RIG-I-like Receptors Direct Inflammatory Macrophage Polarization against West Nile Virus Infection.

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 macrophage polarization in vivo and the control of WNV infection through potential downstream control of ATF4 and SMAD4 to regulate target gene expression for cell polarization. These analyses reveal the RLR-driven signature of macrophage polarization, innate immune protection, and immune programming against WNV infection

TRA-928: FISH BARRIER MITIGATION OF AN OVERSTEEPENED CULVERT WITHIN SAUGEEN FIRST NATION RESERVE

A deteriorated concrete box culvert conveying a tributary of the Saugeen River under Highway 21 in Ontario had reached the end of its lifespan and was in need of replacement. The tributary supports a diverse range of coldwater fish species such as Rainbow Trout; however, fish passage, particularly upstream migration, has been cut off since the culvert and highway were constructed over seventy-five years ago. Specifically, fish passage has been hindered by shallow sheet flow along the sixty metre flat bottom, excessive velocities associated with the smooth, seven percent gradient, and a perched barrier at the downstream outlet. A key component of the culvert replacement was an effort to improve the overall condition of the tributary’s natural environment, including the promotion of fish passage and migration opportunities. The culvert replacement project undertaken by the Ontario Ministry of Transportation (MTO) and MMM Group, coupled resources with the Saugeen Ojibway Nation (SON) Environment office, Parsons biologists, and Aquafor geomorphologists. The most ecologically sensitive replacement methodology of an open bottom structure was not viable for this project as it would have required a full closure of the Highway for approximately four months. A circular steel pipe culvert installed through tunneling was designed to by-pass and replace the existing concrete box culvert. In an effort to mitigate the current barriers to fish with the new pipe culvert, a prefabricated corrugated steel slip liner with engineered baffle arrangement was integrated into the design. The baffle configuration and geometry was designed by Jason Duguay (Université de Sherbrooke) and Ken Hannaford (Gov. NFLD), and the slip liner construction by the Corrugated Steel Pipe Institute. Construction of the new culvert and slip liner was completed in December, 2015, and a two year monitoring program will be undertaken to assess the effectiveness of barrier mitigation and geomorphic stability of the tributary

Mapping structural diversity in networks sharing a given degree distribution and global clustering: Adaptive resolution grid search evolution with Diophantine equation-based mutations

Methods that generate networks sharing a given degree distribution and global clustering can induce changes in structural properties other than that controlled for. Diversity in structural properties, in turn, can affect the outcomes of dynamical processes operating on those networks. Since exhaustive sampling is not possible, we propose a novel evolutionary framework for mapping this structural diversity. The three main features of this framework are: (a) subgraph-based encoding of networks, (b) exact mutations based on solving systems of Diophantine equations, and (c) heuristic diversity-driven mechanism to drive resolution changes in the MapElite algorithm.We show that our framework can elicit networks with diversity in their higher-order structure and that this diversity affects the behaviour of the complex contagion model. Through a comparison with state of the art clustered network generation methods, we demonstrate that our approach can uncover a comparably diverse range of networks without needing computationally unfeasible mixing times. Further, we suggest that the subgraph-based encoding provides greater confidence in the diversity of higher-order network structure for low numbers of samples and is the basis for explaining our results with complex contagion model. We believe that this framework could be applied to other complex landscapes that cannot be practically mapped via exhaustive sampling

Disability and participation in breast and bowel cancer screening in England: a large prospective study.

BACKGROUND: There is limited information about participation in organised population-wide screening programmes by people with disabilities. METHODS: Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants. RESULTS: Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. CONCLUSION: Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability

From Senseless to Sensory Democracy: Insights from Applied and Participatory Theatre

This article seeks to stimulate a fresh and inter-disciplinary debate which revolves around the need to move from a ‘senseless democracy’ that is insufficiently attuned to the dilemmas and challenges of fostering meaningful political engagement to a more ‘sensory democracy’. It achieves this by first exploring and dissecting recent works within democratic theory that emphasize the role of ‘watching’ and ‘listening’ within socio-political relationships. It then goes on to develop a set of constructive criticisms by applying insights drawn from the fields of practical aesthetics and applied theatre. Not only does this exercise allow us to take the analytical lens far beyond the focus on voice-based forms of expression that have hitherto dominated political analysis, it demonstrates the value of inter-disciplinary scholarship in exposing sensory-subtleties that raise distinctive questions for both politics ‘as theory’ and politics ‘as practice’

Loss of Hairless Confers Susceptibility to UVB-Induced Tumorigenesis via Disruption of NF-kappaB Signaling

In order to model squamous cell carcinoma development in vivo, researchers have long preferred hairless mouse models such as SKH-1 mice that have traditionally been classified as ‘wild-type’ mice irrespective of the genetic factors underlying their hairless phenotype. The work presented here shows that mutations in the Hairless (Hr) gene not only result in the hairless phenotype of the SKH-1 and Hr−/− mouse lines but also cause aberrant activation of NFκB and its downstream effectors. We show that in the epidermis, Hr is an early UVB response gene that regulates NFκB activation and thereby controls cellular responses to irradiation. Therefore, when Hr expression is decreased in Hr mutant animals there is a corresponding increase in NFκB activity that is augmented by UVB irradiation. This constitutive activation of NFκB in the Hr mutant epidermis leads to the stimulation a large variety of downstream effectors including the cell cycle regulators cyclin D1 and cyclin E, the anti-apoptosis protein Bcl-2, and the pro-inflammatory protein Cox-2. Therefore, Hr loss results in a state of uncontrolled epidermal proliferation that promotes tumor development, and Hr mutant mice should no longer be considered merely hairless 'wild-type' mice. Instead, Hr is a crucial UVB response gene and its loss creates a permissive environment that potentiates increased tumorigenesis

Leaf colour as a signal of chemical defence to insect herbivores in wild cabbage (Brassica Oleracea)

Leaf colour has been proposed to signal levels of host defence to insect herbivores, but we lack data on herbivory, leaf colour and levels of defence for wild host populations necessary to test this hypothesis. Such a test requires measurements of leaf spectra as they would be sensed by herbivore visual systems, as well as simultaneous measurements of chemical defences and herbivore responses to leaf colour in natural host-herbivore populations. In a large-scale field survey of wild cabbage (Brassica oleracea) populations, we show that variation in leaf colour and brightness, measured according to herbivore spectral sensitivities, predicts both levels of chemical defences (glucosinolates) and abundance of specialist lepidopteran (Pieris rapae) and hemipteran (Brevicoryne brassicae) herbivores. In subsequent experiments, P. rapae larvae achieved faster growth and greater pupal mass when feeding on plants with bluer leaves, which contained lower levels of aliphatic glucosinolates. Glucosinolate-mediated effects on larval performance may thus contribute to the association between P. rapae herbivory and leaf colour observed in the field. However, preference tests found no evidence that adult butterflies selected host plants based on leaf coloration. In the field, B. brassicae abundance varied with leaf brightness but greenhouse experiments were unable to identify any effects of brightness on aphid preference or performance. Our findings suggest that although leaf colour reflects both levels of host defences and herbivore abundance in the field, the ability of herbivores to respond to colour signals may be limited, even in species where performance is correlated with leaf colour