only treats the symptoms of T1D and not the root cause.

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.

Use of surrogate species to cost-effectively prioritize conservation actions.

Conservation efforts often focus on umbrella species whose distributions overlap with many other flora and fauna. However, because biodiversity is affected by different threats that are spatially variable, focusing only on the geographic range overlap of species may not be sufficient in allocating the necessary actions needed to efficiently abate threats. We developed a problem-based method for prioritizing conservation actions for umbrella species that maximizes the total number of flora and fauna benefiting from management while considering threats, actions, and costs.

Nephron progenitor commitment is a stochastic process influenced by cell migration.

Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express , an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time.

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.

Time to CT head in adult patients with suspected traumatic brain injury: Association with the 'Shorter Stays in Emergency Departments' health target in Aotearoa New Zealand.

A national health target for length of stay in emergency departments (ED) was introduced in 2009 to reduce crowding and improve quality of care. We aimed to determine whether the target was associated with changes in time to CT and appropriateness of CT imaging, as markers of care quality for suspected acute traumatic brain injury (TBI). We undertook a retrospective review of the case records of a random sample of people aged ≥15 years presenting to the ED with TBI from 2006 to 2013.

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.

Is a national time target for emergency department stay associated with changes in the quality of care for acute asthma? A multicentre pre-intervention post-intervention study.

Objective: There is debate whether targets for ED length of stay introduced to reduce ED overcrowding are helpful or harmful, as focus on a process target may divert attention from clinical care. Our objective was to investigate the effect of a national ED target in Aotearoa New Zealand on the recommended care for acute asthma as this is known to suffer in overcrowded departments.

Methods: We conducted a retrospective chart review study across four sites from 2006 to 2012 (target introduced mid 2009).

An integrated pipeline for the multidimensional analysis of branching morphogenesis.

Developmental branching morphogenesis establishes organ architecture, and it is driven by iterative interactions between epithelial and mesenchymal progenitor cell populations. We describe an approach for analyzing this interaction and how it contributes to organ development. After initial in vivo cell labeling with the nucleoside analog 5-ethynyl-2'-deoxyuridine (EdU) and tissue-specific antibodies, optical projection tomography (OPT) and confocal microscopy are used to image the developing organ.

Comparing and distinguishing the structure of biological branching.

Bifurcating developmental branching morphogenesis gives rise to complex organs such as the lung and the ureteric tree of the kidney. However, a few quantitative methods or tools exist to compare and distinguish, at a structural level, the critical features of these important biological systems. Here we develop novel graph alignment techniques to quantify the structural differences of rooted bifurcating trees and demonstrate their application in the analysis of developing kidneys from in normal and mutant mice.

Global quantification of tissue dynamics in the developing mouse kidney.

Although kidneys of equal size can vary 10-fold in nephron number at birth, discovering what regulates such variation has been hampered by a lack of quantitative parameters defining kidney development. Here we report a comprehensive, quantitative, multiscale analysis of mammalian kidney development in which we measure changes in cell number, compartment volumes, and cellular dynamics across the entirety of organogenesis, focusing on two key nephrogenic progenitor populations: the ureteric epithelium and the cap mesenchyme. In doing so, we describe a discontinuous developmental program governed by dynamic changes in interactions between these key cellular populations occurring within a previously unappreciated structurally stereotypic organ architecture.

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.