Dendritic cells activated with products released by schistosome larvae drive Th2-type immune responses, which can be inhibited by manipulation of CD40 costimulation

The early immune events in response to infective larvae of the parasitic helminth Schistosoma mansoni are poorly understood, but here for the first time we report on the potential of products released by schistosome larvae (material released in the first 3 It after transformation [0-3hRP]) to stimulate the maturation of dendritic cells (DC) and alter their T-cell-polarizing function. This was performed in comparison with lipopolysaccharide (LPS) and zymosan A, which classically activate DC to prime for Th1- and Th2-type responses, respectively. In our study, immature bone marrow-derived DC stimulated in vitro with 0-3hRP exhibited up-regulated expression of major histocompatibility complex class II, CD40, and CD86 and increased production of interleukin 12p40 (IL-12p40) and IL-6, albeit at lower levels than in response to LPS or zymosan A. Using an in vitro ovalbumin peptide-restricted priming assay, DC matured with 0-3hRP exhibited a potent capacity to drive Th2 polarization of CD4(+) cells from DO11.10 transgenic mice. This was characterized by increased IL-4 production (but not gamma interferon) of a magnitude similar to that primed by DC matured with zymosan A. Inoculation of DO11.10 mice with 0-3hRP-activated DC pulsed with ovalbumin peptide also led to the development of a Th2-type polarized response in the skin-draining lymph nodes and spleen. However, ligation of CD40 on DC by anti-CD40 antibody treatment reversed the ability of 0-3hRP-activated DC to prime for Th2-type responses and instead caused the induction of a more Th1-type response

Is contextualised admission the answer to the access challenge?

This is the final version of the article. Available from Taylor & Francis (Routledge) via the DOI in this record.This article reviews the idea of contextualising applicants to higher education in order to widen access. First, the meaning of contextualised admissions (CAs) is discussed before laying out the rationale for contextualising applicants and the beneficiaries of the policy. The final sections discuss key critiques of CA and conclude by arguing that CA does go some way to addressing the access challenge. To fully realise its potential as a policy intervention though, it is most helpfully part of integrated support for students throughout university and is mindful of the role of universities in wider society to create more equal progression trajectories for young people from a range of backgrounds.This work was supported by Supporting Professionalism in Admissions

Restoring riparian ecosystems: The challenge of accommodating variability and designing restoration trajectories

Flood disturbance processes play a key role in the functioning of riparian ecosystems and in the maintenance of biodiversity along river corridors. As a result, riparian ecosystems can be described as mobile habitat mosaics characterized by variability and unpredictability. Any river restoration initiative should aim to mimic these attributes. This paper suggests that there needs to be an increased institutional capacity to accept some levels of both variability and unpredictability in the ecological outcomes of river restoration projects. Restoration projects have frequently used some form of historical or contemporary reference system to define objectives and to help in the evaluation process. Using these reference systems can give a false sense of the predictability of ecological outcomes. We suggest that reference systems need to be used with caution for six reasons: (1) there are often no appropriate reference systems to use, (2) many catchment parameters have changed since the times of chosen historic reference systems, (3) climate change has been continuous throughout the Holocene, (4) projected climate change is of uncertain magnitude, (5) alien species cannot be avoided, and (6) landscape context changes through time. As well as defining short-term objectives, we suggest that river restoration projects should also formulate longer-term (decadel) restoration trajectories that are less predictable but more representative of real system attributes. Restoration trajectories could be defined using a range of ecological outcomes to accommodate interannual variability. The challenges of defining what levels of variability are important for restoring European floodplain forests are used to demonstrate the difficulties of broadening approaches and creating trajectories. In particular, the changing significance of variability at different spatial and temporal scales is discussed. An account is given of a restoration project at Wicken Fen in the United Kingdom in which nondeterministic approaches to goal setting have been initiated

Making Connections:John Darwin and his Histories of Empire

John Darwin and his Histories of Empir

Turning It Up To Eleven: Re-Evaluating the Role of Financial Frictions in the 2007–2008 Economic Crisis

We analyze the role of public and private financial frictions in the 2007–2008 economic crisis in the United States by extending the model of Drautzburg and Uhlig (2015) to eleven observable variables using data on all three interest rates in the model (policy, private and public). We also include a preference shock in the model, and present an alternative method for describing shock decompositions during and preceding the crisis designed to isolate the impact of the pre-crisis shocks. The estimated model produces an intuitive description of the evolution of the postwar U.S. economy overall and of the economic crisis at the end of the sample period. We find, in contrast to Drautzburg and Uhlig, that monetary and fiscal policy shocks played a significant role in mitigating the effects of the financial crisis

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Finite-size effects for anisotropic bootstrap percolation: logarithmic corrections

In this note we analyze an anisotropic, two-dimensional bootstrap percolation model introduced by Gravner and Griffeath. We present upper and lower bounds on the finite-size effects. We discuss the similarities with the semi-oriented model introduced by Duarte.Comment: Key words: Bootstrap percolation, anisotropy, finite-size effect

1SXPS: A deep Swift X-ray Telescope point source catalog with light curves and spectra

We present the 1SXPS (Swift-XRT Point Source) catalog of 151,524 X-ray point-sources detected by the Swift-XRT in 8 years of operation. The catalog covers 1905 square degrees distributed approximately uniformly on the sky. We analyze the data in two ways. First we consider all observations individually, for which we have a typical sensitivity of ~3e-13 erg/cm2/s (0.3--10 keV). Then we co-add all data covering the same location on the sky: these images have a typical sensitivity of ~9e-14 erg/cm2/s (0.3--10 keV). Our sky coverage is nearly 2.5 times that of 3XMM-DR4, although the catalog is a factor of ~1.5 less sensitive. The median position error is 5.5" (90% confidence), including systematics. Our source detection method improves on that used in previous XRT catalogs and we report >68,000 new X-ray sources. The goals and observing strategy of the Swift satellite allow us to probe source variability on multiple timescales, and we find ~30,000 variable objects in our catalog. For every source we give positions, fluxes, time series (in four energy bands and two hardness ratios), estimates of the spectral properties, spectra and spectral fits for the brightest sources, and variability probabilities in multiple energy bands and timescales.Comment: 27 pages, 19 figures; accepted for publication in ApJS. The accompanying website, http://www.swift.ac.uk/1SXPS is live; the Vizier entry should be available shortl

Piperazine-based N4-type 16-membered macroheterocycles and their nickel(II) complexes

Square-planar diamagnetic nickel(II) complexes 5a and 5b containing 16-membered diamino-diimino ligands were prepared from the corresponding open-chain complexes 2a and 2b via condensation with o-phthalic dialdehyde in methanol. The solid-state structure of the starting complex 2b revealed the cisoid conformation of aryl groups compared to the transoid one found in the case of 2a. At the same time, the cisoid conformation is not retained in acetone solution: rather, the tert-Bu-substituted complex 2b was fully transformed into the trans form whereas its analogue 2aexhibits both cis and transforms in acetone solution. The cisoid conformation was also observed for the cyclic structures 5a and 5b by X-ray analysis and VT NMR experiments. The borohydride reduction of 5a with subsequent cyanide-assisted removal of nickel led to a new 16-membered tetraazamacrocycle 6. Its X-ray structure showed a cisoid conformation supported by two intramolecular hydrogen bonds that was also sustained in solution. VT NMR experiments revealed the degenerative interconvertion of a macrocycle with activation energy ca. 41.9±0.8 kJ/mol