Functions of T cells in asthma: more than just T(H)2 cells

Asthma has been considered a T helper 2 (T(H)2) cell-associated inflammatory disease, and T(H)2-type cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, are thought to drive the disease pathology in patients. Although atopic asthma has a substantial T(H)2 cell component, the disease is notoriously heterogeneous, and recent evidence has suggested that other T cells also contribute to the development of asthma. Here, we discuss the roles of different T cell subsets in the allergic lung, consider how each subset can contribute to the development of allergic pathology and evaluate how we might manipulate these cells for new asthma therapies.     

The first gene-based map of Lupinus angustifolius L.-location of domestication genes and conserved synteny with Medicago truncatula

We report the first gene-based linkage map of Lupinus angustifolius (narrow-leafed lupin) and its comparison to the partially sequenced genome of Medicago truncatula. The map comprises 382 loci in 20 major linkage groups, two triplets, three pairs and 11 unlinked loci and is 1,846 cM in length. The map was generated from the segregation of 163 RFLP markers, 135 gene-based PCR markers, 75 AFLP and 4 AFLP-derived SCAR markers in a mapping population of 93 recombinant inbred lines, derived from a cross between domesticated and wild-type parents. This enabled the mapping of five major genes controlling key domestication traits in L. angustifolius. Using marker sequence data, the L. angustifolius genetic map was compared to the partially completed M. truncatula genome sequence. We found evidence of conserved synteny in some regions of the genome despite the wide evolutionary distance between these legume species. We also found new evidence of widespread duplication within the L. angustifolius genome.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorised users.     

Should China subsidize cofiring to meet its 2020 bioenergy target? A spatio‐techno‐economic analysis

China has developed ambitious bioenergy installation targets as part of its broader goals to increase its renewable energy‐generating capacity and decarbonize its economy. A key target feedstock for bioenergy is the 800 million tonnes of agricultural residues that China produces each year. At present, the main financial incentive to support bioenergy generation from agricultural residues is a feed‐in‐tariff provided for bioenergy that is produced by units that take 80% or more of their feedstock energy from biomass. Although this policy has catalysed the construction of many bioenergy units, there are reports that these projects are experiencing serious financial and technical problems, leading to low operational efficiency and even closure. An alternative option for China's agricultural residues is cofiring with coal in existing power stations. However, this is currently unprofitable for power station operators, as cofiring is not eligible for financial assistance through the bioenergy feed‐in‐tariff. In the light of China's ambitious target to install 30GW of bioenergy generation capacity by 2020, this study investigates the extent to which extension of the bioenergy feed‐in‐tariff to include cofiring could contribute towards this goal. The results suggest that 39% of China's straw energy resources are located within 50 km of a power station. Assuming cofiring ratios of up to 10% coal energy replacement, an annual 89–117TWh of electricity could be generated by cofiring agricultural residues collected within 50 km radii of power stations. If China extends its bioenergy subsidies to include cofiring, an annual 62–92TWh can be produced at an internal rate of return of 8% or more. This equates to 42–62% of the bioenergy generation that China might expect if it met its 2020 target of installing 30GW of bioenergy capacity. Overall, this indicates a strong case for the Chinese government to extend its existing bioenergy feed‐in‐tariff to include cofiring at low energy replacement ratios.     

Macrophage Migration Inhibitory Factor Deficiency Ameliorates High-Fat Diet Induced Insulin Resistance in Mice with Reduced Adipose Inflammation and Hepatic Steatosis

Macrophage infiltration is a critical determinant of high-fat diet induced adipose tissue inflammation and insulin resistance. The precise mechanisms underpinning the initiation of macrophage recruitment and activation are unclear. Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, displays chemokine-like properties. Circulating MIF levels are elevated during obesity however its role in high-fat diet induced adipose inflammation and insulin resistance remains elusive. Wildtype and MIF^−/− C57Bl\6J mice were fed chow or high-fat diet. Body weight and food intake was assessed. Glucose homeostasis was monitored by glucose and insulin tolerance tests. Adipose tissue macrophage recruitment and adipose tissue insulin sensitivity was evaluated. Cytokine secretion from stromal vascular fraction, adipose explants and bone marrow macrophages was measured. Inflammatory signature and insulin sensitivity of 3T3-L1-adipocytes co-cultured with wildtype and MIF^−/− macrophage was quantified. Hepatic triacylglyceride levels were assessed. MIF^−/− exhibited reduced weight gain. Age and weight-matched obese MIF^−/− mice exhibited improved glucose homeostasis coincident with reduced adipose tissue M1 macrophage infiltration. Obese MIF^−/− stromal vascular fraction secreted less TNFα and greater IL-10 compared to wildtype. Activation of JNK was impaired in obese MIF^−/−adipose, concomitant with pAKT expression. 3T3-L1-adipocytes cultured with MIF^−/− macrophages had reduced pro-inflammatory cytokine secretion and improved insulin sensitivity, effects which were also attained with MIF inhibitor ISO-1. MIF^−/− liver exhibited reduced hepatic triacyglyceride accumulation, enhanced pAKT expression and reduced NFκB activation. MIF deficiency partially protects from high-fat diet induced insulin resistance by attenuating macrophage infiltration, ameliorating adipose inflammation, which improved adipocyte insulin resistance ex vivo. MIF represents a potential therapeutic target for treatment of high-fat diet induced insulin resistance.     

Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model

Death and lack of functional regeneration of midbrain dopaminergic (DA) neurons, decreased DA input in the target striatum and movement anomalies characterise Parkinson's disease (PD). There is currently no cure for PD. One way to promote recovery would be to induce or enhance DA neurogenesis. Whether DA neurogenesis occurs in the adult midbrain is a matter of debate. Here, we describe the creation of a salamander 6-hydroxydopamine model of PD to examine midbrain DA regeneration. We demonstrate a robust and complete regeneration of the mesencephalic and diencephalic DA system after elimination of DA neurons. Regeneration is contributed by DA neurogenesis, leads to histological restoration, and to full recovery of motor behaviour. Molecular analyses of the temporal expression pattern of DA determinants indicate that the regenerating DA neurons mature along a similar developmental program as their mammalian counterparts during embryogenesis. We also find that the adult salamander midbrain can reactivate radial glia-like ependymoglia cells that proliferate. The salamander model provides insights into the mechanisms of DA regeneration/neurogenesis and may contribute to the development of novel regenerative strategies for the mammalian brain.     

Deep sequencing of naupliar-, cyprid- and adult-specific normalised Expressed Sequence Tag (EST) libraries of the acorn barnacle Balanus amphitrite

In order to improve the genetic characterisation of the barnacle Balanus amphitrite, normalised EST libraries for the developmental stages, viz. nauplius (a mix of instars I and II), cyprid and adult, were generated. The libraries were sequenced independently using 454 technologies and 575,666 reads were generated. For adults, 4843 unique isotigs were estimated and 6754 and 7506 in the cyprid and naupliar stage, respectively. It was found that some of the previously proposed cyprid-specific bcs genes were also expressed during the naupliar and adult stage. Furthermore, as lectins have been hypothesised to influence settlement cue recognition in barnacles, the database was searched for lectin-like isotigs. Two proteins, uniquely expressed in either the cyprid or the adult stage, matched a mannose receptor, and their nucleotide sequences were 33% and 31% identical to a lectin (BRA-3) isolated from Megabalanus rosa. Further characterisation of these genes may suggest their involvement in settlement.     

Filament-Filament Switching Can Be Regulated by Separation Between Filaments Together with Cargo Motor Number

How intracellular transport controls the probability that cargos switch at intersections between filaments is not well understood. In one hypothesis some motors on the cargo attach to one filament while others attach to the intersecting filament, and the ensuing tug-of-war determines which filament is chosen. We investigate this hypothesis using 3D computer simulations, and discover that switching at intersections increases with the number of motors on the cargo, but is not strongly dependent on motor number when the filaments touch. Thus, simply controlling the number of active motors on the cargo cannot account for in vivo observations that found reduced switching with increasing motor number, suggesting additional mechanisms of regulation. We use simulations to show that one possible way to regulate switching is by simultaneously adjusting the separation between planes containing the crossing filaments and the total number of active motors on the cargo. Heretofore, the effect of filament-filament separation on switching has been unexplored. We find that the switching probability decreases with increasing filament separation. This effect is particularly strong for cargos with only a modest number of motors. As the filament separation increases past the maximum head-to-head distance of the motor, individual motors walking along a filament will be unable to reach the intersecting filament. Thus, any switching requires that other motors on the cargo attach to the intersecting filament and haul the cargo along it, while motor(s) engaged on the original filament detach. Further, if the filament separation is large enough, the cargo can have difficulty proceeding along the initial filament because the engaged motors can walk underneath the intersecting filament, but the cargo itself cannot fit between the filaments. Thus, the cargo either detaches entirely from the original filament, or must dip to the side of the initial filament and then pass below the crossing filament.     

Olfactory and visual plant cues as drivers of selective herbivory

Food quality is an important consideration in the foraging strategy of all animals, including herbivores. Those that can detect and assess the nutritional value of plants from afar, using senses such as smell and sight, can forage more efficiently than those that must assess food quality by taste alone. Selective foraging not only affects herbivore fitness but can influence the structure and composition of plant communities, yet little is known about how olfactory and visual cues help herbivores to find preferred plants. We tested the ability of a free‐ranging, generalist mammalian browser, the swamp wallaby Wallabia bicolor, to use olfactory and visual plant cues to find and/or browse differentially on Eucalyptus pilularis seedlings grown under different nutrient conditions. Low‐nutrient seedlings differed from high‐nutrient seedlings, having lighter coloured leaves, red stems and lower biomass and nitrogen content. In the absence of visual cues, wallabies used odour to differentiate vials containing cut seedlings. They visited and investigated patches with high‐nutrient seedling odour most, followed by patches with low‐nutrient seedling odour, and patches with no added odour least. However, when visual and olfactory cues of seedlings were present, wallabies reversed their foraging response and were more likely to browse low‐ than high‐nutrient seedlings. This browsing difference, in turn, disappeared when long‐range visual cues were reduced by pinning seedlings horizontal to the ground. We suggest that visual cues overrode the effects of olfactory cues on browsing patterns of intact seedlings. Our study shows that herbivores can respond to odours of higher nutrient plants but in ecologically realistic scenarios they use a variety of visual and olfactory cues, with a context‐dependent outcome that is not always selection of high nutrient food. Our results demonstrate the importance of testing the sensory abilities of herbivores in realistic multi‐sensory settings to understand their function in selective foraging.