Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity in vivo. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies

Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape

Whisker touch guides canopy exploration in a nocturnal, arboreal rodent, the Hazel dormouse (Muscardinus avellanarius)

Dormouse numbers are declining in the UK due to habitat loss and fragmentation. We know that dormice are nocturnal, arboreal, and avoid crossing open spaces between habitats, yet how they navigate around their canopy is unknown. As other rodents use whisker touch sensing to navigate and explore their environment, this study investigates whether Hazel dormice (Muscardinus avellanarius) employ their whiskers to cross between habitats. We analysed high-speed video footage of dormice exploring freely in flat and climbing arenas in near darkness and using infrared light illumination. We confirm that, like rats and mice, dormice move their whiskers back and forth continuously (~10 Hz) in a motion called whisking and recruit them to explore small gaps (<10 cm) by increasing the amplitude and frequency of whisking and also the asymmetry of movement between the left and right whisker fields. When gaps between platforms are larger than 10-15 cm dormice spend more time travelling on the floor. These findings suggest that dormice can actively and purposively move their whiskers to gather relevant information from their canopy at night. As this species is vulnerable to threats on the ground, we also provide evidence that joining habitat patches between dormouse populations is important for promoting natural behaviours and movement between patches

Early Cambrian fuxianhuiids from China reveal origin of the gnathobasic protopodite in euarthropods

Euarthropods owe their evolutionary and ecological success to the morphological plasticity of their appendages. Although this variability is partly expressed in the specialization of the protopodite for a feeding function in the post-deutocerebral limbs, the origin of the former structure among Cambrian representatives remains uncertain. Here, we describe Alacaris mirabilis gen. et sp. nov. from the early Cambrian Xiaoshiba Lagerstätte in China, which reveals the proximal organization of fuxianhuiid appendages in exceptional detail. Proximally, the post-deutocerebral limbs possess an antero-posteriorly compressed protopodite with robust spines. The protopodite is attached to an endopod with more than a dozen podomeres, and an oval flap-shaped exopod. The gnathal edges of the protopodites form an axial food groove along the ventral side of the body, indicating a predatory/scavenging autecology. A cladistic analysis indicates that the fuxianhuiid protopodite represents the phylogenetically earliest occurrence of substantial proximal differentiation within stem-group Euarthropoda illuminating the origin of gnathobasic feeding

Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection

Human Mena Associates with Rac1 Small GTPase in Glioblastoma Cell Lines

Mammarian enabled (Mena), a member of the Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) family of proteins, has been implicated in cell motility through regulation of the actin cytoskeleton assembly, including lamellipodial protrusion. Rac1, a member of the Rho family GTPases, also plays a pivotal role in the formation of lamellipodia. Here we report that human Mena (hMena) colocalizes with Rac1 in lamellipodia, and using an unmixing assisted acceptor depletion fluorescence resonance energy transfer (u-adFRET) analysis that hMena associates with Rac1 in vivo in the glioblastoma cell line U251MG. Depletion of hMena by siRNA causes cells to be highly spread with the formation of lamellipodia. This cellular phenotype is canceled by introduction of a dominant negative form of Rac1. A Rac activity assay and FRET analysis showed that hMena knock-down cells increased the activation of Rac1 at the lamellipodia. These results suggest that hMena possesses properties which help to regulate the formation of lamellipodia through the modulation of the activity of Rac1

CD44 Upregulation in E-Cadherin-Negative Esophageal Cancers Results in Cell Invasion

E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform. Using an organotypic reconstruct model, we show increased CD44 expression in areas of cell invasion is associated with MMP-9 at the leading edge. Moreover, Activin A increases cell invasion through CD44 upregulation after E-cadherin loss. Taken together, our results provide functional evidence of CD44 upregulation in esophageal cancer invasion

The functional head of the Cambrian radiodontan (stem-group Euarthropoda) Amplectobelua symbrachiata

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Economic Evaluations of Occupational Health Interventions from a Company’s Perspective: A Systematic Review of Methods to Estimate the Cost of Health-Related Productivity Loss

Objectives: To investigate the methods used to estimate the indirect costs of health-related productivity in economic evaluations from a company’s perspective. Methods: The primary literature search was conducted in Medline and Embase. Supplemental searches were conducted in the Cochrane NHS Economic Evaluation Database, the National Institute for Occupational Safety and Health database, the Ryerson International Labour, Occupational Safety and Health Index database, scans of reference lists and researcher’s own literature database. Article selection was conducted independently by two researchers based on title, keywords, and abstract, and if needed, full text. Differences were resolved by a consensus procedure. Articles were selected based on seven criteria addressing study population, type of intervention, comparative intervention, outcome, costs, language and perspective, respectively. Characteristics of the measurement and valuation of health-related productivity were extracted and analyzed descriptively. Results: A total of 34 studies were included. Costs of health-related productivity were estimated using (a combination of) data related to sick leave, compensated sick leave, light or modified duty or work presenteeism. Data were collected from different sources (e.g. administrative databases, worker self-report, supervisors) and by different methods (e.g. questionnaires, interviews). Valuation varied in terms of reported time units, composition and source of the corresponding price weights, and whether additional elements, such as replacement costs, were included. Conclusions: Methods for measuring and valuing health-related productivity vary widely, hindering comparability of results and decision-making. We provide suggestions for improvement

A glimpse of the ERM proteins

In all eukaryotes, the plasma membrane is critically important as it maintains the architectural integrity of the cell. Proper anchorage and interaction between the plasma membrane and the cytoskeleton is critical for normal cellular processes. The ERM (ezrin-radixin-moesin) proteins are a class of highly homologous proteins involved in linking the plasma membrane to the cortical actin cytoskeleton. This review takes a succinct look at the biology of the ERM proteins including their structure and function. Current reports on their regulation that leads to activation and deactivation was examined before taking a look at the different interacting partners. Finally, emerging roles of each of the ERM family members in cancer was highlighted