On almost-planar graphs

A nonplanar graph G is called almost-planar if for every edge e of G, at least one of G\e and G/e is planar. In 1990, Gubser characterized 3-connected almost-planar graphs in his dissertation. However, his proof is so long that only a small portion of it was published. The main purpose of this paper is to provide a short proof of this result. We also discuss the structure of almost-planar graphs that are not 3-connected

The Pivotal Role of Macrophages in Metabolic Distress

Obesity is a prevalent condition with several associated co-morbidities including the development of metabolic diseases. In obesity there is immune cell infiltration into the white adipose tissue and this is associated with the generation of inflammation and insulin resistance (IR). A large majority of the infiltrating leukocytes in obese adipose tissue are pro-inflammatory macrophages, which upon activation induce a switch in metabolism from oxidative phosphorylation, as is utilised by macrophages in lean adipose tissue, towards aerobic glycolysis. The signalling pathways evoked in the recruited macrophages induce the release of pro-inflammatory cytokines, in signalling pathways which directly interfere with insulin signalling and thus induce a state of IR. As macrophages appear to play such a pivotal role in the generation of IR and are the largest leukocyte population in the adipose tissue, they provide a promising therapeutic target. Indeed, there are several strategies currently being studied to induce a ‘switch’ in macrophages associated with obese adipose tissue, towards the phenotype of those associated with lean adipose tissue, with arguably the most promising being those strategies designed to target the metabolic pathways within the macrophages. This chapter will discuss the polarisation and activation of macrophages within lean and obese adipose tissue and how these cells can be targeted therapeutically

EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons

RNA-binding proteins (RBPs) function in higher-order assemblages such as RNA granules to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of neuronal Fragile X granules that associate with axonal mRNA and ribosomes in the intact brain. However, the FXR2P domains important for assemblage formation in a cellular system are unknown. Here we used an EGFP insertional mutagenesis approach to probe for FXR2P intrinsic features that influence its structural states. We tested 18 different in-frame FXR2P(EGFP) fusions in neurons and found that the majority did not impact assemblage formation. However, EGFP insertion within a 23 amino acid region of the low complexity (LC) domain induced FXR2P(EGFP) assembly into two distinct fibril states that were observed in isolation or in highly-ordered bundles. FXR2P(EGFP) fibrils exhibited different developmental timelines, ultrastructures and ribosome associations. Formation of both fibril types was dependent on an intact RNA-binding domain. These results suggest that restricted regions of the LC domain, together with the RNA-binding domain, may be important for FXR2P structural state organization in neurons

Strategic analysis of the drought resilience of water supply systems

Severe droughts can result in shortages of water supplies, with widespread social and economic consequences. Here we use a coupled simulation model to assess the reliability of public water supplies in England, in the context of changing scenarios of water demand, water regulation and climate change. The coupled simulation model combines climate simulations, a national-scale hydrological model and a national-scale water resource systems model to demonstrate how extreme meteorological droughts translate into hydrological droughts and water shortages for water users. We use this model to explore the effectiveness of strategic water resource options that are being planned in England to secure water supplies to most of England's population up to a drought return period of 1 in 500 years. We conclude that it is possible to achieve a 1-in-500-years standard in locations where strategic resource options are used, while also reducing water abstraction to restore the aquatic environment. However, the target will be easier to achieve if effective steps are also taken to reduce water demand. This article is part of the Royal Society Science+ meeting issue ‘Drought risk in the Anthropocene’

MHCII-mediated dialog between group 2 innate lymphoid cells and CD4+ T cells potentiates type 2 immunity and promotes parasitic helminth expulsion

Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity

Cutting Edge: Suppression of GM-CSF Expression in Murine and Human T Cells by IL-27:suppression of GM-CSF expression in murine and human T cells by IL-27

GM-CSF is a potent pro-inflammatory cytokine that plays a pathogenic role in the CNS inflammatory disease, EAE. As IL-27 ameliorates EAE, we hypothesised that IL-27 suppresses GM-CSF expression by T cells. We found that IL-27 suppressed GM-CSF expression in CD4(+) and CD8(+) T cells in splenocyte and purified T cell cultures. IL-27 suppressed GM-CSF in Th1, but not Th17 cells. IL-27 also suppressed GM-CSF expression by human T cells in non-polarised and Th1 but not Th17 polarised PBMC cultures. In vivo, IL-27p28 deficiency resulted in increased GM-CSF expression by CNS infiltrating T cells during Toxoplasma gondii infection. While in vitro suppression of GM-CSF by IL-27 was independent of IL-2 suppression, IL-10 up-regulation or SOCS3 signalling, we observed that IL-27-driven suppression of GM-CSF was STAT1 dependent. Our findings demonstrate that IL-27 is a robust negative regulator of GM-CSF expression in T cells which likely inhibits T cell pathogenicity in CNS inflammation

The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism

Induction of a type 2 cellular response in the white adipose tissue leads to weight loss and improves glucose homeostasis in obese animals. Injection of obese mice with recombinant helminth-derived Schistosoma mansoni egg-derived v1 (v1), a potent inducer of type 2 activation, improves metabolic status involving a mechanism reliant upon release of the type 2 initiator cytokine IL-33. IL-33 initiates the accumulation of group 2 innate lymphoid cells (ILC2s), eosinophils, and alternatively activated macrophages in the adipose tissue. IL-33 release from cells in the adipose tissue is mediated by the RNase activity of v1; however, the ability of v1 to improve metabolic status is reliant upon effective binding of v1 to CD206. We demonstrate a novel mechanism for RNasemediated release of IL-33 inducing ILC2-dependent improvements in the metabolic status of obese animals.— Hams, E., Bermingham, R., Wurlod, F. A., Hogan, A. E., O’Shea, D., Preston, R. J., Rodewald, H.-R., McKenzie, A. N. J., Fallon, P. G. The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism